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MS213800	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: BACKGROUND There are few data on the use of alternative therapies in adult asthma and their impact on health outcomes . OBJECTIVE The objective of this study was to study the prevalence and morbidity of asthma self-treatment with herbs , coffee or black tea , and over-the-counter ( OTC ) medications containing ephedrine or epinephrine . METHODS We carried out a cross-sectional analysis of interview data for 601 adults with asthma recruited from a r and om sample of pulmonary and allergy specialists . We estimated the 12-month prevalence of reported use of herbal products , coffee or black tea , or OTC products to self-treat asthma and their association with emergency department visits and hospitalization . RESULTS Herbal asthma self-treatment was reported by 46 ( 8 % ; 95 % confidence interval [ CI ] 6 % to 10 % ) ; coffee or black tea self-treatment by 36 ( 6 % ; 95 % CI 4 % to 8 % ) , epinephrine or ephedrine OTC use by 36 ( 6 % ; 95 % CI 4 % to 8 % ) , and any of the three practice s by 98 subjects ( 16 % ; 95 % CI 13 % to 19 % ) . Adjusting for demographic and illness covariates , herbal use ( odds ratio [ OR ] 2.5 ; 95 % CI 1.1 to 5.6 ) and coffee or black tea use ( OR 3.1 ; 95 % CI 1.2 to 7.8 ) were associated with asthma hospitalization ; OTC use was not ( OR 0.8 ; 95 % CI 0.3 to 2.5 ) . CONCLUSIONS Even among adults with access to specialty care for asthma , self-treatment with nonprescription products was common and was associated with increased risk of reported hospitalization . This association does not appear to be accounted for by illness severity or other disease covariates . It may reflect delay in utilization of more efficacious treatments Difficultes ethiques rencontrees pour l'organisation d'experimentations cliniques concernant l'asthme chez l'enfant ( un appareil pour inhalation de corticosteroides , une method e d'immunotherapie , une method e de desensibilisation Asthma is characterized as a chronic inflammatory process . Pycnogenol((R ) ) , a bioflavonoid mixture extracted from Pinus maritima , is known to scavenge free radicals while possessing antioxidant and antiinflammatory properties . The objective of this study was to evaluate the efficiency of this agent in a r and omized , double-blinded , placebo-controlled , crossover study in patients with varying asthma severity . Twenty-six patients who fulfilled the American Thoracic Society criteria for asthma were enrolled in the study . Medical history , physical examination , blood sample analyses , and spirometric values were obtained at baseline , 4 weeks , and 8 weeks . The patients were r and omly assigned to receive either 1 mg/lb/day ( maximum 200 mg/day ) Pycnogenol or placebo for the first period of 4 weeks and then crossed over to the alternate regimen for the next 4 weeks . No adverse effects were observed related to the study drug . Within the contingent of 22 patients who completed the study , almost all responded favorably to Pycnogenol in contrast to placebo . Pycnogenol treatment also significantly reduced serum leukotrienes compared with placebo . The results of this pilot study indicate that Pycnogenol may be a valuable nutraceutical in the management of chronic asthma . We recommend that further clinical trials be conducted in larger groups of asthmatics to establish its efficacy OBJECTIVE To explore the mechanism of acupoint electro-superconducting therapy with Chinese herbal drugs contained pad in treating children asthma . METHODS Sixty asthma children in the mild to moderate stage of asthma attack were r and omly divided into two groups , the treated group and the control group . Besides the basic treatment , acupoint electro-superconducting therapy with the pad containing Chinese herbal drugs was applied to the treated group , and to the control group the same therapy but with pad of placebo was applied , seven days as a course of treatment . The peak exhalation force ( PEF ) was measured daily , and the cytokines , interleukin-10 ( IL-10 ) and interferon-gamma ( IFN-gamma ) were determined before and after treatment . RESULTS No significant difference was found in the ratio of patients ' PEF to the normal predicted value between the two groups before treatment ( P > 0.05 ) . But on the fourth day of the treatment course , the increase of PEF in the treated group was more obvious than that in the control group ( P < 0.05 ) . The IL-10 levels of two groups were raised after ending the treatment course , but the increment in the treated group was more obvious ( P < 0.01 ) . However , the changes of IFN-gamma levels after treatment showed insignificant difference between the two groups ( P > 0.05 ) . CONCLUSION Acupoint electro-superconducting therapy with Chinese herbal drugs contained pad is helpful to improve the pulmonary function of children with asthma , it could also increase the serum IL-10 level in attack stage of the asthma children The efficacy and tolerability of a butterbur root extract ( Petadolex ) for the treatment of asthma was analyzed in a prospect i ve , non-r and omized , open trial . Subjects included 64 adults and 16 children/adolescents treated for two months with the extract , followed by two months during which the intake of the extract was optional . Concomitant asthma medication was permitted . The number , duration , and severity of asthma attacks decreased , while peak flow , forced expiratory volume ( FEV1 ) , and all measured symptoms improved during therapy . In addition , more than 40 percent of patients using asthma medications at baseline reduced intake of these medications by the end of the study . This study suggests the Petasites hybridus extract Petadolex is an effective and safe therapy for the treatment of asthma CONTEXT A prior national survey documented the high prevalence and costs of alternative medicine use in the United States in 1990 . OBJECTIVE To document trends in alternative medicine use in the United States between 1990 and 1997 . DESIGN Nationally representative r and om household telephone surveys using comparable key questions were conducted in 1991 and 1997 measuring utilization in 1990 and 1997 , respectively . PARTICIPANTS A total of 1539 adults in 1991 and 2055 in 1997 . MAIN OUTCOMES MEASURES Prevalence , estimated costs , and disclosure of alternative therapies to physicians . RESULTS Use of at least 1 of 16 alternative therapies during the previous year increased from 33.8 % in 1990 to 42.1 % in 1997 ( P < or = .001 ) . The therapies increasing the most included herbal medicine , massage , megavitamins , self-help groups , folk remedies , energy healing , and homeopathy . The probability of users visiting an alternative medicine practitioner increased from 36.3 % to 46.3 % ( P = .002 ) . In both surveys alternative therapies were used most frequently for chronic conditions , including back problems , anxiety , depression , and headaches . There was no significant change in disclosure rates between the 2 survey years ; 39.8 % of alternative therapies were disclosed to physicians in 1990 vs 38.5 % in 1997 . The percentage of users paying entirely out-of-pocket for services provided by alternative medicine practitioners did not change significantly between 1990 ( 64.0 % ) and 1997 ( 58.3 % ) ( P=.36 ) . Extrapolations to the US population suggest a 47.3 % increase in total visits to alternative medicine practitioners , from 427 million in 1990 to 629 million in 1997 , thereby exceeding total visits to all US primary care physicians . An estimated 15 million adults in 1997 took prescription medications concurrently with herbal remedies and /or high-dose vitamins ( 18.4 % of all prescription users ) . Estimated expenditures for alternative medicine professional services increased 45.2 % between 1990 and 1997 and were conservatively estimated at $ 21.2 billion in 1997 , with at least $ 12.2 billion paid out-of-pocket . This exceeds the 1997 out-of-pocket expenditures for all US hospitalizations . Total 1997 out-of-pocket expenditures relating to alternative therapies were conservatively estimated at $ 27.0 billion , which is comparable with the projected 1997 out-of-pocket expenditures for all US physician services . CONCLUSIONS Alternative medicine use and expenditures increased substantially between 1990 and 1997 , attributable primarily to an increase in the proportion of the population seeking alternative therapies , rather than increased visits per patient The aim of this study was to evaluate the efficacy and safety of a Chinese herbal formula modified Mai-Men-Dong-Tang ( mMMDT ) for treatment of persistent , mild-to-moderate asthma . A total of 100 asthmatic patients were enrolled and assigned to three treatment groups in this double-blind , r and omized , placebo-controlled clinical trial . Over a period of 4 months , patients in groups A and B received 80 and 40 mg/kg/day of mMMDT , while those in group C received a placebo . Efficacy variables included changes in forced expiratory volume in 1 s ( FEV1 ) , symptom score , serum total immunoglobulin E ( IgE ) , and dust mite-specific IgE. Safety assessment s included complete blood count , and liver and kidney function . Relative to baseline , significantly greater increases in FEV1 were demonstrated for both A and B groups in comparison with the placebo-treated analog ( both p < 0.05 ) . Further , similar improvements in symptom score were observed for both mMMDT treatment groups . The serum total IgE for group A showed a decreasing tendency after treatment but no statistical difference was noted . Furthermore , no drug-related adverse effects were reported . Blood test , and liver and kidney function were within normal range during the study , with no marked changes demonstrated over time . In conclusion , the Chinese herbal formula mMMDT provided improvements in lung function and relieved asthma symptoms in our sample of patients . Given its efficacy and safety , we consider mMMDT a credible treatment regimen for persistent , mild-to-moderate asthma Alternative medicine use has increased at a remarkable pace all over the world in recent years . Although herbal medicine for the treatment of asthma is becoming the focus of public attention , r and omized studies had not been performed , even in Eastern countries including Japan . This study was design ed to investigate whether one of the Japanese government approved herbal complexes Saiboku-to ( TJ-96 ) is effective for the treatment of atopic asthma , and to investigate whether this protective activity is associated with a reduction in eosinophilic inflammation . A double-blind , r and omized , crossover design was used . Subjects received 2.5 g of TJ-96 or placebo orally 3 times daily for 4 weeks and then , after a washout period of at least 4 weeks , crossed over to receive the alternative treatment . We assessed the effects of pretreatment with TJ-96 on bronchoconstriction precipitated by inhalation of methacholine . Furthermore , eosinophil counts and measurement of eosinophilic cationic protein ( ECP ) were performed . After 4 weeks of treatment with TJ-96 , values of PC20 -methacholine significantly improved in the treatment with TJ-96 . Also , patients ' symptoms , blood eosinophils , serum ECP , sputum eosinophils , and sputum ECP were significantly decreased . Our results suggest that TJ-96 has an antiinflammatory effect on bronchial eosinophilic infiltration . This study raises further interesting therapeutic possibilities and argues for further trials of new approaches to the treatment of asthma Essential fatty acids are cl aim ed to have positive effects in atopic diseases . In a double blind , placebo controlled , parallel group study 58 out of 60 children , with atopic dermatitis and the need for regular treatment with topical skin steroids , completed a 16 weeks ' treatment period with either Epogam evening primrose oil or placebo capsules . Twenty two of these subjects also had asthma . The parents used diaries to record symptom scores and concomitant medication . Peak expiratory flow was measured and disease activity was monitored by the clinician every four weeks . The plasma concentrations of essential fatty acids increased significantly in the group treated with Epogam capsules . The study demonstrated significant improvements of the eczema symptoms but no significant difference was found between the placebo and the Epogam groups . No therapeutic effect was shown on asthma symptoms or fidget Dietary gammalinolenic acid ( GLA ) , a potent inhibitor of 5-lipoxygenase ( 5-LOX ) and suppressor of leukotriene B4 ( LTB4 ) , can attenuate the clinical course of rheumatoid arthritics , with negligible side effects . Since Zileuton , also an inhibitor of 5-LOX , attenuates asthma but with an undesirable side effect , we investigated whether dietary GLA would suppress bio synthesis of PMN-LTB4 isolated from asthma patients and attenuate asthma . Twenty-four mild-moderate asthma patients ( 16 - 75 years ) were r and omized to receive either 2.0 g daily GLA ( b Output:	The data that are available from the studies provide only a small insight into the long-term efficacy and harm profiles of these treatments .
MS213801	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Background To reduce the duration of sick leave and loss of productivity due to common mental disorders ( CMDs ) , we developed a return-to-work programme to be provided by occupational physicians ( OPs ) based on the principles of exposure in vivo ( RTW-E programme ) . This study evaluates this programme 's effectiveness and cost-effectiveness by comparing it with care as usual ( CAU ) . The three research questions we have are : 1 ) Is an RTW-E programme more effective in reducing the sick leave of employees with common mental disorders , compared with care as usual ? 2 ) Is an RTW-E programme more effective in reducing sick leave for employees with anxiety disorders compared with employees with other common mental disorders ? 3 ) From a societal perspective , is an RTW-E programme cost-effective compared with care as usual ? Methods / design This study was design ed as a pragmatic cluster-r and omized controlled trial with a one-year follow-up and r and omization on the level of OPs . We aim ed for 60 OPs in order to include 200 patients . Patients in the intervention group received the RTW-E programme . Patients in the control group received care as usual . Eligible patients had been on sick leave due to common mental disorders for at least two weeks and no longer than eight weeks . As primary outcome measures , we calculated the time until full return to work and the duration of sick leave . Secondary outcome measures were time until partial return to work , prevalence rate of sick leave at 3 , 6 , 9 , and 12 months ' follow-up , and scores of symptoms of distress , anxiety , depression , somatization , and fatigue ; work capacity ; perceived working conditions ; self-efficacy for return to work ; coping behaviour ; avoidance behaviour ; patient satisfaction ; and work adaptations . As process measures , we used indices of compliance with the intervention in the intervention group and employee-supervisor communication in both groups . Economic costs were calculated from a societal perspective . The total costs consisted of the costs of consuming health care , costs of production loss due to sick leave and reduced productivity , and out-of-pocket costs of patients for travelling to their OP . Discussion The results will be published in 2009 . The strengths and weaknesses of the study protocol are discussed . Trial registration IS RCT Background Considering the high costs of sick leave and the consequences of sick leave for employees , an early return-to-work of employees with mental disorders is very important . Therefore , a workplace intervention is developed based on a successful return-to-work intervention for employees with low back pain . The objective of this paper is to present the design of a r and omized controlled trial evaluating the cost-effectiveness of the workplace intervention compared with usual care for sick-listed employees with common mental disorders . Methods The study is design ed as a r and omized controlled trial with a follow-up of one year . Employees eligible for this study are on sick leave for 2 to 8 weeks with common mental disorders . The workplace intervention will be compared with usual care . The workplace intervention is a stepwise approach that aims to reach consensus about a return-to-work plan by active participation and strong commitment of both the sick-listed employee and the supervisor . Outcomes will be assessed at baseline , 3 , 6 , 9 and 12 months . The primary outcome of this study is lasting return-to-work , which will be acquired from continuous registration systems of the companies after the follow-up . Secondary outcomes are total number of days of sick leave during the follow-up , severity of common mental disorders , coping style , job content , and attitude , social influence , and self-efficacy determinants . Cost-effectiveness will be evaluated from the societal perspective . A process evaluation will also be conducted . Discussion Return-to-work is difficult to discuss in the workplace for sick-listed employees with mental disorders and their supervisors . Therefore , this intervention offers a unique opportunity for the sick-listed employee and the supervisor to discuss barriers for return-to-work . Results of this study will possibly contribute to improvement of disability management for sick-listed employees with common mental disorders . Results will become available in 2009.Trial registration IS RCT Background Musculoskeletal disorders ( MSDs ) are a major reason for impaired work productivity and sick leave . In 2009 , a national rehabilitation program was introduced in Sweden to promote work ability , and patients with MSDs were offered multimodal rehabilitation . The aim of this study was to analyse the effect of this program on health related quality of life , function , sick leave and work ability . Methods We conducted a prospect i ve , observational cohort study including 406 patients with MSDs attending multimodal rehabilitation . Changes over time and differences between groups were analysed concerning function , health related quality of life , work ability and sick leave . Regression analyses were used to study the outcome variables health related quality of life ( measured with EQ-5D ) , and sick leave . Results Functional ability and health related quality of life improved after rehabilitation . Patients with no sick leave/disability pension the year before rehabilitation , improved health related quality of life more than patients with sick leave/disability pension the year before rehabilitation ( p = 0.044 ) . During a period of −/+ four months from rehabilitation start , patients with EQ-5D ≥ 0.5 at rehabilitation start , reduced their net sick leave days with 0.5 days and patients with EQ-5D < 0.5 at rehabilitation start , increased net sick leave days with 1.5 days ( p = 0.019 ) . Factors negatively associated with sick leave at follow-up were earlier episodes of sick leave/disability pension , problems with exercise tolerance functions and mobility after rehabilitation . Higher age was associated with not being on sick leave at follow-up and reaching an EQ-5D ≥ 0.5 at follow-up . Severe pain after rehabilitation , problems with exercise tolerance functions , born outside of Sweden and full-time sick leave/disability pension the year before rehabilitation were all associated with an EQ-5D level < 0.5 at follow-up . Conclusions Patients with MSDs participating in a national work promoting rehabilitation program significantly improved their health related quality of life and functional ability , especially those with no sick leave . This shows that vocational rehabilitation programs in a primary health care setting are effective . The findings of this study can also be valuable for more appropriate patient selection for rehabilitation programs for MSDs Background Major depressive disorder is among the medical conditions with the highest negative impact on work outcome . However , little is known regarding evidence -based interventions targeting the improvement of work outcomes in depressed employees . In this paper , the design of a r and omized controlled trial is presented in order to evaluate the effectiveness of adjuvant occupational therapy in employees with depression . This occupational intervention is based on an earlier intervention , which was design ed and proven effective by our research group , and is the only intervention to date that specifically targets work outcome in depressed employees . Methods / Design In a two-arm r and omized controlled trial , a total of 117 participants are r and omized to either ' care as usual ' or ' care as usual ' with the addition of occupational therapy . Patients included in the study are employees who are absent from work due to depression for at least 25 % of their contract hours , and who have a possibility of returning to their own or a new job . The occupational intervention consists of six individual sessions , eight group sessions and a work-place visit over a 16-week period . By increasing exposure to the working environment , and by stimulating communication between employer and employee , the occupational intervention aims to enhance self-efficacy and the acquisition of more adaptive coping strategies . Assessment s take place at baseline , and at 6 , 12 , and 18-month follow-ups . Primary outcome measure is work participation ( hours of absenteeism and time until work resumption ) . Secondary outcome measures are work functioning , symptomatology , health-related quality of life , and neurocognitive functioning . In addition , cost-effectiveness is evaluated from a societal perspective . Finally , mechanisms of change ( intermediate outcomes ) and potential patient-treatment matching variables are investigated . Discussion This study hopes to provide valuable knowledge regarding an intervention to treat depression , one of the most common and debilitating diseases of our time . If our intervention is proven ( cost- ) effective , the personal , economic , and health benefits for both patients and employers are far-reaching . Trial registration R and omised controlled trial to evaluate the effectiveness of collaborative care in a Dutch occupational healthcare setting : 126 workers on sick leave with major depressive disorder were r and omised to usual care ( n = 61 ) or collaborative care ( n = 65 ) . After 3 months , collaborative care was more effective on the primary outcome measure of treatment response ( i.e. reduction in symptoms of ≥50 % ) on the Patient Health Question naire-9 ( PHQ-9 ) . However , the groups did not differ on the PHQ-9 as a continuous outcome measure . Implication s of these results are discussed Background There is a paucity of method ologically robust vocational rehabilitation ( VR ) intervention trials . This study assessed the feasibility and acceptability of a VR trial of women with breast cancer to inform the development of a larger interventional study . Methods Women were recruited in Scotl and and r and omised to either a case management VR service or to usual care . Data were collected on eligibility , recruitment and attrition rates to assess trial feasibility , and interviews conducted to determine trial acceptability . Sick leave days ( primary outcome ) were self-reported via postal question naire every 4 weeks during the first 6 months post-surgery and at 12 months . Secondary outcome measures were change in employment pattern , quality of life and fatigue . Results Of the 1,114 women assessed for eligibility , 163 ( 15 % ) were eligible . The main reason for in eligibility was age ( > 65 years , n = 637 , 67 % ) . Of those eligible , 111 ( 68 % ) received study information , of which 23 ( 21 % ) consented to participate in the study . Data for 18 ( 78 % ) women were analysed ( intervention : n = 7 ; control : n = 11 ) . Participants in the intervention group reported , on average , 53 fewer days of sick leave over the first 6 months post-surgery than those in the control group ; however , this difference was not statistically significant ( p = 0.122 ; 95 % confidence interval −15.8 , 122.0 ) . No statistically significant differences were found for secondary outcomes . Interviews with trial participants indicated that trial procedures , including recruitment , r and omisation and research instruments , were acceptable . Conclusions Conducting a pragmatic trial of effectiveness of a VR intervention among cancer survivors is both feasible and acceptable , but more research about the exact components of a VR intervention and choice of outcomes to measure effectiveness is required . VR to assist breast cancer patients in the return to work process is an important component of cancer survivorship plans . Trial registration IS RCT Purpose . Test the feasibility and impact of an automated workplace mental health assessment and intervention . Design . Efficacy was evaluated in a r and omized control trial comparing employees who received screening and intervention with those who received only screening . Setting . Workplace . Subjects . 463 volunteers from Boston Medical Center , Boston University , and EMC and other employed adults , among whom 164 were r and omized to the intervention ( N = 87 ) and control ( N = 77 ) groups . Intervention . The system administers a panel of telephonic assessment instruments followed by tailored information , education , and referrals . Measures . The Work Limitation Question naire , the Medical Outcomes Question naire Short Form-12 , the Patient Health Question naire-9 , question 10 from the Patient Health Question naire to measure functional impairment , and the Perceived Stress Scale-4 and questions written by study psychiatrists to measure emotional distress and social support respectively . The WHO-Five Well-being Index was administered to measure overall well-being . Analysis . Independent sample t-tests and χ2 tests as well as mean change were used to compare the data . Results . No significant differences on 16 of the 20 comparisons at 3- and 6-month time points . The intervention group showed a significant improvement in depression ( p ≤ .05 ) at 3 months and on two Work Limitation Question naire subscales , the Mental-Interpersonal Scale ( p ≤ .05 ) and the Time and Scheduling Scale ( p ≤ .05 ) , at 3 and 6 months respectively with a suggestive improvement in mental health at 6 months ( p ≤ .10 ) . Conclusions . This is a potentially fruitful area for research with important implication s for workplace behavioral interventions . ( Am J Health Promot 2011;25[3]:207–216 . Background To describe the design of a population based r and omized controlled trial ( RCT ) , including a cost-effectiveness analysis , comparing participative ergonomics interventions between 2–8 weeks of sick leave and Grade d Activity after 8 weeks of sick leave with usual care , in occupational back pain management . Methods Design : An RCT and cost-effectiveness evaluation in employees sick-listed for a period of 2 to 6 weeks due to low back pain . Interventions used are 1 . Communication between general practitioner and occupational physician plus Participative Ergonomics protocol performed by an ergonomist . 2 . Grade d Activity based on cognitive behavioural principles by a physiotherapist . 3 . Usual care , provided by an occupational physician according to the Dutch guidelines for the occupational health management of workers with low back pain . The primary outcome measure is return to work . Secondary outcome measures are pain intensity , functional status and general improvement . Intermediate variables are kinesiophobia and pain coping . The cost-effectiveness analysis includes the direct and indirect costs due to low back pain . The outcome measures are assessed before r and omization ( after 2–6 weeks on sick leave ) and 12 weeks , 26 weeks and 52 weeks after first day of sick leave . Discussion The combination of these interventions has been subject of earlier research in Canada . The results of the current RCT will : Output:	We found moderate- quality evidence that workplace interventions reduce time to first RTW , high- quality evidence that workplace interventions reduce cumulative duration of sickness absence , very low- quality evidence that workplace interventions reduce time to lasting RTW , and moderate- quality evidence that workplace interventions increase recurrences of sick leave . Overall , the effectiveness of workplace interventions on work disability showed varying results . Workplace interventions reduce time to RTW and improve pain and functional status in workers with musculoskeletal disorders . We found no evidence of a considerable effect of workplace interventions on time to RTW in workers with mental health problems or cancer . We found moderate- quality evidence to support workplace interventions for workers with musculoskeletal disorders . The quality of the evidence on the effectiveness of workplace interventions for workers with mental health problems and cancer is low , and results do not show an effect of workplace interventions for these workers .
MS213802	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Plantar fasciitis is one of the most common causes of foot pain in adults . In this prospect i ve study , the outcomes of local tenoxicam injection and corticosteroid therapy for the treatment of plantar fasciitis were compared . Patients were r and omly assigned to either the tenoxicam or corticosteroid group . The tenoxicam group ( n=31 ) was treated using a local injection of 1 mL of tenoxicam ( 20 mg/2 mL ) and 1 mL of 2 % lidocaine , whereas the steroid group ( n=30 ) was treated with a local 1-mL injection containing 40 mg of methylprednisolone acetate and 1 mL of 2 % lidocaine . Clinical evaluations , which were performed before the injection and 6 and 12 months after the injection , consisted of patient-assessed pain using a visual analog scale . In addition , patient satisfaction was measured using the Roles and Maudsley score . Comparison of pre- and posttreatment visual analog scale scores demonstrated a statistically significant difference in both groups ( P<.05 ) . Furthermore , no significant difference was found between the steroid and tenoxicam groups in terms of visual analog scale scores measured 12 months after injection ( P>.05 ) . The tenoxicam injection was not significantly more effective than the corticosteroid injection . However , both methods were effective and successful in treating patients with plantar fasciitis . Tenoxicam therapy appears to provide pain relief , but its effectiveness in the long term should be explored in additional studies Background The Visual Analogue Scale ( VAS ) and the Foot Health Status Question naire ( FHSQ ) are two commonly used outcome measures for evaluating foot health . This study aim ed to calculate the Minimal Important Difference ( MID ) of the VAS and the FHSQ . Methods 184 participants with plantar heel pain were recruited from the general public to take part in two r and omised trials ( 92 participants in each trial ) that studied the effectiveness of two conservative interventions for plantar heel pain . Data from these participants were used to calculate the MIDs of the VAS and the FHSQ . An anchor-based method was used to calculate the MIDs . Two distinct types of pain were investigated for the VAS : average pain and first-step pain . All four domains of the FHSQ were investigated : foot pain , foot function , footwear and general foot health . Results The MID for the VAS using the anchor-based approach was -8 mm ( 95 % CI : -12 to -4 ) for average pain and -19 mm ( 95 % CI : -25 to -13 ) for first-step pain on the 100 mm VAS . The MID for the FHSQ was 13 points ( 95 % CI : 6 to 19 ) for pain and 7 points ( 95 % CI : 1 to 13 ) for function . The MID for the footwear domain of the FHSQ was -2 points ( 95 % CI : -8 to 4 ) and 0 points ( 95 % CI : -7 to 6 ) for the general foot health domain of the FHSQ . Conclusion The results of this study provide additional evidence for MID values of the VAS and the FHSQ for plantar heel pain . This is important for clinicians and research ers as it provides a greater underst and ing of how much improvement is required by a patient before a minimal , worthwhile change is experienced . The calculated MIDs will also assist research ers with prospect i ve sample size calculations Plantar fasciitis is a common cause of heel pain . It is a disabling disease in its chronic form . It is a degenerative tissue condition of the plantar fascia rather than an inflammation . Various treatment options are available , including nonsteroidal anti-inflammatory drugs , corticosteroid injections , orthosis , and physiotherapy . This study compared the effects of local platelet-rich plasma , corticosteroid , and placebo injections in the treatment of chronic plantar fasciitis . In this double-blind study , patients were divided r and omly into 3 groups . Local injections of platelet-rich plasma , corticosteroid , or normal saline were given . Patients were assessed with the visual analog scale for pain and with the American Orthopaedic Foot and Ankle Society ( AOFAS ) Ankle and Hindfoot score before injection , at 3 weeks , and at 3-month follow-up . Mean visual analog scale score in the platelet-rich plasma and corticosteroid groups decreased from 7.44 and 7.72 preinjection to 2.52 and 3.64 at final follow-up , respectively . Mean AOFAS score in the platelet-rich plasma and corticosteroid groups improved from 51.56 and 55.72 preinjection to 88.24 and 81.32 at final follow-up , respectively . There was a significant improvement in visual analog scale score and AOFAS score in the platelet-rich plasma and corticosteroid groups at 3 weeks and at 3-month follow-up . There was no significant improvement in visual analog scale score or AOFAS score in the placebo group at any stage of the study . The authors concluded that local injection of platelet-rich plasma or corticosteroid is an effective treatment option for chronic plantar fasciitis . Platelet-rich plasma injection is as effective as or more effective than corticosteroid injection in treating chronic plantar fasciitis Objective The aim of this study was to investigate the effectiveness of device-assisted ultrasound-guided steroid injection for treating plantar fasciitis . Design An ultrasound-guided injection device design ed with space for securing a transducer and syringe was used to guide steroid injection . Patients with unilateral plantar fasciitis were enrolled and r and omly divided into device-assisted ultrasound-guided and palpation-guided groups . Pain intensity was measured using a visual analog scale and tenderness threshold . Ultrasound and pain intensity evaluations were performed before injection and at 3 wks and at 3 mos postinjection . Betamethasone ( 7 mg ) and 1 % lidocaine ( 0.5 ml ) were injected into the inflamed plantar fascia . Results Thirty-three patients who received either device-assisted ultrasound-guided or palpation-guided injection had significantly lower visual analog scale scores ( P < 0.001 ) and higher tenderness threshold ( P < 0.01 ) postinjection . However , the device-assisted group had higher tenderness threshold ( 9.02 ± 1.38 vs. 7.18 ± 2.11 kg/cm2 ; P = 0.007 ) , lower visual analog scale score ( 1.88 ± 2.13 vs. 3.63 ± 2.60 ; P = 0.046 ) , and lower hypoechogenicity incidence in the plantar fascia ( 3/16 vs. 9/16 ; P = 0.033 ) than the palpation-guided group did at 3 mos postinjection . The heel pad was significantly thin ( P = 0.004 ) in the palpation-guided group postinjection . Conclusions Device-assisted ultrasound-guided injection for treating plantar fasciitis results in better therapeutic outcomes than palpation-guided injection does Purpose The aim of this study was to assess the reliability of perifascial oedema as a sonographic criterion for selecting the most appropriate treatment ( ultrasoundguided corticosteroid injection or ultrasound-guided extracorporeal shock wave therapy ) of idiopathic plantar fasciitis ( IPF ) . Material s and methods Sixty-four patients with a clinical diagnosis of unilateral refractory IPF , treated conservatively for at least 8 weeks , were studied with highresolution ultrasound ( HRUS ) . Pain intensity was evaluated with a visual analogue scale ( VAS ) . HRUS was used to confirm IPF and identify the presence of perifascial oedema . Patients with an HRUS diagnosis of IPF were grouped according to the presence ( A ) or absence ( B ) of perifascial oedema and then r and omly allocated to treatment with corticosteroid injection ( 1 ) or extracorporeal shock wave therapy ( 2 ) . Clinical and HRUS follow-up was performed 6 weeks after treatment . Results HRUS confirmed IPF in 68,97 % of patients and identified perifascial oedema in 53.33 % . Clinical and sonographic improvements were observed in 87.5 % and 37.5 % of patients in subgroups A1 and A2 , respectively , and in 35.71 % and 92.85 % of those in subgroups B1 and B2 , respectively . Conclusions The presence of perifascial oedema may represent an effective criterion for guiding treatment decisions towards HRUS-guided corticosteroid injection . RiassuntoObiettivoValutare l’affidabilità del criterio ecografico nell’individuazione dell’edema perifasciale nella scelta della terapia mini-invasiva ( iniezione di corticosteroidi o onde d’urto , ESWT ) con guida dell’ecografia ad alta risoluzione ( HRUS ) nel trattamento della fascite plantare idiopatica ( FPI ) . Material i e metodiSessantaquattro pazienti con diagnosi clinica di FPI monolaterale , recalcitrante , trattata conservativamente per almeno 8 settimane , sono stati sottoposti ad HRUS . Il dolore è stato quantizzato con una visual analogue scale ( VAS ) . La FPI è stata verificata all’HRUS ed è stata valutata la presenza di edema perifasciale . I pazienti con diagnosi HRUS di FPI sono stati suddivisi in ( A ) presenza e ( B ) assenza di edema perifasciale e poi suddivisi r and om in trattati con ( 1 ) infiltrazione di corticosteroidi e ( 2 ) ESWT . Le rivalutazioni clinica e HRUS sono state eseguite a 6 settimane . RisultatiNel 68,97 % dei pazienti l’HRUS ha evidenziato una FPI con edema perifasciale nel 53,33 % . Nei pazienti dei sottogruppi A1 e A2 è stato evidenziato un miglioramento clinico-strumentale nel 87,5 % e nel 37,5 % dei casi , mentre nei pazienti dei sottogruppi B1 e B2 questo è stato evidenziato nel 35,71 % e nel 92,85 % dei casi . Conclusion iLa presenza dell’edema perifasciale potrebbe essere un efficace criterio nell’indirizzare la terapia verso le iniezioni di corticosteroidi con guida HRUS Objective : To investigate the effectiveness of a physiotherapy-based exercise program versus dexamethasone injection for chronic plantar fasciopathy in workers st and ing for prolonged periods of time . Design : A parallel group nonblinded r and omized controlled trial with 12-week follow-up . Setting : An outpatient sports medicine clinic in Vancouver , British Columbia , Canada . Participants : Fifty-six workers required to st and for greater than 5 h/d with chronic plantar fasciopathy took part . Diagnosis from a physiotherapist must include signs of structural changes to the plantar fascia seen on ultrasound . Interventions : The PHYSIO group included 7 physiotherapy-led exercises performed daily over a 12-week period . The INJECTION group received 1 palpation-guided dexamethasone injection followed by a daily routine of calf stretching . Main Outcome Measures : The Foot and Ankle Disability Index ( FADI ) scores 12-weeks postintervention and ultrasound-based measures of ligament appearance . Results : At follow-up , both groups reported significant improvements in FADI and visual analog scales for pain at work and with activities of daily living at 6 and 12 weeks compared with baseline scores ( P < 0.001 ) . There were no significant between-group differences . There were no significant changes to plantar fascia thickness reported at the 6- and 12-week follow-up point . Both the number of cases with focal anechoic areas and the size of these anechoic areas improved significantly in the PHYSIO ( P = 0.003 ) and INJECTION ( P < 0.001 ) groups at 12-week follow-up . Conclusions : Workers st and ing for prolonged periods experienced the same short-term therapeutic effectiveness with a physiotherapy-led exercise program compared with an injection of corticosteroid with stretching PURPOSE To compare the effectiveness of sonographically guided and palpation-guided steroid injection for the treatment of proximal plantar fasciitis . PATIENTS AND METHODS Twenty-five consecutive patients with unilateral proximal plantar fasciitis were recruited and r and omly divided into a sonographically guided group ( n = 12 ) and palpation-guided group ( n = 13 ) . Proximal plantar fascia was assessed with a 5- to 12-MHz linear-array transducer . Pain intensity was quantified using a " tenderness threshold " ( TT ) and a visual analog scale ( VAS ) . Injection of 7 mg ( 1 ml ) of betamethasone and 0.5 ml of 1 % lidocaine into the inflamed proximal plantar fascia was performed under the guidance of sonography or palpation . Patients were evaluated clinical ly and sonographically before injection and at 2 weeks , 2 months , and 1 year after injection . VAS- and TT-measured pain intensity , thickness , and echogenicity of the proximal plantar fascia , as well as the recurrence of heel pain , were assessed . RESULTS Both VAS- and TT-measured levels of pain improved significantly after steroid injection in both groups ( p < 0.001 ) . Also Output:	There was very low quality evidence for fewer treatment failures ( defined variously as persistent heel pain at 8 weeks , steroid injection at 12 weeks , and unrelieved pain at 6 months ) after steroid injection . We found low quality evidence that local steroid injections compared with placebo or no treatment may slightly reduce heel pain up to one month but not subsequently .
MS213803	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: OBJECTIVE To compare the therapeutic effectiveness of daily exposure to narrowb and ( NB ) UV-B vs broadb and ( BB ) UV-B with and without tar . DESIGN Half-body exposures to NB UV-B or BB UV-B were given daily for 4 weeks in this comparative treatment study . Narrowb and UV-B was delivered from TL-01 fluorescent bulbs and BB UV-B from conventional bulbs in the same phototherapy cabinet . Narrowb and UV-B was compared using a paired treatment approach to BB UV-B above the waist and to BB UV-B with tar ( Goeckerman treatment ) below the waist . SETTING General clinical research center of a university hospital inpatient unit . PATIENTS Twenty-two patients with moderate-to-severe plaque-type psoriasis completed the study . MAIN OUTCOME MEASURES Clinical efficacy was measured weekly using psoriasis severity scoring . Therapeutic outcomes after 4 weeks were compared in paired biopsy sample s from treated lesions using objective histopathological measures ( quantitative reduction in epidermal acanthosis and keratin 16 expression ) . RESULTS Clinical resolution of psoriasis was achieved on 86 % of paired sites treated with NB UV-B vs 73 % treated with BB UV-B. Histopathological resolution of epidermal hyperplasia ( marked by keratin 16 expression ) was achieved in 88 % of lesions treated with NB UV-B vs 59 % treated with BB UV-B. Epidermal acanthosis was reduced more completely by NB UV-B treatment . Clinical resolution of psoriatic lesions occurred more rapidly following NB UV-B treatment , with some patients achieving complete resolution after 2 to 3 weeks of treatment . CONCLUSIONS Narrowb and UV-B offers a significant therapeutic advantage over BB UV-B in the treatment of psoriasis , with faster clearing and more complete disease resolution . The erythema response to NB UV-B treatment was significantly more intense and persistent compared with BB UV-B. Considerably more necrotic keratinocytes were observed in histopathological sections of skin treated with NB UV-B after a single 2.0-minimum erythema dose exposure . Treatment should be coupled with obligate minimum erythema dose testing to NB UV-B and close clinical observation during dose increases BACKGROUND A narrow-b and UVB lamp ( Philips TL 01 ) emitting a peak of approximately 311 nm was developed to improve the phototherapy for psoriasis . Only a few studies have been performed with promising results . OBJECTIVE The therapeutic efficacy of the Philips TL 01 lamp in a new 100 W version was compared with conventional broad-b and lamps ( Sylvania UV 6 ) in a controlled trial . METHODS Twenty-three patients with psoriasis were treated with half-body exposures from the different UVB sources . The rate of clearing was monitored by estimation of the Psoriasis Area and Severity Index . All patients used emollients ; excessive scaling was removed with salicylic acid in yellow petrolatum . In 13 patients dithranol in a modified Ingram regimen was added . In most cases the study was discontinued once a difference between the two sides was evident . RESULTS In 20 of 23 cases the TL 01 lamp proved to be significantly more effective than the conventional source . Application of dithranol provided a substantial additional therapeutic effect . With the high-intensity TL 01/100W bulbs , exposure times were comparable to broad-b and UVB phototherapy . CONCLUSION The therapeutic efficacy of Philips TL 01/100W and its practicability for psoriasis phototherapy have been demonstrated The efficacy of trimethylpsoralen bath PUVA and UVB TL01 were compared in chronic plaque psoriasis . Patients were r and omly assigned to receive UVB TL01 on one side and bath PUVA on the contra-lateral side . Altogether 17 patients received treatments and 15 completed the trial . The decrease in the PASI score was greater with UVB TL01 than PUVA . At the end of the treatment period , the difference was highly significant ( p < 0.001 ) . The difference was already significant at week 3 ( p = 0.014 ) . The relative median decrease in the PASI score was 77 % ( 24 - 100 % ) with UVB and 45 % ( 8 - 100 % ) with PUVA . The median cumulative UVB dose was 39.92 ( range 13.95 - 81.56 ) J/cm2 and the corresponding UVA dose was 8.06 ( range 3.31 - 12.51 ) J/cm2 . All patients relapsed within 4 months . Narrowb and UVB improved psoriasis clinical ly and statistically more efficiently than trimethylpsoralen bath PUVA , and UVB was better tolerated Forty patients with pustulosis palmaris et plantaris were treated with tetracycline 250 mg twice daily or with placebo , in a double‐blind trial . In twenty‐eight patients the lesions were confined to the palms and soles , whereas twelve had psoriatic lesions affecting other parts of the skin and /or nails . Radiological signs of focal infection were found in eighteen patients . In thirty‐five patients positive bacteriological culture from pustules was obtained , the most common strain being Staphylococcus albus Twenty-nine patients with psoriasis took part in a study which compared the therapeutic effect of Philips TL12 with a new narrow-b and UVB lamp ( Philips TL01 ) . The patients were treated on an out-patient basis and treatment were given 3 - 5 times weekly for a maximum of 8 weeks . The study was conducted in a r and omized left-right double-blind fashion . The total score on the TL01-side decreased rather more than on the TL12-side . Eleven patients preferred the TL01 lamp and one the TL12-side , whereas 17 patients had no preference . One of the drawbacks with the new lamp is that radiation times are almost doubled INTRODUCTION Studies carried out to date comparing treatment with PUVA baths and narrow-b and UVB ( NBUVB ) in psoriasis show that better results are obtained with NBUVB . Certain features of the protocol s may interfere with the results . MATERIAL AND METHODS Prospect i ve study in a psoriasis unit , with treatment assigned according to availability . Of 167 patients with psoriasis plaques , 32 received PUVA baths ( photosensitizer 8-methoxypsoralen at a concentration of 2.6 mg/l ) and 135 received NBUVB radiation . A clearing rate of over 70 % was considered a good response . The data were described and compared between the two groups , including multivariate analysis techniques , in order to statistically control the effects of gender , number of sessions necessary for success , minimum phototoxic dose and minimum erythema dose . RESULTS A good response was obtained in 87.5 % of the cases with PUVA baths ( 95 % CI : 71.0 - 96.5 ) and in 87.4 % of the cases with NBUVB ( 95 % CI : 80.6 - 92.5 ) . No significant differences were found in the success and ab and onment percentages . Among the patients who responded to the treatment , no differences were found in the number of sessions or in the cumulative dose . Gender , cumulative dose or minimum phototoxic dose and minimum erythema dose values were not associated with the response to the treatments either . CONCLUSIONS With psoriasis plaques , similar response percentages can be expected with both treatments , using the proposed protocol s. The response is regardless of gender , cumulative dose and minimum phototoxic dose and minimum erythema dose values OBJECTIVE This was a double-blind , r and omized multicentre trial comparing efficacy and safety of brivudin ( 125 mg , once a day ) and famciclovir ( 250 mg , three times a day ) , both given orally for 7 days , in the treatment of herpes zoster . METHODS A total of 2027 immunocompetent zoster patients > or=50 years with zoster-related pain at presentation were included . Outcome measures embraced prevalence of postherpetic neuralgia ( PHN ) , defined as at least moderate pain 3 months after treatment initiation , duration of PHN , prevalence and duration of zoster-associated pain ( ZAP ) , duration of vesicle formation and rash healing . RESULTS The prevalence of PHN at month 3 was 11.3 % with brivudin and 9.6 % with famciclovir [ per- protocol ( PP ) population ] . Equivalence of the two drugs could be demonstrated ( P=0.01 , PP and intention-to-treat analysis ) . The median duration of PHN was 46.5 days with brivudin and 58 days with famciclovir ( P=0.54 , PP analysis ) . Prevalence and duration of ZAP did not differ significantly between treatment groups . The prevalence of PHN was higher in patients > or=65 years ( brivudin : 16.4 % , famciclovir : 16.4 % ) , and in patients with severe rash ( brivudin : 13.4 % , famciclovir : 15.7 % ) , without significant differences between treatment groups . In patients > or=65 years , median duration of PHN was shorter with brivudin than with famciclovir ( 39.5 vs. 57.5 days ) , although the difference was not statistically significant . The two drugs had equivalent efficacy in being able to accelerate the stop of vesicle formation , and lesion healing . Adverse events were similar in nature and prevalence among groups . CONCLUSIONS The study demonstrated equivalent efficacy of brivudin and famciclovir in the treatment of herpes zoster regarding the prevention of chronic pain and the resolution of signs and symptoms of acute herpes zoster . Compared with famciclovir , brivudin provides equivalent efficacy and safety at a more convenient once-daily dose schedule BACKGROUND Although PUVA treatment of psoriasis is more effective than conventional or broad-b and UVB phototherapy , two small studies have suggested that narrow-b and or TL-01 phototherapy may have a therapeutic effect equal to PUVA . If confirmed , this would be of considerable importance as TL-01 therapy is likely to be considerably safer in the long term than PUVA . OBJECTIVE The purpose of this study was to compare PUVA with narrow-b and ( TL-01 ) phototherapy in psoriasis . METHODS We studied 100 patients with plaque-type psoriasis who were r and omly allocated to twice-weekly treatment with PUVA or narrow-b and UVB . RESULTS Clearance of psoriasis was achieved in a significantly greater proportion of patients treated with PUVA ( 84 % ) than with TL-01 ( 63 % ) ( P = .018 ) , and with significantly fewer treatments ( median number of treatments for clearance with PUVA , 16.7 ; with TL-01 , 25.3 ; P = .001 ) . Only 12 % of those treated with TL-01 were clear of psoriasis 6 months after finishing treatment compared with 35 % for PUVA ( P = .002 ) . CONCLUSION When given twice weekly , PUVA is more effective for psoriasis than narrow-b and UVB phototherapy Continued prospect i ve study of the 1,380 patients enrolled in the PUVA study for 10 years after first exposure to PUVA demonstrates a strong association between cumulative exposure to PUVA and an increased risk of squamous cell carcinoma of the skin . For tumors occurring at least 58 months after first treatment , after adjustment for age , sex , and area of residence , we observed that patients with more than 260 treatments had an 11-fold increase in risk compared to patients who had received 160 or fewer treatments during the same interval ( P less than 0.01 ) . Comparable increases in relative risk were noted in patients of all skin types , irrespective of prior ionizing radiation exposure . We also noted a modest dose-dependent increase in the risk for the development of basal cell carcinoma for patients who received an excess of 200 treatments compared to those who had received fewer than 160 treatments within the same time period ( P less than 0.05 ) . Tumors detected in our cohort exhibit biologic behavior similar to non-melanoma skin cancers associated with sun exposure . Careful monitoring and early detection should limit the morbidity associated with these tumors A bilateral comparison study of the therapeutic effects of broad-b and ultraviolet ( UBV ) ( FS-40 Sunlamp bulbs ) radiation versus UVB radiation plus methoxsalen was conducted in patients with psoriasis . Ten patients were given up to 30 exposures to the two treatments on paired , similarly affected limbs . There was no detectable difference in the response of limbs treated with UVB plus methoxsalen versus UVB phototherapy alone although all patients did show a therapeutic response . Other areas of the body treated with methoxsalen and broad-b and UVA radiation ( PUVA bulbs ) responded more rapidly and to a greater extent than areas exposed to UVB radiation OBJECTIVE To compare the efficacy of oral psoralen-UV-A ( PUVA ) therapy with that of narrowb and UV-B ( NB-UVB ) therapy in patients with chronic plaque psoriasis . DESIGN Double-blind r and omized study . SET Output:	Evidence regarding NB-UVB versus bath PUVA is also inconsistent . Re-NB-UVB and re-PUVA are similarly effective for treating people with CPP or GP . In practice , NB-UVB may be more convenient to use since exogenous photosensitiser is not required before phototherapy . NB-UVB is considered ineffective for PPP in clinical practice , and a small RCT did not detect a statistically significant difference between NB-UVB and topical PUVA for clearing PPP .
MS213804	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: BACKGROUND AND OBJECTIVE To evaluate predictors of visual outcomes and microbial profile in endophthalmitis . PATIENTS AND METHODS This was a prospect i ve , interventional case series at a tertiary eye care center . Of the 207 patients included , 83 had post-cataract surgery endophthalmitis ( PCE ) , 84 had post-traumatic endophthalmitis ( PTE ) , and 16 had endogenous endophthalmitis . Vitreous sample s were evaluated for microbial profile , and all patients received similar empirical antibiotic therapy . Main outcome measures were good visual acuity , defined as better than 20/400 , and microbial profile with drug resistance . RESULTS Final visual acuity better than 20/400 was seen in 88 % patients previously treated with intravitreal antibiotics ( P < .001 ) , 89 % with presenting vision of less than 3.3 LogMAR units ( P < .001 ) , 61 % without retinal detachment ( RD ) ( P < .001 ) , 58 % without retained intraocular foreign body ( RIOFB ) ( P = .007 ) , 88 % without extensive media haze ( P = .007 ) , 71 % of culture-negative patients ( P = .007 ) , and 65 % with gram-positive bacteria ( P = .03 ) . On multivariate analysis , presenting visual acuity of less than 3.3 LogMAR units was found to have the highest adjusted odds ratio , 26.28 ( 95 % CI , 9.13 - 75.6 ) , for better visual outcome . Culture positivity was nearly 37 % . Gram-positive bacteria were the most common in both PCE ( 90 % ) and PTE ( 55 % ) groups , whereas hyphae form fungus was the most common organism grown in endogenous endophthalmitis ( 50 % ) ( P < .001 ) . In patients without extensive media haze , hyphae form fungus was the most common grown organism ( 42 % ) ( P = .03 ) . PTE was predominant ( 60 % ) in the patients with antibiotic resistance . CONCLUSIONS Presenting visual acuity better than h and motions close to face is the single most common indicator of good visual prognoses . Fungal infections are associated with RD , RIOFB , trauma , and absence of extensive media haze . Microbial resistance may be an important concern in PTE patients . [ Ophthalmic Surg Lasers Imaging Retina . 2016;47:991 - 998 . ] Purpose : The effectiveness of an intraocular injection of combined gentamicin and clindamycin in the prevention of acute posttraumatic bacterial endophthalmitis following penetrating ocular injuries was evaluated in a prospect i ve , double-masked , r and omized pilot study . Methods : Sixty eyes of 60 patients with penetrating ocular injuries were treated at a tertiary care hospital . Following primary repair , the eyes were r and omized in two groups . Group 1 , the antibiotic injection group ( cases ) , was given an intracameral or intravitreal injection of 0.1 mL antibiotic ( 40 μg gentamicin and 45 μg clindamycin ) . Group 2 ( balanced saline solution [ BSS ] injection group [ controls ] ) received intracameral or intravitreal injection of 0.1 mL BSS . All patients received st and ard prophylactic antibiotic therapy ( systemic , subconjunctival , and topical ) . Result : Although the overall incidence of acute posttraumatic bacterial endophthalmitis was 6.6 % ( 4 eyes ) , the results of three cultures were negative . All endophthalmitis cases occurred in the BSS injection group ; however , there was no statistically significant difference between case and control groups ( p = 0.11 ) . The incidence rate for those with retained intraocular foreign bodies was 13.3 % and for those without foreign bodies was 4.4 % . No retinal toxicity was detected . Conclusion : Intraocular injection of gentamicin and clindamycin in addition to the other methods of prophylaxis may be an effective modality in the prevention of posttraumatic endophthalmitis . Early results suggest that these antibiotics may have a role as adjunct therapy to primary repair of injured globes without significant side effects at the dosage used PURPOSE To determine the efficacy of prophylactic intravitreal antibiotics in reducing the incidence of endophthalmitis after trauma . METHODS This was a prospect i ve , r and omised , case control study of 70 consecutive patients with open globe injury . The patients were prospect ively r and omised into group I ( 32 eyes ) and group II ( 38 eyes ) . Group I patients were given prophylactic intravitreal injection of vancomycin 1 mg and ceftazidime 2.25 mg at the conclusion of primary repair . Group II patients were not given prophylactic intravitreal antibiotics . All the patients received intravenous ciprofloxacin . RESULTS The incidence of endophthalmitis was higher in group II ( 7 of 38 eyes ; 18.42 % ) compared to group I ( 2 of 32 eyes ; 6.25 % ) . Both the patients who developed endophthalmitis despite prophylactic intravitreal antibiotics in group I had an initially undetected intraocular foreign body ( eyelash ) in the vitreous cavity . CONCLUSIONS Prophylactic intravitreal broad spectrum antibiotic injection decreases the risk of post-traumatic endophthalmitis OBJECTIVE To evaluate the efficacy of intraocular gentamicin sulfate and clindamycin in the prevention of acute posttraumatic bacterial endophthalmitis following penetrating eye injuries . METHOD We conducted a multicenter , r and omized , double-masked controlled trial of 346 eyes with penetrating eye injury . Following primary repair , eyes were r and omized to intracameral or intravitreal injection of 40 microg of gentamicin sulfate and 45 microg of clindamycin ( cases ) vs balanced salt solution ( controls ) . MAIN OUTCOME MEASURE Occurrence of endophthalmitis within 2 weeks . RESULTS Endophthalmitis occurred in 8 ( 2.3 % ) of 167 eyes in the control group and only in 1 ( 0.3 % ) of 179 eyes in the case group ( P = .04 ; odds ratio , 8.93 [ 95 % confidence interval , 1.11 - 71.43 ] ) . In eyes with an intraocular foreign body , endophthalmitis developed in 7 of 25 control eyes and in none of 27 eyes receiving antibiotics . However , in eyes without an intraocular foreign body , endophthalmitis developed in 1 of 142 eyes and 1 of 152 eyes in the 2 groups , respectively ( P value for interaction = .04 ) . Intravitreal injection was superior to intracameral injection in preventing endophthalmitis ( P value for interaction = .01 ) . Vitreous culture results were positive in 6 ( 67 % ) of 9 eyes with endophthalmitis . CONCLUSION Intraocular gentamicin and clindamycin are effective in the prevention of acute posttraumatic bacterial endophthalmitis in eyes with retained intraocular foreign body . APPLICATION TO CLINICAL PRACTICE Prophylaxis of traumatic endophthalmitis . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00398658 PURPOSE To assess the clinical effect of pars plana vitrectomy ( PPV ) with intravitreous antibiotic drugs or silicone oil endotamponade in post-traumatic endophthalmitis on eyes without detachment of the retina . METHODS Thirty cases of eyes with penetrating injury associated with endophthalmitis without retina detachment had been treated with PPV plus intravitreous antibiotic drugs or silicone oil tamponade . All the patients in the study received intravenous , subconjunctival and topical medications antibiotics . RESULTS All the patients were followed up for 3 to 12 months . Postoperative intraocular infection of 30 eyes ( 30 patients ) were controlled . The best-corrected visual acuity was significantly improved in both groups postoperatively ( P < 0.05 ) . The rate of postoperative retinal detachment in the PPV combined with intravitreal antibiotics group was 21.1 % ( 4/19 ) vs. 9 % (1/11)in the PPV combined with silicone oil There was no significant difference in postoperative endotamponade group . There was no significant difference in postoperative complications between two groups . CONCLUSIONS PPV combined with silicone oil tamponade may have beneficial effect on the surgical treatment of traumatic bacterial endophthalmitis associated without retinal detachment , but the surgery may be used in some cases which have bad retinal condition or uncontrollable inflammation PURPOSE We studied events leading to the development of posttraumatic endophthalmitis by examining the significance of 15 factors on microbial contamination of injured eyes . METHODS A prospect i ve study was done of 30 ruptured globes in patients admitted to an urban medical center . Cultures were taken from the conjunctiva before and after preoperative disinfection and from the anterior chamber at the beginning and end of wound repair . Twenty-five of 30 patients received a three-day regimen of intravenous antibiotics that were begun before surgery . RESULTS Anterior chamber sample s grew microorganisms in ten ( 33 % ) of 30 eyes , with positive cultures recovered from specimens taken at the beginning of wound repair in eight eyes and at the end of wound repair in six eyes . Contamination with indigenous flora may have occurred at the time of injury in one eye and during repair in another eye . Microbes recovered included Staphylococcus , Corynebacterium , and Aspergillus species . No patient developed endophthalmitis . Of the 15 factors studied , only intravenous antibiotics significantly decreased the incidence of positive anterior chamber cultures in eyes treated before wound repair compared with eyes not receiving such therapy ( P = .002 ) . CONCLUSIONS Despite the frequency of anterior chamber microbial contamination during injury or repair of the wound , with our treatment protocol and the presence of physiologic mechanisms to reduce intraocular microbes , no eyes developed clinical endophthalmitis . With our limited sample size only intravenous antibiotic therapy was found significantly to reduce anterior chamber microorganisms at the time of surgical repair , supporting their prophylactic use against the development of posttraumatic endophthalmitis PURPOSE To evaluate the outcomes of pars plana vitrectomy and silicone oil injection for the treatment of infectious endophthalmitis . METHODS 35 cases of endophthalmitis secondary to phacoemulsification ( 20 patients ) , trabeculectomy ( 8 patients ) , perforating trauma ( 2 patients ) , trauma ( 2 patients ) , corneal transplantation ( 1 patient ) , vitrectomy ( 1 patient ) and corneal ulceration ( 1 patient ) were retrospectively studied . Patients were separated into two groups : Group 1 ( n=24 ) : intravitreal antibiotic injection , associated with topical and oral antibiotics ; Group 2 ( n=11 ) : vitrectomy with intravitreal antibiotic injection and silicone oil injection . The follow-up ranged from 1 to 48 months ( mean of 16 months ) . RESULTS From 24 patients in group 1 , 11 patients ( 45.83 % ) , had infection controlled with intravitreal antibiotic injection only ; 13 patients ( 54.15 % ) regressed to uncontrolled endophthalmitis , in which two patients ( 8.33 % ) were su bmi tted to evisceration and one patient ( 4.16 % ) had corneal melting . The remaining 10 patients ( 41.66 % ) with uncontrolled endophthalmitis were su bmi tted to pars plana vitrectomy and silicone oil injection . Six patients ( 25 % ) from Group I had retinal detachment during the first month of follow-up and also required pars plana vitrectomy and silicone oil injection . In Group 2 patients ( n=11 ) , all of them had controlled infection at the first procedure . In one case ( 9.09 % ) , a severe proliferative vitreoretinopathy induced loss of vision . CONCLUSION These results suggest that silicone oil tamponade might be beneficial in the treatment strategy of infectious endophthalmitis Purpose : To compare the use of systemic oral and intravenous antibiotics as a prophylactic measure to prevent endophthalmitis in patients with open globe injuries . Methods : This prospect i ve study was conducted on 1,255 consecutive patients with open globe injuries due to sharp or blunt trauma in a hospital setting in Tehran , Iran from January , 2011 to May , 2013 . The patients were r and omly divided into two groups and either received intravenous or oral systemic antibiotics as a measure to prevent endophthalmitis . The patients who developed endophthalmitis were followed for 1 year . Results : In the first group , 12 patients ( 1.8 % ) developed Output:	Intracameral/intravitreal antibiotics reduce the risk of endophthalmitis in open globe injuries ; although , there was no improvement in the visual acuity .
MS213805	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: The appropriateness of recess in the elementary program continues to be question ed although generally it is believed to be useful by elementary principals despite a dearth of supportive data . This study was a developmental study of the effects of physical activity on concentration . Comparison of passive and directed physical education activities on the concentration of second- , third- , and fourth- grade children was made . The Woodcock-Johnson Test of Concentration showed better performance by the fourth grade rs and within Grade 4 in favor of the physical activity group . A structured physical activity or a classroom activity immediately prior to a concentration task was not detrimental to children in Grade s 2 and 3 . Fourth- grade children performed significantly better on a test of concentration after engaging in a physical activity Teachers complain about growing concentration deficits and reduced attention in adolescents . Exercise has been shown to positively affect cognitive performance . Due to the neuronal connection between the cerebellum and the frontal cortex , we hypothesized that cognitive performance might be influenced by bilateral coordinative exercise ( CE ) and that its effect on cognition might be already visible after short bouts of exercise . One hundred and fifteen healthy adolescents aged 13 - 16 years of an elite performance school were r and omly assigned to an experimental and a control group and tested using the d2-test , a test of attention and concentration . Both groups performed the d2-test after a regular school lesson ( pre-test ) , after 10 min of coordinative exercise and of a normal sport lesson ( NSL , control group ) , respectively ( post-test ) . Exercise was controlled for heart rate ( HR ) . CE and NSL enhanced the d2-test performance from pre- to post-test significantly . ANOVA revealed a significant group ( CE , NSL ) by performance interaction in the d2-test indicating a higher improvement of CE as compared to NSL . HR was not significantly different between the groups . CE was more effective in completing the concentration and attention task . With the HR being the same in both groups we assume that the coordinative character of the exercise might be responsible for the significant differences . CE might lead to a pre-activation of parts of the brain which are also responsible for mediating functions like attention . Thus , our results support the request for more acute CE in schools , even in elite performance schools PURPOSE This study evaluated the effects of a classroom-based physical activity program on children 's in-school physical activity levels and on-task behavior during academic instruction . METHODS Physical activity of 243 students was assessed during school hours . Intervention-group students ( N = 135 ) received a classroom-based program ( i.e. , Energizers ) . The control group ( N = 108 ) did not receive Energizers . On-task behavior during academic instruction time was observed for 62 third- grade ( N = 37 ) and fourth- grade students ( N = 25 ) before and after Energizers activities . An independent groups t-test compared in-school physical activity levels between intervention and control classes . A multiple-baseline across-classrooms design was used to evaluate the effectiveness of the Energizers on on-task behavior . Additionally , a two-way ( time [ pre- vs postobservation ] x period [ baseline vs intervention ] ) repeated- measures analysis of variance compared on-task behavior between observation periods . Magnitudes of mean differences were evaluated with Cohen 's delta ( ES ) . RESULTS Students in the intervention group took significantly ( P < 0.05 ) more in-school steps ( 5587 + /- 1633 ) than control-group students ( 4805 + /- 1543 ) , and the size of this difference was moderate ( ES = 0.49 ) . The intervention was effective in improving on-task behavior ; after the Energizers were systematic ally implemented , on-task behavior systematic ally improved . The improvement in on-task behavior of 8 % between the pre-Energizers and post-Energizers observations was statistically significant ( P < 0.017 ) , and the difference was moderate ( ES = 0.60 ) . Likewise , the least on-task students improved on-task behavior by 20 % after Energizers activities . This improvement was statistically significant ( P < 0.001 ) and meaningful ( ES = 2.20 ) . CONCLUSION A classroom-based physical activity program was effective for increasing daily in-school physical activity and improving on-task behavior during academic instruction BACKGROUND This study examined associations of fitness and fatness with cognitive processes , academic achievement , and behavior , independent of demographic factors , at the baseline of an exercise trial . METHODS Overweight , sedentary but otherwise healthy 7 - 11 year olds ( N=170 ) participated in a study of health , cognition and achievement in the Augusta , GA area from 2003 - 2006 . Children underwent evaluations of fatness and fitness , psychological assessment s of cognition and academic achievement , and behavior ratings by parents and teachers . Partial correlations examined associations of fitness and fatness with cognitive and achievement scores and behavior ratings , controlling for demographic factors . RESULTS Fitness was associated with better cognition , achievement and behavior , and fatness with worse scores . Specifically , executive function , mathematics and reading achievement , and parent ratings of child behavior were related to fitness and fatness . Teacher ratings were related to fitness . CONCLUSION These results extend prior studies by providing reliable , st and ardized measures of cognitive processes , achievement , and behavior in relation to detailed measures of fitness and fatness . However , cross-sectional associations do not necessarily indicate that improving one factor , such as fatness or fitness , will result in improvements in factors that were associated with it . Thus , r and omized clinical trials are necessary to determine the effects of interventions This study tested the effect of a structured aerobic exercise program on anger expression in healthy overweight children . Overweight sedentary children were r and omly assigned to an aerobic exercise program or a no-exercise control condition . All children completed the Pediatric Anger Expression Scale at baseline and posttest . Anger Out and Anger Expression scores were lower for the exercise condition at posttest . Fitness improvements contributed significantly to final models , and points earned for adherence correlated negatively with posttest Anger Out . An aerobic exercise program might be an effective strategy to reduce anger expression , including reduction of aggressive behavior , in overweight children NEW FINDINGS What is the central question of this study ? Children are spending more than 60 % of their waking day sedentary . The consequences of excessive sedentary behaviour are not well understood in the child , but there is growing evidence that with increasing sedentary time , cardiovascular risk in childhood also increases . What is the main finding and its importance ? Our findings show that a 3 h period of uninterrupted sitting causes a profound ( 33 % ) reduction in vascular function in young girls . Importantly , we also demonstrate that breaking up sitting with regular exercise breaks can prevent this . Excessive sedentary behaviour has serious clinical and public health implication s ; however , the physiological changes that accompany prolonged sitting in the child are not completely understood . Herein , we examined the acute effect a prolonged period of sitting has upon superficial femoral artery function in 7- to 10-year-old girls and the impact of interrupting prolonged sitting with exercise breaks . Superficial femoral artery endothelium-dependent flow-mediated dilatation , total shear rate , antero grade and retro grade shear rates and oscillatory shear index were assessed before and after two experimental conditions : a 3 h uninterrupted period of sitting ( SIT ) and a 3 h period of sitting interrupted each hour with 10 min of moderate-intensity exercise ( EX ) . A mixed-model analysis of variance was used to compare between-condition and within-condition main effects , controlling for the within-subject nature of the experiment by including r and om effects for participant . Superficial femoral artery endothelium-dependent flow-mediated dilatation decreased significantly from pre- to post-SIT ( mean difference 2.2 % flow-mediated dilatation ; 95 % confidence interval = 0.60 - 2.94 % , P < 0.001 ) . This relative decline of 33 % was abolished in the EX intervention . Shear rates were not significantly different within conditions . Our data demonstrate the effectiveness of short but regular exercise breaks in off setting the detrimental effects of uninterrupted sitting in young girls Output:	RESULTS Overall , PA interventions commonly found positive effects on academic behavior , with few exceptions . There were additional unique findings regarding differences in outcome measures and PA treatments . CONCLUSIONS The findings from these studies are significant and support the implementation or continuation of PA in schools to improve academic behavior and associated performance .
MS213806	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Background This study aim ed to evaluate the associations of selected demographic , individual , social , and environmental factors with moderate-to-vigorous physical activity ( MVPA ) in a sample of children and adolescents . Methods MVPA was assessed among youth ( n = 294 ) 10 - 17-years-old using the ActiGraph accelerometer . Youth completed measures of demographic and individual variables related to physical activity ( PA ) , perceived social support by parents and peers , and perceived neighborhood characteristics . Parents completed the long-form of the International Physical Activity Question naire . The Physical Activity and Media Inventory was used to measure the home environment and Geographical Information Systems software was used to measure the physical neighborhood environment . Bivariate correlations and hierarchical multiple regression were conducted stratified by gender . Results Boys participated in significantly more MVPA than girls . In hierarchical analyses , peer support , home PA equipment , and temperature were significantly associated with MVPA among boys whereas distance to the school they attended was associated with MVPA among girls . The final models accounted for 25 % and 15 % of the variance in MVPA among boys and girls , respectively . Conclusions Important differences exist among the individual , social , and environmental factors related to MVPA between boys and girls . Boys ' levels of activity appear to be influenced by factors closely linked to unstructured and social types of activities whereas girls ' activities relate to internal and external barriers as well as their proximity to their schools . The prospect i ve contribution of these important individual , social , and environmental factors to changes in MVPA among children and adolescents remains to be determined PURPOSE The objectives of this study were to describe longitudinal trends in adolescent physical activity in a sample of U.S. adolescents and to assess the effect of multiple individual , parental , and environmental factors on initial level and rates of change in adolescent physical activity . METHODS Study subjects were 12,812 boys and girls 10 to 18 years of age who were participating in the Growing Up Today Study and their mothers . We used accelerated longitudinal analysis to describe trajectories of physical activity from 1997 - 1999 , and r and om effects linear mixed models to determine which factors were independently associated with baseline physical activity and changes in physical activity over time . RESULTS Mean hours of physical activity ranged from 7.3 - 11.6 hours per week in boys and from 8.0 - 11.2 hours per week in girls . Physical activity was best modeled as a quadratic function of age , increasing until early adolescence and declining after age 13 in boys and girls . Multivariable modeling demonstrated that variables associated with physical activity level at baseline in boys and girls were age , body mass index , psychosocial variables , personal attitudes about body shape , perceived peer attitudes about body shape/fitness , parental attitudes about physical activity , parental physical activity , and environmental barriers to physical activity . Age was the only factor that predicted change in physical activity over time . CONCLUSIONS Interventions to increase physical activity in adolescents should begin before adolescence . Interventions may be more effective if they are multimodal and focus on modifiable individual , parental , and environmental factors OBJECTIVE To test whether self-efficacy for overcoming barriers to physical activity has direct , indirect ( i.e. , mediated ) , or moderating relations with naturally occurring change in perceived social support and declines in physical activity during high school . METHODS Latent growth modeling was used with measures completed in the 8th , 9th , and 12th grade s by a cohort of 195 Black and White girls . RESULTS Self-efficacy was stable and moderated the relation between changes in physical activity and perceived social support . Girls who maintained a perception of strong social support had less of a decline in physical activity if they also had high self-efficacy . However , girls having high self-efficacy had a greater decline in physical activity if they perceived declines in social support . CONCLUSIONS R and omized controlled trials of physical activity interventions based on social cognitive theory should consider that the influence of girls ' perceptions of social support on their physical activity may differ according to their efficacy beliefs about barriers to physical activity Background Few studies have examined the mediators of behavior change in successful school-based physical activity interventions . The aim of this study was to explore potential mediators of physical activity in the Fit-4-Fun program for primary school children . Design Group r and omized controlled trial . Methods Four primary schools were recruited in April , 2011 and r and omized by school into intervention or control conditions . Participants included 213 children ( mean age = 10.7 years ± 0.6 ; 52.2 % female ) with the treatment group ( n = 118 ) completing the 8-week multi-component Fit-4-Fun program . Participants were assessed at baseline , 3- and 6-months . Physical activity was measured using Yamax SW700 pedometers ( mean steps/day ) and question naires were used to assess constructs from Social Cognitive Theory and Competence Motivation Theory . Hypothesized mediators measured included social support from peers , parents and teachers ; physical activity self-efficacy ( barrier and task ) ; enjoyment ; and perceived school physical environment . Mediation was assessed using Preacher and Hayes ’ multiple mediation regression SPSS macro . Action theory ( A ) , conceptual theory ( B ) and the significance of the product of coefficients ( AB ) are reported . Results The intervention had a significant effect on physical activity ( p<0.001 ) . The action theory test results revealed significant treatment effects at 3-months for perceived school environment ( A=0.28 , p<0.001 ) ; and at 6-month follow-up for perceived school environment ( A=0.058 , p<0.001 ) , teacher social support ( A=0.54 , p<0.05 ) and enjoyment ( A=-0.23 , p<0.05 ) . The conceptual theory test revealed a significant relationship between changes in teacher social support and changes in physical activity at 6-month follow-up ( B=828 , P<0.05 ) . Teacher social support was shown to have a significant mediating effect on physical activity ( AB = 445 , CI = 77 - 1068 steps , proportion= 13 % ) , and perceived school environment approached significance ( AB = 434 , CI= -415 to 1507 steps , proportion= 13 % ) . Conclusions The Fit-4-Fun program successfully targeted social support for physical activity provided by classroom teachers which contributed to improved physical activity in children . These results demonstrate that classroom teachers play a key role in influencing physical activity behavior outcomes in children . Trial Registration No : Aims : Habits of leisure time sports activity , similar to other health behaviours , are established during late childhood and early adolescence . While regular leisure time sports activity is a natural part of children 's lifestyle , it starts to decrease during adolescence , particularly among girls . Among the factors influencing children 's sports activity , the role of parents , peers , and other members of children 's social networks seem to be crucial . The purpose of this study was to determine the role of social influences in early adolescents ' leisure time sports activity and to examine gender differences . Methods : Data were collected from middle school students using r and omly selected classes from four schools in distinct school districts in Szeged , Hungary , using a self-administered question naire ( n = 548 ) in which a response rate of 91 % was achieved . Respondents were 10—15 years of age ( mean = 12.2 years , SD = 1.2 years ) with 54.9 % of the sample male and 45.1 % female . Results : Results show significant others as an important influence on sport-related behaviours and suggest that during early adolescence girls ' sports participation is particularly influenced by the social influence of peers ( e.g. friends , classmates , boy/girlfriend ) . Conclusions : Our findings suggest that health promotion programmes should build on possible social influences , i.e. the role of peers , parents and significant others in general , in fostering adolescents ' physical activity Output:	Longitudinal research supported the cross-sectional analyses .
MS213807	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: OBJECTIVE To determine the bacteriologic efficacy of ceftriaxone in nonresponsive acute otitis media in children . METHODS In a prospect i ve study 92 patients ages 3 to 36 months ( median , 11 months ) with culture-proved nonresponsive acute otitis media were studied from January , 1995 , through August , 1997 . The patients were treated with intramuscular ceftriaxone ( 50 mg/kg/l/day ) for 3 days . Middle ear fluid was aspirated for culture by tympanocentesis on day of enrollment ( Day 1 ) ; a second tap was performed on Days 4 to 10 . Additional middle ear fluid cultures were obtained if clinical relapse occurred . Bacteriologic failure was defined by positive culture on Days 4 to 10 . Patients were followed until Day 17+/-2 . Susceptibility was measured by E test . RESULTS The main drugs administered before enrollment were amoxicillin ( 38 % ) , amoxicillinclavulanate ( 25 % ) and cefaclor ( 20 % ) . Organisms recovered ( n=105 ) were : Haemophilus influenzae , 54 ; Streptococcus pneumoniae , 47 ; Moraxella catarrhalis , 2 ; and Streptococcus pyogenes , 2 . Thirty-four ( 72 % ) of the 47 S. pneumoniae isolates were intermediately resistant to penicillin ( MIC 0.1 to 1.0 microg/ml ) , but all were susceptible to ceftriaxone ( MIC < 0.5 microg/ml ) . Bacteriologic eradication was achieved in 100 of 105 ( 95 % ) cases : 54 of 54 ( 10O% ) H. influenzae , 43 of 47 ( 92 % ) S. pneumoniae , 1 of 2 ( 50 % ) M. catarrhalis and 2 of 2 ( 100 % ) S. pyogenes . Bacteriologic success ( with no relapse ) occurred in 13 of 13 ( 100 % ) penicillin-susceptible S. pneumoniae vs. 28 of 34 ( 82 % ) S. pneumoniae intermediately resistant to penicillin ( 4 cases of bacteriologic failure and 2 cases of relapse ) . CONCLUSION A 3-day intramuscular ceftriaxone regimen is efficacious for the treatment of nonresponsive acute otitis media . The optimal duration of treatment in cases of nonresponsive acute otitis media and whether ceftriaxone is efficacious for the treatment of nonresponsive otitis media caused by S. pneumoniae highly resistant to penicillin is yet to be determined Background The immunogenicity , reactogenicity , and safety of the 10-valent pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine ( PHiD-CV ) co-administered with routine childhood vaccines were evaluated among infants from Singapore and Malaysia , where PHiD-CV has been licensed . Methods In the primary vaccination phase , 298 infants from Singapore and 168 infants from Malaysia were r and omised to receive the Phase III Clinical ( Clin ) or the Commercial ( Com ) lot of PHiD-CV at 2 , 3 , and 5 months of age . In the booster vaccination phase , 238 toddlers from Singapore received one dose of the PHiD-CV Commercial lot at 18–21 months of age . Immune responses to pneumococcal polysaccharides were measured using 22F-inhibition enzyme-linked immunosorbent assay ( ELISA ) and functional opsonophagocytic activity ( OPA ) assay and to protein D , using ELISA . Results Immune responses induced by primary vaccination with the PHiD-CV Commercial lot were non-inferior to the Phase III Clinical lot in terms of adjusted antibody geometric mean concentration ( GMC ) ratios for each vaccine pneumococcal serotype and protein D. For each vaccine pneumococcal serotype , ≥93.6 % and ≥88.5 % of infants from Malaysia and Singapore had post- primary vaccination antibody concentrations ≥0.2 μg/mL and OPA titres ≥8 , in the Clin and Com groups , respectively . For each vaccine pneumococcal serotype , ≥60.8 % and ≥98.2 % of toddlers from Singapore had pre- and post-booster antibody concentrations ≥0.2 μg/mL , in the Clin and Com groups , respectively . All children , except one , had measurable anti-protein D antibodies and the primary and booster doses of the co-administered vaccines were immunogenic . The incidence of each grade 3 solicited symptom was ≤11.1 % in both study phases . No serious adverse events considered causally related to vaccination were reported throughout the study . Conclusions PHiD-CV given as three-dose primary vaccination to infants in Singapore and Malaysia and booster vaccination to toddlers in Singapore was shown to be immunogenic with a clinical ly acceptable-safety profile . This study has been registered at http://www . clinical trials.govNCT00808444 and NCT01119625 Objective : To describe NP and AOM otopathogens during the time frame 2007 to 2009 , 6 to 8 years after the introduction of 7-valent pneumococcal conjugate ( PCV7 ) in the United States and to compare nasopharyngeal ( NP ) colonization and acute otitis media ( AOM ) microbiology in children 6 to 36 months of age having first and second AOM episodes with children who are otitis prone . Methods : Prospect ively , the microbiology of NP colonization and AOM episodes was determined in 120 children with absent or infrequent AOM episodes . NP sample s were collected at 7 routine visits between 6 and 30 months of age and at the time of AOM . For first and subsequent AOM episodes , middle ear fluid ( MEF ) was obtained by tympanocentesis . Eighty otitis prone children were comparatively studied . All 200 children received age-appropriate doses of PCV7 . Results : We found PCV7 serotypes were virtually absent : ( 0.9 % isolated from both NP and MEF ) in both study groups . However , non-PCV7 serotypes replaced PCV serotypes such that the frequency of isolation of S. pneumoniae ( Spn ) was nearly equal to that of non-typeable Haemophilus influenzae ( NTHi ) . M. catarrhalis ( Mcat ) was less common and Staphylococcus aureus infrequent in the NP and MEF from the 2 groups . The proportion of Spn , NTHi and Mcat causing AOM was similar in children with first and second AOM episodes compared to otitis prone children . However , oxacillin-resistant Spn isolated from the NP and MEF was 19 % for the absent/infrequent and 58 % for the otitis prone groups , P < 0.0001 . Beta-lactamase producing NTHi occurred more frequently in the otitis prone group , P = 0.04 . Conclusions : Six to 8 years after widespread use of PCV7 , Spn strains expressing vaccine-type serotypes have virtually disappeared from the NP and MEF of vaccinated children . NP colonization and AOM has changed to non-PCV7 strains of Spn . NTHi continues to be a major AOM pathogen . The otopathogens in first and second AOM and in otitis prone children are very similar although Spn and NTHi are more often antibiotic resistant in the otitis prone Background Acute Otitis Media ( AOM ) is an important and common disease of childhood . Bacteria isolated from cases of clinical ly problematic AOM in German children were identified and characterized . Methods In a prospect i ve non-interventional study in German children between 3 months and less than 60 months of age with Ear , Nose and Throat Specialist –confirmed AOM , middle ear fluid was obtained by tympanocentesis ( when clinical ly indicated ) or by careful sampling of otorrhea through/at an existing perforation . Results In 100 children with severe AOM , Haemophilus influenzae was identified in 21 % ( 18/21 , 85.7 % were non-typeable [ NTHi ] ) , Streptococcus pneumoniae in 10 % , S. pyogenes in 13 % and Moraxella catarrhalis in 1 % . H. influenzae was the most frequently identified pathogen in children from 12 months of age . H. influenzae and S. pneumoniae were equally prevalent in children aged 3–11 months , but S. pyogenes was most frequently isolated in this age group . NTHi AOM disease appeared prevalent in all ages . Conclusions NTHi , S. pneumoniae and S. pyogenes are implicated as important causes of complicated AOM in children in Germany . NTHi disease appears prevalent in all ages . The impact of vaccination to prevent NTHi and S. pneumoniae AOM may be substantial in this population and is worth investigating The safety and immunogenicity of the 10-valent pneumococcal nontypeable Haemophilus influenzae protein D conjugate vaccine ( PHiD-CV , Synflorix ™ ) were assessed in 240 healthy Chilean children r and omized to receive 3 doses of PHiD-CV ( PHiD-CV group ) or hepatitis A vaccine ( HAV control group ) at 2 - 4 - 6 months of age . All were offered 1 HAV dose at 12 months ( outside study ) . The PHiD-CV group received a second HAV dose at 18 - 21 months and PHiD-CV booster at 20 - 23 months . The HAV control group received 2 PHiD-CV catch-up doses at 18 - 21 and 20 - 23 months . Adverse events were recorded and pneumococcal antibody responses and opsonophagocytic activity ( OPA ) were measured . Both PHiD-CV vaccination schedules were well tolerated and immunogenic against the pneumococcal vaccine serotypes and protein D. The reactogenicity of PHiD-CV primary , booster and catch-up doses was in line with previous PHiD-CV studies , although generally higher than with HAV . For each vaccine serotype , the percentage of subjects with antibody concentrations ≥0.2 µg/ml ( GSK 's 22F-inhibition ELISA ) was at least 93.2 % following 3 PHiD-CV primary doses and at least 97.4 % post-booster ; percentages with OPA titers ≥8 were at least 91.7 % post-booster . After 2-dose catch-up , at least 94.3 % of children had antibody concentrations ≥0.2 µg/ml against each serotype except 6B ( 84.3 % ) ; at least 95.2 % had OPA titers ≥8 except against serotypes 1 , 5 and 6B . In conclusion , the safety profiles of 2 PHiD-CV vaccination schedules ( 3-dose primary plus booster and 2-dose catch-up ) were in line with previous studies and PHiD-CV was immunogenic for all 10 vaccine serotypes and protein BACKGROUND Clinical symptoms and signs in acute otitis media ( AOM ) may differ depending on the various pneumococcal serotypes causing the disease . Alteration in clinical presentation of AOM could be expected after wide-scale pneumococcal vaccinations if there were considerable differences between vaccine serotypes and nonvaccine serotypes . METHODS In this study , data from 831 children in the control arm of the Finnish Otitis Media Vaccine Trial were used . The children were followed up prospect ively in 8 study clinics from 2 to 24 months of age . If AOM was diagnosed , myringotomy was done , and middle ear fluid was aspirated for bacterial culture . Clinical symptoms and signs of AOM were routinely recorded on structured case report forms . RESULTS Consistent with previous studies , 60 % of pneumococcal episodes were caused by vaccine serotypes . There were no major differences between the clinical presentations of AOM due to different serotypes or serotype categories . However , earache was more often associated with AOM caused by vaccine and cross-reactive serotypes , compared with AOM caused by non-vaccine-related serotypes ( 42 % vs. 29 % ; odds ratio , 1.66 ; 95 % confidence interval , 1.02 - 2.70 ) . CONCLUSIONS Introduction of the currently available pneumococcal conjugate vaccine is unlikely to result in a remarkable alteration in the clinical presentation of pneumococcal AOM in infants BACKGROUND Because of the increasing number of resistant middle ear pathogens reported from different centers worldwide , an active surveillance of the microbiology and susceptibility pattern of middle ear pathogens is required for proper antimicrobial recommendations among different regions of the world . OBJECTIVE To study the microbiology and susceptibility pattern of middle ear pathogens obtained from Costa Rican children with acute otitis media . METHODS Between 1992 and 1997 a diagnostic tympanocentesis was performed in 398 Costa Rican patients with acute otitis media . Middle ear fluid was obtained for culture and minimal inhibitory concentr Output:	Molecular methods can also improve monitoring of regional changes in the serotypes and identification frequency of S. pneumoniae and H. influenzae over time or after vaccine implementation , such as after introduction of the 7-valent pneumococcal conjugate vaccine . Globally , S. pneumoniae and H. influenzae remain the predominant otopathogens associated with OM as identified through bacterial culture ; however , molecular methods continue to improve the frequency and accuracy of detection of individual serotypes .
MS213808	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Objective : Workplace cancer prevention initiatives have been least successful with blue-collar workers . This study assesses whether an intervention integrating health promotion with occupational health and safety results in significant and meaningful increases in smoking cessation and consumption of fruits and vegetables , compared to a st and ard health promotion intervention , for workers overall and for blue-collar workers in particular . Methods : A r and omized controlled design was used , with 15 manufacturing worksites assigned to a health promotion ( HP ) or a health promotion plus occupational health and safety intervention ( HP/OHS ) , and compared from baseline ( 1997 ) to final ( 1999 ) . The response rates to the survey were 80 % at baseline ( n = 9019 ) and 65 % at final ( n = 7327 ) . Both groups targeted smoking and diet ; the HP/OHS condition additionally incorporated reduction of occupational exposures . Results : Smoking quit rates among blue-collar workers in the HP/OHS condition more than doubled relative to those in the HP condition ( OR = 2.13 , p = 0.04 ) , and were comparable to quit rates of white-collar workers . No statistically significant differences between groups were found for mean changes in fruits and vegetables . Conclusions : Integration of occupational health and safety and health promotion may be an essential means of enhancing the effectiveness of worksite tobacco control initiatives with blue-collar workers BACKGROUND Environmental influences on health and health behavior have an important place in research on worksite health promotion . We tested the validity and internal consistency of a new measure of organizational health and safety climate that was used in a large r and omized trial of a worksite cancer prevention program ( the Working Well Trial ) . The result ing scales then were applied to assess intervention effects . METHODS This study uses data from a subset of 40 worksites in the Working Well Trial . Employees at 20 natural gas pipeline worksite and 20 rural electrical cooperatives completed a cross-sectional question naire at baseline and 3-year follow-up . RESULTS A factor analysis of this self-report instrument produced a two-factor solution . The result ing health and safety climate scales had good internal consistency ( Cronbach 's alpha = 0.74 and 0.82 , respectively ) and concurrent validity . The health climate scale was correlated more highly with organizational measures that were indicative of a supportive health climate than those indicating supportive safety climate , while the reverse was true of the safety climate scale . Changes in health climate were associated with the number of smoking and smokeless tobacco programs offered at the worksites at the time of the 3-year follow-up ( r = 0.46 and 0.42 , respectively ) . The scales were not correlated with most employee health behaviors . The health climate scores increased at intervention worksites , compared with scores at control worksites ( F[1,36 ] = 7.57 , P = 0.009 ) . CONCLUSIONS The health and safety climate scales developed for this study provide useful instruments for measuring organizational change related to worksite health promotion activities . The Working Well Intervention result ed in a significant improvement in worksite health climate AIM This paper is the report of a pilot study to assess if an Integrated Health Programme would reduce sick leave and subjective health complaints , and increase coping in a population of nursing personnel . BACKGROUND . The work group in Norway with most sick leave is healthcare workers . More than 50 % of the sick leave is because of subjective health complaints . Work place physical exercise interventions have a documented positive effect on sick leave . METHOD After baseline screening , employees who had agreed to participate ( n=40 ) were r and omized to an intervention or control group . The intervention group participated in an Integrated Health Programme twice weekly during working hours . The programme consisted of physical exercise , stress management training , health information and an examination of the participants ' workplace . The control group was offered the same intervention after the project was finished . This study was carried out from 2001 to 2002 . FINDINGS There were no statistically significant effects on sick leave or health-related quality of life . The intervention group reported fewer neck complaints compared to the control group , but otherwise there were no effects on subjective health complaints . However , the subjective effects were large and highly statistically significant , the intervention group reporting improvement in health , physical fitness , muscle pain , stress management , maintenance of health and work situation . CONCLUSION The Integrated Health Programme was not effective in reducing sick leave and subjective health complaints , but may be of use to employers wanting to increase employee job satisfaction and well-being According to prior reports , blue-collar workers are less likely to participate in worksite health promotion programs than are white-collar workers . This study examined worker participation in the WellWorks worksite cancer prevention intervention , which integrated health promotion and health protection . Analyses were conducted to assess relationships among participation in health promotion and health protection programs , and workers ' perceptions of management changes to reduce potential occupational exposures . Results indicate that blue-collar workers were less likely to report participating in health promotion activities than white-collar workers . A significant association was observed between participation in nutrition- and exposure-related activities , suggesting that participation in programs to reduce exposures to occupational hazards might contribute to blue-collar workers ' participation in health promotion activities . Furthermore , when workers were aware of changes their employer had made to reduce exposures to occupational hazards , they were more likely to participate in both smoking control and nutrition activities , even when controlling for job category . These findings have clear implication s for future worksite cancer prevention efforts OBJECTIVES We examined the efficacy of a cancer prevention intervention design ed to improve health behaviors among working-class , multiethnic population s employed in small manufacturing businesses . METHODS Worksites were r and omly assigned to an intervention or minimal-intervention control condition . The intervention targeted fruit and vegetable consumption , red meat consumption , multivitamin use , and physical activity . RESULTS Employees in the intervention group showed greater improvements for every outcome compared with employees in the control group . Differences in improvement were statistically significant for multivitamin use and physical activity . Intervention effects were larger among workers than among managers for fruit and vegetable consumption and for physical activity . CONCLUSIONS The social- context model holds promise for reducing disparities in health behaviors . Further research is needed to improve the effectiveness of the intervention PROBLEM STATEMENT Nurses have one of the highest rates of work-related musculoskeletal injury of any profession . Over the past 30 years , efforts to reduce work-related musculoskeletal disorders in nurses have been largely unsuccessful . SPECIFIC AIMS The primary goal of this program was to create safer working environments for nursing staff who provide direct patient care . Our first objective was to design and implement a multifaceted program that successfully integrated evidence -based practice , technology , and safety improvement . The second objective was to evaluate the impact of the program on injury rate , lost and modified work days , job satisfaction , self-reported unsafe patient h and ling acts , level of support for program , staff and patient acceptance , program effectiveness , costs , and return on investment . INTERVENTION The intervention included six program elements : ( 1 ) Ergonomic Assessment Protocol , ( 2 ) Patient H and ling Assessment Criteria and Decision Algorithms , ( 3 ) Peer Leader role , " Back Injury Re source Nurses " , ( 4 ) State-of-the-art Equipment , ( 5 ) After Action Review s , and ( 6 ) No Lift Policy . METHODS A pre-/post design without a control group was used to evaluate the effectiveness of a patient care ergonomics program on 23 high risk units ( 19 nursing home care units and 4 spinal cord injury units ) in 7 facilities . Injury rates , lost work days , modified work days , job satisfaction , staff , and patient acceptance , program effectiveness , and program costs/savings were compared over two nine month periods : pre-intervention ( May 2001-January 2002 ) and post-intervention ( March 2002-November 2002 ) . Data were collected prospect ively through surveys , weekly process logs , injury logs , and cost logs . RESULTS The program elements result ed in a statistically significant decrease in the rate of musculoskeletal injuries as well as the number of modified duty days taken per injury . While the total number of lost workdays decreased by 18 % post-intervention , this difference was not statistically significant . There were statistically significant increases in two subscales of job satisfaction : professional status and tasks requirements . Self-reports by nursing staff revealed a statistically significant decrease in the number of ' unsafe ' patient h and ling practice s performed daily . Nurses ranked program elements they deemed to be " extremely effective " : equipment was rated as most effective ( 96 % ) , followed by No Lift Policy ( 68 % ) , peer leader education program ( 66 % ) , ergonomic assessment protocol ( 59 % ) , patient h and ling assessment criteria and decision algorithms ( 55 % ) , and lastly after action review s ( 41 % ) . Perceived support and interest for the program started at a high level for managers and nursing staff and remained very high throughout the program implementation . Patient acceptance was moderate when the program started but increased to very high by the end of the program . Although the ease and success of program implementation initially varied between and within the facilities , after six months there was strong evidence of support at all levels . The initial capital investment for patient h and ling equipment was recovered in approximately 3.75 years based on annual post-intervention savings of over $ 200,000/year in workers ' compensation expenses and cost savings associated with reduced lost and modified work days and worker compensation . CONCLUSIONS This multi-faceted program result ed in an overall lower injury rate , fewer modified duty days taken per injury , and significant cost savings . The program was well accepted by patients , nursing staff , and administrators . Given the significant increases in two job satisfaction subscales ( professional status and task requirements ) , it is possible that nurse recruitment and retention could be positively impacted Objective Blue-collar workers are difficult to reach and less likely to successfully quit smoking . The objective of this study was to test a training site-based smoking cessation intervention . Methods This study is a r and omized-controlled trial of a smoking cessation intervention that integrated occupational health concerns and was delivered in collaboration with unions to apprentices at 10 sites ( n = 1,213 ) . We evaluated smoking cessation at 1 and 6 months post-intervention . Results The baseline prevalence of smoking was 41 % . We observed significantly higher quit rates in the intervention versus control group ( 26 % vs. 16.8 % ; p = 0.014 ) 1 month after the intervention . However , the effects diminished over time so that the difference in quit rate was not significant at 6 month post-intervention ( 9 % vs. 7.2 % ; p = 0.48 ) . Intervention group members nevertheless reported a significant decrease in smoking intensity ( OR = 3.13 ; 95 % CI : 1.55–6.31 ) at 6 months post-intervention , compared to controls . Conclusion The study demonstrates the feasibility of delivering an intervention through union apprentice programs . Furthermore , the notably better 1-month quit rate results among intervention members and the greater decrease in smoking intensity among intervention members who continued to smoke underscore the need to develop strategies to help reduce relapse among blue-collar workers who quit smoking This study is a prospect i ve multicentre cohort study entitled Work and Health in the Processing and Engineering Industries , the AHA Study ( AHA is the Swedish abbreviation for the study ) . Four large workplaces in Sweden participated during the years from 2000 to 2003 . The present report has two objectives : ( 1 ) to present a comprehensive occupational health intervention programme and ( 2 ) to evaluate this programme with a focus on lifestyle ( smoking and exercise ) , health related quality of life ( HRQoL ) and sick leave . Interventions were provided on an individual and group level , including evidence -based methods for four health/focus areas ( individual level ) and a group intervention based on a survey-feedback methodology . The analyses in this report were exclusively employed at an organizational level . The proportion of smokers decreased at three companies and the course of the HRQoL was advantageous at two of the companies as compared to a gainfully employed reference group . A significant decrease in sick leave was revealed at one company , whereas a break in an ascending sick-leave trend appeared at a second company as compared to their respective corporate groups . This comprehensive workplace intervention programme appears to have had positive effects on smoking habits , HRQoL and sick leave Disparities in chronic disease risk by occupation call for newapproaches to health promotion . Well Works-2 was a r and omized , controlled study comparing the effectiveness of a health promotion/occupational health program ( HP/OHS ) with a st and ard intervention ( HP ) . Interventions in both studies were based on the same theoretical foundations . Results from process evaluation revealed that a similar number of activities were offered in both conditions and that in the HP/OHS condition there were higher levels of worker participation using three measures : mean participation per activity ( HP : 14.2 % vs. HP/OHS : 21.2 % ) , mean minutes of worker exposure to the intervention/site ( HP : 14.9 vs. HP/OHS : 33.3 ) , and overall mean participation per site ( HP : 34.4 % vs. HP/ OHS : 45.8 % ) . There were a greater number of contacts with management ( HP : 8.8 vs. HP/OHS : 24.9 ) in the HP/ OHS condition . Addressing occupational health may have contributed to higher levels of worker and management participation and smoking cessation among blue-collar workers Objective : PHLAME ’s ( Promoting Healthy Lifestyles : Alternative Models ’ Effects ) objective was to assess and compare two means to promote healthy lifestyles . Methods : Prospect i ve trial among 599 firefighters r and omized by station to 1 ) team-centered curriculum , 2 ) one-on-one motivational interviewing ( MI ) , and 3 ) controls . Assessment included dietary behavior , physical activity , weight , Output:	Effective interventions were most of those aim ed at improving employee physical or mental health . Less consistent results were reported from integrated interventions targeting occupational health and safety management , injury prevention , or organizational cost savings . Integrated approaches have been posed as comprehensive solutions to complex issues .
MS213809	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Background : Transient elastography ( FibroScan ) is a new , non-invasive , rapid , and reproducible method allowing evaluation of liver fibrosis by measurement of liver stiffness . In cirrhotic patients , liver stiffness measurements range from 12.5 to 75.5 kPa . However , the clinical relevance of these values is unknown . The aim of this prospect i ve study was to evaluate the accuracy of liver stiffness measurement for the detection of cirrhosis in patients with chronic liver disease . Methods : A total of 711 patients with chronic liver disease were studied . Aetiologies of chronic liver diseases were hepatitis C virus or hepatitis B virus infection , alcohol , non-alcoholic steatohepatitis , other , or a combination of the above aetiologies . Liver fibrosis was evaluated according to the METAVIR score . Results : Stiffness was significantly correlated with fibrosis stage ( r = 0.73 , p<0.0001 ) . Areas under the receiver operating characteristic curve ( 95 % confidence interval ) were 0.80 ( 0.75–0.84 ) for patients with significant fibrosis ( F>2 ) , 0.90 ( 0.86–0.93 ) for patients with severe fibrosis ( F3 ) , and 0.96 ( 0.94–0.98 ) for patients with cirrhosis . Using a cut off value of 17.6 kPa , patients with cirrhosis were detected with a positive predictive value and a negative predictive value ( NPV ) of 90 % . Liver stiffness was significantly correlated with clinical , biological , and morphological parameters of liver disease . With an NPV > 90 % , the cut off values for the presence of oesophageal varices stage 2/3 , cirrhosis Child-Pugh B or C , past history of ascites , hepatocellular carcinoma , and oesophageal bleeding were 27.5 , 37.5 , 49.1 , 53.7 , and 62.7 kPa , respectively . Conclusion : Transient elastography is a promising non-invasive method for detection of cirrhosis in patients with chronic liver disease . Its use for the follow up and management of these patients could be of great interest and should be evaluated further BACKGROUND Liver biopsy is thought m and atory for management of patients with hepatitis C virus ( HCV ) infection , especially for staging fibrosis . We aim ed , in our prospect i ve study , to assess the predictive value of a combination of basic serum biochemical markers for diagnosis of clinical ly significant fibrosis ( including early stages ) . METHODS We assessed liver-biopsy patients with detectable HCV by PCR , for eligibility , and took a blood sample on the day of the procedure . The analysis was done in a first-year period for 205 patients and then tested in a second period on 134 patients . We devised a fibrosis index that included the most informative markers ( combined with age and sex ) for the first-year group . 11 serum markers were assessed as well as fibrosis stage : F0=no fibrosis and F1=portal fibrosis ; and for clinical ly significant fibrosis , F2=few septa , F3=many septa , and F4=cirrhosis . Statistical analysis was by logistic regression , neural connection , and receiver-operating characteristic ( ROC ) curves . FINDINGS First-year and second-year patient-group characteristics and biochemical markers did not differ . The overall frequency of clinical ly significant fibrosis was 40 % ( 138 patients ) . The most informative markers were : alpha2 macroglobulin , alpha2 globulin ( or haptoglobin ) , gamma globulin , apolipoprotein A1 , gamma glutamyltranspeptidase , and total bilirubin . The areas ( SD ) under the ROC curves for the first-year ( 0.836 [ 0.430 ] ) and second-year groups ( 0.870 [ 0.340 ] ) did not differ ( p=0.44 ) . With the best index , a high negative predictive value ( 100 % certainty of absence of F2 , F3 , or F4 ) was obtained for scores ranging from zero to 0.10 ( 12 % [ 41 ] of all patients ) , and high positive predictive value ( > 90 % certainty of presence of F2 , F3 , or F4 ) for scores ranging from 0.60 to 1.00 ( 34 % [ 115 ] of all patients ) . INTERPRETATION A combination of basic serum markers could be used to substantially reduce the number of liver biopsies done in patients with chronic HCV infection The aim of this study was to assess the feasibility of using non-invasive MR elastography for determining the stage of liver fibrosis . Twenty-five consecutive patients who had liver biopsy for suspicion of chronic liver disease were included in the study . The stage of fibrosis on the biopsies was assessed according to the METAVIR scoring system from F0 , no fibrosis , to F4 , cirrhosis . MR elastography was performed by transmitting low-frequency ( 65 Hz ) mechanical waves into the liver with a transducer placed at the back of the patients . The MR pulse sequence was a motion-sensitized spin-echo sequence , phase-locked to the mechanical excitation . The phase maps were processed to obtain shear elasticity and shear viscosity maps . The mean hepatic shear elasticity increased with increasing stage of fibrosis . The mean elasticity was 2.24 + /- 0.23 kPa in the 11 patients without substantial fibrosis ( F0-F1 grade s ) , 2.56 + /- 0.24 kPa in the four patients with substantial fibrosis ( F2-F3 ) and 4.68 + /- 1.61 kPa in the 10 patients with cirrhosis ( F4 ) . The differences between groups were statistically significant ( p < or= 0.05 ) . The mean shear viscosity was significantly higher in the patients with cirrhosis ( 5.19 + /- 1.85 Pa x s ) than in the patients without cirrhosis ( 2.39 + /- 0.86 Pa x s in F0-F1 and 2.27 + /- 0.38 Pa x s in F2-F3 patients ) . It is concluded that non-invasive MR elastography is a feasible method to assess the stage of liver fibrosis PURPOSE To prospect ively compare transit times of Levovist and SonoVue in healthy volunteers and patients with biopsy-proved hepatitis C-related liver disease . MATERIAL S AND METHODS Institutional review board approval and informed consent were obtained . Forty patients and 25 healthy volunteers were examined . Subjects fasted , a bolus of SonoVue ( 0.6 mL ) was injected into a cubital fossa vein , and hepatic venous time-intensity profiles were measured with spectral Doppler tracing . This was repeated with two injections of Levovist ( 2 g ) and another injection of SonoVue . Time-intensity curves of spectral Doppler signals of right and middle hepatic veins were analyzed . A sustained signal intensity increase of 10 % above baseline levels indicated hepatic vein transit time ( HVTT ) . Carotid artery audio intensity was measured in volunteers . Analysis of variance and t tests were used for statistical analysis . RESULTS Twelve patients had mild hepatitis ; 18 , moderate or severe hepatitis ; and 10 , cirrhosis . Mean HVTTs in control , mild hepatitis , moderate or severe hepatitis , and cirrhosis groups were 38.3 seconds + /- 2.4 ( st and ard error ) , 47.5 seconds + /- 6.5 , 29.5 seconds + /- 10.8 , and 17.6 seconds + /- 5.0 , respectively , with Levovist ( P < .001 ) and 29.4 seconds + /- 6.9 , 27.4 seconds + /- 9.3 , 22.9 seconds + /- 4.7 , and 16.4 seconds + /- 4.9 , respectively , with SonoVue ( P < .001 ) . HVTT decreased as severity increased at imaging with both contrast agents . There was no significant difference in HVTT between mild and moderate hepatitis groups with SonoVue ; however , there were significant differences in HVTT between all patient groups with Levovist . HVTT of SonoVue was shorter than that of Levovist in all groups ( P < .001 ) except the cirrhosis group ; in this group , HVTT of the two contrast agents was similar ( P = .05 ) . No difference was observed in mean cardiopulmonary transit time for SonoVue or Levovist ( 9.1 seconds + /- 2.4 [ st and ard error ] and 8.4 seconds + /- 2.5 , respectively , P = .18 ) . CONCLUSION HVTT was significantly shorter with SonoVue than with Levovist ; there was no significant difference in cardiopulmonary transit time AIM To evaluate the method of noninvasive transient elastography for assessment of histological stage of liver fibrosis in patients with chronic hepatitis C ( CHC ) . METHODS Two hundred and thirty-seven patients with CHC were included in this study . Liver biopsy was performed under ultrasonography on 217 of the patients , excluding twenty with clear clinical evidence of liver cirrhosis . Fifty subjects without liver disease were enrolled as a control group ( stage 0 ) . Twenty-five patients with sustained virological response ( SVR ) to interferon ( IFN ) therapy were also enrolled . These patients underwent liver biopsy before IFN therapy . Examination of liver stiffness ( LS ) was performed by elastography . RESULTS Medians ( 50 % levels ) of LS were 4.1 ( 3.5 - 4.9 ) , 6.3 ( 4.8 - 8.5 ) , 8.8 ( 6.8 - 12.0 ) , 14.6 ( 10.5 - 18.6 ) , and 22.2 ( 15.4 - 28.0 ) , respectively , in the fibrosis stages 0 - 4 ( P < 0.001 ) . LS was significantly correlated with four serum fibrosis markers . LS values in patients with SVR were 3.8 ( 3.5 - 5.6 ) , 5.2 ( 4.4 - 6.8 ) , 6.8 ( 6.1 - 7.6 ) , and 6.1 ( 3.6 - 7.9 ) , respectively , in the fibrosis stages 1 - 4 . In all stages , LS for patients with SVR was significantly lower than that for patients who did not undergo IFN therapy . LS was significantly correlated with serum concentrations of hyaluronic acid , type IV collagen , type IV collagen 7S , and type III procollagen N peptide . CONCLUSION LS correlated well with the histological stage of fibrosis . Changes in liver fibrosis stage may thus be estimated noninvasively using transient elastography The course of hepatitis C virus ( HCV ) infection carriers with normal/near-normal aminotransferases ( NALT ) is usually mild ; however , in a few , fibrosis progression occurs . We aim ed to verify whether monitoring by liver biopsy might be replaced by noninvasive methods and to identify factors associated with fibrosis progression in patients with persistently normal alanine aminotransferases . We studied 40 untreated HCV-RNA-positive subjects ( 22 male ; median age , 44 years ) , who underwent two liver biopsies , with a median interval of 78.5 months , during which alanine aminotransferase concentrations ( median number of determinations : 12 ) never exceeded 1.2 times the upper normal limit . Within 9 months from the second biopsy , they were tested by the shear elasticity probe ( Fibroscan ) and the artificial intelligence algorithm FibroTest . METAVIR fibrosis scores were analyzed in relationship to demographic , clinical , and viral parameters . Weighted kappa analysis was used to verify whether the results of noninvasive methods agreed with histology . Significant fibrosis ( > or = F2 ) , present at the first biopsy in only one patient ( 2.5 % ) , was observed at the second biopsy in 14 patients ( 35 % ) . At multivariate analysis , excess alcohol consumption in the past ( > 20 g/d ; P = .017 ) and viral load ( > 8.0 x 10(6 ) copies/mL ; P = .021 ) were independent predictors of progression . In identifying patients with significant fibrosis , inter-rater agreement was excellent for Fibroscan ( weighted kappa = 1.0 ) , and poor for FibroTest ( weighted kappa = -0.041 ) . In conclusion , among HCV carriers with NALT , Fibroscan is superior to the FibroTest in the noninvasive identification of fibrosis , for which excess alcohol consumption in the past and high viral load represent risk factors The risk of complications from percutaneous liver biopsy is low , but discomfort is common and complications require hospitalization in approximately 4 % of patients . The optimal method of performing these biopsies is unknown . The goal of our study was to determine whether the use of ultrasonography in the biopsy room immediately prior to or during the procedure would lessen the risk of complications and to compare the safety and efficacy in obtaining tissue by use of a Trucut needle versus an automatic biopsy needle . Between 1992 and 1994 , 836 patients were Output:	Although no single non-invasive test or model developed to date can match that information obtained from actual histology ( i.e. inflammation , fibrosis , steatosis ) , combinations of two modalities of non-invasive methods can reliably differentiate between minimal and significant fibrosis , and thereby avoid liver biopsy in a significant percentage of patients
MS213810	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Two hundred and seventy-four women admitted for delivery of singleton infants were studied for the effects of a preparatory enema on faecal contamination , duration of labour , and the incidence of infection in the newborn . Altogether 149 of the women were given an enema ( controls ) and 125 were not . The two groups showed no significant difference in the degree of faecal contamination during the first and second stages of labour , and the incidences of gross contamination were similar . Contamination after an enema was especially difficult to control , since it was more likely to be fluid . Seven neonates in each group showed evidence of infection , bowel organisms being isolated from four in the no-enema group and two in the control group . Duration s of labour , though not strictly comparable , were similar in the two groups . The findings suggest that when preparing for normal labour the enema should be reserved for women who have not had their bowels open in the past 24 hours and have an obviously loaded rectum on initial pelvic examination The effect of a soap enema on the progress of labour was studied in 160 women admitted for delivery in Esigodini District Hospital . The study was set up as a 1:1 r and omised case control study in 200 women . It was changed to a 1:3 case control study after 82 subjects had been studied , when it became apparent that the midwives were no longer willing to follow the study protocol . Forty women received an enema and 120 did not . Two focus group discussion s were held with 16 women who had an enema . The 12 hospital midwives were asked to give their opinion on enemas . Focus group discussion s were also held with 28 traditional midwives . Dilation of the cervix was 2.19 cm/hour in the non-enema group ( 95pc confidence interval 1.86 - 2.52 ) and 2.00 cm/hour in the enema group ( 95pc confidence interval 1.38 - 2.62 ) . The difference is not significant ( t-test : p-value = 0.58 ) . Pregnant women did not like enemas , midwives preferred not to administer them and were not concerned with contamination during delivery . Traditional midwives do not use enemas in labouring women and consider the possible contamination as normal . It is concluded that there is no benefit from routine enemas in labour Abstract Background Enemas are used during labour in obstetric setting s with the belief that they reduce puerperal and neonatal infections , shorten labour duration , and make delivery cleaner for attending personnel . However , a systematic review of the literature found insufficient evidence to support the use of enemas . The objective of this RCT was to address an identified knowledge gap by determining the effect of routine enemas used during the first stage of labour on puerperal and neonatal infection rates . Methods Design : RCT ( r and omised controlled trial ; r and omized clinical trial ) . Outcomes : Clinical diagnosis of maternal or neonatal infections , labour duration , delivery types , episiotomy rates , and prescription of antibiotics Setting : Tertiary care referral hospital at the Javeriana University ( Bogotá , Colombia ) that attended 3170 births during study period with a caesarean section rate of 26 % . Participants : 443 women admitted for delivery to the obstetrics service ( February 1997 to February 1998 ) and followed for a month after delivery . Inclusion criteria were women with : low risk pregnancy and expected to remain in Bogotá during follow up ; gestational age ≥ 36 weeks ; no pelvic or systemic bacterial infection ; intact membranes ; cervix dilatation ≤7 cm . Intervention : 1 litre saline enema , versus no enema , allocated following a block r and om allocation sequence and using sealed opaque envelopes . Results Allocation provided balanced groups and 86 % of the participants were followed up for one month . The overall infection rate for newborns was 21 % , and 18 % for women . We found no significant differences in puerperal or neonatal infection rates ( Puerperal infection : 41/190 [ 22 % ] with enema v 26/182 [ 14 % ] without enema ; RR 0.66 CI 95 % : 0.43 to 1.03 ; neonatal infection 38/191 [ 20 % ] with enema v 40/179 [ 22 % ] without enema ; RR 1.12 , 95 % CI 95 % 0.76 to 1.66 ) , and median labour time was similar between groups ( 515 min . with enema v 585 min . without enema ; P = 0.24 ) . Enemas did n't significantly change episiorraphy dehiscence rates ( 21/182 [ 12 % ] with enema v 32/190 [ 17 % ] without enema ; P = 0.30 ) . Conclusion This RCT found no evidence to support routine use of enemas during labour . Although these results can not rule out a small clinical effect , it seems unlikely that enemas will improve maternal and neonatal outcomes and provide an overall benefit OBJECTIVE To compare the maternal and neonatal outcomes between enema and no-enema in pregnant women on admission in labor . MATERIAL AND METHOD One thous and and one hundred term pregnant women with labor pain were selected r and omly on admission to be assigned into two groups at Rajavithi Hospital from 1 February 2002 to 15 June 2002 . Five -hundred and thirty-nine cases received enema and five-hundred and sixty one cases received noenema . Seventy three women ( 39 and 34 cases from the enema and no-enema groups , respectively ) were excluded because of cesarean section due to obstetric indications . Five hundred cases received enema and five-hundred and twenty -seven cases received no-enema . All cases were delivered vaginally . RESULTS There was no statistical significant difference between the two groups with regards to maternal age , gestational age , gravidity , parity , mode of delivery , type of episiotomy and degree of perineal tear . Fecal contamination rate during the second stage of labor was significantly higher in the women who received no-enema ( 34.9 % ) in comparision with those receiving enema ( 22.8 % ( p < 0.001 ) . No neonatal infection occurred in both groups . Duration of labor was significantly longer in the women who received no-enema ( 459.8 min ) compared with those who received enema ( 409.4 min ) ( p < 0.001 ) . CONCLUSION No-enema methods on admission in labor had significantly more increase infecal contamination in the second stage of labor and longer duration of labor than the enema method But there was no difference in perineal wound infection and neonatal infection between both groups BACKGROUND Intervention rates in maternity practice s vary considerably across Canadian provinces and territories . The objective of this study was to describe the use of routine interventions and practice s in labor and birth as reported by women in the Maternity Experiences Survey of the Canadian Perinatal Surveillance System . Rates of interventions and practice s are considered in the light of current evidence and both Canadian and international recommendations . METHODS A sample of 8,244 estimated eligible women was identified from a r and omly selected sample of recently born infants drawn from the May 2006 Canadian Census and stratified primarily by province and territory . Birth mothers living with their infants at the time of interview were invited to participate in a computer-assisted telephone interview conducted by Statistics Canada on behalf of the Public Health Agency of Canada . Interviews averaged 45 minutes long and were completed when infants were between 5 and 10 months old ( 9 - 14 mo in the territories ) . Completed responses were obtained from 6,421 women ( 78 % ) . RESULTS Women frequently reported electronic fetal monitoring , a health care practitioner starting or speeding up their labor ( or trying to do so ) , epidural anesthesia , episiotomy , and a supine position for birth . Some women also reported pubic or perineal shaves , enemas , and pushing on the top of their abdomen . CONCLUSIONS Several practice s and interventions were commonly reported in labor and birth in Canada , although evidence and Canadian and international guidelines recommend against their routine use . Practice s not recommended for use at all , such as shaving , were also reported While taking an enema to induce labor is a controversial issue worldwide , in Taiwan it remains a routine procedure in many hospitals in preparation for birth . Episiotomy is also a prevalent procedure performed during the birthing process . Some physicians believe that enemas help reduce the risk of feces contamination of the episiotomy incision and , therefore , are justified as a routine procedure . This study compared the neonatal infection rates , times to appearance of fetal head , times to first post-labor bowel movement , and rates of episiotomy dehiscence of women receiving a pre-labor enema against those who did not . A total of 534 women classified with low-risk pregnancies were recruited from a medical center in central Taiwan and assigned r and omly into one of two groups for a six-month period . The first group ( 264 subjects ) received routine enema procedures prior to delivery in the first 6 months . The second group ( 270 subjects ) did not receive enemas . Study results revealed no significant difference between enema and non-enema groups in terms of infection rates in mothers or infants or in terms of average time to fetal head appearance . While labor duration was the same for the two groups in the first and third stages of labor , the enema group experienced a relatively shorter second stage . No significant difference was observed in times to first post-labor bowel movement or episiotomy dehiscence rates . The results of this study indicate that the administration of enemas as a routine practice prior to labor is not substantiated by medical necessity . However , limitations of the research design suggest that a r and omized clinical trial be adopted in the future to explore further the scientific validity of study results Output:	The evidence provided by the three included RCTs shows that enemas do not have a significant effect on infection rates such as perineal wound infection or other neonatal infections and women 's satisfaction .
MS213811	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: The phase III MMY-3021 study compared safety and efficacy of subcutaneous versus intravenous administration of the proteasome inhibitor bortezomib in patients with relapsed myeloma . The initial report demonstrated non-inferior efficacy with subcutaneous versus intravenous bortezomib for the primary end point : overall response rate after four cycles of single-agent bortezomib . We report up date d outcome analyses after prolonged follow up . Best response rate ( after up to ten cycles of bortezomib ± dexamethasone ) remained 52 % in each arm , including 23 % and 22 % complete or near-complete responses with subcutaneous and intravenous bortezomib , respectively . Time to progression ( median 9.7 vs. 9.6 months ; hazard ratio 0.872 , P=0.462 ) , progression-free survival ( median 9.3 vs. 8.4 months ; hazard ratio 0.846 , P=0.319 ) , and overall survival ( 1-year : 76.4 % vs. 78.0 % , P=0.788 ) were comparable with subcutaneous versus intravenous bortezomib . Peripheral neuropathy rates remained significantly lower with subcutaneous versus intravenous bortezomib , with increased rates of improvement/resolution at the time of this analysis BACKGROUND Thalidomide plus dexamethasone ( TD ) is a st and ard induction therapy for myeloma . We aim ed to assess the efficacy and safety of addition of bortezomib to TD ( VTD ) versus TD alone as induction therapy before , and consolidation therapy after , double autologous stem-cell transplantation in newly diagnosed multiple myeloma . METHODS Patients ( aged 18 - 65 years ) with previously untreated symptomatic myeloma were enrolled from 73 sites in Italy between May , 2006 , and April , 2008 , and data collection continued until June 30 , 2010 . Patients were r and omly allocated ( 1:1 ratio ) by a web-based system to receive three 21-day cycles of thalidomide ( 100 mg daily for the first 14 days and 200 mg daily thereafter ) plus dexamethasone ( 40 mg daily on 8 of the first 12 days , but not consecutively ; total of 320 mg per cycle ) , either alone or with bortezomib ( 1·3 mg/m(2 ) on days 1 , 4 , 8 , and 11 ) . The r and omisation sequence was computer generated by the study coordinating team and was stratified by disease stage . After double autologous stem-cell transplantation , patients received two 35-day cycles of their assigned drug regimen , VTD or TD , as consolidation therapy . The primary endpoint was the rate of complete or near complete response to induction therapy . Analysis was by intention to treat . Patients and treating physicians were not masked to treatment allocation . This study is still underway but is not recruiting participants , and is registered with Clinical Trials.gov , number NCT01134484 , and with EudraCT , number 2005 - 003723 - 39 . FINDINGS 480 patients were enrolled and r and omly assigned to receive VTD ( n=241 patients ) or TD ( n=239 ) . Six patients withdrew consent before start of treatment , and 236 on VTD and 238 on TD were included in the intention-to-treat analysis . After induction therapy , complete or near complete response was achieved in 73 patients ( 31 % , 95 % CI 25·0 - 36·8 ) receiving VTD , and 27 ( 11 % , 7·3 - 15·4 ) on TD ( p<0·0001 ) . Grade 3 or 4 adverse events were recorded in a significantly higher number of patients on VTD ( n=132 , 56 % ) than in those on TD ( n=79 , 33 % ; p<0·0001 ) , with a higher occurrence of peripheral neuropathy in patients on VTD ( n=23 , 10 % ) than in those on TD ( n=5 , 2 % ; p=0·0004 ) . Resolution or improvement of severe peripheral neuropathy was recorded in 18 of 23 patients on VTD , and in three of five patients on TD . INTERPRETATION VTD induction therapy before double autologous stem-cell transplantation significantly improves rate of complete or near complete response , and represents a new st and ard of care for patients with multiple myeloma who are eligible for transplant . FUNDING Seràgnoli Institute of Haematology at the University of Bologna , Bologna , Italy The phase 3 VISTA study ( Clinical Trials.gov NCT00111319 ) in transplant‐ineligible myeloma patients demonstrated superior efficacy with bortezomib‐melphalan‐prednisone ( VMP ; nine 6‐wk cycles ) vs. melphalan‐prednisone ( MP ) but also increased toxicity . Health‐related quality of life ( HRQoL ; exploratory endpoint ) was evaluated using the European Organization for Research and Treatment of Cancer ( EORTC ) Quality of Life Question naire ( QLQ‐C30 ) Combinations of bortezomib ( V ) and dexamethasone ( D ) with either lenalidomide ( R ) or cyclophosphamide ( C ) have shown significant efficacy . This r and omized phase 2 trial evaluated VDC , VDR , and VDCR in previously untreated multiple myeloma ( MM ) . Patients received V 1.3 mg/m2 ( days 1 , 4 , 8 , 11 ) and D 40 mg ( days 1 , 8 , 15 ) , with either C 500 mg/m2 ( days 1 , 8) and R 15 mg ( days 1 - 14 ; VDCR ) , R 25 mg ( days 1 - 14 ; VDR ) , C 500 mg/m2 ( days 1 , 8 ; VDC ) or C 500 mg/m2 ( days 1 , 8 , 15 ; VDC-mod ) in 3-week cycles ( maximum 8 cycles ) , followed by maintenance with V 1.3 mg/m2 ( days 1 , 8 , 15 , 22 ) for four 6-week cycles ( all arms)≥very good partial response was seen in 58 % , 51 % , 41 % , and 53 % ( complete response rate of 25 % , 24 % , 22 % , and 47 % ) of patients ( VDCR , VDR , VCD , and VCD-mod , respectively ) ; the corresponding 1-year progression-free survival was 86 % , 83 % , 93 % , and 100 % , respectively . Common adverse events included hematologic toxicities , peripheral neuropathy , fatigue , and gastrointestinal disturbances . All regimens were highly active and well tolerated in previously untreated MM , and , based on this trial , VDR and VCD-mod are preferred for clinical practice and further comparative testing . No substantial advantage was noted with VDCR over the 3-drug combinations . This trial is registered at www . clinical trials.gov ( NCT00507442 ) In a r and omized , phase 3 study , superior complete/near-complete response ( CR/nCR ) rates and extended progression-free survival were demonstrated with bortezomib-thalidomide-dexamethasone ( VTD ) versus thalidomide-dexamethasone ( TD ) as induction therapy before , and consolidation after , double autologous stem cell transplantation for newly diagnosed myeloma patients ( intention-to-treat analysis ; VTD , n = 236 ; TD , n = 238 ) . This per- protocol analysis ( VTD , n = 160 ; TD , n = 161 ) specifically assessed the efficacy and safety of consolidation with VTD or TD . Before starting consolidation , CR/nCR rates were not significantly different in the VTD ( 63.1 % ) and TD arms ( 54.7 % ) . After consolidation , CR ( 60.6 % vs 46.6 % ) and CR/nCR ( 73.1 % vs 60.9 % ) rates were significantly higher for VTD-treated versus TD-treated patients . VTD consolidation significantly increased CR and CR/nCR rates , but TD did not ( McNemar test ) . With a median follow-up of 30.4 months from start of consolidation , 3-year progression-free survival was significantly longer for the VTD group ( 60 % vs 48 % for TD ) . Grade 2 or 3 peripheral neuropathy ( 8.1 % vs 2.4 % ) was more frequent with VTD ( grade 3 , 0.6 % ) versus TD consolidation . The superior efficacy of VTD versus TD as induction was retained despite readministration as consolidation therapy after double autologous transplantation . VTD consolidation therapy significantly contributed to improved clinical outcomes observed for patients r and omly assigned to the VTD arm of the study . The study is registered at www . clinical trials.gov as # NCT01134484 The Intergroupe Francophone du Myelome conducted a r and omized trial to compare bortezomib-dexamethasone ( VD ) as induction before high-dose therapy ( HDT ) and autologous stem cell transplantation ( ASCT ) to a combination consisting of reduced doses of bortezomib and thalidomide plus dexamethasone ( vtD ) in patients with multiple myeloma . Overall , a total of 199 patients were central ly r and omly assigned to receive VD or vtD. After 4 cycles , the complete response ( CR ) rate was the same in both groups ( 13 % in the vtD arm , 12 % in the VD arm , P = .74 ) . However , the CR plus very good partial response ( VGPR ) rate was significantly higher in the vtD arm ( 49 % vs 36 % , P = .05 ) . After ASCT , the CR plus VGPR rate was significantly higher in the vtD arm ( 74 % vs 58 % , P = .02 ) . The reduced doses of bortezomib and thalidomide translated into a reduced incidence of peripheral neuropathy ( PN ) : grade ≥ 2 PN were reported in 34 % in the VD arm versus 14 % in the vtD arm ( P = .001 ) . vtD , including reduced doses of bortezomib and thalidomide , yields higher VGPR rates compared with VD and can be considered a new effective triplet combination before HDT/ASCT Initial analysis of the Assessment of Proteasome Inhibition for Extending Remissions ( APEX ) trial of relapsed multiple myeloma patients showed significantly longer time to progression , higher response rate , and improved survival with single-agent bortezomib versus high-dose dexamethasone . In this up date d analysis ( median follow-up : 22 months ) , survival was assessed in both arms , and efficacy up date d for the bortezomib arm . Median survival was 29.8 months for bortezomib versus 23.7 months for dexamethasone , a 6-month benefit , despite substantial crossover from dexamethasone to bortezomib . Overall and complete response rates with bortezomib were 43 % and 9 % , respectively ; among responding patients , 56 % improved response with longer therapy beyond initial response , leading to continued improvement in overall quality of response . Higher response quality ( 100 % M-protein reduction ) was associated with longer response duration ; response duration was not associated with time to response . These data confirm the activity of bortezomib and support extended treatment in relapsed multiple myeloma patients tolerating therapy The Nordic Myeloma Study Group conducted an open r and omized trial to compare bortezomib as consolidation therapy given after high-dose therapy and autologous stem cell transplantation ( ASCT ) with no consolidation in bortezomib-naive patients with newly diagnosed multiple myeloma . Overall , 370 patients were central ly r and omly assigned 3 months after ASCT to receive 20 doses of bortezomib given during 21 weeks or no consolidation . The hypothesis was that consolidation therapy would prolong progression-free survival ( PFS ) . The PFS after r and omization was 27 months for the bortezomib group compared with 20 months for the control group ( P = .05 ) . Fifty-one of 90 patients in the treatment group compared with 32 of 90 controls improved their response after r and omization ( P = .007 ) . No difference in overall survival was seen . Fatigue was reported more commonly by the bortezomib-treated patients in self-reported quality -of-life ( QOL ) question naires , whereas no other major differences in QOL were recorded between the groups . Consolidation therapy seemed to be beneficial for patients not achieving at least a very good partial response ( VGPR ) but not for patients in the ≥ VGPR category at r and omization . Consolidation with bortezomib after ASCT in bortezomib-naive patients improves PFS without interfering with QOL . This trial was registered at www . clinical trials.gov as # NCT00417911 Objectives Thalidomide and bortezomib have been frequently used for second-line therapy in patients with myeloma relapsing after or refractory to initial melphalan-based treatment , but no r and omized trials have been published comparing these two treatment alternatives . Methods Output:	Subgroup analyses by disease setting revealed improvements in all outcomes , whereas for therapy setting , an improved benefit for bortezomib was observed in all outcomes and subgroups except for OS following consolidation therapy . This meta- analysis found that myeloma patients receiving bortezomib benefited in terms of OS , PFS and response rate compared to those who did not receive bortezomib . This benefit was observed in trials of bortezomib versus no bortezomib with the same background therapy and in trials of bortezomib versus no bortezomib with different background therapy in each arm or compared to other agent(s ) .
MS213812	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Purpose Patients with squamous non-small-cell lung cancer ( NSCLC ) have poor prognosis and limited treatment options . This r and omized , double-blind , phase III study investigated the efficacy and safety of first-line ipilimumab or placebo plus paclitaxel and carboplatin in advanced squamous NSCLC . Patients and Methods Patients with stage IV or recurrent chemotherapy-naïve squamous NSCLC were r and omly assigned ( 1:1 ) to receive paclitaxel and carboplatin plus blinded ipilimumab 10 mg/kg or placebo every 3 weeks on a phased induction schedule comprising six chemotherapy cycles , with ipilimumab or placebo from cycles 3 to 6 and then , after induction treatment , ipilimumab or placebo maintenance every 12 weeks for patients with stable disease or better . The primary end point was overall survival ( OS ) in patients receiving at least one dose of blinded study therapy . Results Of 956 r and omly assigned patients , 749 received at least one dose of blinded study therapy ( chemotherapy plus ipilimumab , n = 388 ; chemotherapy plus placebo , n = 361 ) . Median OS was 13.4 months for chemotherapy plus ipilimumab and 12.4 months for chemotherapy plus placebo ( hazard ratio , 0.91 ; 95 % CI , 0.77 to 1.07 ; P = .25 ) . Median progression-free survival was 5.6 months for both groups ( hazard ratio , 0.87 ; 95 % CI , 0.75 to 1.01 ) . Rates of grade 3 or 4 treatment-related adverse events ( TRAEs ) , any- grade serious TRAEs , and TRAEs leading to discontinuation were numerically higher with chemotherapy plus ipilimumab ( 51 % , 33 % , and 28 % , respectively ) than with chemotherapy plus placebo ( 35 % , 10 % , and 7 % , respectively ) . Seven treatment-related deaths occurred with chemotherapy plus ipilimumab , and one occurred with chemotherapy plus placebo . Conclusion The addition of ipilimumab to first-line chemotherapy did not prolong OS compared with chemotherapy alone in patients with advanced squamous NSCLC . The safety profile of chemotherapy plus ipilimumab was consistent with that observed in previous lung and melanoma studies . Ongoing studies are evaluating ipilimumab in combination with nivolumab in this population BACKGROUND Atezolizumab is a humanised antiprogrammed death-lig and 1 ( PD-L1 ) monoclonal antibody that inhibits PD-L1 and programmed death-1 ( PD-1 ) and PD-L1 and B7 - 1 interactions , reinvigorating anticancer immunity . We assessed its efficacy and safety versus docetaxel in previously treated patients with non-small-cell lung cancer . METHODS We did a r and omised , open-label , phase 3 trial ( OAK ) in 194 academic or community oncology centres in 31 countries . We enrolled patients who had squamous or non-squamous non-small-cell lung cancer , were 18 years or older , had measurable disease per Response Evaluation Criteria in Solid Tumors , and had an Eastern Cooperative Oncology Group performance status of 0 or 1 . Patients had received one to two previous cytotoxic chemotherapy regimens ( one or more platinum based combination therapies ) for stage IIIB or IV non-small-cell lung cancer . Patients with a history of autoimmune disease and those who had received previous treatments with docetaxel , CD137 agonists , anti-CTLA4 , or therapies targeting the PD-L1 and PD-1 pathway were excluded . Patients were r and omly assigned ( 1:1 ) to intravenously receive either atezolizumab 1200 mg or docetaxel 75 mg/m2 every 3 weeks by permuted block r and omisation ( block size of eight ) via an interactive voice or web response system . Co primary endpoints were overall survival in the intention-to-treat ( ITT ) and PD-L1-expression population TC1/2/3 or IC1/2/3 ( ≥1 % PD-L1 on tumour cells or tumour-infiltrating immune cells ) . The primary efficacy analysis was done in the first 850 of 1225 enrolled patients . This study is registered with Clinical Trials.gov , number NCT02008227 . FINDINGS Between March 11 , 2014 , and April 29 , 2015 , 1225 patients were recruited . In the primary population , 425 patients were r and omly assigned to receive atezolizumab and 425 patients were assigned to receive docetaxel . Overall survival was significantly longer with atezolizumab in the ITT and PD-L1-expression population s. In the ITT population , overall survival was improved with atezolizumab compared with docetaxel ( median overall survival was 13·8 months [ 95 % CI 11·8 - 15·7 ] vs 9·6 months [ 8·6 - 11·2 ] ; hazard ratio [ HR ] 0·73 [ 95 % CI 0·62 - 0·87 ] , p=0·0003 ) . Overall survival in the TC1/2/3 or IC1/2/3 population was improved with atezolizumab ( n=241 ) compared with docetaxel ( n=222 ; median overall survival was 15·7 months [ 95 % CI 12·6 - 18·0 ] with atezolizumab vs 10·3 months [ 8·8 - 12·0 ] with docetaxel ; HR 0·74 [ 95 % CI 0·58 - 0·93 ] ; p=0·0102 ) . Patients in the PD-L1 low or undetectable subgroup ( TC0 and IC0 ) also had improved survival with atezolizumab ( median overall survival 12·6 months vs 8·9 months ; HR 0·75 [ 95 % CI 0·59 - 0·96 ] ) . Overall survival improvement was similar in patients with squamous ( HR 0·73 [ 95 % CI 0·54 - 0·98 ] ; n=112 in the atezolizumab group and n=110 in the docetaxel group ) or non-squamous ( 0·73 [ 0·60 - 0·89 ] ; n=313 and n=315 ) histology . Fewer patients had treatment-related grade 3 or 4 adverse events with atezolizumab ( 90 [ 15 % ] of 609 patients ) versus docetaxel ( 247 [ 43 % ] of 578 patients ) . One treatment-related death from a respiratory tract infection was reported in the docetaxel group . INTERPRETATION To our knowledge , OAK is the first r and omised phase 3 study to report results of a PD-L1-targeted therapy , with atezolizumab treatment result ing in a clinical ly relevant improvement of overall survival versus docetaxel in previously treated non-small-cell lung cancer , regardless of PD-L1 expression or histology , with a favourable safety profile . FUNDING F. Hoffmann-La Roche Ltd , Genentech , BACKGROUND Nivolumab plus ipilimumab showed promising efficacy for the treatment of non – small‐cell lung cancer ( NSCLC ) in a phase 1 trial , and tumor mutational burden has emerged as a potential biomarker of benefit . In this part of an open‐label , multipart , phase 3 trial , we examined progression‐free survival with nivolumab plus ipilimumab versus chemotherapy among patients with a high tumor mutational burden ( ≥10 mutations per megabase ) . METHODS We enrolled patients with stage IV or recurrent NSCLC that was not previously treated with chemotherapy . Those with a level of tumor programmed death lig and 1 ( PD‐L1 ) expression of at least 1 % were r and omly assigned , in a 1:1:1 ratio , to receive nivolumab plus ipilimumab , nivolumab monotherapy , or chemotherapy ; those with a tumor PD‐L1 expression level of less than 1 % were r and omly assigned , in a 1:1:1 ratio , to receive nivolumab plus ipilimumab , nivolumab plus chemotherapy , or chemotherapy . Tumor mutational burden was determined by the FoundationOne CDx assay . RESULTS Progression‐free survival among patients with a high tumor mutational burden was significantly longer with nivolumab plus ipilimumab than with chemotherapy . The 1‐year progression‐free survival rate was 42.6 % with nivolumab plus ipilimumab versus 13.2 % with chemotherapy , and the median progression‐free survival was 7.2 months ( 95 % confidence interval [ CI ] , 5.5 to 13.2 ) versus 5.5 months ( 95 % CI , 4.4 to 5.8 ) ( hazard ratio for disease progression or death , 0.58 ; 97.5 % CI , 0.41 to 0.81 ; P<0.001 ) . The objective response rate was 45.3 % with nivolumab plus ipilimumab and 26.9 % with chemotherapy . The benefit of nivolumab plus ipilimumab over chemotherapy was broadly consistent within subgroups , including patients with a PD‐L1 expression level of at least 1 % and those with a level of less than 1 % . The rate of grade 3 or 4 treatment‐related adverse events was 31.2 % with nivolumab plus ipilimumab and 36.1 % with chemotherapy . CONCLUSIONS Progression‐free survival was significantly longer with first‐line nivolumab plus ipilimumab than with chemotherapy among patients with NSCLC and a high tumor mutational burden , irrespective of PD‐L1 expression level . The results vali date the benefit of nivolumab plus ipilimumab in NSCLC and the role of tumor mutational burden as a biomarker for patient selection . ( Funded by Bristol‐Myers Squibb and Ono Pharmaceutical ; CheckMate 227 Clinical Trials.gov number , NCT02477826 . BACKGROUND Nivolumab , a fully human IgG4 programmed death 1 ( PD-1 ) immune-checkpoint-inhibitor antibody , disrupts PD-1-mediated signaling and may restore antitumor immunity . METHODS In this r and omized , open-label , international phase 3 study , we assigned patients with nonsquamous non-small-cell lung cancer ( NSCLC ) that had progressed during or after platinum-based doublet chemotherapy to receive nivolumab at a dose of 3 mg per kilogram of body weight every 2 weeks or docetaxel at a dose of 75 mg per square meter of body-surface area every 3 weeks . The primary end point was overall survival . RESULTS Overall survival was longer with nivolumab than with docetaxel . The median overall survival was 12.2 months ( 95 % confidence interval [ CI ] , 9.7 to 15.0 ) among 292 patients in the nivolumab group and 9.4 months ( 95 % CI , 8.1 to 10.7 ) among 290 patients in the docetaxel group ( hazard ratio for death , 0.73 ; 96 % CI , 0.59 to 0.89 ; P=0.002 ) . At 1 year , the overall survival rate was 51 % ( 95 % CI , 45 to 56 ) with nivolumab versus 39 % ( 95 % CI , 33 to 45 ) with docetaxel . With additional follow-up , the overall survival rate at 18 months was 39 % ( 95 % CI , 34 to 45 ) with nivolumab versus 23 % ( 95 % CI , 19 to 28 ) with docetaxel . The response rate was 19 % with nivolumab versus 12 % with docetaxel ( P=0.02 ) . Although progression-free survival did not favor nivolumab over docetaxel ( median , 2.3 months and 4.2 months , respectively ) , the rate of progression-free survival at 1 year was higher with nivolumab than with docetaxel ( 19 % and 8 % , respectively ) . Nivolumab was associated with even greater efficacy than docetaxel across all end points in subgroups defined according to prespecified levels of tumor-membrane expression ( ≥1 % , ≥5 % , and ≥10 % ) of the PD-1 lig and . Treatment-related adverse events of grade 3 or 4 were reported in 10 % of the patients in the nivolumab group , as compared with 54 % of those in the docetaxel group . CONCLUSIONS Among patients with advanced nonsquamous NSCLC that had progressed during or after platinum-based chemotherapy , overall survival was longer with nivolumab than with docetaxel . ( Funded by Bristol-Myers Squibb ; CheckMate 057 Clinical Trials.gov number , NCT01673867 . ) Purpose Patients with extensive-stage disease small-cell lung cancer Output:	Conclusions : Stratified meta- analysis demonstrates that smoking status is not significantly associated with the response to IO in the treatment of advanced solid organ malignancies
MS213813	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Background Afghanistan 's national guidelines recommend chloroquine for the treatment of Plasmodium vivax infection , the parasite responsible for the majority of its malaria burden . Chloroquine resistance in P. vivax is emerging in Asia . Therapeutic responses across Afghanistan have not been evaluated in detail . Methods Between July 2007 and February 2009 , an open-label , r and omized controlled trial of chloroquine and dihydroartemisinin-piperaquine in patients aged three months and over with slide-confirmed P. vivax mono-infections was conducted . Consistent with current national guidelines , primaquine was not administered . Subjects were followed up daily during the acute phase of illness ( days 0 - 3 ) and weekly until day 56 . The primary endpoint was the overall cumulative parasitological failure rate at day 56 after the start of treatment , with the hypothesis being that dihydroartemisinin-piperaquine was non-inferior compared to chloroquine ( Δ = 5 % difference in proportion of failures ) . Results Of 2,182 individuals with positive blood films for P. vivax , 536 were enrolled in the trial . The day 28 cure rate was 100 % in both treatment groups . Parasite clearance was more rapid with dihydroartemisinin-piperaquine than chloroquine . At day 56 , there were more recurrent infections in the chloroquine arm ( 8.9 % , 95 % CI 6.0 - 13.1 % ) than the dihydroartemisinin-piperaquine arm ( 2.8 % , 95 % CI 1.4 - 5.8 % ) , a difference in cumulative recurrence rate of 6.1 % ( 2-sided 90%CI + 2.6 to + 9.7 % ) . The log-rank test comparing the survival curves confirmed the superiority of dihydroartemisinin-piperaquine over chloroquine ( p = 0.003 ) . Multivariate analysis showed that a lower initial haemoglobin concentration was also independently associated with recurrence . Both regimens were well tolerated and no serious adverse events were reported . Conclusions Chloroquine remains an efficacious treatment for the treatment of vivax malaria in Afghanistan . In a setting where radical therapy can not be administered , dihydroartemisinin-piperaquine provides additional benefit in terms of post-treatment prophylaxis , reducing the incidence of recurrence from 4 - 8 weeks after treatment . Trial Registration The trial was registered at Clinical Trials.gov under identifier NCT00682578 Background Malaria is a very important cause of anaemia in tropical countries . Anaemia is assessed either by measurement of the haematocrit or the haemoglobin concentration . For comparisons across studies , it is often necessary to derive one measure from the other . Methods Data on patients with slide-confirmed uncomplicated falciparum malaria were pooled from 85 antimalarial drug trials conducted in 25 different countries , to assess the haemoglobin/haematocrit relationship at different time points in malaria . Using a linear r and om effects model , a conversion equation for haematocrit was derived based on 3,254 measurements from various time points ( ranging from day 0 to day 63 ) from 1,810 patients with simultaneous measurements of both parameters . Haemoglobin was also estimated from haematocrit with the commonly used threefold conversion . Results A good fit was obtained using Haematocrit = 5.62 + 2.60 * Haemoglobin . On average , haematocrit/3 levels were slightly higher than haemoglobin measurements with a mean difference ( ± SD ) of -0.69 ( ± 1.3 ) for children under the age of 5 ( n = 1,440 measurements from 449 patients ) . Conclusion Based on this large data set , an accurate and robust conversion factor both in acute malaria and in convalescence was obtained . The commonly used threefold conversion is also valid Background Radical cure of Plasmodium vivax malaria with 8-aminoquinolines ( primaquine or tafenoquine ) is complicated by haemolysis in individuals with glucose-6-phosphate dehydrogenase ( G6PD ) deficiency . G6PD heterozygous females , because of individual variation in the pattern of X-chromosome inactivation ( Lyonisation ) in erythroid cells , may have low G6PD activity in the majority of their erythrocytes , yet are usually reported as G6PD “ normal ” by current phenotypic screening tests . Their haemolytic risk when treated with 8-aminoquinolines has not been well characterized . Methods and Findings In a cohort study nested within a r and omised clinical trial that compared different treatment regimens for P. vivax malaria , patients with a normal st and ard NADPH fluorescent spot test result ( ≳30%–40 % of normal G6PD activity ) were r and omised to receive 3 d of chloroquine or dihydroartemisinin-piperaquine in combination with primaquine , either the st and ard high dose of 0.5 mg base/kg/day for 14 d or a higher dose of 1 mg base/kg/d for 7 d. Patterns of haemolysis were compared between G6PD wild-type and G6PD heterozygous female participants . Between 21 February 2012 and 04 July 2014 , 241 female participants were enrolled , of whom 34 were heterozygous for the G6PD Mahidol variant . Haemolysis was substantially greater and a larger proportion of participants reached the threshold of clinical ly significant haemolysis ( fractional haematocrit reduction > 25 % ) in G6PD heterozygotes taking the higher ( 7 d ) primaquine dose ( 9/17 [ 53 % ] ) compared with G6PD heterozygotes taking the st and ard high ( 14 d ) dose ( 2/16 [ 13 % ] ; p = 0.022 ) . In heterozygotes , the mean fractional haematocrit reductions were correspondingly greater with the higher primaquine dose ( 7-d regimen ) : −20.4 % ( 95 % CI −26.0 % to −14.8 % ) ( nadir on day 5 ) compared with the st and ard high ( 14 d ) dose : −13.1 % ( 95 % CI −17.6 % to −8.6 % ) ( nadir day 6 ) . Two heterozygotes taking the higher ( 7 d ) primaquine dose required blood transfusion . In wild-type participants , mean haematocrit reductions were clinical ly insignificant and similar with both doses : −5.8 ( 95 % CI −7.2 % to −4.4 % ) ( nadir day 3 ) compared with −5.5 % ( 95 % CI −7.4 % to −3.7 % ) ( nadir day 4 ) , respectively . Limitations to this nested cohort study are that the primary objective of the trial was design ed to measure efficacy and not haemolysis in relation to G6PD genotype and that the heterozygote groups were small . Conclusion Higher daily doses of primaquine have the potential to cause clinical ly significant haemolysis in G6PD heterozygous females who are reported as phenotypically normal with current point of care tests . Trial Registration Clinical Trials.gov NCT01640574 Background New antimalarials are needed for P. vivax and P. falciparum malaria . This study compared the efficacy and safety of pyronaridine-artesunate with that of chloroquine for the treatment of uncomplicated P. vivax malaria . Methods and Findings This phase III r and omized , double-blind , non-inferiority trial included five centers across Cambodia , Thail and , India , and Indonesia . In a double-dummy design , patients ( aged > 3–≤60 years ) with microscopically confirmed P. vivax mono-infection were r and omized ( 1∶1 ) to receive pyronaridine-artesunate ( target dose 7.2∶2.4 mg/kg to 13.8∶4.6 mg/kg ) or chloroquine ( st and ard dose ) once daily for three days . Each treatment group included 228 r and omized patients . Outcomes for the primary endpoint , Day-14 cure rate in the per- protocol population , were 99.5 % , ( 217/218 ; 95%CI 97.5 , 100 ) with pyronaridine-artesunate and 100 % ( 209/209 ; 95%CI 98.3 , 100 ) with chloroquine . Pyronaridine was non-inferior to chloroquine : treatment difference −0.5 % ( 95%CI −2.6 , 1.4 ) , i.e. , the lower limit of the 2-sided 95%CI for the treatment difference was greater than −10 % . Pyronaridine-artesunate cure rates were non-inferior to chloroquine for Days 21 , 28 , 35 and 42 . Parasite clearance time was shorter with pyronaridine-artesunate ( median 23.0 h ) versus chloroquine ( 32.0 h ; p<0.0001 ) , as was fever clearance time ( median 15.9 h and 23.8 h , respectively ; p = 0.0017 ) . Kaplan-Meier estimates of post-baseline P. falciparum infection incidence until Day 42 were 2.5 % with pyronaridine-artesunate , 6.1 % with chloroquine ( p = 0.048 , log-rank test ) . Post-baseline P. vivax or P. falciparum infection incidence until Day 42 was 6.8 % and 12.4 % , respectively ( p = 0.022 , log rank test ) . There were no deaths . Adverse events occurred in 92/228 ( 40.4 % ) patients with pyronaridine-artesunate and 72/228 ( 31.6 % ) with chloroquine . Mild and transient increases in hepatic enzymes were observed for pyronaridine-artesunate . Conclusion Pyronaridine-artesunate efficacy in acute uncomplicated P. vivax malaria was at least that of chloroquine . As pyronaridine-artesunate is also efficacious against P. falciparum malaria , this combination has potential utility as a global antimalarial drug . Trial registration Clinical trials.gov Background Severe malaria ( SM ) is classically associated with Plasmodium falciparum infection . Little information is available on the contribution of P. vivax to severe disease . There are some epidemiological indications that P. vivax or mixed infections protect against complications and deaths . A large morbidity surveillance conducted in an area where the four species coexist allowed us to estimate rates of SM among patients infected with one or several species . Methods and Findings This was a prospect i ve cohort study conducted within the framework of the Malaria Vaccine Epidemiology and Evaluation Project . All presumptive malaria cases presenting at two rural health facilities over an 8-y period were investigated with history taking , clinical examination , and laboratory assessment . Case definition of SM was based on the World Health Organization ( WHO ) criteria adapted for the setting ( i.e. , clinical diagnosis of malaria associated with asexual blood stage parasitaemia and recent history of fits , or coma , or respiratory distress , or anaemia [ haemoglobin < 5 g/dl ] ) . Out of 17,201 presumptive malaria cases , 9,537 ( 55 % ) had a confirmed Plasmodium parasitaemia . Among those , 6.2 % ( 95 % confidence interval [ CI ] 5.7%–6.8 % ) fulfilled the case definition of SM , most of them in children < 5 y. In this age group , the proportion of SM was 11.7 % ( 10.4%–13.2 % ) for P. falciparum , 8.8 % ( 7.1%–10.7 % ) for P. vivax , and 17.3 % ( 11.7%–24.2 % ) for mixed P. falciparum and P. vivax infections . P. vivax SM presented more often with respiratory distress than did P. falciparum ( 60 % versus 41 % , p = 0.002 ) , but less often with anaemia ( 19 % versus 41 % , p = 0.0001 ) . Conclusion P. vivax monoinfections as well as mixed Plasmodium infections are associated with SM . There is no indication that mixed infections protected against SM . Interventions targeted toward P. falciparum only might be insufficient to eliminate the overall malaria burden , and especially severe disease , in areas where P. falciparum and P. vivax coexist Azithromycin has demonstrated activity in a prevention of Plasmodium vivax infection , but no controlled treatment studies have been performed . We conducted a double-blinded trial in P. vivax malaria in which patients were r and omized to either azithromycin 1,000 mg q.d . x 3 or chloroquine 600 mg q.d . x 2 then 300 mg on Day 3 followed by primaquine on Days 7 through 20 . Eighty-five of 97 ( 88 % ) of those on azithromycin and 10 Output:	Seven days after starting primaquine , G6PD normal patients had a 0.3 % ( 1/389 ) risk of clinical ly significant haemolysis ( fall in haemoglobin > 25 % to < 7 g/dL ) and a 1 % ( 4/389 ) risk of a fall in haemoglobin > 5 g/dL. Conclusions Primaquine has the potential to reduce malaria-related anaemia at day 42 and beyond by preventing recurrent parasitaemia .
MS213814	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: This study tested a family-based skills-building intervention in veterans with chronic combat-related posttraumatic stress disorder ( PTSD ) . Veterans and a family member were r and omly assigned to 1 of 3 conditions : ( a ) waiting list , ( b ) 18 sessions of twice-weekly exposure therapy , or ( c ) 18 sessions of twice-weekly exposure therapy followed by 16 sessions of behavioral family therapy ( BFT ) . Participation in exposure therapy reduced PTSD positive symptoms ( e.g. , reexperiencing and hyperarousal ) but not PTSD negative symptoms . Positive symptom gains were maintained at 6-month follow-up . However , participation in BFT had no additional impact on PTSD symptoms OBJECTIVE The memory-enhancing drug methylene blue ( MB ) administered after extinction training improves fear extinction retention in rats and humans with claustrophobia . Robust findings from animal research , in combination with established safety and data showing MB-enhanced extinction in humans , provide a foundation to extend this work to extinction-based therapies for posttraumatic stress disorder ( PTSD ) such as prolonged exposure ( PE ) . METHODS Patients with chronic PTSD ( DSM-IV-TR ; N = 42 ) were r and omly assigned to imaginal exposure plus MB ( IE + MB ) , imaginal exposure plus placebo ( IE + PBO ) , or waitlist ( WL/st and ard PE ) from September 2011 to April 2013 . Following 5 daily , 50-minute imaginal exposure sessions , 260 mg of MB or PBO was administered . Waitlist controls received PE following 1-month follow-up . Patients were assessed using the independent evaluator-rated PTSD Symptom Scale-Interview version ( primary outcome ) , patient-rated PTSD , trauma-related psychopathology , and functioning through 3-month follow-up . RESULTS Both IE + MB and IE + PBO showed strong clinical gains that did not differ from st and ard PE at 3-month follow-up . MB-augmented exposure specifically enhanced independent evaluator-rated treatment response ( number needed to treat = 7.5 ) and quality of life compared to placebo ( effect size d = 0.58 ) . Rate of change for IE + MB showed a delayed initial response followed by accelerated recovery , which differed from the linear pattern seen in IE + PBO . MB effects were facilitated by better working memory but not by changes in beliefs . CONCLUSIONS The findings provide preliminary efficacy for a brief IE treatment for PTSD and point to the potential utility of MB for enhancing outcome . Brief interventions and better tailoring of MB augmentation strategies , adjusting for observed patterns , may have the potential to reduce dropout , accelerate change , and improve outcomes . TRIAL REGISTRATION Clinical Trials.gov identifier : NCT01188694 Abstract This r and omized controlled trial was design ed to determine if art therapy in conjunction with Cognitive Processing Therapy ( CPT ) was more effective for reducing symptoms of combat posttraumatic stress disorder ( PTSD ) than CPT alone . Veterans ( N = 11 ) were r and omized to receive either individual CPT , or individual CPT in conjunction with individual art therapy . PTSD Checklist – Military Version and Beck Depression Inventory – II scores improved with treatment in both groups with no significant difference in improvement between the experimental and control groups . Art therapy in conjunction with CPT was found to improve trauma processing and veterans considered it to be an important part of their treatment as it provided healthy distancing , enhanced trauma recall , and increased access to emotions BACKGROUND Posttraumatic stress disorder ( PTSD ) is prevalent among military veterans and is associated with significant negative health outcomes . However , stigma and other barriers to care prevent many veterans from pursuing traditional mental health treatment . We developed a group-based Integrative Exercise ( IE ) program combining aerobic and resistance exercise , which is familiar to veterans , with mindfulness-based practice s suited to veterans with PTSD . This study aim ed to evaluate the effects of IE on PTSD symptom severity and quality of life , as well as assess the feasibility and acceptability of IE . METHODS Veterans ( N = 47 ) were r and omized to either IE or waitlist control ( WL ) . Veterans in IE were asked to attend three 1-h group exercise sessions for 12 weeks . RESULTS Compared with WL , veterans r and omized to IE demonstrated a greater reduction in PTSD symptom severity ( d = -.90 ) , a greater improvement in psychological quality of life ( d = .53 ) and a smaller relative improvement in physical quality of life ( d = .30 ) Veterans ' ratings of IE indicated high feasibility and acceptability . LIMITATIONS The sample was relatively small and recruited from one site . The comparison condition was an inactive control . CONCLUSIONS This initial study suggests that IE is an innovative approach to treating veterans with symptoms of PTSD that reduces symptoms of posttraumatic stress and improves psychological quality of life . This approach to recovery may exp and the reach of PTSD treatment into non-traditional setting s and to veterans who may prefer a familiar activity , such as exercise , over medication or psychotherapy Rationale To improve outcomes for patients undergoing extinction-based therapies ( e.g. , exposure therapy ) for anxiety disorders such as post-traumatic stress disorder ( PTSD ) , there has been interest in identifying pharmaceutical compounds that might facilitate fear extinction learning and recall . Oxytocin ( OT ) is a mammalian neuropeptide that modulates activation of fear extinction-based neural circuits and fear responses . Little is known , however , about the effects of OT treatment on conditioned fear responding and extinction in humans . Objectives The purpose of the present study was to assess the effects of OT in a fear-potentiated startle task of fear conditioning and extinction . Methods A double-blind , placebo-controlled study of 44 healthy human participants was conducted . Participants underwent a conditioned fear acquisition procedure , after which they were r and omized to treatment group and delivered OT ( 24 IU ) or placebo via intranasal ( IN ) spray . Forty-five minutes after treatment , participants underwent extinction training . Twenty-four hours later , subjects were tested for extinction recall . Results Relative to placebo , the OT group showed increased fear-potentiated startle responding during the earliest stage of extinction training relative to placebo ; however , all treatment groups showed the same level of reduced responding by the end of extinction training . Twenty-four hours later , the OT group showed significantly higher recall of extinction relative to placebo . Conclusions The current study provides preliminary evidence that OT may facilitate fear extinction recall in humans . These results support further study of OT as a potential adjunctive treatment for extinction-based therapies in fear-related disorders OBJECTIVE The authors examined the effectiveness of virtual reality exposure augmented with D-cycloserine or alprazolam , compared with placebo , in reducing posttraumatic stress disorder ( PTSD ) due to military trauma . METHOD After an introductory session , five sessions of virtual reality exposure were augmented with D-cycloserine ( 50 mg ) or alprazolam ( 0.25 mg ) in a double-blind , placebo-controlled r and omized clinical trial for 156 Iraq and Afghanistan war veterans with PTSD . RESULTS PTSD symptoms significantly improved from pre- to posttreatment across all conditions and were maintained at 3 , 6 , and 12 months . There were no overall differences in symptoms between D-cycloserine and placebo at any time . Alprazolam and placebo differed significantly on the Clinician-Administered PTSD Scale score at posttreatment and PTSD diagnosis at 3 months posttreatment ; the alprazolam group showed a higher rate of PTSD ( 82.8 % ) than the placebo group ( 47.8 % ) . Between-session extinction learning was a treatment-specific enhancer of outcome for the D-cycloserine group only . At posttreatment , the D-cycloserine group had the lowest cortisol reactivity and smallest startle response during virtual reality scenes . CONCLUSIONS A six-session virtual reality treatment was associated with reduction in PTSD diagnoses and symptoms in Iraq and Afghanistan veterans , although there was no control condition for the virtual reality exposure . There was no advantage of D-cycloserine for PTSD symptoms in primary analyses . In secondary analyses , alprazolam impaired recovery and D-cycloserine enhanced virtual reality outcome in patients who demonstrated within-session learning . D-cycloserine augmentation reduced cortisol and startle reactivity more than did alprazolam or placebo , findings that are consistent with those in the animal literature Abstract Although trauma-focused cognitive behavioral therapy ( TF-CBT ) with exposure is an effective treatment for posttraumatic stress disorder ( PTSD ) , not all patients recover . Addition of breathing biofeedback to exposure in TF-CBT is suggested as a promising complementary technique to improve recovery of PTSD symptoms . Patients ( n = 8) with chronic PTSD were r and omized to regular TF-CBT or TF-CBT with complementary breathing biofeedback to exposure . PTSD symptoms were measured before , during and after TF-CBT with the Impact of Event Scale-Revised . The results show that breathing biofeedback is feasible and can easily be complemented to TF-CBT . Although PTSD symptoms significantly decreased from pre to post treatment in both conditions , there was a clear trend towards a significantly faster ( p = .051 ) symptom reduction in biofeedback compared to regular TF-CBT . The most important limitation was the small sample size . The hastened clinical improvement in the biofeedback condition supports the idea that breathing biofeedback may be an effective complementary component to exposure in PTSD patients . The mechanism of action of breathing biofeedback may relate to competing working memory re sources decreasing vividness and emotionality , similar to eye movement desensitization and reprocessing . Future research is needed to examine this Exposure to combat experiences is associated with increased risk of developing Post Traumatic Stress Disorder . Prolonged exposure therapy and cognitive processing therapy have garnered a significant amount of empirical support for PTSD treatment ; however , they are not universally effective with some patients continuing to struggle with residual PTSD symptoms . Heart rate variability ( HRV ) is a measure of the autonomic nervous system functioning and reflects an individual ’s ability to adaptively cope with stress . A pilot study was undertaken to determine if veterans with PTSD ( as measured by the Clinician-Administered PTSD Scale and the PTSD Checklist ) would show significantly different HRV prior to an intervention at baseline compared to controls ; specifically , to determine whether the HRV among veterans with PTSD is more depressed than that among veterans without PTSD . The study also aim ed at assessing the feasibility , acceptability , and potential efficacy of providing HRV biofeedback as a treatment for PTSD . The findings suggest that implementing an HRV biofeedback as a treatment for PTSD is effective , feasible , and acceptable for veterans . Veterans with combat-related PTSD displayed significantly depressed HRV as compared to subjects without PTSD . When the veterans with PTSD were r and omly assigned to receive either HRV biofeedback plus treatment as usual ( TAU ) or just TAU , the results indicated that HRV biofeedback significantly increased the HRV while reducing symptoms of PTSD . However , the TAU had no significant effect on either HRV or symptom reduction . A larger r and omized control trial to vali date these findings appears warranted Behavioral exposure therapy of anxiety disorders is believed to rely on fear extinction . Because pre clinical studies have shown that glucocorticoids can promote extinction processes , we aim ed at investigating whether the administration of these hormones might be useful in enhancing exposure therapy . In a r and omized , double-blind , placebo-controlled study , 40 patients with specific phobia for heights were treated with three sessions of exposure therapy using virtual reality exposure to heights . Cortisol ( 20 mg ) or placebo was administered orally 1 h before each of the treatment sessions . Subjects returned for a posttreatment assessment 3–5 d after the last treatment session and for a follow-up assessment after 1 mo . Adding cortisol to exposure therapy result ed in a significantly greater reduction in fear of heights as measured with the acrophobia question naire ( AQ ) both at posttreatment and at follow-up , compared with placebo . Furthermore , subjects receiving cortisol showed a significantly greater reduction in acute anxiety during virtual exposure to a phobic situation at posttreatment and a significantly smaller exposure-induced increase in skin conductance level at follow-up . The present findings indicate that the administration of cortisol can enhance extinction-based psychotherapy OBJECTIVE Despite the success of empirically supported treatments for posttraumatic stress disorder ( PTSD ) , sleep impairment frequently remains refractory after treatment . This single-site , r and omized controlled trial examined the effectiveness of sleep-directed hypnosis as a complement to an empirically supported psychotherapy for PTSD ( cognitive processing therapy [ CPT ] ) . METHOD Participants completed either 3 weeks of hypnosis ( n = 52 ) or a symptom monitoring control condition ( n = 56 ) before beginning st and ard CPT . Multilevel modeling was used to investigate differential patterns of change to determine whether hypnosis result ed in improvements in sleep , PTSD , and depression . An intervening variable approach was then used to determine whether improvements in sleep achieved during hypnosis augmented change in PTSD and depression during CPT . RESULTS After the initial phase of treatment ( hypnosis or symptom monitoring ) , the hypnosis condition showed significantly greater improvement than the control condition in sleep and depression , but not PTSD . After CPT , both conditions demonstrated significant improvement in sleep and PT Output:	Preliminary evidence suggests that exercise and cortisol administration may have an adjuvant effect on PTSD symptom reduction . Breathing biofeedback showed a trend for an adjuvant effect and an effect for accelerated symptom reduction . Conclusions : Currently , it is not possible to formulate evidence -based clinical recommendations regarding adjuvants interventions .
MS213815	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: A r and omized cross-over trial of herpes simplex virus type 2 (HSV-2)-suppressive therapy ( valacyclovir , 500 mg twice daily , or placebo for 8 weeks , a 2-week washout period , then the alternative therapy for 8 weeks ) was conducted among 20 Peruvian women coinfected with HSV-2 and human immunodeficiency virus type 1 ( HIV-1 ) who were not on antiretroviral therapy . Plasma sample s ( obtained weekly ) and endocervical swab specimens ( obtained thrice weekly ) were collected for HIV-1 RNA polymerase chain reaction . Plasma HIV-1 level was significantly lower during the valacyclovir arm , compared with the placebo arm ( -0.26 log10 copies/mL , a 45 % decrease [ P < .001 ] ) , as was cervical HIV-1 level ( -0.35 log10 copies/swab , a 55 % decrease [ P < .001 ] ) . Suppressive HSV-2 therapy has the potential to reduce HIV-1 infectiousness and slow HIV-1 disease progression A r and omised trial was done to evaluate the impact of improved sexually transmitted disease ( STD ) case management at primary health care level on the incidence of HIV infection in the rural Mwanza region of Tanzania . HIV incidence was compared in six intervention communities and six pair-matched comparison communities . A r and om cohort of about 1000 adults aged 15 - 54 years from each community was surveyed at baseline and at follow-up 2 years later . Intervention consisted of establishment of an STD reference clinic , staff training , regular supply of drugs , regular supervisory visits to health facilities , and health education about STDs . 12,537 individuals were recruited . Baseline HIV prevalences were 3.8 % and 4.4 % in the intervention and comparison communities , respectively . At follow-up , 8845 ( 71 % ) of the cohort were seen . Of those initially seronegative , the proportions seroconverting over 2 years were 48 of 4149 ( 1.2 % ) in the intervention communities and 82 of 4400 ( 1.9 % ) in the comparison communities . HIV incidence was consistently lower in the intervention communities in all six matched pairs . Allowing for the community-r and omised design and the effects of confounding factors , the estimated risk ratio was 0.58 ( 95 % CI 0.42 - 0.79 , p = 0.007 ) . No change in reported sexual behaviour was observed in either group . We conclude that improved STD treatment reduced HIV incidence by about 40 % in this rural population . This is the first r and omised trial to demonstrate an impact of a preventive intervention on HIV incidence in a general population Background Underst and ing the correlates of HIV shedding is important to inform strategies to reduce HIV infectiousness . We examined correlates of genital HIV-1 RNA in women who were seropositive for both herpes simplex virus (HSV)-2 and HIV-1 and who were enrolled in a r and omised controlled trial of HSV suppressive therapy ( aciclovir 400 mg b.i.d vs. placebo ) in Tanzania . Methodology Sample s , including a cervico-vaginal lavage , were collected and tested for genital HIV-1 and HSV and reproductive tract infections ( RTIs ) at r and omisation and 6 , 12 and 24 months follow-up . Data from all women at r and omisation and women in the placebo arm during follow-up were analysed using generalised estimating equations to determine the correlates of cervico-vaginal HIV-1 RNA detection and load . Principal Findings Cervico-vaginal HIV-1 RNA was detected at 52.0 % of 971 visits among 482 women , and was independently associated with plasma viral load , presence of genital ulcers , pregnancy , bloody cervical or vaginal discharge , abnormal vaginal discharge , cervical ectopy , Neisseria gonorrhoeae , Chlamydia trachomatis , Trichomonas vaginalis , an intermediate bacterial vaginosis score and HSV DNA detection . Similar factors were associated with genital HIV-1 RNA load . Conclusions RTIs were associated with increased presence and quantity of genital HIV-1 RNA in this population . These results highlight the importance of integrating effective RTI treatment into HIV care services To determine the frequency and risk factors for female to male sexual transmission of human immunodeficiency virus type 1 ( HIV-1 ) , a prospect i ve study was carried out in 422 men who had acquired a sexually transmitted disease ( STD ) from a group of prostitutes with a prevalence of HIV-1 infection of 85 % . The initial seroprevalence of HIV among the men was 12 % . 24 of 293 ( 8.2 % ) initially seronegative men seroconverted to HIV-1 . Newly acquired infection was independently associated with frequent prostitute contact ( risk ratio 3.2 , 95 % confidence interval 1.2 - 8.1 ) , with the acquisition of genital ulcer disease ( risk ratio 4.7 , 95 % confidence interval 1.3 - 17.0 ) , and with being uncircumcised ( risk ratio 8.2 , 95 % confidence interval 3.0 - 23.0 ) . 96 % of documented seroconversions occurred in men with one or both of the latter two risk factors . In a subgroup of 73 seronegative men who reported a single prostitute sexual contact , the frequency of HIV-1 infection was 8.2 % during 12 weeks of observation . No man without a genital ulcer seroconverted . A cumulative 43 % of uncircumcised men who acquired an ulcer seroconverted to HIV-1 after a single sexual exposure . These data indicate an extremely high rate of female to male transmission of HIV-1 in the presence of STD and confirm a causal relation between lack of male circumcision , genital ulcer disease , and susceptibility to HIV-1 infection BACKGROUND Syphilis remains an important source of morbidity worldwide . Long-acting penicillin is the only therapy currently recommended for syphilis in much of the world . Because of hesitation to use penicillin for fear of anaphylaxis , there is a need for an effective , well-tolerated alternative to penicillin for syphilis therapy . METHODS This multicenter , r and omized clinical trial was conducted in clinics for the treatment of persons with sexually transmitted diseases . We compared serological cure rates for human immunodeficiency virus (HIV)-negative persons with early syphilis treated with azithromycin at a dosage of 2.0 g administered orally as a single dose with cure rates for those treated with benzathine penicillin G at a dosage of 2.4 million units administered intramuscularly . RESULTS A total of 517 participants were enrolled in the trial . In the intention-to-treat analysis , after 6 months of follow-up , serological cure was observed in 180 ( 77.6 % ) of 232 azithromycin recipients and 186 ( 78.5 % ) of 237 penicillin recipients ( 1-sided lower bound 95 % confidence interval , 7.2 % ) . Nonserious adverse events were more common among azithromycin recipients than they were among penicillin recipients ( 61.5 % vs 46.3 % ) , and such adverse events were accounted for , in large part , by self-limited gastrointestinal complaints . CONCLUSIONS In this trial , the efficacy of azithromycin at a dosage of 2.0 g administered orally was equivalent to that of benzathine penicillin G for the treatment of early syphilis in persons without HIV infection Genital ulcers are implicated as a risk factor enhancing susceptibility to human immunodeficiency virus type 1 ( HIV-1 ) infection . A prospect i ve study to determine the incidence of and risk factors associated with acquisition of HIV-1 in women with genital ulcers was done . HIV-1-seronegative women with genital ulcers attending a clinic for sexually transmitted diseases in Nairobi were followed to HIV-1 seroconversion over a 6-month period . Of 81 women , 10 seroconverted to HIV-1 . The crude 6-month incidence of HIV-1 infection was 12 % . Risk factors associated with seroconversion included cervical ectopy ( rate ratio [ RR ] , 4.9 ; 95 % confidence interval [ CI ] , 1.5 - 15.6 ) and pelvic inflammatory disease ( RR , 6.3 ; 95 % CI , 1.9 - 20.4 ) . Thus , cervical ectopy and pelvic inflammatory disease may increase susceptibility to HIV-1 in women with genital ulcers Background : An association has been demonstrated between herpes simplex type 2 ( HSV-2 ) and HIV infection among men , but prospect i ve studies in women have yielded mixed results . Objective : To estimate the effects of prevalent and incident HSV-2 infection on subsequent HIV acquisition among women in two African countries . Design : Prospect i ve cohort study . Methods : HSV-2 and HIV serostatus were evaluated at enrollment and quarterly for 15–24 months among 4531 sexually active , HIV-uninfected women aged 18–35 years from Ug and a and Zimbabwe . The association between prior HSV-2 infection and HIV acquisition was estimated using a marginal structural discrete survival model , adjusted for covariates . Results : HSV-2 seroprevalence at enrollment was 52 % in Ug and a and 53 % in Zimbabwe ; seroincidence during follow-up was 9.6 and 8.8/100 person-years in Ug and a and Zimbabwe , respectively . In Ug and a , the hazard ratio ( HR ) for HIV was 2.8 [ 95 % confidence interval ( CI ) , 1.5–5.3 ] among women with seroprevalent HSV-2 and 4.6 ( 95 % CI , 1.6–13.1 ) among women with seroincident HSV-2 , adjusted for confounding . In Zimbabwe , the HR for HIV was 4.4 ( 95 % CI , 2.7–7.2 ) among women with seroprevalent HSV-2 , and 8.6 ( 95 % CI , 4.3–17.1 ) among women with seroincident HSV-2 , adjusted for confounding . The population attributable risk percent for HIV due to prevalent and incident HSV-2 infection was 42 % in Ug and a and 65 % in Zimbabwe . Conclusions : HSV-2 plays an important role in the acquisition of HIV among women . Efforts to implement known HSV-2 control measures , as well as identify additional measures to control HSV-2 , are urgently needed to curb the spread of HIV BACKGROUND Reports of neurosyphilis and invasion of cerebrospinal fluid by Treponema pallidum in patients with human immunodeficiency virus ( HIV ) infection have led to doubts about the adequacy of the recommended penicillin G benzathine therapy for early syphilis . METHODS In a multicenter , r and omized , double-blind trial , we assessed two treatments for early syphilis : 2.4 million units of penicillin G benzathine and that therapy enhanced with a 10-day course of amoxicillin and probenecid . The serologic and clinical responses of patients with and without HIV infection were studied during one year of follow-up . RESULTS From 1991 through 1994 , 541 patients were enrolled , including 101 patients ( 19 percent ) who had HIV infection but differed little from the uninfected patients in their clinical presentations . The rates at which chancres and rashes resolved did not differ significantly according to treatment assignment or HIV status . Serologically defined treatment failures were more common among the HIV-infected patients . The single clinical ly defined treatment failure was in an HIV-infected patient . Rates of serologically defined treatment failure did not differ according to treatment group ( 18 percent at six months with usual therapy ; 17 percent with enhanced therapy ) . T. pallidum was found at enrollment in the cerebrospinal fluid of 32 of 131 patients ( 24 percent ) and after therapy in 7 of 35 patients tested . None had clinical ly evident neurosyphilis , and the rate of detection of T. pallidum did not differ according to HIV status . CONCLUSIONS After treatment for primary or secondary syphilis , the HIV-infected patients responded less well serologically than the patients without HIV infection , but clinical ly defined failure was uncommon in both groups . Enhanced treatment with amoxicillin and probenecid did not improve the outcomes . Although T. pallidum was detected in cerebrospinal fluid before therapy in a quarter of the patients tested , such a finding did not predict treatment failure . The current recommendations for treating early syphilis appear adequate for most patients , whether or not they have HIV infection Background : Several studies suggest that herpes simplex virus type 2 ( HSV-2 ) may enhance HIV-1 transmission and disease progression . Methods : We conducted a r and omized , double-blind , placebo-controlled trial of aciclovir 400 mg twice daily for 3 months in 300 HSV-2/HIV-1 co-infected women not yet on highly active antiretroviral Output:	At present , there is insufficient evidence to determine whether curative treatment of genital ulcer disease would reduce the risk of HIV acquisition . The very low quality of the evidence implies that the true effect of genital ulcer disease treatment on sexual acquisition of HIV may be substantially different from the effect estimated from currently available data .
MS213816	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: BACKGROUND Combination therapy has been widely used for the clinical management of acute pain . By combining 2 drugs with different mechanisms of action , such therapy provides additive analgesic effects while reducing the risk for adverse effects . OBJECTIVE This study compared the efficacy and tolerability of oxycodone 5 mg/ibuprofen 400 mg with those of oxycodone 5 mg/acetaminophen 325 mg , hydrocodone 7.5 mg/acetaminophen 500 mg , and placebo in a dental pain model . METHODS This was a multicenter , r and omized , double-blind , placebo- and active-controlled , parallel-group , single-dose study in patients experiencing moderate to severe pain after surgical removal of > or = 2 ipsilateral impacted third molars . Patients were r and omly assigned to receive oxycodone 5 mg/ibuprofen 400 mg , oxycodone 5 mg/acetaminophen 325 mg , hydrocodone 7.5 mg/acetaminophen 500 mg , or placebo . The primary outcome measures were total pain relief through 6 hours after dosing ( TOTPAR6 ) , sum of pain intensity differences through 6 hours ( SPID6 ) , and adverse events . Secondary efficacy measures included SPID3 and TOTPAR3 , peak pain relief , peak pain intensity difference , time to onset of pain relief , time to use of rescue medication , proportion of patients reporting pain half gone , and the patient 's global evaluation . RESULTS Two hundred forty-nine patients ( 43.5 % male ; 87.5 % white ; mean age , 19.1 years ; mean body weight , 153.6 pounds ) were r and omized to treatment as follows : 62 to oxycodone 5 mg/ibuprofen 400 mg , 61 to oxycodone 5 mg/acetaminophen 325 mg , 63 to hydrocodone 7.5 mg/acetaminophen 500 mg , and 63 to placebo . Oxycodone 5 mg/ibuprofen 400 mg provided significantly greater analgesia compared with oxycodone 5 mg/acetaminophen 325 mg , hydrocodone 7.5 mg/acetaminophen 500 mg , and placebo ( mean [ SD ] TOTPAR6 , 14.98 [ 5.37 ] , 9.53 [ 6.77 ] , 8.36 [ 6.68 ] , and 5.05 [ 6.49 ] , respectively ; P < 0.001 , oxycodone 5 mg/ibuprofen 400 mg vs all other treatments ) . SPID6 values also differed significantly for oxycodone 5 mg/ibuprofen 400 mg compared with all other treatments ( mean : 7.78 [ 4.11 ] , 3.58 [ 4.64 ] , 3.32 [ 4.73 ] , and 0.69 [ 4.85 ] ; P < 0.001 ) . Oxycodone 5 mg/ibuprofen 400 mg was significantly more effective compared with the other treatments on all secondary end points ( P < 0.001 , all variables except peak PID vs oxycodone 5 mg/acetaminophen 325 mg [ P = 0.006 ] ) , with the exception of the time to onset of analgesia . The lowest frequency of nausea and vomiting occurred in the groups that received oxycodone 5 mg/ibuprofen 400 mg ( 6.5 % and 3.2 % , respectively ) and placebo ( 3.2 % and 1.6 % ) . Rates of nausea and vomiting were significantly lower with oxycodone 5 mg/ibuprofen 400 mg compared with oxycodone 5 mg/acetaminophen 325 mg ( P = 0.011 and P = 0.009 , respectively ) but not with hydrocodone 7.5 mg/acetaminophen 500 mg . CONCLUSIONS In this study in patients with moderate to severe pain after surgery to remove impacted third molars , oxycodone 5 mg/ibuprofen 400 mg provided significantly better analgesia throughout the 6-hour study compared with the other opioid/nonopioid combinations tested , and was associated with fewer adverse events Abstract Variability in patients ' response to interventions in pain and other clinical setting s is large . Many explanations such as trial methods , environment or culture have been proposed , but this paper sets out to show that the main cause of the variability may be r and om chance , and that if trials are small their estimate of magnitude of effect may be incorrect , simply because of the r and om play of chance . This is highly relevant to the questions of ‘ How large do trials have to be for statistical accuracy ? ’ and ‘ How large do trials have to be for their results to be clinical ly valid ? ’ The true underlying control event rate ( CER ) and experimental event rate ( EER ) were determined from single‐dose acute pain analgesic trials in over 5000 patients . Trial group size required to obtain statistically significant and clinical ly relevant ( 0.95 probability of number‐needed‐to‐treat within ±0.5 of its true value ) results were computed using these values . Ten thous and trials using these CER and EER values were simulated using varying group sizes to investigate the variation due to r and om chance alone . Most common analgesics have EERs in the range 0.4–0.6 and CER of about 0.19 . With such efficacy , to have a 90 % chance of obtaining a statistically significant result in the correct direction requires group sizes in the range 30–60 . For clinical relevance nearly 500 patients are required in each group . Only with an extremely effective drug ( EER>0.8 ) will we be reasonably sure of obtaining a clinical ly relevant NNT with commonly used group sizes of around 40 patients per treatment arm . The simulated trials showed substantial variation in CER and EER , with the probability of obtaining the correct values improving as group size increased . We contend that much of the variability in control and experimental event rates is due to r and om chance alone . Single small trials are unlikely to be correct . If we want to be sure of getting correct ( clinical ly relevant ) results in clinical trials we must study more patients . Credible estimates of clinical efficacy are only likely to come from large trials or from pooling multiple trials of conventional ( small ) size & NA ; There is uncertainty over whether the patient group in which acute pain studies are conducted ( pain model ) has any influence on the estimate of analgesic efficacy . Data from four recently up date d systematic review s of aspirin 600/650 mg , paracetamol 600/650 mg , paracetamol 1000 mg and ibuprofen 400 mg were used to investigate the influence of pain model . Area under the pain relief versus time curve equivalent to at least 50 % maximum pain relief over 6 h was used as the outcome measure . Event rates with treatment and placebo , and relative benefit ( RB ) and number needed to treat ( NNT ) were used as outputs from the meta‐analyses . The event rate with placebo was systematic ally statistically lower for dental than postsurgical pain for all four treatments . Event rates with analgesics , RB and NNT were infrequently different between the pain models . Systematic difference in the estimate of analgesic efficacy between dental and postsurgical pain models remains unproven , and , on balance , no major difference is likely In a double-blind , single dose study of analgesic efficacy , 165 patients who were expected to develop moderate to severe pain following the removal of an impacted m and ibular third molar tooth were allocated to receive aspirin , placebo , or an increasing dose of a fixed ratio ibuprofen/codeine combination . The degree of pain experienced prior to medication was noted and the patients were asked to record the degree of pain and of pain relief hourly for the following 5 hours . The study produced clear evidence of the superior efficacy of the combinations when compared to placebo and aspirin . In addition , the high dose combination appeared to be superior with respect to pain relief and the need for additional analgesia compared to the low dose treatment . There were few side effects and only one severe reaction was reported by a patient in the high dose group . To avoid side effects it is suggested that the medium-dose combination , ibuprofen 400 mg/codeine 30 mg , is optimal In a double-blind , single dose study of analgesic efficacy , 202 patients who had undergone lower 3rd molar extraction were divided into 5 groups to receive aspirin , placebo , ibuprofen , codeine , or an ibuprofen/codeine combination . Ibuprofen 200 mg ( with or without codeine phosphate 15 mg ) and aspirin 600 mg were significantly superior to either placebo or codeine phosphate 15 mg alone . Codeine phosphate at a dose of 15 mg was ineffective as an analgesic either alone or in combination Background Previous analysis of a single data set in acute pain following third molar extraction demonstrated a strong relationship between the speed of reduction of pain intensity and overall pain relief , as well as need for additional analgesia . Methods Individual patient data analysis of a single r and omized , double-blind trial of placebo , paracetamol 1000 mg , ibuprofen sodium 400 mg and ibuprofen-poloxamer 400 mg following third molar extraction . Visual analogue scale pain intensity ( VASPI ) and other measurements were made at baseline , every 5–45 min , and at 60 , 90 , 120 , 180 , 240 , 300 and 360 min . Results Most patients produced consistent VASPI results over time . For placebo and paracetamol , few patients achieved low VASPI scores and maintained them . For both ibuprofen formulations , VASPI scores fell rapidly during the first hour and were then typically maintained until later re-medication . Analysis of all patients showed that rapid VASPI reduction in the first hour was strongly correlated with good overall pain relief ( high total pain relief over 0–6 h ) , and with lesser need for additional analgesia within 6 h. Results for this analysis were in very good agreement with a previous analysis , validating the relationship between fast initial pain intensity reduction and overall good pain relief in this setting . Conclusions In acute pain following third molar extraction , faster acting analgesic formulations provide earlier onset of pain relief , better overall pain relief and a less frequent need for additional analgesia , indicating longer lasting pain relief Non-steroidal anti-inflammatory analgesics are commonly prescribed to out- patients who have undergone oral surgical procedures , since they are said to provide excellent pain relief for mild to moderate pain , allied with minimal side-effects . One hundred patients were entered into a r and omised clinical trial to compare the efficacy of a simple non-steroidal analgesic with that of a combination analgesic compound following the removal of lower third molars under local anaesthesia . Pain scores were measured for patients post-operatively by means of a verbal rating scale for 3 days and data were analysed using the Mann-Whitney U-test . Results suggest that this combination product offers no advantages ( but shows definite disadvantages ) when compared to an effective non-steroidal anti-inflammatory In a r and omised , double‐blind , double‐dummy , multiple dose , crossover study in 30 patients we compared an ibuprofen/codeine combination ( 400 mg ibuprofen/25.6 mg codeine phosphate ) with a paracetamol/codeine/caffeine combination ( 1 g paracetamol/ 16 mg codeine phosphate/60 mg caffeine ) for pain relief over 6 days after two‐stage bilateral lower third molar removal . The ibuprofen combination produced significantly greater analgesia than the paracetamol combination , both on single‐dose analysis of the first and second days and on multiple‐dose measures for days 1 , 2 , 3 and 4 . The mean incidence of adverse effects over the 6 days was 20 % for both combinations . This trial design ( crossover with multiple dosing in out patients ) is a sensitive way of testing for analgesia , and is potentially more predictive of adverse effect problems than single‐dose studies . It confirms that multiple dosing may show increased efficacy Abstract A previously established relationship for deriving dichotomous from continuous information in r and omised controlled trials ( RCTs ) of analgesics has been tested using an independent data set . Individual patient information from 18 RCTs of parallel‐group design in acute postoperative pain ( after abdominal , gynaecological and oral surgery ) was used to calculate the percentage of the maximum possible pain relief score ( % maxTOTPAR ) and the proportion of patients with > 50%maxTOTPAR for the different treatments . The relationship between the measures was investigated in 85 treatments with over 3400 patients . In 80 of 85 treatments ( 94 % ) agreement between calculated and actual number of patients with > 50%maxTOTPAR was within four patients per treatment and in 72 ( 85 % ) was within three ( average of 40 patients per treatment , range 21–58 patients ) . Summing the positive and negative differences between actual and calculated numbers of patients with > 50%maxTOTPAR gave an average difference of 0.30 patients per treatment arm . Reports of RCTs of analgesics frequently describe results of studies in the form of mean derived indices , rather than using discontinuous events , such as number or proportion of patients with 50 % pain relief . Because mean data inadequately describe information with a non‐normal distribution , combining mean data in systematic review s may compromise the results . Showing that dichotomous data can reliably be derived from mean Output:	BACKGROUND There is good evidence that combining two different analgesics in fixed doses in a single tablet can provide better pain relief in acute pain and headache than either drug alone , and that the drug-specific benefits are essentially additive . These values were close to those predicted by published models for combination analgesics in acute pain , and were supported by low ( good ) NNT values for prevention of remedication . For ibuprofen 200 mg + caffeine 100 mg particularly , the low NNT value is among the lowest ( best ) values for analgesics in this pain model . In principle , this can deliver good analgesia at lower doses of ibuprofen
MS213817	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: BACKGROUND The comparative effectiveness of treatments for prostate cancer that is detected by prostate-specific antigen ( PSA ) testing remains uncertain . METHODS We compared active monitoring , radical prostatectomy , and external-beam radiotherapy for the treatment of clinical ly localized prostate cancer . Between 1999 and 2009 , a total of 82,429 men 50 to 69 years of age received a PSA test ; 2664 received a diagnosis of localized prostate cancer , and 1643 agreed to undergo r and omization to active monitoring ( 545 men ) , surgery ( 553 ) , or radiotherapy ( 545 ) . The primary outcome was prostate-cancer mortality at a median of 10 years of follow-up . Secondary outcomes included the rates of disease progression , metastases , and all-cause deaths . RESULTS There were 17 prostate-cancer-specific deaths overall : 8 in the active-monitoring group ( 1.5 deaths per 1000 person-years ; 95 % confidence interval [ CI ] , 0.7 to 3.0 ) , 5 in the surgery group ( 0.9 per 1000 person-years ; 95 % CI , 0.4 to 2.2 ) , and 4 in the radiotherapy group ( 0.7 per 1000 person-years ; 95 % CI , 0.3 to 2.0 ) ; the difference among the groups was not significant ( P=0.48 for the overall comparison ) . In addition , no significant difference was seen among the groups in the number of deaths from any cause ( 169 deaths overall ; P=0.87 for the comparison among the three groups ) . Metastases developed in more men in the active-monitoring group ( 33 men ; 6.3 events per 1000 person-years ; 95 % CI , 4.5 to 8.8 ) than in the surgery group ( 13 men ; 2.4 per 1000 person-years ; 95 % CI , 1.4 to 4.2 ) or the radiotherapy group ( 16 men ; 3.0 per 1000 person-years ; 95 % CI , 1.9 to 4.9 ) ( P=0.004 for the overall comparison ) . Higher rates of disease progression were seen in the active-monitoring group ( 112 men ; 22.9 events per 1000 person-years ; 95 % CI , 19.0 to 27.5 ) than in the surgery group ( 46 men ; 8.9 events per 1000 person-years ; 95 % CI , 6.7 to 11.9 ) or the radiotherapy group ( 46 men ; 9.0 events per 1000 person-years ; 95 % CI , 6.7 to 12.0 ) ( P<0.001 for the overall comparison ) . CONCLUSIONS At a median of 10 years , prostate-cancer-specific mortality was low irrespective of the treatment assigned , with no significant difference among treatments . Surgery and radiotherapy were associated with lower incidences of disease progression and metastases than was active monitoring . ( Funded by the National Institute for Health Research ; ProtecT Current Controlled Trials number , IS RCT N20141297 ; Clinical Trials.gov number , NCT02044172 . ) OBJECTIVES Establishing realistic health-related quality -of-life ( HRQOL ) expectations before the choice of cancer treatment is made is an important goal of patient counseling . We prospect ively studied the pretreatment expectations of prostate cancer-specific HRQOL with an adapted Exp and ed Prostate Cancer Index Composite instrument . METHODS Baseline pretreatment Exp and ed Prostate Cancer Index Composite scores , pretreatment expectation scores , and 1-year posttreatment scores were prospect ively collected for 50 patients undergoing radical prostatectomy or external beam radiotherapy . The pretreatment expectations and observed HRQOL scores at 1 year after treatment were compared for the urinary incontinence , urinary irritation , bowel , sexual , and hormonal domains . RESULTS The expectation scores did not differ from the HRQOL scores at 1 year for urinary irritation , bowel function , and the hormonal domain . However , the sexual domain expectations were 22.5 % greater than observed sexual domain scores 1 year after treatment ( P < 0.0001 , 99 % confidence interval 11 to 34 ) for both surgery and radiotherapy subjects . Anxiety , depression , education level , and income did not correlate with the expectations for HRQOL outcomes . A modest correlation was found between optimism and greater expectations for the sexual domain ( Pearson correlation coefficient 0.38 , P < 0.001 ) . CONCLUSIONS Measuring HRQOL expectations before treatment may eluci date discrepancies between patient expectations and observed outcomes . This pilot study found that patients ' expectations regarding urinary and bowel outcomes more closely reflected their eventual observed outcome than did their expectations regarding sexual outcome BACKGROUND Most localized prostate cancers are believed to have an indolent course . Within 15 yr of diagnosis , most deaths among men with prostate cancer ( PCa ) can be attributed to other competing causes . However , data from studies with extended follow-up are insufficient to determine appropriate treatment for men with localized disease . OBJECTIVE To investigate the long-term natural history of untreated , early-stage PCa . DESIGN , SETTING , AND PARTICIPANTS We conducted a population -based , prospect ive-cohort study using a consecutive sample of 223 patients with untreated , localized PCa from a regionally well-defined catchment area in central Sweden . All subjects were initially managed with observation . And rogen deprivation therapy was administered when symptomatic tumor progression occurred . OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS Based on > 30 yr of follow-up , the main outcome measures were : progression-free , cause-specific , and overall survival , and rates of progression and mortality per 1000 person-years . RESULTS AND LIMITATIONS After 32 yr of follow-up , all but 3 ( 1 % ) of the 223 men had died . We observed 90 ( 41.4 % ) local progression events and 41 ( 18.4 % ) cases of progression to distant metastasis . In total , 38 ( 17 % ) men died of PCa . Cause-specific survival decreased between 15 and 20 yr , but stabilized with further follow-up . All nine men with Gleason grade 8 - 10 disease died within the first 10 yr of follow-up , five ( 55 % ) from PCa . Survival for men with well-differentiated , nonpalpable tumors declined slowly through 20 yr , and more rapidly between 20 and 25 yr ( from 75.2 % [ 95 % confidence interval , 48.4 - 89.3 ] to 25 % [ 95 % confidence interval , 22.0 - 72.5 ] ) . It is unclear whether these data are relevant for tumors detected by elevated prostate-specific antigen levels . CONCLUSIONS Although localized PCa most often has an indolent course , local progression and distant metastasis can develop over the long term , even among patients considered low risk at diagnosis For patients with low‐risk prostate cancer ( PCa ) , active surveillance ( AS ) may produce oncologic outcomes comparable to those achieved with radical prostatectomy ( RP ) . Health‐related quality ‐of‐life ( HRQoL ) outcomes are important to consider , yet few studies have examined HRQoL among patients with PCa who were managed with AS . In this study , the authors compared longitudinal HRQoL in a prospect i ve , racially diverse , and contemporary cohort of patients who underwent RP or AS for low‐risk PCa PURPOSE Earlier studies evaluating the effect on quality of life ( QoL ) of localized prostate cancer interventions included patients receiving adjuvant hormone therapy , which could have affected their outcomes . Our objective was to compare the QoL impact of the three most common primary treatments on patients who were not receiving adjuvant hormonal treatment . PATIENTS AND METHODS This was a prospect i ve study of 435 patients treated with radical prostatectomy , external-beam radiotherapy , or brachytherapy . QoL was assessed before and after treatment with the Short Form-36 and the Exp and ed Prostate Cancer Index Composite . Differences between groups were tested by analysis of variance . Distribution of outcome at 3 years was examined by stratifying according to baseline status . Generalized estimating equation models were constructed to assess the effect of treatment over time . RESULTS Compared with the brachytherapy group , the prostatectomy group showed greater deterioration on urinary incontinence and sexual scores but better urinary irritative-obstructive results ( -18.22 , -13.19 , and + 6.38 , respectively , at 3 years ; P < .001 ) . In patients with urinary irritative-obstructive symptoms at baseline , improvement was observed in 64 % of those treated with nerve-sparing radical prostatectomy . Higher bowel worsening ( -2.87 , P = .04 ) was observed in the external radiotherapy group , with 20 % of patients reporting bowel symptoms . CONCLUSION Radical prostatectomy caused urinary incontinence and sexual dysfunction but improved pre-existing urinary irritative-obstructive symptoms . External radiotherapy and brachytherapy caused urinary irritative-obstructive adverse effects and some sexual dysfunction . External radiotherapy also caused bowel adverse effects . Relevant differences between treatment groups persisted for up to 3 years of follow-up , although the difference in sexual adverse effects between brachytherapy and prostatectomy tended to decline over long-term follow-up . These results provide valuable information for clinical decision making PURPOSE The American College of Surgeons Oncology Group phase III Surgical Prostatectomy Versus Interstitial Radiation Intervention Trial comparing radical prostatectomy ( RP ) and brachytherapy ( BT ) closed after 2 years due to poor accrual . We report health-related quality of life ( HRQOL ) at a mean of 5.3 years for 168 trial-eligible men who either chose or were r and omly assigned to RP or BT following a multidisciplinary educational session . PATIENTS AND METHODS After initial lack of accrual , a multidisciplinary educational session was introduced for eligible patients . In all , 263 men attended 47 sessions . Of those , 34 consented to r and om assignment , 62 chose RP , and 94 chose BT . Five years later , these 190 men underwent HRQOL evaluation by using the cancer-specific 50-item Exp and ed Prostate Cancer Index Composite , the Short Form 12 Physical Component Score , and Short Form 12 Mental Component Score . Response rate was 88.4 % . The Wilcoxon rank sum test was used to compare summary scores between the two interventions . RESULTS Of 168 survey responders , 60.7 % had BT ( 9.5 % r and omly assigned ) and 39.3 % had RP ( 9.5 % r and omly assigned ) . Median age was 61.4 years for BT and 59.4 for RP ( P = .05 ) . Median follow-up was 5.2 years ( range , 3.2 to 6.5 years ) . For BT versus RP , there was no difference in bowel or hormonal domains , but men treated with BT scored better in urinary ( 91.8 v 88.1 ; P = .02 ) and sexual ( 52.5 v 39.2 ; P = .001 ) domains , and in patient satisfaction ( 93.6 v 76.9 ; P < .001 ) . CONCLUSION Although treatment allocation was r and om in only 19 % , all patients received identical information in a multidisciplinary setting before selecting RP , BT , or r and om assignment . HRQOL evaluated 3.2 to 6.5 years after treatment showed an advantage for BT in urinary and sexual domains and in patient satisfaction BACKGROUND AND PURPOSE The aim of the study was to compare quality of life after permanent I-125 brachytherapy ( BT ) and external beam radiotherapy ( EBRT ) for prostate cancer . MATERIAL S AND METHODS A group of 104 patients ( 52 in each group ) have been surveyed prospect ively before EBRT/BT ( time A ) , at the last day of EBRT ( 70.2 - 72.0 Gy ) or one month after BT ( time B ) , and a median time of 16 months after EBRT/BT ( time C ) using a vali date d question naire ( Exp and ed Prostate Cancer Index Composite ) . Pairs were matched according to the following criteria : age + /-5 years , prostate volume + /-10 cc , use of anti and rogens , and erectile function . RESULTS Urinary function/bother scores decreased significantly more after BT both at time B and time C. Bowel function/bother scores tended to be higher after BT , with a lower percentage of patients with painful bowel movements ( BT : 12%/27%/15 % ; EBRT : 19%/52%/35 % at time A/B/C ; p<0.05 for differences at times B/C ) and rectal bleeding ( BT : 12%/12%/12 % ; EBRT : 8%/14%/17 % ) Output:	For a follow-up of up to 6 yr , active surveillance was found to have the lowest impact on cancer-specific QoL , surgery had a negative impact on urinary and sexual function when compared with active surveillance and EBRT , and EBRT had a negative impact on bowel function when compared with active surveillance and surgery . This is the first systematic review comparing the impact of different primary treatments on cancer-specific QoL for men with clinical ly localised prostate cancer , using vali date d cancer-specific patient-reported outcome measures only . PATIENT SUMMARY Our review of the current evidence suggests that for a period of up to 6 yr after treatment , men with localised prostate cancer who were managed with active surveillance reported high levels of quality of life ( QoL ) . Men treated with surgery reported mainly urinary and sexual problems , while those treated with external beam radiotherapy reported mainly bowel problems . Men eligible for brachytherapy reported urinary problems up to a year after therapy , but then their QoL returned gradually to as it was before treatment
MS213818	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: This study was design ed to compare the results of immediate and delayed loading of implants with implant-retained m and ibular overdentures . Ten patients ( test group ) received 40 Brånemark System MKII implants ( 4 per patient ) placed in the interforaminal area of the m and ible . St and ard abutments were immediately screwed to the implants , rigidly connected with a bar , and immediately loaded with an overdenture . Ten patients ( control group ) received the same type and number of implants in the same area , but the implants were left to heal submerged . Four to 8 months later , st and ard abutments were screwed to the implants and the same prosthetic procedure was applied . Each implant was evaluated at the time of prosthetic loading and at 6 , 12 , and 24 months after the initial prosthetic load with the following parameters : modified Plaque Index ( MPI ) , modified Bleeding Index ( MBI ) , probing depth ( PD ) , and Periotest . Peri-implant bone resorption was evaluated on panoramic radiographs taken 12 and 24 months after initial prosthetic loading . No significant differences were found between the 2 groups regarding MPI , MBI , Periotest , peri-implant bone resorption , and PD at 6 and 24 months ( P > .05 ) . The only difference was found regarding PD values on the mesial and lingual sites at 12 months ( P < .05 ) . The cumulative success rate of implants was 97.5 % in both groups . Results from this study showed that immediate loading of endosseous implants rigidly connected with a U-shaped bar does not seem to have any detrimental effect on osseointegration . Conversely , this method significantly shortens the duration of treatment with relevant satisfaction for the patients The aim of this 1-year study was to evaluate and compare crestal bone loss and clinical outcomes of immediate and delayed loaded implants supporting m and ibular overdentures with Locator attachments . In a r and omised controlled clinical trial , 36 completely edentulous patients ( mean age 59.6 years ) who desired to improve the stability of their m and ibular dentures were r and omly assigned into two groups . Each patient received two implants in the canine area of the m and ible after a minimal flap reflection . Implants were loaded by m and ibular overdentures either 3 months ( delayed loading group , G1 ) or the same day ( immediate loading group , G2 ) after implant placement . Locator attachments were used to retain all overdentures to the implants . Peri-implant vertical ( VBL ) and horizontal ( HBLO ) bone losses and clinical parameters [ plaque scores ( PI ) , gingival scores ( GI ) , probing depths ( PD ) and implant stability ( ISQ ) ] were assessed at time of overdenture insertion ( T0 ) , 6 months ( T6 ) and 12 months ( T12 ) after overdenture insertion . After 12 months of overdenture insertion , two implants ( 5.5 % ) failed in G2 . Vertical bone loss was significantly higher in G2 compared with G1 , while HBLO demonstrated insignificant differences between groups . All clinical parameters ( PI , GI , PD and ISQ ) did not differ significantly between groups . Vertical bone loss was significantly correlated with PD and HBLO . Immediately loaded two implants supporting a Locator-retained m and ibular overdenture are associated with more vertical bone resorption when compared to delayed loaded implants after 1 year . Clinical outcomes do not differ significantly between loading protocol Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more Objectives To appraise the feasibility of loading four implants with a pre-existing denture converted to a fixed dental prosthesis ( FDP ) on the day of implant surgery compared with waiting for 3- to 4-month healing . Methods Patients with an edentulous , fully healed m and ible were recruited in a faculty clinic to partake in a blinded two-arm parallel r and omized controlled trial ( RCT ) . The participants received four parallel intraforamina m and ibular implants with a moderately rough titanium surface ( Brånemark System Mk III or Mk IV TiUnite ; Nobel Biocare AB , Göteborg , Sweden ) . The implants were loaded on the same day by converting the participants ' pre-existing denture in the experimental group . The implants were placed using a one-stage surgery procedure , and the participants ' pre-existing denture were soft-relined in the control group . For both groups , the permanent 10- to 12-unit FDP consisting of a type-3 cast precious alloy veneered with acrylic and artificial teeth was placed 3–4 months after implant surgery . All participants have been recalled annually for 5 years for appraisal of bone loss and registration of adverse events . Results Thirty-five of the original 42 participants ( 83 % ) returned for clinical and radiological examinations at the 5-year follow-up recall . No selective dropout or specific reasons for dropout was identified in the two study arms ; leaving n = 17 ( Intention-to-treat group , ITT ) in the experimental group , alternatively n = 13 as per protocol group ( PP ) , and n = 18 participants in the control group ( ITT = PP ) . At study commencement , five of the participants assigned to the experimental group did not receive their planned intervention . In the control group , one implant failed to osseointegrate and another failed due to bone loss after 5 years . The crestal bone level changes over 5 years were identical in the experimental and control groups , that is , 1.2 mm ( SD = 0.7 ) . There were no differences between the two study arms with regard to incidence of biological and technical adverse events . Conclusions Implants in the anterior m and ible loaded immediately with a converted pre-existing denture appear to yield analogous clinical outcomes compared with waiting for 3–4 months over the first 5 years following implant surgery It was the aim of this 24-mo r and omized controlled clinical trial to investigate whether the survival of a single median implant placed in the edentulous m and ible to retain a complete denture is not compromised by immediate loading . Secondary outcomes were differences in prosthetic complications between the loading principles . Each of the 158 patients who received an implant was r and omly assigned to the immediate loading group ( n = 81 ) or the delayed loading group ( n = 77 ) . Recall visits were performed 1 mo after implant placement ( for only the delayed loading group ) and 1 , 4 , 12 , and 24 mo after implant loading . Nine implants failed in the immediate loading group , all within the first 3 mo of implant loading , and 1 implant failed in the delayed loading group prior to loading . Noninferiority of implant survival of the immediate loading group , as compared with the delayed loading group , could not be shown ( P = 0.81 ) . Consistent with this result , a secondary analysis with Fisher exact test revealed that the observed difference in implant survival between the treatment groups was indeed statistically significant ( P = 0.019 ) . The most frequent prosthetic complications and maintenance interventions in the m and ible were retention adjustments , denture fractures , pressure sores , and matrix exchanges . There was only 1 statistically significant difference between the groups regarding the parameter “ fracture of the denture base in the ball attachment area ” ( P = 0.007 ) . The results indicate that immediate loading of a single implant in the edentulous m and ible reveals inferior survival than that of delayed loading and therefore should be considered only in exceptional cases ( German Clinical Trials Register : DRKS00003730 ) BACKGROUND Implant-retained overdentures have become a st and ard option for the prosthetic treatment of the edentulous m and ible in the elderly . PURPOSE This prospect i ve study aim ed to compare immediate and conventional loading of four interforaminal implants supporting a Locator-retained m and ibular overdenture in elderly patients regarding implant survival , implant stability , and implant-related complications . MATERIAL AND METHODS The study population comprised 20 completely edentulous patients ( 11 males ) aged 60 years and older with severe m and ible resorption . Each patient received four interforaminal implants ( Neoss Ltd. , Harrogate , UK ) . Following r and omization , implants were loaded either immediately after dental implant surgery or 3 months after implant placement with the Locator-abutment system . At follow-up visits 3 , 6 12 , 24 , and 36 months after loading , implant stability was evaluated with Periotest and Ostell . RESULTS Twenty patients received 80 implants . In eight patients , 32 implants were loaded immediately . Two patients had to be switched from the immediate to the conventional loading group due to insufficient primary stability ( ≤30 Ncm ) . Implant survival was similar in both groups after 36 months . No implant was lost . Decreasing Periotest , and accordingly , increasing Ostell measurements indicated adequate osseointegration in both groups . The course of treatment was not significantly different in the two groups . There were comparable incidences of postoperative complaints like swelling , hematoma , or wound dehiscence , as well as need for prosthetic treatment due to abutment loosening or occlusal discrepancies . Incidence of pressure marks and number of patient visits were significantly higher in the conventional loading group . CONCLUSION With sufficient primary stability , immediate loading of four interforaminal implants in the edentulous m and ible might be the preferential choice in the elderly , reducing total treatment time , and number of patient visits PURPOSE A 1-year blinded two-arm parallel r and omized controlled clinical trial was conducted to test the null hypothesis that immediate loading of four dental implants between the mental foramina with a fixed prosthesis has no benefits compared with the conventional loading technique in terms of implant success and clinical function . MATERIAL S AND METHODS Forty-five patients , completely edentulous in the m and ibles seeking implant-supported prostheses at the Faculty of Dentistry , University of Toronto , were recruited . Four TiUnite dental implants ( NobelBiocare ® , Göteborg , Sweden ) were placed following the one-stage surgical protocol . Immediately after surgery , the patients were r and omly assigned to either study arms by a third independent party . In the experimental arm ( EA ) , existing m and ibular denture was converted into an interim implant-supported fixed bridge ( ISFB ) on the same day of surgery . In the control arm ( CA ) , the m and ibular denture was hollowed out and relined with a soft tissue reline . The implants were loaded with the permanent ISFB at least 3 months postsurgery . Patients were assessed by a calibrated independent investigator at 2 , 6 , and 12 months following completion of treatment . RESULTS A total of one hundred sixty implants were placed . Due to anatomical limitations , one patient was excluded from the study . Four patients in the EA did not receive intervention as allocated and were transferred to the CA . Implant success rate was comparable between the two arms and exceeded 96 % . Marginal bone loss was statistically significantly more in the immediate loading arm , -0.296 mm versus -0.037 mm ( intention to treat : p = .002 ; per protocol : p = .021 ) . The relatively early intervention and insertion of the final prosthesis in the immediate arm , when bone healing and remodeling process had not yet been completed , might explain the difference in the amount of bone loss . CONCLUSION Immediate loading of four dental implants with a fixed prosthesis in the edentulous m and ible is a feasible treatment option and leads to a substantial improvement in perceived oral health status OBJECTIVES The aim of this study was to evaluate and compare marginal bone loss and clinical outcomes of conventionally and immediately loaded two implants supporting a ball-retained m and ibular overdenture . MATERIAL S AND METHODS Thirty six completely edentulous patients ( 22 males and 14 females ) were r and omly assigned into two groups . Each patient received two implants in the canine area of the m and ible after a minimal flap reflection . Implants were loaded by m and ibular overdentures either 3 months ( conventional loading group ) or the same day ( immediate loading group ) after implant placement . Ball attachments were used to retain all overdentures to the implants . Vertical and horizontal alveolar bone losses were evaluated in both groups 1 and 3 years after implant placement using multislice computed tomography , which allow evaluation of peri-implant buccal and lingual alveolar bone . Plaque scores , gingival scores , probing depths and periotest values ( PTVs ) were evaluated at 4 months ( baseline ) , 1 and 3 years after implant placement . Clinical and radiographic evaluations were performed at distal , labial , mesial and lingual peri-implant sites . RESULTS After 3 years of follow-up period , the immediate loading group recorded significant vertical bone loss at distal and labial sites than the conventional loading group and no significant differences in horizontal bone loss between groups were observed . Probing depth at distal and labial sites in the immediate loading group were higher than the conventional loading group , while plaque scores , gingival scores and PTVs showed no significant differences between the two groups . A low level of positive correlation between plaque scores , gingival scores , probing depths and vertical bone loss was noted . CONCLUSION Immediately loaded two implants supporting a ball-retained m and ibular overdenture are associated with more marginal bone resorption and increased probing depths when compared with conventionally loaded implants after 3 years . The bone resorption and probing depths at distal and labial sites are significantly higher than those at mesial and lingual sites . Clinical outcomes do not differ significantly between loading protocol This prospect i ve study has been design ed to compare the results of immediate and delayed loading of Output:	The risk of early loss in the IL group was higher than that in the DL group . For removable prostheses and nonsplinted implants , DL was preferred . The quality of scientific evidence significantly favors DL
MS213819	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: BACKGROUND Telehome care has been proposed as a solution to the challenges of providing effective and affordable care for patients with diabetes . METHODS A total of 100 adult patients with type 2 diabetes-divided between insulin and noninsulin requiring-was enrolled in a r and omized , controlled trial aim ed at investigating the effects of telehome monitoring . The experimental group ( n = 50 ) received an in-home wireless glucose monitor and transmitter , whereas the control group ( n = 50 ) was instructed to follow the conventional arrangement . RESULTS There was an overall reduction in HbA1c values in both experimental and control groups after 6 months . A significant difference in HbA1c values between the groups was observed only among the noninsulin-requiring patients ( decline from 6.95 % ± 0.82 % to 6.66 % ± 0.86 % in IB vs. 7.21 % ± 2.02 % to 7.2 % ± 1.86 % in IIB ; p = 0.02 ) . The experimental group reported considerably less hyperglycemic and hypoglycemic events . The profile of the patient who benefited the most from telemonitoring consisted of older , more educated patient who had acquired the disease relatively recently , and who spends most of the time at home . The experimental group had higher overall scores on quality of life measures and sense of control over diabetes . There was a positive association between educational attainment and ability to use the telemonitoring system without help ( p = 0.045 ) . CONCLUSIONS Although not conclusive because of the small sample and short observation period , the study suggests that telehome monitoring is an effective tool in controlling type 2 diabetes in a primary care setting OBJECTIVE To assess the effects of web-based care management on glucose and blood pressure control over 12 months in patients with poorly controlled diabetes . RESEARCH DESIGN AND METHODS For this study , 104 patients with diabetes and HbA(1c ) ( A1C ) > or = 9.0 % who received their care at a Department of Veterans Affairs medical center were recruited . All participants completed a diabetes education class and were r and omized to continue with their usual care ( n = 52 ) or receive web-based care management ( n = 52 ) . The web-based group received a notebook computer , glucose and blood pressure monitoring devices , and access to a care management website . The website provided educational modules , accepted uploads from monitoring devices , and had an internal messaging system for patients to communicate with the care manager . RESULTS Participants receiving web-based care management had lower A1C over 12 months ( P < 0.05 ) when compared with education and usual care . Persistent website users had greater improvement in A1C when compared with intermittent users ( -1.9 vs. -1.2 % ; P = 0.051 ) or education and usual care ( -1.4 % ; P < 0.05 ) . A larger number of website data uploads was associated with a larger decline in A1C ( highest tertile -2.1 % , lowest tertile -1.0 % ; P < 0.02 ) . Hypertensive participants in the web-based group had a greater reduction in systolic blood pressure ( P < 0.01 ) . HDL cholesterol rose and triglycerides fell in the web-based group ( P < 0.05 ) . CONCLUSIONS Web-based care management may be a useful adjunct in the care of patients with poorly controlled diabetes Purpose The purpose of this study is to investigate the impact of a 6-month Web-based intervention on the psychosocial well-being of older adults with diabetes . Methods This study was a r and omized controlled trial ( N = 62 ) comparing the effects of a 6-month Web-based intervention plus usual care with usual care alone among adults aged 60 years or older with diabetes . The outcomes included quality of life , depression , social support , and self-efficacy . Results The intervention group showed significant improvement , F(4.48 ) = 4.03 P = .007 , when compared with the control group on measures of depression , quality of life , social support , and self-efficacy when controlling for all baseline outcome variables ( age , gender , and number of years with diabetes ) . Conclusions These findings provide support for the conclusion that a Web-based intervention is effective in improving the psychosocial well-being of participants at a 6-month follow-up . Future research needs to investigate the long-term effectiveness of Web-based interventions for sustaining psychosocial well-being , including factors that may affect quality of life , such as diabetes-specific beliefs , attitudes , social support , and disease-specific coping skills OBJECTIVE —To test Web-based care management of glycemic control using a shared electronic medical record with patients who have type 2 diabetes . RESEARCH DESIGN AND METHODS —We conducted a trial of 83 adults with type 2 diabetes r and omized to receive usual care plus Web-based care management or usual care alone between August 2002 and May 2004 . All patients had GHb ≥7.0 % , had Web access from home , and could use a computer with English language –based programs . Intervention patients received 12 months of Web-based care management . The Web-based program included patient access to electronic medical records , secure e-mail with providers , feedback on blood glucose readings , an educational Web site , and an interactive online diary for entering information about exercise , diet , and medication . The primary outcome was change in GHb . RESULTS —GHb levels declined by 0.7 % ( 95 % CI 0.2−1.3 ) on average among intervention patients compared with usual-care patients . Systolic blood pressure , diastolic blood pressure , total cholesterol levels , and use of in-person health care services did not differ between the two groups . CONCLUSIONS —Care management delivered through secure patient Web communications improved glycemic control in type 2 diabetes OBJECTIVE To assess the effect of an Internet-based glucose monitoring system ( IBGMS ) on A1C levels in patients with type 2 diabetes treated with insulin . RESEARCH DESIGN AND METHODS This trial involved 50 patients r and omly assigned to receive either conventional treatment alone or with additional follow-up through an IBGMS for 6 months . Patients r and omized to the intervention group uploaded blood glucose readings every 2 weeks to a secure Web site for review and receipt of feedback from their endocrinologist . A1C and laboratory test results were collected at 0 , 3 , and 6 months . RESULTS The baseline parameters were not significantly different . Over a 6-month follow-up , A1C dropped from 8.8 to 7.6 % ( P < 0.001 ) in the intervention group compared with 8.5 to 8.4 % ( P = 0.51 ) in the control group . CONCLUSIONS The use of IBGMS significantly improved A1C levels in patients with type 2 diabetes treated with insulin OBJECTIVE The Internet is used worldwide as a communication tool . To improve the quality of diabetes control , we investigated the effectiveness of an Internet-based blood glucose monitoring system ( IBGMS ) on controlling the changes in HbA(1c ) levels . RESEARCH DESIGN AND METHODS We conducted a r and omized clinical trial involving 110 patients who visited the outpatient clinic at the Kangnam St. Mary 's Hospital for 3 months . The study subjects were treated with IBGMS for 12 weeks , and the control group received the usual outpatient management over the same period . HbA(1c ) and other laboratory tests were performed twice , once at the beginning of the study and again at the end of the study . RESULTS The test results from the beginning of the study established that there were no significant differences between the two groups with respect to age , sex , diabetes duration , BMI , blood pressure , HbA(1c ) , and other laboratory data . On follow-up examination 12 weeks later , HbA(1c ) levels were significantly decreased from 7.59 to 6.94 % within the intervention group ( P < 0.001 ) . At the end of the study , HbA(1c ) levels in the intervention group were significantly lower than in the control group after adjusting the baseline HbA(1c ) ( 6.94 vs. 7.62 % ; P < 0.001 , respectively ) . Among patients with baseline HbA(1c ) < 7.0 % , the patients in the intervention group had lower HbA(1c ) than those in the control group ( 6.38 vs. 6.99 % ; P < 0.05 ) . Among the patients with a baseline HbA(1c ) > or = 7.0 % , the difference between the two groups appeared more obvious : HbA(1c ) levels at the end of the study were 8.12 % . CONCLUSIONS This new IBGMS result ed in a significant reduction of HbA(1c ) during the study period . We propose that this IBGMS be used as a method for improving diabetes control OBJECTIVE We compared the short-term efficacy of home telemonitoring coupled with active medication management by a nurse practitioner with a monthly care coordination telephone call on glycemic control in veterans with type 2 diabetes and entry A1C ≥7.5 % . RESEARCH DESIGN AND METHODS Veterans who received primary care at the VA Pittsburgh Healthcare System from June 2004 to December 2005 , who were taking oral hypoglycemic agents and /or insulin for ≥1 year , and who had A1C ≥7.5 % at enrollment were r and omly assigned to either active care management with home telemonitoring ( ACM+HT group , n = 73 ) or a monthly care coordination telephone call ( CC group , n = 77 ) . Both groups received monthly calls for diabetes education and self-management review . ACM+HT group participants transmitted blood glucose , blood pressure , and weight to a nurse practitioner using the Viterion 100 TeleHealth Monitor ; the nurse practitioner adjusted medications for glucose , blood pressure , and lipid control based on established American Diabetes Association targets . Measures were obtained at baseline , 3-month , and 6-month visits . RESULTS Baseline characteristics were similar in both groups , with mean A1C of 9.4 % ( CC group ) and 9.6 % ( ACM+HT group ) . Compared with the CC group , the ACM+HT group demonstrated significantly larger decreases in A1C at 3 months ( 1.7 vs. 0.7 % ) and 6 months ( 1.7 vs. 0.8 % ; P < 0.001 for each ) , with most improvement occurring by 3 months . CONCLUSIONS Compared with the CC group , the ACM+HT group demonstrated significantly greater reductions in A1C by 3 and 6 months . However , both interventions improved glycemic control in primary care patients with previously inadequate control Background Persistently poor glycemic control in adult type 1 diabetes patients is a common , complex , and serious problem initiating significant damage to the cardiovascular , renal , neural , and visual systems . Currently , there is a plethora of low-cost and free diabetes self-management smartphone applications available in online stores . Objective The aim of this study was to examine the effectiveness of a freely available smartphone application combined with text-message feedback from a certified diabetes educator to improve glycemic control and other diabetes-related outcomes in adult patients with type 1 diabetes in a two-group r and omized controlled trial . Methods Patients were recruited through an online type 1 diabetes support group and letters mailed to adults with type 1 diabetes throughout Australia . In a 6-month intervention , followed by a three-month follow-up , patients ( n=72 ) were r and omized to usual care ( control group ) or usual care and the use of a smartphone application ( Glucose Buddy ) with weekly text-message feedback from a Certified Diabetes Educator ( intervention group ) . All outcome measures were collected at baseline and every three months over the study period . Patients ’ glycosylated hemoglobin levels ( HbA1c ) were measured with a blood test and diabetes-related self-efficacy , self-care activities , and quality of life were measured with online question naires . Results The mean age of patients was 35.20 years ( SD 10.43 ) ( 28 male , 44 female ) , 39 % ( 28/72 ) were male , and patients had been diagnosed with type 1 diabetes for a mean of 18.94 years ( SD 9.66 ) . Of the initial 72 patients , 53 completed the study ( 25 intervention , 28 control group ) . The intervention group significantly improved glycemic control ( HbA1c ) from baseline ( mean 9.08 % , SD 1.18 ) to 9-month follow-up ( mean 7.80 % , SD 0.75 ) , compared to the control group ( baseline : mean 8.47 % , SD 0.86 , follow-up : mean 8.58 % , SD 1.16 ) . No significant change over time was found in either group in relation to self-efficacy , self-care activities , and quality of life . Conclusions In adjunct to usual care , the use of a diabetes-related smartphone application combined with weekly text-message support from a health care professional can significantly improve glycemic control in adults with type 1 diabetes . Trial Registration Australian New Zeal and Clinical Trials Registry : ACTRN12612000132842 ; https://www.anzctr.org.au/Trial/ Registration /Trial Review .aspx?ACTRN=12612000132842 ( Archived by WebCite at http://www.webcitation.org/6Kl4jqn5u ) OBJECTIVE Output:	Internet blood glucose monitoring systems ( IBGMS ) are associated with improved glycemic control in patients with type 2 diabetes ( T2D ) who are pharmacologically managed , using oral agents or insulin . IBGMS improves glycemic levels in patients with type 1 diabetes ( T1D ) . IBGMS has not led to increased hypoglycemia . Mechanisms underlying IBGMS-associated glycemic improvement extend beyond optimizing insulin dose titration . The most important effects seem to be associated with increased patient self-motivation and improved patient-physician communication . IBGMS have been recommended in clinical practice guidelines , and their effectiveness and safety in trials suggest that this approach is appropriate for patients with T1D or T2D
MS213820	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Overwhelming evidence shows the quality of reporting of r and omised controlled trials ( RCTs ) is not optimal . Without transparent reporting , readers can not judge the reliability and validity of trial findings nor extract information for systematic review s. Recent method ological analyses indicate that inadequate reporting and design are associated with biased estimates of treatment effects . Such systematic error is seriously damaging to RCTs , which are considered the gold st and ard for evaluating interventions because of their ability to minimise or avoid bias . A group of scientists and editors developed the CONSORT ( Consoli date d St and ards of Reporting Trials ) statement to improve the quality of reporting of RCTs . It was first published in 1996 and up date d in 2001 . The statement consists of a checklist and flow diagram that authors can use for reporting an RCT . Many leading medical journals and major international editorial groups have endorsed the CONSORT statement . The statement facilitates critical appraisal and interpretation of RCTs . During the 2001 CONSORT revision , it became clear that explanation and elaboration of the principles underlying the CONSORT statement would help investigators and others to write or appraise trial reports . A CONSORT explanation and elaboration article was published in 2001 alongside the 2001 version of the CONSORT statement . After an expert meeting in January 2007 , the CONSORT statement has been further revised and is published as the CONSORT 2010 Statement . This up date improves the wording and clarity of the previous checklist and incorporates recommendations related to topics that have only recently received recognition , such as selective outcome reporting bias . This explanatory and elaboration document-intended to enhance the use , underst and ing , and dissemination of the CONSORT statement-has also been extensively revised . It presents the meaning and rationale for each new and up date d checklist item providing examples of good reporting and , where possible , references to relevant empirical studies . Several examples of flow diagrams are included . The CONSORT 2010 Statement , this revised explanatory and elaboration document , and the associated website ( www.consort-statement.org ) should be helpful re sources to improve reporting of r and omised trials Background The only three r and omized trials on the treatment of MTSS were all performed in military population s. The treatment options investigated in this study were not previously examined in athletes . This study investigated if functional outcome of three common treatment options for medial tibial stress syndrome ( MTSS ) in athletes in a non-military setting was the same . Methods The study design was r and omized and multi-centered . Physical therapists and sports physicians referred athletes with MTSS to the hospital for inclusion . 81 athletes were assessed for eligibility of which 74 athletes were included and r and omized to three treatment groups . Group one performed a grade d running program , group two performed a grade d running program with additional stretching and strengthening exercises for the calves , while group three performed a grade d running program with an additional sports compression stocking . The primary outcome measure was : time to complete a running program ( able to run 18 minutes with high intensity ) and secondary outcome was : general satisfaction with treatment . Results 74 Athletes were r and omized and included of which 14 did not complete the study due a lack of progress ( 18.9 % ) . The data was analyzed on an intention-to-treat basis . Time to complete a running program and general satisfaction with the treatment were not significantly different between the three treatment groups . Conclusion This was the first r and omized trial on the treatment of MTSS in athletes in a non-military setting . No differences were found between the groups for the time to complete a running program . Trial registration CCMO ; The effect of low-energy laser therapy on shin splints was examined in a r and omized study with an unblinded design . Constripts from the Jutl and Dragoon regiment with shin splints were given either active laser treatment ( 40 mW in 60 sec per cm tender tibia edge ) or placebo laser . All patients were exempted from normal duty concerning activities like running and march . Forty-nine patients participated in the study , 23 in the laser group and 26 in the control group . From the start the study was design ed to be double-blind , but by accident the code was broken towards the end of the study . We found no significant differences between the groups regarding pain visual analog score and readiness to return to active duty after 14 days Objective The purpose of this study was to describe the results of two treatment regimens for medial tibial stress syndrome ( MTSS ) ; a grade d running programme and the same running programme with additional shockwave therapy ( extracorporeal shockwave therapy ; ESWT ) . Design A prospect i ve observational controlled trial . Setting Two different sports medicine departments . Participants 42 athletes with MTSS were included . Intervention Patients from one hospital were treated with a grade d running programme , while patients from the other hospital were treated with the same grade d running programme and focused ESWT ( five sessions in 9 weeks ) . Main Outcome Measures Time to full recovery ( the endpoint was being able to run 18 min consecutively without pain at a fixed intensity ) . Results The time to full recovery was significantly faster in the ESWT group compared with the patients who only performed a grade d running programme , respectively 59.7±25.8 and 91.6±43.0 days ( p=0.008 ) . Conclusions This prospect i ve observational study showed that MTSS patients may benefit from ESWT in addition to a grade d running programme . ESWT as an additional treatment warrants further investigation in a prospect i ve controlled trial with the addition of r and omisation and double blinding Objective To study the additional effect of a pneumatic leg brace with st and ard rehabilitation for the treatment of medial tibial stress syndrome ( MTSS ) in recruits . Methods In a single blinded r and omized study , 15 recruits ( age 17 - 22 ) followed a rehabilitation programme consisting of leg exercises and a grade d running programme . Recruits performed daily exercises and ran three times a week . The running programme consisted of 6 consecutive phases . One group was , after r and omization , additionally provided with a pneumatic leg brace . Follow-up was provided every other week . Days to completing the running programme was the primary outcome measure , the Sports Activity Rating Scale ( SARS ) score and satisfaction with the treatment were secondary outcome measures . Results In total 14 recruits completed the rehabilitation programme . No differences were found in the number of days until phase six of the running schedule was finished between the brace and the control group ( Brace 58.8 ± 27.7 ( mean ± SD ) vs Non-Brace 57.9 ± 26.2 ( mean ± SD , p = 0.57 ) . Also no differences were found in the SARS scores between the groups . Overall satisfaction with the treatment was 6.4 ± 1.1 ( mean ± SD ) on a 1 - 10 scale for the brace group and 7.1 ± 0.7 ( mean ± SD ) for the control group ( p = 0.06 ) . Comfort of the brace was assessed as 4.8 ± 1.3 ( mean ± SD ) on a 1 - 10 scale . Conclusions No additional large effect of the pneumatic leg brace could be found in recruits and wearing of the brace was not feasible , since the wearing comfort was low OBJECTIVE The purpose of this study was twofold : to determine whether asymptomatic distance runners exhibit cortical tibial abnormalities on CT and to determine the diagnostic accuracy of CT in athletes with medial tibial stress syndrome . MATERIAL S AND METHODS A cross-sectional study with high-resolution CT of both tibiae was performed on 41 subjects : 20 asymptomatic distance runners , 11 distance runners with unilateral or bilateral pain due to medial tibial stress syndrome ( 14 painful tibiae ) , and 10 volunteers not involved in a sport . The group was composed of 13 women and 28 men , ranging in age from 18 to 26 years . A total of 82 tibiae , 14 painful and 68 painless , were evaluated . On the basis of CT findings , tibiae were classified in three groups , and correlation between CT classification and symptoms was made . RESULTS Among distance runners , the presence of CT abnormalities was found in 14 ( 100 % ) of 14 painful tibiae in patients with medial tibial stress syndrome and in 8 ( 16.6 % ) of 48 painless tibiae . The difference was statistically significant ( p < 0.001 , Fisher 's exact test ) . Sensitivity , specificity , positive predictive value , negative predictive value , and accuracy of CT in diagnosing medial tibial stress syndrome were 100 % , 88.2 % , 63.6 % , 100 % , and 90.2 % , respectively . CONCLUSION High-resolution CT has high diagnostic accuracy in depicting medial tibial stress syndrome . Cortical abnormalities can also be seen in some asymptomatic distance runners Purpose To identify the incidence of medial tibial stress syndrome ( MTSS ) in a group of naval recruits undergoing a 10-week basic training period and to determine potential risk factors . Method One hundred and twenty-four recruits ( 84 men and 40 women ) were followed prospect ively during basic training . Anthropometric and lower limb biomechanical data were recorded at the start of the program along with injury history and previous sporting activity for the 3 months prior to enlisting . Recruits were monitored during training for development of medial tibial strees syndrome and were asked to complete an exit interview at the end of the program . Results Forty recruits ( 22 men and 18 women ) developed medial tibial stress syndrome , giving an incidence of 35 % . A significant relationship existed between gender and medial tibial stress syndrome ( P= .012 ) , with female recruits more likely to develop medial tibial stress syndrome than male recruits ( 53 % vs 28 % ) . A risk estimate revealed a relative risk of 2.03 . The biomechanical results indicated a more pronated foot type ( P= .002 ) in the medial tibial stress syndrome group when compared to the control group . A risk estimate established that recruits with a more pronated foot type had a relative risk of 1.70 . Conclusion Identifying a pronated foot type prior to training may help reduce the incidence of medial tibial stress syndrome by early intervention to control abnormal pronation . Findings of a higher incidence of medial tibial stress syndrome among female recruits require further investigation Diagnosis and management strategies for shin splints in active duty military population s closely resemble those in civilian athletic population s. There is a paucity of evidence supporting the use of many of these interventions . The purpose of this study was to present data on the Shin Saver orthosis as a treatment for shin splints in an active duty military population and to review current condition management . Twenty-five subjects diagnosed with shin splints by a U.S. Army physical therapist were r and omly assigned to a shin orthosis treatment group or a control group . There was no significant difference between treatment and control groups in days to finish a 0.5-mile run pain free . Visual analog scales for pain at intake versus after 1 week of relative rest revealed no significant improvement in symptoms in either group . Current best- practice guidelines support a treatment program of rest , cryotherapy , and a graduated walk-to-run program Background Although the exact cause of medial tibial stress syndrome is unclear , changes in bone metabolism are likely to be involved . Hypothesis Localized low bone mineral density at the junction of the middle and distal thirds of the tibia in patients with medial tibial stress syndrome develops in conjunction with the symptoms ; these changes are reversible and are not inherited . Study Design Prospect i ve cohort study . Methods Bone mineral density in 14 adult male athletes with long-st and ing medial tibial stress syndrome was measured when they were symptomatic and after recovery ( mean follow-up , 5.7 years ) . Repeat measurements were also made prospect ively in 13 nonathlete control subjects and single measurements were made in 18 healthy athletes . Results Bone mineral density was 9 % ± 11 % higher in the proximal tibia but 11 % ± 12 % lower in the tibial region corresponding to pain in patients when compared with nonathlete control subjects . It increased by 19 % ± 11 % in the region of pain after recovery from symptoms and , at follow-up , was no lower than in nonathlete control subjects . Conclusion Athletes with medial tibial stress syndrome and increased scintigraphic uptake regain normal tibial bone mineral density after recovery from symptoms . Initially localized low bone mineral density is not an inherited condition , but instead may develop in conjunction with the symptoms Output:	Conclusion None of the studies are sufficiently free from method ological bias to recommend any of the treatments investigated . Of those examined , ESWT appears to have the most promise
MS213821	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Purpose . To conduct a pilot test of a decision aid design ed to help patients choose among currently recommended colorectal cancer screening programs . Methods . R and omized controlled trial comparing a patient decision aid based on multi criteria decision-making theory with a simple educational intervention . Patient population . 96 patients at average risk for colorectal cancer seen in an Internal Medicine practice in Rochester , New York . Outcome measures . The two primary outcome measures were patient decision process and the decision outcome . Patient decision process was assessed using the decisional conflict scale . Decision outcome was defined as the proportion of colorectal cancer screening plans carried out . Results . After controlling for the effects of the physicians in a factorial analysis of variance , patients who used the decision aid had lower decisional conflict regarding colorectal cancer screening decisions ( F ratio6.47 , P = 0.01 ) due to increased knowledge , better clarity of values , and higher ratings of the quality of the decisions they made . There was no difference between the groups in decision outcomes : 52 % of patients in the control group and 49 % in the experimental group completed planned screening tests ( P = 1.0 ) . Conclusions . In a pilot study , a multi criteria -based patient decision aid for colorectal cancer screening improved patients ’ decision-making processes but had no effect on the implementation of screening plans Developing an evidence base for making public health decisions will require using data from evaluation studies with r and omized and nonr and omized design s. Assessing individual studies and using studies in quantitative research syntheses require transparent reporting of the study , with sufficient detail and clarity to readily see differences and similarities among studies in the same area . The Consoli date d St and ards of Reporting Trials ( CONSORT ) statement provides guidelines for transparent reporting of r and omized clinical trials . We present the initial version of the Transparent Reporting of Evaluations with Nonr and omized Design s ( TREND ) statement . These guidelines emphasize the reporting of theories used and descriptions of intervention and comparison conditions , research design , and methods of adjusting for possible biases in evaluation studies that use nonr and omized design BACKGROUND The availability of several effective screening options for colorectal cancer ( CRC ) screening calls for involving patients in decision making about CRC screening . The current study examined ( 1 ) participant characteristics associated with their preferences for participation in CRC screening decision making , ( 2 ) correspondence between participant preferences for decision making and their usual participation in decision making , and ( 3 ) associations between participant decision-making preferences and CRC screening practice s and attitudes . METHODS Data were obtained using a r and om , population -based telephone survey , conducted during August 2001 and April 2002 , of 2119 community-living adults aged 50 to 75 years ( 56 % female ) residing in Long Isl and , NY . RESULTS Overall , 77 % reported that preferences for CRC screening decision making matched how screening decisions were usually made ( simple kappa coefficient=0.67 [ 0.64 - 0.69 ] ) . Fifteen percent preferred to make screening decisions themselves , while 25 % preferred to make decisions after considering their physician 's opinion ; nearly 50 % preferred to share decision making , and 16 % preferred that their physician make all screening decisions . Less education was associated with preferring that the physician make all screening decisions . Preferring physician involvement in screening decision making was associated with greater odds of citing no physician recommendation as a barrier to CRC screening , when compared to those who preferred no physician involvement . Preferring no physician involvement in decision making was associated with lower odds of reporting a recent CRC screening exam , as well as lower odds of endorsing positive attitudes and greater odds of endorsing negative attitudes toward CRC screening , when compared to participants who preferred physician involvement in decision making . Their attitudes also reflected intentions not to screen for CRC if they were asymptomatic , as well as the perception that they were not at personal risk for CRC . CONCLUSIONS Several factors were identified as significantly associated with preferences for decision making and deserve further exploration for their application to clinical practice The purpose of this study was to determine if providing men with information about screening for prostate cancer would enable them to assume a more active role in decision making with their family physician , and lower levels of anxiety and decisional conflict . Men were recruited from one family medical clinic in Winnipeg , Manitoba . One hundred men scheduled for a periodic health examination ( PHE ) were r and omly assigned to receive verbal and written information either prior to the PHE , or following the second interview . Men completed measures of preferred decisional role and anxiety prior to the PHE ; and assumed decisional role , decisional conflict , and anxiety post PHE . Results demonstrated that men who received the information prior to the PHE assumed a significantly more active role in making a screening decision , and had lower levels of decisional conflict post PHE . The two groups did not differ with regard to levels of state anxiety . Providing men with information enables them to make informed screening decisions with their family physicians BACKGROUND We tested an intervention based on social learning theory ( SLT ) to improve colorectal cancer ( CRC ) screening among Native Hawaiians , a group with low CRC screening rates . METHOD Sixteen Hawaiian civic clubs agreed to r and omization . Eight control clubs received a culturally targeted presentation , a free Fecal Occult Blood Test ( FOBT ) , and a reminder call . Eight experimental clubs also received culturally targeted education and free testing ; but , in line with SLT , education was delivered by a Native Hawaiian physician and Native Hawaiian CRC survivor , and members received an FOBT demo , were challenged to involve a family member in screening , and were telephoned multiple times to address change-related emotions and barriers . RESULTS One hundred twenty-one members age 50 and older from 16 clubs participated . At the club level , screening rates were modestly increased in four experimental clubs and six control clubs . Surprisingly , 64 % of participants reported being up to date with CRC screening at baseline . Only 13 individuals ( five in experimental arm and eight in the control arm ) were screened for the first time through this intervention , increasing the percent screened from 59 % to 67 % in the experimental group and from 69 % to 85 % in the control group . Although individuals in the experimental arm were more likely to rate the intervention as culturally appropriate , both arms realized similar and significant gains in CRC knowledge , attitudes , intent , and self-efficacy . CONCLUSIONS For Native Hawaiian individuals belonging to a network of civic clubs , an intervention based on SLT delivered by a Native Hawaiian physician and CRC survivor was less effective at further increasing compliance than was a culturally targeted educational session delivered by a non-Hawaiian nurse . That CRC screening compliance was high prior to our intervention suggests that we targeted a very health conscious segment of the Native Hawaiian population . Future work should focus on underserved segments of this indigenous group Patient satisfaction measures have previously addressed satisfaction with medical care , satisfaction with providers , and satisfaction with outcomes , but not satisfaction with the health care decision itself . As patients become more involved in health care decisions , it is important to underst and specific dynamics of the decision itself The Satisfaction with Decision ( SWD ) scale measures satisfaction with health care decisions . It was developed in the context of postmenopausal hormone-replacement therapy decisions The six-item scale has excellent reliability ( Cronbach 's alpha = 0.86 ) . Discriminant validity , tested by performing principal- components analysis of items pooled from the SWD scale and two conceptually related measures , was good . Correlation of the SWD scale with measures of satisfaction with other aspects of the decision-making process showed the SWD scale was correlated most highly ( 0.64 ) with " decisional confidence , " and least with " desire to participate in health care de cisions " and " satisfaction with provider " The SWD scale predicts decision certainty in this study . Use in an independent study showed that the SWD scale was correlated with the likelihood of patients ' intentions to get a flu shot . Further investigation in relation to other health decisions will establish the utility of the SWD scale as an outcome measure Key words : patient satisfaction ; medical decision making ; decision support ( Med Decis Making 1996;16:58 - 64 BACKGROUND Studies have shown that a majority of women with a family history of breast cancer have exaggerated perceptions of their own risk of this disease and experience excessive anxiety . In response to the need to communicate more accurate risk information to these women , specialized programs for breast cancer risk counseling have been initiated in medical centers across the United States . PURPOSE Our purpose was 1 ) to evaluate the impact of a st and ardized protocol for individualized breast cancer risk counseling on comprehension of personal risk among first-degree relatives of index breast cancer patients and 2 ) to identify women most and least likely to benefit from such counseling . METHODS This study is a prospect i ve r and omized trial comparing individualized breast cancer risk counseling to general health counseling ( control ) . We studied 200 women aged 35 years and older who had a family history of breast cancer in a first-degree relative . Women with a personal history of cancer were excluded . Risk comprehension was assessed as the concordance between perceived " subjective " lifetime breast cancer risk and estimated " objective " lifetime risk . RESULTS The results of logistic regression analysis showed that women who received risk counseling were significantly more likely to improve their risk comprehension , compared with women in the control condition ( odds ratio [ OR ] = 3.5 ; 95 % confidence interval [ CI ] = 1.3 - 9.5 ; P = .01 ) . However , in both groups , about two thirds of women continued to overestimate their lifetime risks substantially following counseling . Examination of subjects by treatment interaction effects indicated that risk counseling did not produce improved comprehension among the large proportion of women who had high levels of anxious preoccupation with breast cancer at base line ( P = .02 ) . In addition , white women were less likely to benefit than African-American women ( OR = 0.34 ; 95 % CI = 0.11 - 0.99 ; P = .05 ) . CONCLUSION Efforts to counsel women about their breast cancer risks are not likely to be effective unless their breast cancer anxieties are also addressed . IMPLICATION S Attention to the psychological aspects of breast cancer risk will be critical in the development of risk-counseling programs that incorporate testing for the recently cloned breast cancer susceptibility gene , BRCA1 ( and BRCA2 when that gene has also been cloned ) OBJECTIVE To describe women 's breast screening knowledge , attitudes , intentions and practice s. DESIGN Telephone survey . PARTICIPANTS R and om population -based sample of 383 women aged 50 to 69 , living in Ottawa-Carleton , and having no history of breast cancer . Participation rates were 81 % . RESULTS Only 47 % reported having had a mammogram within the two years before the survey , and 57 % had received a physical breast exam within the previous year . Intentions to arrange screening were positively correlated to income , previous mammography , encouragement to have a mammogram , knowledge , knowing a person with breast cancer , an absence of negative attitudes ( i.e. , mammograms unnecessary ) , and low decisional conflict . CONCLUSIONS Improvements in participation rates will be achieved only if women are convinced of the need for screening , and physicians encourage them to be screened BACKGROUND Little is known about what information affects men 's decisions about prostate cancer screening . METHODS We developed a four-part decision aid about prostate cancer screening and tested it in men , ages 45 - 85 , to determine how the information in each part--(1 ) the epidemiology of prostate cancer ; ( 2 ) the PSA test ; ( 3 ) prostate biopsy and treatment options for prostate cancer ; and ( 4 ) balance sheets to aid decision-making -- affected men 's interest in screening . RESULTS One hundred eighty-eight men from one general internal medicine clinic participated in our study ( response rate 65 % ) . Before the decision aid , 76 % were interested in screening ; 8 % were not ; and 16 % were undecided . The decision aid increased the proportion of men who knew the advantages ( + 28 % ; 95 % CI : 21 - 35 ) and disadvantages ( + 55 % ; 95 % CI : 48 - 63 % ) of screening . It also increased the proportion who knew enough to make a decision ( + 24 ; 95 % CI : 16 - 32 % ) . It did not change men 's interest in screening ( P = 0.134 ) . Twenty percent of men , however , did change their interest category . Men who were undecided at baseline were more likely to change than those who were interested or not interested . There were no clinical ly meaningful changes in interest following each component part of the decision aid . CONCLUSION Interest in prostate cancer screening is high and remained high after a 10 min decision aid . The decision aid increased the proportion of men with sufficient information to decide about screening . It also changed 20 % of men 's interest in screening . Because no single piece of information was influential to decision-making in all men , clinicians may want to tailor information to men 's individual needs OBJECTIVES Efforts to educate men about the controversy surrounding prostate cancer screening are well intended but rarely evaluated rigorously . We evaluated an evidence -based ( EB ) booklet for men design ed to promote informed decision-making . We also determined whether men 's preference for involvement in decision-making ( " passive " , " collaborative " or " active " ) modified its impact . SETTING AND METHODS Men aged 40 - 70 years were recruited from the practice s of 13 local general practitioners ( GPs ) in Sydney , Australia . They completed a self-administered question naire before seeing their GP , who , according to pre-r and omised codes , distributed either our EB booklet or conventional information . Post-test question naires were mailed to men three days later . Of the 248 eligible men recruited , 214 ( 86 % response rate ) returned post-test question naires . Knowledge of evidence and of risk of developing and dying from pro Output:	Our findings revealed that most studies measured screening ( or intention ) and knowledge ; fewer measured recommended IDM-related constructs and none measured all outcomes proposed for evaluating IDM interventions .
MS213822	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: BACKGROUND AND OBJECTIVE : Most clinic-based weight control treatments for youth have been design ed for preadolescent children by using family-based care . However , as adolescents become more autonomous and less motivated by parental influence , this strategy may be less appropriate . This study evaluated a primary care – based , multicomponent lifestyle intervention specifically tailored for overweight adolescent females . METHODS : Adolescent girls ( N = 208 ) 12 to 17 years of age ( mean ± SD : 14.1 ± 1.4 years ) , with a mean ± SD BMI percentile of 97.09 ± 2.27 , were assigned r and omly to the intervention or usual care control group . The gender and developmentally tailored intervention included a focus on adoptable healthy lifestyle behaviors and was reinforced by ongoing feedback from the teen ’s primary care physician . Of those r and omized , 195 ( 94 % ) completed the 6-month posttreatment assessment , and 173 ( 83 % ) completed the 12-month follow-up . The primary outcome was reduction in BMI z score . RESULTS : The decrease in BMI z score over time was significantly greater for intervention participants compared with usual care participants ( −0.15 in BMI z score among intervention participants compared with −0.08 among usual care participants ; P = .012 ) . The 2 groups did not differ in secondary metabolic or psychosocial outcomes . Compared with usual care , intervention participants reported less reduction in frequency of family meals and less fast-food intake . CONCLUSIONS : A 5-month , medium-intensity , primary care – based , multicomponent behavioral intervention was associated with significant and sustained decreases in BMI z scores among obese adolescent girls compared with those receiving usual care BACKGROUND Despite the high prevalence and negative physical and psychosocial consequences of overweight and obesity in adolescents , very little research has evaluated treatment in this population . Consequently , clinicians working with overweight and obese adolescents have little empirical research on which to base their practise . Cognitive behavioural therapy has demonstrated efficacy in promoting behaviour change in many treatment resistant disorders . Motivational interviewing has been used to increase motivation for change and improve treatment outcomes . In this paper we describe the rationale and design of a r and omised controlled trial testing the efficacy of motivational interviewing and cognitive behaviour therapy in the treatment of overweight and obese adolescents . METHODS Participants took part in a motivational interview or a st and ard semi-structured assessment interview and were then r and omly allocated to a cognitive behavioural intervention or a wait-list control condition . The cognitive behavioural intervention , the CHOOSE HEALTH Program , consisted of 13 individual treatment sessions ( 12 face-to-face , 1 phone call ) followed by 9 maintenance sessions ( 7 phone calls , 2 face-to-face ) . Assessment s were conducted prior to participation , after the treatment phase and after the maintenance phase of intervention . Improvement in body composition was the primary outcome ; secondary outcomes included improved cardiovascular fitness , eating and physical activity habits , family and psychosocial functioning . CONCLUSION Despite the demonstrated effectiveness of motivational interviewing and cognitive behavioural therapy in the long-term management of many treatment resistant disorders , these approaches have been under-utilised in adolescent overweight and obesity treatment . This study provides baseline data and a thorough review of the study design and treatment approach to allow for the assessment of the efficacy of motivational interviewing and cognitive behavioural therapy in the treatment of adolescent overweight and obesity . Data obtained in this study will also provide much needed information about the behavioural and psychosocial factors associated with adolescent overweight and obesity Background : The best outcomes for treating childhood obesity have come from comprehensive family-based programmes . However there are questions over their generalizability . Objective : To examine the acceptability and effectiveness of ‘ family-based behavioural treatment ’ ( FBBT ) for childhood obesity in an ethnically and socially diverse sample of families in a UK National Health Service ( NHS ) setting . Methods : In this parallel group , r and omized controlled trial , 72 obese children were r and omized to FBBT or a waiting-list control . Primary outcomes were body mass index ( BMI ) and BMI s.d . scores ( SDSs ) . Secondary outcomes were weight , weight SDSs , height , height SDSs , waist , waist SDSs , FM index , FFM index , blood pressure ( BP ) and psychosocial measures . The outcomes were assessed at baseline and after treatment , with analyses of 6-month data performed on an intent-to-treat ( ITT ) basis . Follow-up anthropometric data were collected at 12 months for the treatment group . Results : ITT analyses included all children with baseline data ( n=60 ) . There were significant BMI SDS changes ( P<0.01 ) for the treatment and control groups of −0.11 ( 0.16 ) and −0.10 ( 1.6 ) . The treatment group showed a significant reduction in systolic BP ( −0.24 ( 0.7 ) , P<0.05 ) and improvements in quality of life and eating attitudes ( P<0.05 ) , with no significant changes for the control group . However the between-group treatment effects for BMI , body composition , BP and psychosocial outcomes were not significant . There was no overall change in BMI or BMI SDSs from 0–12 months for the treatment group . No adverse effects were reported . Conclusions : Both treatment and control groups experienced significant reductions in the level of overweight , but with no significant difference between them . There were no significant group differences for any of the secondary outcomes . This trial was registered at http://www.controlled-trials.com/ under IS RCT N 51382628 Abstract Background The Loozit ® Study is a r and omised controlled trial investigating extended support in a 24 month community-based weight management program for overweight to moderately obese , but otherwise healthy , 13 to 16 year olds . Methods This pre-post study examines the two month outcomes of the initial Loozit ® group intervention received by both study arms . Adolescents ( n = 151 ; 48 % male ) and their parents separately attended seven weekly group sessions focused on lifestyle modification . At baseline and two months , adolescents ' anthropometry , blood pressure , and fasted blood sample were assessed . Primary outcomes were two month changes in body mass index ( BMI ) z-score and waist-to-height-ratio ( WHtR ) . Secondary outcomes included changes in metabolic profile , self-reported dietary intake/patterns , physical and sedentary activities , psychological characteristics and social status . Changes in outcome measures were assessed using paired sample s t-tests for continuous variables or McNemar 's test for dichotomous categorical variables . Results Of the 151 adolescents who enrolled , 130 ( 86 % ) completed the two month program . Among these 130 adolescents ( 47 % male ) , there was a statistically significant ( P < 0.01 ) reduction in mean [ 95 % CI ] BMI ( 0.27 kg/m2 [ 0.41 , 0.13 ] ) , BMI z-score ( 0.05 [ 0.06 , 0.03 ] ) , WHtR ( 0.02 [ 0.03 , 0.01 ] ) , total cholesterol ( 0.14 mmol/L [ 0.24 , 0.05 ] ) and low-density lipoprotein cholesterol ( 0.12 mmol/L [ 0.21 , 0.04 ] ) . There were improvements in all psychological measures , the majority of the dietary intake measures , and some physical activities ( P < 0.05 ) . Time spent watching TV and participating in non-screen sedentary activities decreased ( P < 0.05 ) . Conclusions The Loozit ® program may be a promising option for stabilizing overweight and improving various metabolic factors , psychological functioning and lifestyle behaviors in overweight adolescents in a community setting .Trial registration Australian New Zeal and Clinical Trials Registry OBJECTIVE We examined the effect of a 12-week family-based cognitive behavioural weight management programme developed for use in primary care setting s. METHODS The sample consisted of 49 children with obesity ( aged 7 - 13 years ; mean ± SD : 10.68 ± 1.24 ) . Families were r and omly assigned to immediate start-up of treatment or to a 12-week waiting list condition . Outcome measures were body mass index st and ard deviation score ( BMI SDS ) , self-esteem , symptoms of depression and blood parameters indicative of cardio-metabolic risk . Assessment s were conducted at baseline , post-treatment , post-waiting list and 12 months after treatment termination . RESULTS The mean reduction for the treatment group was -0.16 BMI SDS units compared with an increase of 0.04 units for the waiting list group ( p = .001 ) . For the entire sample , there was a significant post-treatment improvement on BMI SDS ( p = .001 ) , all self-esteem measures ( p = .001-.041 ) and symptoms of depression ( p = .004 ) . The mean BMI SDS reduction was -0.18 units post-treatment , and it was maintained at 12-month follow-up . Significant reductions were found in blood lipid levels of total cholesterol ( p = .03 ) , LDL-cholesterol ( p = .005 ) and HDL-cholesterol ( p = .01 ) at 12-month follow-up . The favourable effect on most of the psychological measures waned from post-treatment to follow-up , but not approaching baseline levels . Boys demonstrated significantly greater reductions in BMI SDS than girls ( p = .001 ) , while baseline psychiatric co-morbidity did not influence BMI SDS outcome . CONCLUSIONS The treatment shows significant and favourable effects on BMI SDS , self-esteem and symptoms of depression compared with a waiting list condition The aim of the study was to investigate prospect ively the direction of the relationship between adolescent girls ' body dissatisfaction and self-esteem . Participants were 242 female high school students who completed question naires at two points in time , separated by 2 years . The question naire contained measures of weight ( BMI ) , body dissatisfaction ( perceived overweight , figure dissatisfaction , weight satisfaction ) and self-esteem . Initial body dissatisfaction predicted self-esteem at Time 1 and Time 2 , and initial self-esteem predicted body dissatisfaction at Time 1 and Time 2 . However , linear panel analysis ( regression analyses controlling for Time 1 variables ) found that aspects of Time 1 weight and body dissatisfaction predicted change in self-esteem , but not vice versa . It was concluded that young girls with heavier actual weight and perceptions of being overweight were particularly vulnerable to developing low self-esteem AIM This study evaluates the efficacy of the Choose Health program , a family-based cognitive behavioural lifestyle program targeting improved eating and activity habits , in improving body composition , cardiovascular fitness , eating and activity behaviours in overweight and obese adolescents . METHOD The sample comprised 29 male and 34 female overweight ( n = 15 ) or obese ( n = 48 ) adolescents aged 11.5 - 18.9 years ( M = 14.3 , SD = 1.9 ) . Participants were r and omly allocated to treatment or waitlist control conditions ; waitlist condition participants were offered treatment after 6 months . DEXA-derived and anthropometric measures of body composition ; laboratory-based cycle ergometer and field-assessed cardiovascular fitness data ; objective and self-report physical activity measures ; and self-report measures of eating habits and 7-day weighed food diaries were used to assess treatment outcome . Adherence to treatment protocol s was high . RESULTS Treatment result ed in significant ( p < .05 ) and sustained improvements in a range of body composition ( body fat , percent body fat , lean mass ) and anthropometric measures ( weight , BMI , BMI -for-age z-score and percentiles ) . Minimal improvements were seen in cardiovascular fitness . Similar results were obtained in completer and intention-to-treat analysis . Poor adherence to assessment protocol s limits conclusions that can be drawn from physical activity and dietary data . CONCLUSIONS Participation in the Choose Health program result ed in significant improvement in body composition . Longer-term follow up is required to determine the durability of intervention effects . Alternative approaches to the measurement of diet and physical activity may be required for adolescents Objective : Since peers have such an important influence on adolescents , we evaluated the efficacy of adding peer-based ‘ adventure therapy ’ to a st and ard cognitive-behavioral weight control program for overweight adolescents . Methods : Adolescents ( N=76 ) aged 13–16 years and 20 to 80 % overweight ( M=60.56 % , s.d.=15.17 % ) , were r and omly assigned to one of two treatment conditions : cognitive-behavioral group treatment with ‘ adventure therapy ’ similar to Outward Bound ® ( cognitive-behavioral treatment with peer-enhanced adventure therapy ( CBT+PEAT ) ) or cognitive-behavioral group treatment with aerobic exercise ( CBT+EXER ) . Anthropometric and psychosocial measures were obtained at baseline , at the end of the 16-week intervention , and at 10 months following r and omization . Results : Adolescents assigned to both treatment conditions demonstrated significant weight loss over time , F=29.06 , df=2 , 53 , P<0.01 . Average weight loss did not differ significantly between groups ( −5.31 Output:	Conclusion The lack of change in self-esteem suggests weight loss alone is insufficient to improve self-esteem . Multicomponent weight management interventions require a specific focus on self-esteem to improve this outcome in overweight and obese adolescents
MS213823	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Background and aims : There is a need for objective easily determined pathological prognostic parameters in Dukes ' B colon carcinoma to allow selection of such patients for further treatment as the role of adjuvant chemotherapy for these patients remains unclear . This study was initiated to assess the influence of pathological factors on prognosis in an unselected prospect i ve series of Dukes ' B colonic cancer . Methods : The Gloucester Colorectal Cancer study , established in 1988 , recruited more than 1000 cases . Meticulous pathological assessment of the 268 Dukes ' B colonic cancer resections in this series included evaluation of all pathological factors that could influence staging and prognosis . All patients entered a comprehensive follow up system . Results : Four pathologically determined factors — peritoneal involvement , venous spread ( both submucosal and extramural ) , spread to involve a surgical margin , and perforation through the tumour — were independent prognostic factors in multivariate analysis . Combining these four factors into a simple cumulative scoring system generated clinical ly useful prognostic groups . Conclusions : The cumulative prognostic index allows apportionment of patients with Dukes ' B colon cancer into defined prognostic groups , which in turn could allow more objective selection of patients for adjuvant therapy , especially as part of clinical trials Objective : To examine the clinical utility of improved detection of venous invasion ( VI ) in patients undergoing potentially curative resection of colorectal cancer . Background : VI is a feature of colorectal cancer ( CRC ) progression . Elastica staining can be used to improve detection of VI and correspondingly its prediction of patient survival . Methods : A single-center , observational study of pathology variables , including detection of VI by staining for elastica , using 631 stage I to III CRC specimens , collected from 1997 to 2009 ( 176 analyzed retrospectively and 455 analyzed prospect ively ) , was performed . Results : VI was detected in 56 % of patients with CRC . Over a median follow-up period of 73 months , 238 patients died ( 134 from cancer ) . On multivariate analysis , VI by elastica staining was associated with a shorter survival duration , independent of other pathology features , in all cases [ hazard ratio ( HR ) = 3.94 , 95 % confidence interval ( CI ) : 2.33–6.65 , P < 0.001 ] and in node-negative cases ( HR = 3.55 , 95 % CI : 1.81–6.97 ; P < 0.001 ) . In the absence of elastica-detected VI , with the exception of T stage , no other pathology features were associated with survival time . Therefore , the combination of T stage and VI ( TVI ) on survival was examined . Five-year cancer mortality could be stratified between 100 % and 54 % for patients with node-negative tumors and between 100 % and 33 % for patients with node-positive tumors . In all cases , the TVI had similar predictive value as that of T stage and node status ( TNM ) . In node-negative disease , TVI had superior predictive value . Conclusions : The results of the present study have prompted the development of a novel tumor staging system based on TVI . The TVI has clinical utility , especially in node-negative disease , in predicting outcome following curative resection for CRC Colorectal cancer is a common malignancy and a leading cause of cancer related death . Cancer staging following resection is key to determining any adjuvant therapy in those patients with high risk disease . In colorectal cancer , tumour stage and lymph node stage are the main pathological factors which have been considered to influence outcome . Increasing emphasis is now being placed on other factors , especially the presence of extramural venous invasion ( EMVI ) . It is important to underst and the relationship of EMVI with other pathological factors and to confirm that in an individual centre that EMVI is being detected at an appropriate rate and is of prognostic significance . This comprehensive study assesses the reporting and prognostic significance of EMVI in a single centre , using prospect ively collected data from histopathology reports of a cohort of 2405 patients who underwent surgery for colorectal cancer over a nine year period . Overall , EMVI was reported in 27.9 % of colorectal cancer excision specimens . In tumours ( n = 1928 ) that had not received neoadjuvant therapy , the presence of EMVI varied significantly depending on tumour site ( χ2 = 12.03 , p<0.005 ) , tumour stage ( χ2 = 268.188 , p<0.001 ) , lymph node stage ( χ2 = 294.368 , p<0.001 ) and Dukes ’ stage ( χ2 = 253.753 , p<0.001 ) . Multivariate analysis confirmed EMVI as a significant independent prognostic indicator ( p<0.001 ) . In conclusion , the presence of EMVI as an independent prognostic indicator is shown and is related to other pathological and prognostic factors . This study emphasises the requirement for the accurate identification of EMVI in colorectal cancer excision specimens and also underst and ing the relationship of EMVI with other prognostic factors BACKGROUND : Extramural venous invasion is a known independent predictor of poor prognosis after resection of colorectal adenocarcinoma , but the prognostic value of mural venous invasion alone and the association between venous invasion and prognosis within tumor stages has received little research attention . OBJECTIVE : This study aim ed to determine whether associations between mural and extramural venous invasion and outcome differ among tumor stages after adjustment for other factors known to influence prognosis . DESIGN : This study is a retrospective analysis of prospect ively collected data . SETTING S : Data were drawn from a registry of 3040 consecutive patients undergoing resection between 1980 and 2005 under the care of specialist surgeons in a tertiary referral public hospital and an affiliated private hospital . A st and ardized protocol was used for the pathological assessment of specimens . MAIN OUTCOME MEASURES : The primary outcomes measured were overall survival , cancer-specific survival , and recurrence . RESULTS : There was no significant association between venous invasion and survival in stages A ( n = 544 ) or B ( n = 1078 ) . In stage C ( n = 899 ) , overall survival time was significantly shorter in patients with mural invasion alone or extramural invasion ( both p < 0.001 ) than in those without invasion , and this persisted after adjustment for other prognostic variables . Equivalent bivariate associations were found in stage D , but only the effect of extramural invasion persisted after adjustment . LIMITATIONS : Our findings arise from the experience of a single surgical group and may not be generalizable to other setting s. Only hematoxylin and eosin staining was used . CONCLUSIONS : The association between venous invasion and prognosis was stage specific . Both mural venous invasion alone and extramural venous invasion independently predicted overall survival in patients with stage C tumors , but not in patients with stages A , B , or D tumors . Although mural invasion alone was rare , the separate reporting of both mural and extramural invasion in patients with stage C tumor is informative and desirable We performed a long-term prospect i ve study on venous invasion of colorectal cancer . The degree of venous invasion was divided into four stages ( V0 through V3 ) . Venous invasion was classified into three types by location ( Vx , Vy , and Vz ) . Hepatic metastasis occurred in 27 % , 33 % , and 20 % of patients with V2 , V3 , and Vz tumors , respectively . Local recurrence occurred in 33 % and 15 % of the V3 and Vz groups , respectively . However , there were no significant differences among the groups in terms of the rate of pulmonary metastasis . The 6-year survival rate for Dukes ' stage B tumors was 94 % , 88 % , and 74 % in the V0 , V1 , and V2 groups , respectively . There was a significant difference in the survival rate between patients with V0 tumors and V2 and V3 tumors . However , no significant difference was noted in the location . In Dukes ' stage C tumors , on the other h and , the survival rate was 77 % , 56 % , and 44 % in the V1 , V2 , and V3 groups , respectively . Also , it was 85 % , 73 % , and 45 % in Vx , Vy , and Vz cases , respectively . Significant differences were noted between V1 and V3 ( or V2 ) , and between Vz and Vx ( or Vy ) . It appears that the degree and location of venous invasion influence not only hepatic metastasis , local recurrence , and survival rates but also have prognostic value Output:	In conclusion , despite the limited number of studies , there is a clear association with outcome in the presence of IMVI .
MS213824	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Aim To determine the effectiveness and cost-effectiveness of a mobile phone intervention to improve exercise capacity and physical activity behaviour in people with ischaemic heart disease ( IHD ) . Methods and results In this single-blind , parallel , two-arm , r and omized controlled trial adults ( n = 171 ) with IHD were r and omized to receive a mobile phone delivered intervention ( HEART ; n = 85 ) plus usual care , or usual care alone ( n = 86 ) . Adult participants aged 18 years or more , with a diagnosis of IHD , were clinical ly stable as out patients , able to perform exercise , able to underst and and write English , and had access to the Internet . The HEART ( Heart Exercise And Remote Technologies ) intervention involved a personalized , automated package of text messages and a secure website with video messages aim ed at increasing exercise behaviour , delivered over 24 weeks . All participants were able to access usual community-based cardiac rehabilitation , which involves encouragement of physical activity and an offer to join a local cardiac support club . All outcomes were assessed at baseline and 24 weeks and included peak oxygen uptake ( PVO2 ; primary outcome ) , self-reported physical activity , health-related quality of life , self-efficacy and motivation ( secondary outcomes ) . Results showed no differences in PVO2 between the two groups ( difference −0.21 ml kg−1 min−1 , 95 % CI : −1.1 , 0.7 ; p = 0.65 ) at 24 weeks . However significant treatment effects were observed for selected secondary outcomes , including leisure time physical activity ( difference 110.2 min/week , 95 % CI : −0.8 , 221.3 ; p = 0.05 ) and walking ( difference 151.4 min/week , 95 % CI : 27.6 , 275.2 ; p = 0.02 ) . There were also significant improvements in self-efficacy to be active ( difference 6.2 % , 95 % CI : 0.2 , 12.2 ; p = 0.04 ) and the general health domain of the SF36 ( difference 2.1 , 95 % CI : 0.1 , 4.1 ; p = 0.03 ) at 24 weeks . The HEART programme was considered likely to be cost-effective for leisure time activity and walking . Conclusions A mobile phone intervention was not effective at increasing exercise capacity over and above usual care . The intervention was effective and probably cost-effective for increasing physical activity and may have the potential to augment existing cardiac rehabilitation services Background : The CardioFit internet-based expert system was design ed to promote physical activity in patients with coronary heart disease ( CHD ) who were not participating in cardiac rehabilitation . Design : This r and omized controlled trial compared CardioFit to usual care to assess its effects on physical activity following hospitalization for acute coronary syndromes . Methods : A total of 223 participants were recruited at the University of Ottawa Heart Institute or London Health Sciences Centre and r and omly assigned to either CardioFit ( n = 115 ) or usual care ( n = 108 ) . The CardioFit group received a personally tailored physical-activity plan upon discharge from the hospital and access to a secure website for activity planning and tracking . They completed five online tutorials over a 6-month period and were in email contact with an exercise specialist . Usual care consisted of physical activity guidance from an attending cardiologist . Physical activity was measured by pedometer and self-reported over a 7-day period , 6 and 12 months after r and omization . Results : The CardioFit internet-based physical activity expert system significantly increased objective ly measured ( p = 0.023 ) and self-reported physical activity ( p = 0.047 ) compared to usual care . Emotional ( p = 0.038 ) and physical ( p = 0.031 ) dimensions of heart disease health-related quality of life were also higher with CardioFit compared to usual care . Conclusions : Patients with CHD using an internet-based activity prescription with online coaching were more physically active at follow up than those receiving usual care . Use of the CardioFit program could extend the reach of rehabilitation and secondary -prevention services OBJECTIVE To evaluate the effectiveness of a home-based cardiac rehabilitation ( CR ) program on post-coronary arteries bypass graft patients . METHODS This is a r and omized study conducted in King Fahd Armed Forces Hospital , Jeddah , Kingdom of Saudi Arabia between June 2008 and January 2010 . Forty-nine participants were r and omized to either a control group ( st and ard hospital treatment , n=21 ) or an intervention group ( home-based CR , n=28 ) . Data were collected before hospital discharge ( baseline test ) and repeated 6 months after hospital discharge ( follow-up test ) . RESULTS There were no significant differences between the groups in the body mass index , hemodynamics , serum fasting lipid profile , and Quality of Life question naire ( QoL ) ( p>0.05 ) , with differences in physical function and Hospital Anxiety and Depression Scales ( HADS ) ( p<0.05 ) at the baseline test . At the follow-up test , the intervention group showed greater improvement in health-related QoL and risk factors compared to the control group , with significant differences in fasting blood glucose , triglycerides , high density lipoprotein cholesterol , physical function , and both QoL and HADS question naires ( p<0.05 ) . The intervention group also demonstrated significant improvements in QoL , HADS , body mass index , heart rate , high density lipoprotein cholesterol and physical function ( p<0.05 ) , while significant differences were observed in the control group in heart rate , QoL and physical function ( p<0.05 ) . CONCLUSION The home-based CR program improves health-related QoL and risk factor profiles for patients following coronary arteries bypass graft to greater extent than the st and ard hospital care Background : The results of research into the outcomes of physical rehabilitation and its relationship with post-myocardial ischaemia survival and readmissions are inconclusive . Our primary aim was to evaluate the efficacy of a supervised exercise training programme in terms of decreasing hospital cardiac readmission in patients with myocardial ischaemia . Methods : We conducted a r and omised controlled trial including patients with myocardial ischaemia . Eligible patients were assigned to a control group receiving st and ard care or to an intervention group that took part in a supervised exercise training programme . The follow-up period was 12 months after hospital discharge . Results : Of 478 patients assessed for eligibility , 86 were r and omised to the control group ( n = 44 ) or the intervention group ( n = 42 ) . Cardiac readmission rates were 14 % versus 5 % ( p = 0.268 ) in the control and intervention groups , respectively , and all-cause readmission rates were 23 % versus 15 % ( p = 0.34 ) . There were no deaths in either group . More control patients were treated in the emergency services ( 50 % vs. 24 % ; p = 0.015 ) . In terms of health-related quality of life , patients in the intervention group presented with significant increases in functional capacity and mobility . More intervention patients returned to work ( 77.3 % vs. 36.0 % ; p = 0.005 ) . Conclusions : The supervised physical exercise programme was effective at reducing the number of emergency room visits and at increasing the percentage of patients who returned to work . It also improved patients ’ exercise capacity and increased their health-related quality of life . Although the results were promising , the programme was not associated with a significant reduction in cardiac and all-cause readmission rates The Women ’s Lifestyle Heart Trial was a small ( N=28 ) r and omized controlled trial to evaluate the effects of a comprehensive lifestyle self-management program ( very low-fat vegetarian diet , stress-management training , exercise , group support , and smoking cessation ) on reduction of cardiovascular risk factors in postmenopausal women with coronary heart disease ( CHD ) . Women assigned to the treatment condition ( Prime Time ) participated in a week-long retreat followed by twice-weekly 4-hour meetings . Endpoints were program adherence ; changes in lipid profiles , body mass , blood pressure , hypolipidemic and antihypertensive medications ; and quality of life . Risk factor and psychosocial evaluations were conducted at baseline and at 4 , 12 , and 24 months . Repeated measures analyses of covariance revealed that the dietary , stress management , and physical activity changes made by intervention women were dramatic and lasting . There were significantly greater improvements in the Prime Time condition compared to the usual care control group on body mass , angina symptoms , and quality of life , and a tendency for a greater reduction in blood pressure-lowering medications . Similar patterns were seen in lipids , blood pressure , and lipid-lowering medications , but did not reach significance . These results demonstrate that postmenopausal CHD women can make lasting lifestyle changes , and that these changes may reduce the need for cardiac medications and improve CHD risk factors and quality of life Drug therapy for hypercholesterolaemia has remained controversial mainly because of insufficient clinical trial evidence for improved survival . The present trial was design ed to evaluate the effect of cholesterol lowering with simvastatin on mortality and morbidity in patients with coronary heart disease ( CHD ) . 4444 patients with angina pectoris or previous myocardial infa rct ion and serum cholesterol 5.5 - 8.0 mmol/L on a lipid-lowering diet were r and omised to double-blind treatment with simvastatin or placebo . Over the 5.4 years median follow-up period , simvastatin produced mean changes in total cholesterol , low-density-lipoprotein cholesterol , and high-density-lipoprotein cholesterol of -25 % , -35 % , and + 8 % , respectively , with few adverse effects . 256 patients ( 12 % ) in the placebo group died , compared with 182 ( 8 % ) in the simvastatin group . The relative risk of death in the simvastatin group was 0.70 ( 95 % CI 0.58 - 0.85 , p = 0.0003 ) . The 6-year probabilities of survival in the placebo and simvastatin groups were 87.6 % and 91.3 % , respectively . There were 189 coronary deaths in the placebo group and 111 in the simvastatin group ( relative risk 0.58 , 95 % CI 0.46 - 0.73 ) , while noncardiovascular causes accounted for 49 and 46 deaths , respectively . 622 patients ( 28 % ) in the placebo group and 431 ( 19 % ) in the simvastatin group had one or more major coronary events . The relative risk was 0.66 ( 95 % CI 0.59 - 0.75 , p < 0.00001 ) , and the respective probabilities of escaping such events were 70.5 % and 79.6 % . This risk was also significantly reduced in subgroups consisting of women and patients of both sexes aged 60 or more . Other benefits of treatment included a 37 % reduction ( p < 0.00001 ) in the risk of undergoing myocardial revascularisation procedures . This study shows that long-term treatment with simvastatin is safe and improves survival in CHD patients Background It is widely believed that cardiac rehabilitation following acute myocardial infa rct ion ( MI ) reduces mortality by approximately 20 % . This belief is based on systematic review s and meta-analyses of mostly small trials undertaken many years ago . Clinical management has been transformed in the past 30–40 years and the findings of historical trials may have little relevance now . Objectives The principal objective was to determine the effect of cardiac rehabilitation , as currently provided , on mortality , morbidity and health-related quality of life in patients following MI . The secondary objectives included seeking programmes that may be more effective and characteristics of patients who may benefit more . Design , setting , patients , outcome measures A multi-centre r and omised controlled trial in representative hospitals in Engl and and Wales compared 1813 patients referred to comprehensive cardiac rehabilitation programmes or discharged to ‘ usual care ’ ( without referral to rehabilitation ) . The primary outcome measure was all-cause mortality at 2 years . The secondary measures were morbidity , health service use , health-related quality of life , psychological general well-being and lifestyle cardiovascular risk factors at 1 year . Patient entry ran from 1997 to 2000 , follow-up of secondary outcomes to 2001 and of vital status to 2006 . A parallel study compared 331 patients in matched ‘ elective ’ rehabilitation and ‘ elective ’ usual care ( without rehabilitation ) hospitals . Results There were no significant differences between patients referred to rehabilitation and controls in mortality at 2 years ( RR 0.98 , 95 % CI 0.74 to 1.30 ) or after 7–9 years ( 0.99 , 95 % CI 0.85 to 1.15 ) , cardiac events , seven of eight domains of the health-related quality of life scale ( ‘ Short Form 36 ’ , SF36 ) or the psychological general well-being scale . Rehabilitation patients reported slightly less physical activity . No differences between groups were reported in perceived overall quality of cardiac aftercare . Data from the ‘ elective ’ hospitals comparison concurred with these findings . Conclusion In this trial , comprehensive rehabilitation following MI had no important effect on mortality , cardiac or psychological morbidity , risk factors , health-related quality of life or activity . This finding is consistent with systematic review s of all trials reported since 1983 . The value of cardiac rehabilitation as pract Output:	AND IMPLICATION S OF KEY FINDINGS Our analysis indicates conclusively that the current approach to exercise-based CR has no effect on all-cause mortality or cardiovascular mortality , when compared with a no-exercise control . There may be a small reduction in hospital admissions following exercise-based CR that is unlikely to be clinical ly important .
MS213825	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: BACKGROUND The aim of the present prospect i ve longitudinal study of periodontally diseased and periodontally healthy patients was a clinical , microbiological , and radiographic comparison of teeth and implants and an assessment of the implant success rate . METHODS Thirty-nine partially edentulous patients provided with a total of 150 implants were enrolled in the study . Oral rehabilitation was undertaken in 15 patients treated for generalized aggressive periodontitis ( GAgP ) , 12 patients treated for generalized chronic periodontitis ( GCP ) , and 12 periodontally healthy patients . The examinations of the teeth and implants were carried out within the framework of a 3-month recall schedule over a 3-year period . At each session , clinical parameters for probing depth ( PD ) , gingival recession ( GR ) , attachment level ( AL ) , gingival index ( GI ) , and plaque index ( PI ) were recorded , and the composition of the subgingival microflora determined by dark-field microscopy . In the periodontally diseased patients , Actinobacillus actinomycetemcomitans ( A.a . ) , Porphyromonas gingivalis ( P.g . ) , and Prevotella intermedia ( P.i . ) were detected at teeth and implants by DNA analysis in the first and third years after insertion of the superstructure . Intraoral radiographs of the teeth and implants were taken at baseline , immediately after insertion of the superstructure , and then 1 and 3 years later . RESULTS The GI and PI at implants and teeth remained below 0.25 and 0.6 , respectively , in all patient groups throughout the study period . At the implants and teeth , a slight increase in PD and a continuous attachment loss was recorded in the GAgP patients . The attachment loss was greater at the implants than at the teeth in all groups . The morphological distribution of the microorganisms revealed virtually healthy conditions in all groups . A.a . was detected in two GAgP patients , whereas P.g . and P.i . were found more frequently both in the GAgP and in the GCP patients . Radiographically detected bone loss was higher after 3 years at implants and teeth in the GAgP patients than in the other two groups . The implant success rates recorded were 100 % in the periodontally healthy and GCP patients , and 95.7 % in the maxilla and 100 % in the m and ible of the GAgP patients . CONCLUSIONS The results show that oral rehabilitation can be performed with implants in patients treated for generalized aggressive and chronic periodontitis . However , slight attachment loss and bone loss were registered at the implants and teeth in the patients with aggressive periodontitis OBJECTIVES To evaluate the long-term survival rates of dental implants according to the patient 's periodontal status , as well as to estimate if the effect of periodontal status regarding implant failure is constant throughout the long-term follow-up . MATERIAL S AND METHODS This was a historical prospect i ve cohort study design of all consecutive patients operated from 1996 to 2006 at a periodontal clinic . The cohort consisted of 736 patients , with a total of 2336 dental implants . An extended Cox proportional hazards model , which includes interaction terms between survival time and variables of interest , was used . RESULTS Patients ' mean ( SD ) age was 51.13 ( 12.35 ) . The follow-up time was up to 144 months , with a mean ( SD ) of 54.4 ( 35.6 ) months . The overall implant raw survival rate was 95.9 % . The Kaplan-Meier estimates for the cumulative survival rate ( CSR ) at 108 months were 0.96 and 0.95 for implants inserted into healthy and moderate chronic periodontal patients , respectively . The CSR declined to 0.88 at 108 months for the severe periodontitis group . The extended Cox model revealed that severe chronic status turned out to be a significant risk factor for implant failure after 50 months of follow-up [ hazard ratio (HR)=8.06 ; p<0.01 ] . The extended Cox model for smoking indicates a near-significant effect after 50 months ( HR=2.76 ; p=0.061 ) . CONCLUSIONS Periodontal status and smoking are significant risk factors for late implant failures . The HR for periodontal and smoking status are not constant throughout the follow-up period PURPOSE The purpose of this study was to analyze the current literature s and to assess outcomes of implant treatment in patients with generalized aggressive periodontitis . MATERIAL S AND METHODS Studies considered for inclusion were search ed in Pub-Med . The literature search for studies published in English between 2000 and 2012 was performed . Our findings included literature assessing implant treatment in patients with a history of generalized aggressive periodontitis ( GAP ) . All studies were screened according to inclusion criteria . The outcome measures were survival rate of superstructures , marginal bone loss around implant and survival rate of implants . All studies were divided into two follow-up period : short term study ( < 5 years ) and long term study ( ≥ 5 years ) . RESULTS Seven prospect i ve studies were selected , including four short-term and three long-term studies . The survival rates of the superstructures were generally high in patients with GAP , i.e. 95.9 - 100 % . Marginal bone loss around implant in patients with GAP as compared with implants in patients with chronic periodontitis or periodontally healthy patients was not significantly greater in short term studies but was significantly greater in long term studies . In short term studies , the survival rates of implants were between 97.4 % and 100 % in patients with GAP-associated tooth loss , except one study . The survival rates of implants were between 83.3 % and 96 % in patients with GAP in long term studies . CONCLUSION Implant treatment in patients with GAP is not contraindicated provided that adequate infection control and an individualized maintenance program are assured BACKGROUND The successful use of osseointegrated implants in periodontally healthy patients has been documented in numerous longitudinal studies in recent years . However , the extent to which these positive results apply to periodontally diseased patients remains unclear . The aim of the present prospect i ve longitudinal study of partially edentulous patients treated for generalized chronic periodontitis and generalized aggressive periodontitis was a clinical , microbiological , and radiographic comparison of teeth and implants and assessment of the implant success rate . METHODS Five partially edentulous patients treated for generalized aggressive periodontitis ( GAgP ) and 5 treated for generalized chronic periodontitis ( GCP ) were enrolled in this study . The GAgP patients received 36 implants , and the GCP patients 12 implants . The teeth were examined 2 to 4 weeks before extraction of the non-retainable teeth ( baseline ) , and 3 weeks after insertion of the final abutments ( second examination ) . All further examinations were performed during a 3-month recall schedule over a 5-year period for the GAgP patients and over a 3-year period for the GCP patients . At each session clinical parameters were recorded at teeth and implants and the composition of the subgingival microflora was determined by dark-field microscopy and DNA analysis . Intraoral radiographs of the teeth and implants were taken for control purpose s at baseline ; after insertion of the superstructure ; and 1 , 3 , and 5 years later . RESULTS The clinical findings indicated healthy periodontal and peri-implant conditions in both patient groups throughout the study . However , an increased probing depth and an attachment loss were recorded in the GAgP patients after the third year ( P<0.001 ) . The distribution of the microorganisms revealed no significant differences between the patient groups or between implants and teeth . Moderate bone loss at teeth and implants was registered in both groups . The success rates recorded were 100 % in the GCP patients and 88.8 % ( maxilla : 85.7 % ; m and ible : 93.3 % ) in the GAgP patients . CONCLUSIONS The 3-year and 5-year follow-ups show that osseointegrated implants may be successful in oral rehabilitation of partially edentulous patients treated for generalized aggressive periodontitis and generalized chronic periodontitis . However , as no significant differences were recorded between conditions at teeth and at implants , progression of the disease can not be ruled out BACKGROUND The aim of this prospect i ve 10-year study of partially edentulous subjects treated for generalized aggressive periodontitis and periodontally healthy subjects was a clinical , microbiologic , and radiographic comparison of teeth and implants and assessment of the implants ' success rate . METHODS Five subjects treated for generalized aggressive periodontitis ( GAgP ) and five periodontally healthy subjects who were orally rehabilitated with osseointegrated implants participated in the study . First , they were examined 2 to 4 weeks before extraction of the non-retainable teeth ( baseline ) and 3 weeks after insertion of the final abutments . All further examinations were performed during a 3-month recall schedule over a 10-year period . At every session , clinical parameters were recorded , and the composition of the subgingival microflora was determined . Radiographs were taken at baseline after insertion of the superstructure and 1 , 3 , 5 , 8 , and 10 years later . RESULTS Throughout the follow-up period , the peri-implant gingival index of GAgP subjects was significantly higher than in periodontally healthy subjects . There was no difference in plaque index between teeth and implants or between the two groups . The peri-implant probing depths were comparable in the two groups and remained < or = 4 mm throughout the follow-up . The probing depth was significantly higher around the teeth of the GAgP subjects compared to periodontally healthy subjects . Implants of GAgP subjects showed a significantly higher attachment loss ( Ø 2.4 mm ) . The attachment level at teeth and implants of the periodontally healthy subjects and at teeth of the GAgP subjects was almost unchanged . Microbiologically , GAgP subjects had fewer cocci and more motile rods and filaments at teeth and implants than periodontally healthy subjects . GAgP subjects showed significantly more peri-implant bone loss in the first year ( Ø 2.07 mm ) and in the subsequent 9 years ( total 1.3 mm ) . Bone loss at teeth also was significantly higher at baseline ( Ø 26.39 % ) and in the following years ( total 9.3 % ) . Implant survival rates were 100 % in periodontally healthy subjects versus 83.33 % in GAgP subjects . CONCLUSIONS This 10-year study showed that partially edentulous subjects treated for GAgP can be rehabilitated successfully with osseointegrated implants . However , the bone and attachment loss at the implants were higher than in periodontally healthy subjects This study evaluated the efficacy of implant supported dental restorations in patients with chronic periodontal diseases at various stages within 2 years of completing treatment . 30 patients with periodontal diseases and 30 patients without periodontal diseases were studied . Total counts of 276 implant bodies were divided into group A ( patients with periodontal diseases ; a total of 149 implants ) and group B ( patients with healthy periodontium ; a total of 127 implants ) . In group A subjects , periodontitis was treated prior to implant placement . The study focused on patients ' modified sulcus bleeding index , modified plaque index , implant mobility index , periodontal probing depth and implant success rate 12 and 24 months after the completion of the treatment . The result show : there were no significant differences in implant success rate between groups A and B ; modified sulcus bleeding index scores showed differences between the groups 24 months after treatment ; there were no significant differences in other clinical indexes during the study between the groups ; there were no significant differences in periodontal probing depth between the groups ; modified plaque index and modified sulcus bleeding index were positively correlated in implant supported dental restoration patients with chronic periodontal diseases Output:	Strong evidence suggests that periodontitis is a risk factor for implant loss ; moderate evidence revealed that periodontitis is a risk factor for peri-implantitis and that patients with periodontitis have higher implant-bone loss
MS213826	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Background Stepping impairments are associated with physical and cognitive decline in older adults and increased fall risk . Exercise interventions can reduce fall risk , but adherence is often low . A new exergame involving step training may provide an enjoyable exercise alternative for preventing falls in older people . Purpose To assess the feasibility and safety of unsupervised , home-based step pad training and determine the effectiveness of this intervention on stepping performance and associated fall risk in older people . Design Single-blinded two-arm r and omized controlled trial comparing step pad training with control ( no-intervention ) . Setting / Participants Thirty-seven older adults residing in independent-living units of a retirement village in Sydney , Australia . Intervention Intervention group ( IG ) participants were provided with a computerized step pad system connected to their TVs and played a step game as often as they liked ( with a recommended dose of 2–3 sessions per week for 15–20 minutes each ) for eight weeks . In addition , IG participants were asked to complete a choice stepping reaction time ( CSRT ) task once each week . Main Outcome Measures CSRT , the Physiological Profile Assessment ( PPA ) , neuropsychological and functional mobility measures were assessed at baseline and eight week follow-up . Results Thirty-two participants completed the study ( 86.5 % ) . IG participants played a median 2.75 sessions/week and no adverse events were reported . Compared to the control group , the IG significantly improved their CSRT ( F31,1 = 18.203 , p<.001 ) , PPA composite scores ( F31,1 = 12.706 , p = 0.001 ) , as well as the postural sway ( F31,1 = 4.226 , p = 0.049 ) and contrast sensitivity ( F31,1 = 4.415 , p = 0.044 ) PPA sub-component scores . In addition , the IG improved significantly in their dual-task ability as assessed by a timed up and go test/verbal fluency task ( F31,1 = 4.226 , p = 0.049 ) . Conclusions Step pad training can be safely undertaken at home to improve physical and cognitive parameters of fall risk in older people without major cognitive and physical impairments . Trial Registration Australian New Zeal and Clinical Trials Registry ACTRN12611001081909 Different types of exercise training have the potential to induce structural and functional brain plasticity in the elderly . Thereby , functional brain adaptations were observed during cognitive tasks in functional magnetic resonance imaging studies that correlated with improved cognitive performance . This study aim ed to investigate if exercise training induces functional brain plasticity during challenging treadmill walking and elicits associated changes in cognitive executive functions . Forty-two elderly participants were recruited and r and omly assigned to either interactive cognitive-motor video game dancing ( DANCE ) or balance and stretching training ( BALANCE ) . The 8-week intervention included three sessions of 30 min per week and was completed by 33 participants ( mean age 74.9 ± 6.9 years ) . Prefrontal cortex ( PFC ) activity during preferred and fast walking speed on a treadmill was assessed applying functional near infrared spectroscopy pre- and post-intervention . Additionally , executive functions comprising shifting , inhibition , and working memory were assessed . The results showed that both interventions significantly reduced left and right hemispheric PFC oxygenation during the acceleration of walking ( p < 0.05 or trend , r = 0.25–0.36 ) , while DANCE showed a larger reduction at the end of the 30-s walking task compared to BALANCE in the left PFC [ F(1 , 31 ) = 3.54 , p = 0.035 , r = 0.32 ] . These exercise training induced modulations in PFC oxygenation correlated with improved executive functions ( p < 0.05 or trend , r = 0.31–0.50 ) . The observed reductions in PFC activity may release cognitive re sources to focus attention on other processes while walking , which could be relevant to improve mobility and falls prevention in the elderly . This study provides a deeper underst and ing of the associations between exercise training , brain function during walking , and cognition in older adults Cognitive control is defined by a set of neural processes that allow us to interact with our complex environment in a goal -directed manner . Humans regularly challenge these control processes when attempting to simultaneously accomplish multiple goals ( multitasking ) , generating interference as the result of fundamental information processing limitations . It is clear that multitasking behaviour has become ubiquitous in today ’s technologically dense world , and substantial evidence has accrued regarding multitasking difficulties and cognitive control deficits in our ageing population . Here we show that multitasking performance , as assessed with a custom- design ed three-dimensional video game ( NeuroRacer ) , exhibits a linear age-related decline from 20 to 79 years of age . By playing an adaptive version of NeuroRacer in multitasking training mode , older adults ( 60 to 85 years old ) reduced multitasking costs compared to both an active control group and a no-contact control group , attaining levels beyond those achieved by untrained 20-year-old participants , with gains persisting for 6 months . Furthermore , age-related deficits in neural signatures of cognitive control , as measured with electroencephalography , were remediated by multitasking training ( enhanced midline frontal theta power and frontal – posterior theta coherence ) . Critically , this training result ed in performance benefits that extended to untrained cognitive control abilities ( enhanced sustained attention and working memory ) , with an increase in midline frontal theta power predicting the training-induced boost in sustained attention and preservation of multitasking improvement 6 months later . These findings highlight the robust plasticity of the prefrontal cognitive control system in the ageing brain , and provide the first evidence , to our knowledge , of how a custom- design ed video game can be used to assess cognitive abilities across the lifespan , evaluate underlying neural mechanisms , and serve as a powerful tool for cognitive enhancement Exergames are videogames that require gross motor activity , thereby combining gaming with physical activity . This study examined the role of competitive versus cooperative exergame play on short-term changes in executive function skills , following a 10-week exergame training intervention . Fifty-four low-income overweight and obese African American adolescents were r and omly assigned to a competitive exergame condition , a cooperative exergame condition , or a no-play control group . Youths in the competitive exergame condition improved in executive function skills more than did those in the cooperative exergame condition and the no-play control group . Weight loss during the intervention was also significantly positively correlated with improved executive function skills . The findings link competitive exergame play to beneficial cognitive outcomes for at-risk ethnic minority adolescents Aging is usually accompanied with deterioration of physical abilities , such as muscular strength , sensory sensitivity , and functional capacity . Recently , intervention methods with virtual reality have been introduced , providing an enjoyable therapy for elderly . The aim of this study was to investigate whether a 3-D virtual reality kayak program could improve the cognitive function , muscle strength , and balance of community-dwelling elderly . Importantly , kayaking involves most of the upper body musculature and needs the balance control . Seventy-two participants were r and omly allocated into the kayak program group ( n = 36 ) and the control group ( n = 36 ) . The two groups were well matched with respect to general characteristics at baseline . The participants in both groups performed a conventional exercise program for 30 min , and then the 3-D virtual reality kayak program was performed in the kayak program group for 20 min , two times a week for 6 weeks . Cognitive function was measured using the Montreal Cognitive Assessment . Muscle strength was measured using the arm curl and h and grip strength tests . St and ing and sitting balance was measured using the Good Balance system . The post-test was performed in the same manner as the pre-test ; the overall outcomes such as cognitive function ( p < 0.05 ) , muscle strength ( p < 0.05 ) , and balance ( st and ing and sitting balance , p < 0.05 ) were significantly improved in kayak program group compared to the control group . We propose that the 3-D virtual reality kayak program is a promising intervention method for improving the cognitive function , muscle strength , and balance of elderly Background Cognitive impairment is a health problem that concerns almost every second elderly person . Physical and cognitive training have differential positive effects on cognition , but have been rarely applied in combination . This study evaluates synergistic effects of multicomponent physical exercise complemented with novel simultaneous cognitive training on cognition in older adults . We hypothesized that simultaneous cognitive – physical components would add training specific cognitive benefits compared to exclusively physical training . Methods Seniors , older than 70 years , without cognitive impairment , were r and omly assigned to either : 1 ) virtual reality video game dancing ( DANCE ) , 2 ) treadmill walking with simultaneous verbal memory training ( MEMORY ) , or 3 ) treadmill walking ( PHYS ) . Each program was complemented with strength and balance exercises . Two 1-hour training sessions per week over 6 months were applied . Cognitive performance was assessed at baseline , after 3 and 6 months , and at 1-year follow-up . Multiple regression analyses with planned comparisons were calculated . Results Eighty-nine participants were r and omized to the three groups initially , 71 completed the training , while 47 were available at 1-year follow-up . Advantages of the simultaneous cognitive – physical programs were found in two dimensions of executive function . “ Shifting attention ” showed a time × intervention interaction in favor of DANCE/MEMORY versus PHYS ( F[2 , 68 ] = 1.95 , trend P=0.075 , r=0.17 ) ; and “ working memory ” showed a time × intervention interaction in favor of DANCE versus MEMORY ( F[1 , 136 ] = 2.71 , trend P=0.051 , R2=0.006 ) . Performance improvements in executive functions , long-term visual memory ( episodic memory ) , and processing speed were maintained at follow-up in all groups . Conclusion Particular executive functions benefit from simultaneous cognitive – physical training compared to exclusively physical multicomponent training . Cognitive – physical training programs may counteract widespread cognitive impairments in the elderly Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more The hippocampus shrinks in late adulthood , leading to impaired memory and increased risk for dementia . Hippocampal and medial temporal lobe volumes are larger in higher-fit adults , and physical activity training increases hippocampal perfusion , but the extent to which aerobic exercise training can modify hippocampal volume in late adulthood remains unknown . Here we show , in a r and omized controlled trial with 120 older adults , that aerobic exercise training increases the size of the anterior hippocampus , leading to improvements in spatial memory . Exercise training increased hippocampal volume by 2 % , effectively reversing age-related loss in volume by 1 to 2 y. We also demonstrate that increased hippocampal volume is associated with greater serum levels of BDNF , a mediator of neurogenesis in the dentate gyrus . Hippocampal volume declined in the control group , but higher preintervention fitness partially attenuated the decline , suggesting that fitness protects against volume loss . Cau date nucleus and thalamus volumes were unaffected by the intervention . These theoretically important findings indicate that aerobic exercise training is effective at reversing hippocampal volume loss in late adulthood , which is accompanied by improved memory function BACKGROUND Age-associated motor and cognitive deficits increase the risk of falls , a major cause of morbidity and mortality . Because of the significant ramifications of falls , many interventions have been proposed , but few have aim ed to prevent falls via an integrated approach targeting both motor and cognitive function . We aim ed to test the hypothesis that an intervention combining treadmill training with non-immersive virtual reality ( VR ) to target both cognitive aspects of safe ambulation and mobility would lead to fewer falls than would treadmill training alone . METHODS We carried out this r and omised controlled trial at five clinical centres across five countries ( Belgium , Israel , Italy , the Netherl and s , and the UK ) . Adults aged 60 - 90 years with a high risk of falls based on a history of two or more falls in the 6 months before the study and with varied motor and cognitive deficits were r and omly assigned by use of computer-based allocation to receive 6 weeks of either treadmill training plus VR or treadmill training alone . R and omisation was stratified by subgroups of patients ( those with a history of idiopathic falls , those with mild cognitive impairment , and those with Parkinson 's disease ) and sex , with stratification per clinical site . Group allocation was done by a third party not involved in onsite study procedures . Both groups aim ed to train three times per week for 6 weeks , with each session lasting about 45 min and structured training progression individualised to the participant 's level of performance . The VR system consisted of a motion-capture camera and a computer-generated simulation projected on to a large screen , which was specifically design ed to reduce fall risk in older adults by including real-life challenges such as obstacles , multiple pathways , and distracters that required continual adjustment of steps . The primary outcome was the incident rate of falls during the 6 months after the end of training , which was assessed in a modified intention-to-treat population . Safety was assessed in all patients who were assigned a treatment . This study is registered with Clinical Trials.gov , NCT01732653 . FINDINGS Between Jan 6 , 2013 , and April 3 , 2015 , 30 Output:	Exergames improved cognition in both clinical and non‐ clinical population s . Significant effects were found executive functions , attention and visuospatial skills . Significant effects still existed when excluding waitlist‐only controlled studies , and when comparing to physical activity interventions . Domain‐specific analyses found exergames improved executive functions , attentional processing and visuospatial skills . The findings present the first meta‐analytic evidence for effects of exergames on cognition .
MS213827	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Introduction To investigate the predictive value of clinical and biological markers for a pathological complete remission after a preoperative dose-dense regimen of doxorubicin and docetaxel , with or without tamoxifen , in primary operable breast cancer . Methods Patients with a histologically confirmed diagnosis of previously untreated , operable , and measurable primary breast cancer ( tumour ( T ) , nodes ( N ) and metastases ( M ) score : T2 - 3(≥ 3 cm ) N0 - 2 M0 ) were treated in a prospect ively r and omised trial with four cycles of dose-dense ( bi-weekly ) doxorubicin and docetaxel ( ddAT ) chemotherapy , with or without tamoxifen , prior to surgery . Clinical and pathological parameters ( menopausal status , clinical tumour size and nodal status , grade , and clinical response after two cycles ) and a panel of biomarkers ( oestrogen and progesterone receptors , Ki-67 , human epidermal growth factor receptor 2 ( HER2 ) , p53 , bcl-2 , all detected by immunohistochemistry ) were correlated with the detection of a pathological complete response ( pCR ) . Results A pCR was observed in 9.7 % in 248 patients r and omised in the study and in 8.6 % in the subset of 196 patients with available tumour tissue . Clinical ly negative axillary lymph nodes , poor tumour differentiation , negative oestrogen receptor status , negative progesterone receptor status , and loss of bcl-2 were significantly predictive for a pCR in a univariate logistic regression model , whereas in a multivariate analysis only the clinical nodal status and hormonal receptor status provided significantly independent information . Backward stepwise logistic regression revealed a response after two cycles , with hormone receptor status and lymph-node status as significant predictors . Patients with a low percentage of cells stained positive for Ki-67 showed a better response when treated with tamoxifen , whereas patients with a high percentage of Ki-67 positive cells did not have an additional benefit when treated with tamoxifen . Tumours overexpressing HER2 showed a similar response to that in HER2-negative patients when treated without tamoxifen , but when HER2-positive tumours were treated with tamoxifen , no pCR was observed . Conclusion Reliable prediction of a pathological complete response after preoperative chemotherapy is not possible with clinical and biological factors routinely determined before start of treatment . The response after two cycles of chemotherapy is a strong but dependent predictor . The only independent factor in this subset of patients was bcl-2.Trial registration Our aim was to determine whether biological molecular markers can predict response to neoadjuvant chemoendocrine therapy in patients with early breast cancer . Ninety patients ( median age 56 years ; range , 28 - 69 years ) with primary operable breast carcinoma were studied . They were treated with four 3-weekly cycles of chemotherapy with mitozantrone , methotrexate ( + /- mitomycin C ) , and tamoxifen prior to surgery . Fine-needle aspiration was used to obtain sample s from patients prior to therapy , and the following parameters were assessed : estrogen receptor ( ER ) , progesterone receptor ( PgR ) , p53 , Ki67 , Bcl-2 , and c-erbB-2 measured by immunocytochemistry , and ploidy and S-phase fraction ( SPF ) by flow cytometry . The tumors of 78 % of the subjects responded ( complete response , 9 % ; partial response , 69 % ) and 22 % did not ( no change , 20 % ; progressive disease , 2 % ) . Response rates according to disease stage and patient age were as follows : T1 , 74 % ; T2 , 79 % ; T3/T4 , 78 % ; age < /=50 years , 76 % ; > 50 , 79 % ( P = not significant ) . Response rates for other parameters were as follows : ER-positive , 82 % , and -negative , 70 % ; PgR-positive , 86 % , and -negative , 71 % ; p53-positive , 74 % , and -negative , 81 % ; Bcl-2-positive , 85 % , and -negative 61 % ; c-erbB-2-positive , 57 % , and -negative , 93 % ; Ki67 high , 77 % , and low , 81 % ; SPF high , 77 % , and low , 77 % ; aneuploid , 71 % ; and diploid , 85 % . Only the difference for c-erbB-2 was statistically significant ( P = 0.007 ) . A trend for higher response rates to neoadjuvant chemoendocrine therapy for tumors that were positive for ER , PgR , and Bcl-2 was observed but did not reach statistical significance . Tumors negative for c-erbB-2 had a higher response rate , which was statistically significant . In contrast , Ki67 , ploidy , SPF , and p53 failed to predict for response INTRODUCTION Response to neoadjuvant chemotherapy for locally advanced breast cancer can be correlated with long-term outcomes . Surrogate end-point biomarkers may be used to assess response to the treatment . Most reported studies assessed the effects of combination chemotherapy . We assessed the feasibility of obtaining serial core breast biopsies , and correlated rates of apoptosis , proliferation , and expression of related proteins at baseline , during , and after neoadjuvant single agent chemotherapy for locally advanced breast cancer with response . EXPERIMENTAL DESIGN Women with a histologically confirmed unresected T(3 ) or T(4 ) infiltrating carcinoma of the breast were eligible . The first 20 patients received three cycles of doxorubicin 90 mg/m(2 ) followed by three cycles of paclitaxel 250 mg/m(2 ) , or the reverse . Nine women received four cycles of each ( doxorubicin 60 mg/m(2 ) and paclitaxel 175 mg/m(2 ) ) . Cycles were administered 14 days apart with filgastrim . End points included : ( a ) . clinical and pathological response ; ( b ) . serial apoptotic [ terminal deoxynucleotidyl transferase (Tdt)-mediated nick end labeling ] and proliferation ( immunohistochemistry , IHC ) rates ; and ( c ) . expression ( IHC ) of estrogen receptor , HER2 , bcl2 , and p53 . RESULTS From April 1997 to June 2001 , 29 women were r and omized . Twelve patients ( 42 % ) had a clinical complete response ( cCR ) , and 16 ( 55 % ) had a clinical partial response . Five women ( 17 % ) had a pathological complete response , 7 ( 24 % ) had microscopic residual disease , and 17 ( 58 % ) had macroscopic residual disease . Higher baseline apoptosis and proliferation were associated with an improved pathological response ( P = 0.006 and 0.003 , respectively ) . Among 14 evaluable patients , apoptosis increased in women who had a cCR to the first agent but not in women without a cCR . Estrogen receptor-positive patients had a worse pathological response ( P = 0.004 ) . CONCLUSIONS The selected regimen is efficacious . It is feasible to obtain serial core biopsies that are informative for studies of apoptosis and IHC . This clinical design can serve as a model for combining st and ard chemotherapy and novel agents BACKGROUND Biological considerations support the use of primary chemotherapy in operable breast cancer ; and despite wide variations of used regimens , clinical studies consistently show a significant tumor response allowing breast conservation in many patients otherwise c and i date s for mastectomy . We investigated the efficacy and the acceptance of a combination chemotherapy with vinorelbine , 5-fluorouracil and high-dose folinic acid in operable breast cancer with favorable prognostic factors and tested the relationship of hormone receptor status , Ki67,p53 , c-erbB2 and bcl-2 with treatment response . PATIENTS AND METHODS Thirty-nine patients ( median age 51 years , range 36 - 71 years ) , eight with T1 , twenty-eight with T2 and two with T3 lesions , were treated with 5-fluorouracil ( 350 mg/m2 , i.v . on day 1 to 3 ) preceded by folinic acid ( 100 mg/m2 i.v . on day 1 to 3 ) and vinorelbine , given on days 1 and 3 at the dose of 20 mg/m2 ( FLN regimen ) . Therapy was administered on an outpatient basis every three weeks . Non responders had surgery after three courses , while complete or partial responders underwent surgery after six courses . All but one were evaluable for response and toxicity . RESULTS Objective responses were observed in 23 of the 38 evaluable patients ( 61 % ; 95 % CI : 46%-76 % ) : three complete responses ( 8 % ) and 20 partial responses ( 53 % ) . Fifteen patients ( 39 % ) had stable disease , of whom nine ( 23 % ) had minor response . None of the patients had disease progression during treatment . Objective responses were significantly associated with no expression of estrogen and /or progesterone receptors and > 50 % decrease in Ki67 after induction chemotherapy . Tolerance was excellent and none of the patients experienced grade 2 alopecia . CONCLUSIONS The ' moderate ' efficacy of this regimen might be partially due to the selection of patients with high expression of steroid hormone receptors and low proliferation rate , which have an unfavorable impact on response to this chemotherapy Aim : To evaluate the relationship between apoptosis induced by chemotherapy and clinical response in breast cancer . Methods : Apoptosis index ( AI ) , mutant p53 and Bcl‐2 protein expression were evaluated in 44 breast tumour sample s from patients su bmi tted to neoadjuvant chemotherapy . Objective response ( OR ) to primary chemotherapy was observed in 37 patients ( 84 % ) and no response ( NR ) in seven . AI was measured by the rate of apoptotic cells identified using morphological criteria . p53 and Bcl‐2 protein expression were evaluated using an immunoperoxidase staining technique . Results : The median AI change observed between pre‐chemotherapy AI and post‐chemotherapy AI was 0.84 in the OR group and 0.01 in the NR group , ( rho = 0.4 ; p = 0.006 ) . There was no change in Bcl‐2 protein expression following chemotherapy . In the OR group , p53 protein expression was positive in 41.6 % of patients before and in 22.2 % after chemotherapy ( difference = 16.6 % ; p = 0.03 ) . No change was detected in the NR group . Conclusion : A positive correlation was found between the increase in AI and clinical response to neoadjuvant chemotherapy in locally advanced breast cancer Abstract Purpose . Primary chemotherapy is commonly used in patients with breast cancer to downstage the primary tumour prior to surgery . There is a need to establish , prior to commencement of chemotherapy , predictors of clinical and pathological response , which may then be surrogate markers for patient survival and thus allow identification of patients who are most likely to benefit from such treatment . Patients and methods . A total of 104 patients with large and locally advanced breast cancers received an anthracycline/docetaxel-based regimen prior to surgery . Immunohistochemistry was carried out on pre-treatment core biopsies of the tumour to detect hormone receptors ( oestrogen-ER ; progesterone-PR ) , a proliferation marker ( MIB-1 ) , the oncoprotein Bcl-2 , an extracellular matrix degradation enzyme ( cathepsin D ) , p53 , and an oestrogen associated protein ( pS2 ) . Both clinical and pathological response were assessed following completion of chemotherapy . Results . Patients whose tumours did not express oestrogen receptor ( p= 0.02 ) or did not express Bcl-2 ( p < 0.01 ) had a better pathological response in a univariate analysis . However , in a multivariate model , it was only the absence of detectable Bcl-2 protein that predicted a better pathological response ( p= 0.001 ) . Conclusions . This study has identified that patients whose breast cancers are most likely to experience the greatest degree of tumour destruction by primary chemotherapy do not express either oestrogen receptors or Bcl-2 . This may have important implication s in the selection of patients with breast cancer for primary chemotherapy who are most likely to gain a survival benefit TP53 status [ mutations , immunostaining , and loss of heterozygosity ( LOH ) ] , expression of c-erbB-2 , bcl-2 , and histological grading were correlated to the response to doxorubicin monotherapy ( 14 mg/m2 ) administered weekly to 90 patients with locally advanced breast cancer . Mutations in the TP53 gene , in particular those affecting or disrupting the loop domains L2 or L3 of the p53 protein , were associated with lack of response to chemotherapy ( P = 0.063 for all mutations and P = 0.008 for mutations affecting L2/L3 , respectively ) . Similarly , expression of c-erbB-2 ( P = 0.041 ) , a high histological grade ( P = 0.023 ) , and lack of expression of bcl-2 ( P = 0.018 ) all predicted chemoresistance . No statistically significant association between either p53 immunostaining or TP53 LOH and response to therapy was recorded , Output:	Besides , negative Bcl-2 expression was significantly associated with good OR and pathological CR in anthracycline-based chemotherapy subgroup . Furthermore , there were significant links between negative Bcl-2 expression and taxane-based chemotherapy with pathological CR , but not OR . Conclusion The results of the present meta- analysis suggest that Bcl-2 expression is a predictive factor for chemotherapy sensitivity in breast cancer patients . They could also potentially benefit further clinical treatment for breast cancers
MS213828	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Objectives : The cytokine interleukin (IL)-1 mediates ischaemic brain damage in rodents . The endogenous , highly selective , IL-1 receptor antagonist ( IL-1ra ) protects against ischaemic cerebral injury in a range of experimental setting s , and IL-1ra causes a marked reduction of cell death when administered peripherally or at a delay in transient cerebral ischaemia . We report here the first r and omised , double blind , placebo controlled trial of recombinant human IL-1ra ( rhIL-1ra ) in patients with acute stroke . Methods : Patients within 6 hours of the onset of symptoms of acute stroke were r and omised to rhIL-1ra or matching placebo . Test treatment was administered intravenously by a 100 mg loading dose over 60 seconds , followed by a 2 mg/kg/h infusion over 72 h. Adverse events and serious adverse events were recorded for up to 3 months , serial blood sample s were collected for biological markers up to 3 months , and 5–7 day brain infa rct volume was measured by computed tomography . Results : No adverse events were attributed to study treatment among 34 patients r and omised . Markers of biological activity , including neutrophil and total white cell counts , C reactive protein , and IL-6 concentrations , were lower in rhIL-1ra treated patients . Among patients with cortical infa rcts , clinical outcomes at 3 months in the rhIL-1ra treated group were better than in placebo treated . Conclusions : These data suggest that rhIL-1ra is safe and well tolerated in acute stroke . In addition , rhIL-1ra exhibited biological activity that is relevant to the pathophysiology and clinical outcome of ischaemic stroke . Our findings identify rhIL-1ra as a potential new therapeutic agent for acute stroke Background and Purpose . Inflammation exists in inception , progression , and reperfusion of acute ischemic stroke . Insightful underst and ing of correlation in inflammatory mediators and stroke severity with intracranial artery stenosis may improve rational stroke therapy . Methods . We prospect ively recruited 977 patients with acute noncardioembolic ischemic stroke with MCA stenosis by MRA as none to mild ( < 50 % ) , moderate ( 50–69 % ) , severe ( 70–99 % ) , or occlusive ( 100 % ) . The peripheral levels of WBC , homocysteine ( HCY ) , and high sensitivity C-reactive protein ( hs-CRP ) were recorded . All patients were assessed of 1-year outcome by mRS as favorable ( 0–2 ) or poor ( 3–6 ) . Results . The levels of WBC , HCY , and hs-CRP had no significant differences in patients with categorized MCA stenosis ( all P > 0.05 ) . Higher levels of WBC , HCY , and hs-CRP were found in patients with 1-year poor outcome ( all P < 0.05 ) , but only hs-CRP is an independent predictor ( OR 1.06 , 95 % CI 1.027–1.093 , P = 0.0003 ) . The combination of any two of increased hs-CRP ( > 3 mg/L ) , WBC ( > 6.91 × 109/L ) , and HCY ( > 15 μmol/L ) had higher power in predicting 1-year poor outcome than the single elevated mediator . Conclusions . Elevated hs-CRP independently predicts 1-year poor outcome in acute stroke . The combination of increased hs-CRP , WBC , or HCY had a stronger predictive value in poor outcome than individual elevated mediator BACKGROUND Statins reportedly have anti-inflammatory effects aside from their cholesterol-lowering effect . We investigated the effects of statins on serum hs-CRP level and clinical outcome of acute ischemic stroke ( IS ) patients . METHODS This prospect i ve cohort study consequently evaluated patients with acute IS in a single medical center . Serum hs-CRP levels were measured at different time points ( within 48 h and 30 days post-stroke ) . The patients ' clinical and laboratory data on admission were analyzed . RESULTS Total 100 patients with acute IS were divided in the statin group ( n=50 ) and the non-statin group ( n=50 ) . Serum hs-CRP level was similar in the 2 groups within 48 h after acute IS , but was significantly lower in the statin group on Day 30 compared to the non-statin group ( p<0.05 ) . The statin group also had favorable 3-month outcome compared to the non-statin group ( p<0.05 ) . After adjustments for covariance using stepwise logistic regression , only NIHSS on admission ( OR=1.38 , 95 % CI=1.06 - 1.80 ; p=0.02 ) and hs-CRP in the acute phase ( OR=1.74 , 95 % CI=1.30 - 2.33 ; p=0.001 ) were significantly and independently predictive of 3-month outcome . CONCLUSION Statin therapy reduces serum hs-CRP level and may be associated with favorable 3-month outcome in patients after acute IS Background Inflammation is known to worsen cerebral damage at the acute phase of stroke . In this setting , cell adhesion molecules ( CAMs ) play a crucial role mediating migration of immune cells into the infa rct ed area . However , their value in long-term outcome prediction for patients with cerebrovascular diseases ( CVD ) is less described . Methods Levels of four CAMs ( E-selectin , P-selectin glycoprotein lig and -1 , intercellular adhesion molecule-1 , and vascular cell adhesion molecule-1 ( VCAM-1 ) ) and six other known biomarkers ( C-reactive protein ( CRP ) , interleukin-6 ( IL-6 ) , N-terminal pro-brain natriuretic peptide ( NT-proBNP ) , troponin I , vasopressin-neurophysin 2-copeptin , and S100 calcium-binding protein B ) were measured in a population of patients presenting CVD . Blood collection s for analysis were performed within different time windows after stroke onset : 0–6 h , 6–36 h , 2–3 days , 5–7 days , and 2–3 weeks . Independent associations with poor outcome at 3 months ( modified Rankin Scale score > 2 ) were sought using univariate and multivariate analysis after adjustments for age and National Institute of Health Stroke Scale score . Predictive ability of each biomarker has also been assessed with ROC analysis . Results One hundred patients were prospect ively included whom 75 presented with ischemic strokes , nine with hemorrhagic strokes and 16 with transient ischemic attacks . During the first 6 h after stroke onset , E-selectin was found to be an independent predictor of 3-month outcome ( odds ratio ( OR ) = 24 ; 95 % confidence interval ( 95 % CI ) , 2–354 ; p = 0.022 ) ( area under the curve ( AUC ) = 78 % ) , as was VCAM-1 during the third week after onset ( OR = 8 ; 95 % CI , 2–37 ; p = 0.01 ) ( AUC = 73 % ) . Associations remained after the exclusion of patients with hemorrhagic strokes and transient ischemic attacks . Independent associations with outcome were also found for CRP ( OR = 5 ; 95 % CI , 1–22 ; p = 0.023 ) and IL-6 ( OR = 5 ; 95 % CI , 1–17 ; p = 0.021 ) at 2–3 days and for NT-proBNP at 6–36 h ( OR = 20 ; 95 % CI , 1–337 ; p = 0.04 ) . Conclusions E-selectin and VCAM-1 were independent predictors of outcome in a population of patients with CVD . The predictive capability of other biomarkers known to be indicators for prognosis also emerged , confirming the study ’s robustness . CAMs levels could be considered as objective biological criteria for prognosis in CVD Background and Purpose — There is growing evidence of the prognostic importance of C-reactive protein ( CRP ) in ischemic stroke . However , the independent value of CRP at different stages after stroke has not been established . Therefore , we assessed the prognostic values of CRP in ischemic stroke . We also compared the relation of CRP at admission and discharge with 1-year outcome . Methods — One hundred ninety-three patients were included in a derivation set ( n=128 ) and a validation set ( n=65 ) . Serum CRP was measured , within 24 hours after index ischemic stroke , within 48 to 72 hours , and at hospital discharge . We examined the association between the level of CRP at different stages after stroke and outcome . We adjusted for the possible confounding effect using a multivariate Cox proportional hazard model . Results — A cutoff point of 1.5 mg/dL for CRP at discharge provided optimum sensitivity and specificity for adverse outcome , based on the receiver operator curves . CRP at admission ( hazard ratio [ HR ] 2.78 , 95 % CI 1.45 to 5.33;P = 0.0021 ) and discharge ( HR 9.42 , 95 % CI 4.27 to 19.05;P < 0.0001 ) were predictors of the combined end point of new vascular events or death at 1 year . CRP at hospital discharge was the strongest independent marker of adverse outcome ( HR 7.42 , 95 % CI 2.75 to 20.03;P = 0.0001 ) . These results were confirmed in the validation set ( HR 15.66 , 95 % CI 3.36 to 72.97;P = 0.0005 ) . Conclusions — CRP is a marker of increased 1-year risk in ischemic stroke . CRP at discharge is better related to later outcome and could be of greater utility for risk stratification . These findings are consistent with the hypothesis that elevated CRP may predict future cardiovascular events or death Background Cerebral ischaemia initiates an inflammatory response in the brain and periphery . We assessed the relationship between peak values of plasma interleukin-6 ( IL-6 ) in the first week after ischaemic stroke , with measures of stroke severity and outcome . Methods Thirty-seven patients with ischaemic stroke were prospect ively recruited . Plasma IL-6 , and other markers of peripheral inflammation , were measured at pre-determined timepoints in the first week after stroke onset . Primary analyses were the association between peak plasma IL-6 concentration with both modified Rankin score ( mRS ) at 3 months and computed tomography ( CT ) brain infa rct volume . Results Peak plasma IL-6 concentration correlated significantly ( p < 0.001 ) with CT brain infa rct volume ( r = 0.75 ) and mRS at 3 months ( r = 0.72 ) . It correlated similarly with clinical outcome at 12 months or stroke severity . Strong associations were also noted between either peak plasma C-reactive protein ( CRP ) concentration or white blood cell ( WBC ) count , and all outcome measures . Conclusions These data provide evidence that the magnitude of the peripheral inflammatory response is related to the severity of acute ischaemic stroke , and clinical outcome Inflammatory markers have been associated with functional outcome and mortality of stroke . We investigated the changes in procalcitonin ( PCT ) and high-sensitivity C-reactive protein ( Hs-CRP ) levels during the acute period of ischemic stroke and evaluated the relationship between these levels and the long-term functional outcome and mortality . We prospect ively studied 376 patients with acute ischemic stroke ( AIS ) who were admitted within 24 h after the onset of symptoms . PCT , Hs-CRP , and NIH Stroke Scale ( NIHSS ) were measured at the time of admission . Long-term functional outcome were measured by modified Rankin scale ( mRS ) at 1 year after admission . The correlations between the levels of PCT , Hs-CRP , and mortality at 1 year after stroke onset were analyzed . Patients with poor with functional outcome and non-survivors had significantly increased PCT and Hs-CRP levels on admission . Multivariate logistic regression analysis showed that PCT was an independent prognostic marker of 1-year functional outcome and death [ odds ratio ( OR ) 2.33 ( 95 % CI , 1.33–3.44 ) and 3.11 ( 2.02–4.43 ) , respectively , P < 0.0001 for both , adjusted for age , NIHSS , other predictors , and vascular risk factors ] in patients with AIS . The area under the receiver operating characteristic curve of PCT was 0.77 ( 95 % CI , 0.72–0.83 ) for functional outcome and 0.88 ( 95 % CI , 0.84–0.93 ) for mortality . PCT improved the area under the receiver operating characteristic curve of the NIHSS score for functional outcome from 0.74 ( 95 % CI , 0.66–0.81 ) to 0.85 ( 95 % CI , 0.76–0.92 ; P < 0.0001 ) and for mortality from 0.77 ( 95 % CI , 0.70–0.83 ) to Output:	Globally , we identified uncertainty with regard to the association of the evaluated biomarkers with stroke outcome , with little added value on top of clinical predictors such as age or stroke severity , which makes its implementation unlikely in clinical practice for global outcome prediction .
MS213829	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: OBJECTIVE The European Registry on Cushing 's syndrome ( ERCUSYN ) is design ed to collect prospect i ve and follow-up data at EU level on Cushing 's syndrome ( CS ) . DESIGN AND METHODS Baseline data on 481 CS patients ( 390 females , 91 males ; mean age ( ±s.d . ) : 44±14 years ) collected from 36 centres in 23 countries , including new patients from 2008 and retrospective cases since 2000 . Patients were divided into four major aetiologic groups : pituitary-dependent CS ( PIT-CS ) ( 66 % ) , adrenal-dependent CS ( ADR-CS ) ( 27 % ) , CS from an ectopic source ( ECT-CS ) ( 5 % ) and CS from other aetiologies ( 2 % ) . RESULTS Proportion of men in the ECT-CS group was higher than in the other groups ( P<0.05 ) . The ADR-CS group was older than the PIT-CS ( P<0.05 ) . Prevalence of hirsutism ( 92 % ) and diabetes ( 74 % ) in ECT-CS was higher than in the other groups ( P<0.05 and P<0.01 respectively ) . PIT-CS had more skin alterations , menstrual irregularities and hirsutism than ADR-CS ( P<0.01 ) . Reduced libido was more prevalent in men than women ( P<0.01 ) . Prevalence of spine osteoporosis was higher in men than women ( P<0.05 ) , and males had more vertebral and rib fractures than females ( 52 vs 18 % for vertebrae ; P<0.001 and 34 vs 23 % for ribs ; P<0.05 ) . ECT-CS consulted a diabetologist more frequently than ADR-CS ( P<0.05 ) , while a gynaecologist was consulted more often by women with PIT-CS or ADR-CS than with ECT-CS ( P<0.05 ) . Overall , weight gain was more common in women than men ( P<0.01 ) . CushingQoL and EuroQoL visual analogue scale scores did not differ between the groups . CONCLUSIONS The ERCUSYN project demonstrates a heterogeneous clinical presentation of CS at a European level , depending on gender and aetiology The aim of this study was to assess the effects of replacement with recombinant human growth hormone ( rhGH ) in patients with GH deficiency ( GHD ) after treatment of acromegaly . Intervention study . Sixteen patients ( 8 men , age 56 years ) , treated for acromegaly by surgery and radiotherapy , with an insufficient GH response to insulin-induced hypoglycaemia , were treated with 1 year of rhGH replacement . Study parameters were assessed at baseline and after 1 year of rhGH replacement . Study parameters were cardiac function , body composition , bone mineral density ( BMD ) , fasting lipids , glucose , bone turnover markers , and Quality of Life ( QoL ) . During rhGH replacement IGF-I concentrations increased from −0.4 ± 0.7 to 1.0 ± 1.5 SD ( P = 0.001 ) , with a mean daily dose of 0.2 ± 0.1 mg in men and 0.3 ± 0.2 mg in women . Nonetheless , rhGH replacement did not alter cardiac function , lipid and glucose concentrations , body composition or QoL. Bone turnover markers ( PINP and β crosslaps ) levels increased ( P = 0.005 and P = 0.021 , respectively ) , paralleled by a small , but significant decrease in BMD of the hip . The beneficial effects of rhGH replacement in patients with GHD during cure from acromegaly are limited in this study OBJECTIVE To develop and test the psychometric properties of a 25-item version of the National Eye Institute Visual Function Question naire ( NEI VFQ-25 ) . DESIGN Prospect i ve observational cohort study of persons with 1 of 5 chronic eye diseases or low vision who were scheduled for nonurgent visits in ophthalmology practice s and a reference sample of persons without eye disease . SETTING Eleven university-based ophthalmology practice s and the NEI Clinical Center . PATIENTS Eligible participants had to have 1 of the following eye conditions : age-related cataracts , age-related macular degeneration , diabetic retinopathy , primary open-angle glaucoma , cytomegalovirus retinitis , or low vision from any cause . Seven of the 12 sites also enrolled persons in a reference sample . Reference sample participants had no evidence of underlying eye disease but were scheduled for either screening eye examinations or correction of refractive error . All eligible persons had to be 21 years or older , English speaking , and cognitively able to give informed consent and participate in a health status interview . MEASUREMENTS AND MAIN RESULTS To provide the data needed to create the NEI VFQ-25 , all subjects completed an interview that included the 51-item NEI VFQ . Estimates of internal consistency indicate that the subscales of the NEI VFQ-25 are reliable . The validity of the NEI VFQ-25 is supported by high correlations between the short- and long-form versions of the measure , observed between-group differences in scores for persons with different eye diseases of varying severity , and the moderate-to-high correlations between the NEI VFQ-25 subscales that have the most to do with central vision and measured visual acuity . CONCLUSIONS The reliability and validity of the NEI VFQ-25 are comparable to those of the 51-item NEI VFQ field test version of the survey . This shorter version will be more feasible in setting s such as clinical trials where interview length is a critical consideration . In addition , preliminary analyses indicate that the psychometric properties of the NEI VFQ-25 are robust for the eye conditions studied ; this suggests that the measure will provide reproducible and valid data when used across multiple conditions of varying severity Objective To verify whether patients with pituitary disorders in remission and on appropriate treatment display significant differences in psychological distress compared to healthy controls and other patients treated for nonpituitary endocrine disorders OBJECTIVE Vali date the acromegaly quality of life ( AcroQoL ) question naire as a disease-generated question naire , which analyses physical and psychological domains , the latter subdivided into appearance and personal relationship sub-scales , to evaluate health-related quality of life ( HRQoL ) in acromegaly . DESIGN Prospect i ve , observational multicenter study . METHODS One hundred and six patients with acromegaly , 42 with active disease studied basally and 6 months after treatment ( ' sensitivity to change ' group ) , and 64 with treated , stable disease , studied twice within 1 month ( ' reliability ' group ) were included . As controls , a reference Spanish population ( n=12,245 for the EuroQoL question naire ) and 157 obese patients ( body mass index>30 kg/m2 ) were studied basally . Socio-demographic data , clinical activity , co-morbidity , GH , IGF-I , and HRQoL ( overall perception of health state , EuroQoL and AcroQoL in the obese controls and acromegalic patients ) were evaluated . RESULTS Globally , AcroQoL scored worse in the ' sensitivity to change ' group than in the ' reliability ' group ( 56+/-20 vs 65+/-18 , P<0.05 ) , but did not discriminate between patients and obese controls . The psychological domain was worse in the ' sensitivity to change ' group than obese controls ( P<0.05 ) . Appearance was the most affected sub-scale in acromegaly and significantly worse than in obese controls . The sub-scale personal relationships of AcroQoL were less affected in the ' reliability ' group than in obese controls ( P<0.05 ) . Patients with acromegaly and obese controls showed more problems on the EuroQoL than general Spanish population . Significant correlations were observed globally and for each dimension between AcroQoL and the generic question naires . On re-testing , no change was observed in the ' reliability ' group in any question naire , demonstrating good test-re-test reliability . In the ' sensitivity to change ' group after 6 months of treatment , there was improvement in the generic question naires and in AcroQoL score ( P<0.01 ) . Internal consistency of AcroQoL was good ( Cronbach 's alpha>0.7 ) . No correlation between AcroQoL and GH or IGF-I was observed . CONCLUSION AcroQoL question naire is a valid tool for the assessment of HRQoL in clinical practice in patients with acromegaly CONTEXT Cotreatment of acromegaly with pegvisomant and a somatostatin analog ( SA ) has proven feasible . Previous studies in the field have focused on patients with an insufficient response to SA monotherapy in whom pegvisomant was added without changing the SA dose . OBJECTIVE The objective of the study was to study whether patients sufficiently controlled on SA monotherapy can be transferred to combination therapy with low-dose pegvisomant and a reduced SA dose . DESIGN Eighteen acromegalic patients well controlled on SA monotherapy , mean ± se aged 54 ± 3 yr , were r and omized in a parallel study over 24 wk to unchanged SA monotherapy or cotreatment with pegvisomant ( 15 - 30 mg twice a week ) and SA ( half the usual dosage ) . SETTING This was an investigator-initiated study in a single tertiary referral center . MAIN OUTCOME MEASURES Glucose tolerance , substrate metabolism , insulin sensitivity , body composition , and quality of life were measured . RESULTS Median pegvisomant dose was 52.5 mg/wk ( range 30 - 60 ) . IGF-I ( micrograms per liter ) was comparable both at baseline ( P = 0.88 ) and after 24 wk of treatment ( P = 0.48 ) . The change in IGF-I between baseline and wk 24 also did not differ between groups ( P = 0.15 ) . Apart from increased peak insulin levels during the oral glucose tolerance test in the cotreatment group , no substantial differences between the two groups were detected . Moderately elevated liver enzymes were found in 17 % of the patients on pegvisomant therapy . CONCLUSION Acromegalic patients well controlled on SA monotherapy can maintain safe IGF-I levels during 24 wk of cotreatment with low-dose pegvisomant and a 50 % reduced SA dose . This treatment modality , however , does not seem to provide significant benefits for the patients Background There is a paucity of research about health-related quality of life ( HRQL ) among adolescents , as studies have to a large extent focused on adults . The main aim was to provide information for future studies in this growing field by presenting normative data for the Short Form 36 ( SF-36 ) and the Hospital Anxiety and Depression Scale ( HADS ) for Swedish adolescents and young adults . Additionally , the influence of age and gender , as well as method of administration , was investigated . Methods A sample of 585 persons aged 13–23 was r and omly chosen from the general population , and stratified regarding age group ( young adolescents : 13–15 years ; older adolescents : 16–19 years , and young adults : 20–23 years ) and gender ( an equal amount of males and females ) . Within each stratum , the participants were r and omized according to two modes of administration , telephone interview and postal question naire , and asked to complete the SF-36 and the HADS . Descriptive statistics are presented by survey mode , gender , and age group . A gender comparison was made by independent t-test ; and one-way ANOVA was conducted to evaluate age differences . Results Effects of age and gender were found : males reported better health-related quality of life than females , and the young adolescents ( 13–15 years old ) reported better HRQL than the two older age groups . The older participants ( 16–23 years old ) reported higher scores when interviewed over the telephone than when they answered a postal question naire , a difference which was more marked among females . Interestingly , the 13–15-year-olds did not react to the mode of administration to the same extent . Conclusion The importance of taking age , gender , and method of administration into consideration , both when planning studies and when comparing results from different groups , studies , or over time , is stressed The purpose of the study was to evaluate changes in general self-efficacy , health related quality of life ( HRQoL ) , and stress among patients with neuroendocrine tumors ( NET ) following a multidisciplinary educational intervention . Forty-one patients were enrolled in this exploratory pilot study . A total of 37 patients completed the full 26-week intervention based on the principles of self-efficacy . General self-efficacy was measured by the General Self-Efficacy Scale , HRQoL was measured with the SF-36 , and stress was measured with the Impact of Event Scale . Mixed effect models were used to evaluate changes in general self-efficacy , mental and physical components of HRQoL , and stress adjusting for demographic and clinical variables . Results showed significant improvements in patients ' general self-efficacy ( β = 0.71 ; P < 0.05 ) , physical component scores of HRQoL ( β = 3.09 ; P < 0.01 ) , and stress ( β = −2.10 , P = 0.008 ) . Findings suggest that patients with NET have the capacity to improve their ability to cope with their disease , problem- Output:	QoL was found to be impaired in patients with active disease relative to controls , and generally improved during biochemical cure . Intervention studies ( predominantly evaluating medical interventions ) have been found to improve QoL. Conclusions The growing number of studies assessing QoL generally described the negative impact of pituitary adenomas . Surgical and pharmacological interventions improve but not normalize QoL. We postulate that there might be margin for further improvement of QoL , for instance by using psychosocial interventions , in addition to optimal medical treatment
MS213830	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Aims : To estimate the impact of school fruit tuck shops on children ’s consumption of fruit and sweet and savoury snacks . Design : Cluster r and omised effectiveness trial with school as the unit of r and omisation . Setting : 43 primary schools in deprived areas in south Wales and south-west Engl and with a range of school food policies . Intervention : Schools operated fruit tuck shops throughout one academic year . Control schools did not do so . Measures : Repeated cross-sections of children aged 9–11 years completed a computerised 24-hour recall question naire at baseline ( n = 1902 ) and at 1-year follow-up ( n = 1924 ) , when a brief question naire was also completed ( n = 1976 ) . Results : Approximately 70 000 fruits were sold in the 23 intervention schools over the year , equivalent to 0.06 fruits per student per day . Children in intervention schools were more likely to report eating fruit as a snack at school ‘ often ’ ( OR 1.49 , 95 % CI 1.15 to 1.95 ) . There were no significant differences in children ’s intake of fruit or other snacks . There was a significant interaction ( p<0.02 ) between the intervention group and school food policy : where students were only allowed to bring fruit to school , fruit consumption was 0.37 portions per day ( 0.11 to 0.64 ) higher in intervention schools , compared to 0.14 portions ( −0.30 to 0.58 ) where no food was allowed and −0.13 portions ( −0.33 to 0.07 ) where there were no restrictions . Conclusions : In isolation , fruit tuck shops were not effective in changing children ’s snacking behaviour in schools . However , the results suggest that fruit tuck shops had a greater impact when reinforced by school policies restricting the types of foods students were allowed to bring to school Study objective : To examine associations between food and nutrient intake , measured in childhood , and adult cancer in a cohort with over 60 years follow up . Design and setting : The study is based on the Boyd Orr cohort . Intake of fruit and vegetables , energy , vitamins C and E , carotene , and retinol was assessed from seven day household food inventories carried out during a study of family diet and health in 16 rural and urban areas of Engl and and Scotl and in 1937–39 . Participants : 4999 men and women , from largely working class background s , who had been children in the households participating in the pre-war survey . Analyses are based on 3878 traced subjects with full data on diet and social circumstances . Main results : Over the follow up period there were 483 incident malignant neoplasms . Increased childhood fruit intake was associated with reduced risk of incident cancer . In fully adjusted logistic regression models , odds ratios ( 95 % confidence intervals ) with increasing quartiles of fruit consumption were 1.0 ( reference ) , 0.66 ( 0.48 to 0.90 ) , 0.70 ( 0.51 to 0.97 ) , 0.62 ( 0.43 to 0.90 ) ; p value for linear trend=0.02 . The association was weaker for cancer mortality . There was no clear pattern of association between the other dietary factors and total cancer risk . Conclusions : Childhood fruit consumption may have a long term protective effect on cancer risk in adults . Further prospect i ve studies , with individual measures of diet are required to further eluci date these relations Abstract Objective : To assess if a school based intervention was effective in reducing risk factors for obesity . Design : Group r and omised controlled trial . Setting : 10 primary schools in Leeds . Participants : 634 children aged 7 - 11 years . Intervention : Teacher training , modification of school meals , and the development of school action plans targeting the curriculum , physical education , tuck shops , and playground activities . Main outcome measures : Body mass index , diet , physical activity , and psychological state . Results : Vegetable consumption by 24 hour recall was higher in children in the intervention group than the control group ( weighted mean difference 0.3 portions/day , 95 % confidence interval 0.2 to 0.4 ) , representing a difference equivalent to 50 % of baseline consumption . Fruit consumption was lower in obese children in the intervention group ( −1.0 , −1.8 to −0.2 ) than those in the control group . The three day diary showed higher consumption of high sugar foods ( 0.8 , 0.1 to 1.6 ) ) among overweight children in the intervention group than the control group . Sedentary behaviour was higher in overweight children in the intervention group ( 0.3 , 0.0 to 0.7 ) . Global self worth was higher in obese children in the intervention group ( 0.3 , 0.3 to 0.6 ) . There was no difference in body mass index , other psychological measures , or dieting behaviour between the groups . Focus groups indicated higher levels of self reported behaviour change , underst and ing , and knowledge among children who had received the intervention . Conclusion : Although it was successful in producing changes at school level , the programme had little effect on children 's behaviour other than a modest increase in consumption of vegetables . What is already known on this topic Obesity is increasing among school children and dem and s preventive strategies R and omised controlled trials of school based primary prevention programmes have all used a prescriptive approach What this study adds Behavioural changes were disappointing with this programme based on the health promoting schools philosophy , despite changes at school level The only positive outcome was a modest increase in vegetable consumption The discrepancy between changes achieved at the individual and school level raises issues regarding the problems inherent in such Reports of cluster r and omised trials require additional information to allow readers to interpret them accurately The effective reporting of r and omised controlled trials has received useful attention in recent years . Many journals now require that reports conform to the guidelines in the Consoli date d St and ards of Reporting Trials ( CONSORT ) statement , first published in 1996 and revised in 2001 . The statement includes a checklist of items that should be included in the trial report . These items are evidence based whenever possible and are regularly review ed . The statement also recommends including a flow diagram to show the flow of participants from group assignment through to the final analysis . The CONSORT statement focused on reporting parallel group r and omised trials in which individual participants are r and omly assigned to study groups . However , in some situations it is preferable to r and omly assign groups of individuals ( such as families or medical practice s ) rather than individuals . Reasons include the threat of contamination of some interventions ( such as dietary interventions ) if individual r and omisation is used . 5 Also , in certain setting s r and omisation by group may be the only feasible method of conducting a trial . Trials with this design are variously known as field trials , community based trials , place based trials , or ( as in this paper ) cluster r and omised trials . In an earlier discussion paper we considered the implication s of the CONSORT statement for the reporting of cluster r and omised trials . Here we present up date d guidance , based on the 2001 revision of the CONSORT statement OBJECTIVE To measure the effect of a school fruit and vegetable subscription on children 's intake of fruit and vegetables after 5 weeks of intervention . SETTING Seven primary schools in Denmark . DESIGN AND METHODS Intervention schools ( n=4 ) were offered a fruit and vegetable subscription comprising one piece per day . Control schools situated in another municipality were not offered the subscription . Intake of fruit and vegetables was measured at baseline and 5 weeks after the start of the subscription . Two methods were used for dietary assessment : a pre-coded 24-hour recall form including total food intake and a food-frequency question naire ( FFQ ) including only fruit and vegetables . SUBJECTS Children aged 6 - 10 years ( n=804 from intervention schools and n=689 from control schools ) . Response rate in the dietary assessment was 31 % . RESULTS At intervention schools 45 % of the children enrolled in the subscription . After 5 weeks of intervention , both subscribers and non-subscribers had increased their intake of fruit by 0.4 ( P=0.019 ) and 0.3 ( P=0.008 ) pieces per school day , respectively , but no change was observed in vegetable intake . Total intake increased only for non-subscribers by 0.4 piece/school day ( P=0.008 ) mainly due to the consistent increase in fruit intake . No change in intake was measured at control schools . Only the 24-hour recall question naire was sensitive enough to pick up the changes of the subscription , whereas the FFQ was not . CONCLUSION Five weeks with the subscription affected both subscribers and non-subscribers to increase intake of fruit . This may indicate that the subscription had an additional effect of stimulating parents of non-subscribers to supply their children with fruit . The results stress the importance of evaluating the effect of this type of programme , and the carefulness needed in design ing the evaluation study OBJECTIVE To assess the impact of a school-based nutrition education intervention aim ed at increasing the consumption of fruits and vegetables . DESIGN The intervention programme increased the provision of fruits and vegetables in schools and provided a range of point-of-purchase marketing material s , newsletters for children and parents , and teacher information . Curriculum material s at age 6 - 7 and 10 - 11 years were also developed and utilised . Evaluation was undertaken with groups of younger ( aged 6 - 7 years ) and older ( aged 10 - 11 years ) children . Methods included 3-day dietary records with interview and cognitive and attitudinal measures at baseline , with follow-up at 9 months , in intervention and control schools . SETTING The work was undertaken in primary schools in Dundee , Scotl and . SUBJECTS Subjects comprised 511 children in two intervention schools with a further 464 children from two schools acting as controls . RESULTS Children ( n=64 ) in the intervention schools had an average increase in fruit intake ( 133+/-1.9 to 183+/-17.0 g day(-1 ) ) that was significantly ( P<0.05 ) greater than the increase ( 100+/-11.7 to 107+/-14.2 g day(-1 ) ) estimated in children ( n=65 ) in control schools . No other changes in food or nutrient intake were detected . Increases in scores for variables relating to knowledge about fruits and vegetables and subjective norms were also greater in the intervention than in the control group , although taste preferences for fruits and vegetables were unchanged . CONCLUSIONS It is concluded that a whole school approach to increasing intakes of fruits and vegetables has a modest but significant effect on cognitive and attitudinal variables and on fruit intake BACKGROUND This study evaluated the effects of a school-based dietary intervention program to increase fruit and vegetable consumption among fourth- grade rs . METHODS Twenty-eight elementary schools were r and omized to an immediate intervention condition or to a delayed intervention control condition . Measures of diet and psychosocial variables were collected at base line and 1 and 2 years post-baseline . The intervention included classroom , parent , and cafeteria components . RESULTS Mean daily consumption of fruit and vegetables was higher for the intervention children compared with controls at Follow-up 1 ( X(t ) = 3.96 , X(c ) = 2.28 ) and at Follow-up 2 ( X(t ) = 3.20 , X(c ) = 2.21 ) . Macro- and micronutrient changes favoring the intervention children were also observed at both Follow-up 1 and Follow-up 2 . Mean daily consumption of fruit and vegetables was higher for intervention parents compared with controls at Follow-up 1 ( X(t ) = 4.23,X(c ) = 3.94 ) but not at Follow-up 2 . CONCLUSIONS Strong effects were found for the High 5 intervention on fruit and vegetable consumption , on macro- and micro-nutrients , and on psychosocial variables . Future work is needed to enhance the intervention effects on parents ' consumption and to test the effectiveness of the intervention when delivered by classroom teachers This study identified fruit , 100 % juice and vegetables ( FJV ) consumption changes by meal among fourth grade students participating in Squire 's Quest ! , a 10-session individually focused psychoeducational multimedia game with many meal/environment specific behavioral change techniques incorporated into the programming . Participants in 26 elementary schools were r and omly assigned to treatment or control groups . Four days of dietary intake were assessed before and after the intervention to determine FJV servings consumed by meal . Overall , students receiving the intervention consumed 1.0 serving FJV more per day compared with control condition students . Using mixed model analysis of covariance , significant increases were found for servings of fruit and 100 % fruit juice at snacks , and regular vegetables at lunch for intervention school children compared with children in control condition schools . These meals and snacks were targeted by the intervention activities and appear to represent eating occasions for which the children might have had more control . Interventions need to incorporate new procedures to more directly target intake at breakfast and dinner OBJECTIVE To measure the effects of two school-based interventions on children 's intake of fruit and vegetables ( F&V ) . DESIGN AND METHODS A total of six primary schools were r and omly assigned to ( 1 ) a free F&V distribution programme , or ( 2 ) a multicomponent programme , consisting of a classroom curriculum and parental involvement . The two interventions were evaluated on their effects and compared with six control schools in a pre-test-post-test design . Two methods were used for dietary assessment : a pre-structured food recall and a food-frequency question naire including only F&V. SUBJECTS A total of 939 parents of children aged 4 - 12 years filled out the question naire at both pre-test and post-test . The response rate was 54 % . RESULTS Multilevel analyses showed that both programmes Output:	Meta- analysis shows that computer-based interventions were effective in increasing FV consumption . Multicomponent interventions and free/subsidized FV interventions were not effective . Although these results are preliminary , computer-based interventions could be considered in schools , given that they are effective and cheaper than other alternatives
MS213831	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: We compared postoperative recovery after desflurane ( n = 25 ) versus sevoflurane ( n = 25 ) anesthesia in morbidly obese adults ( body mass index ≥35 ) who underwent gastrointestinal bypass surgery via an open laparotomy . After premedication with midazolam and metoclopramide 1 h before surgery , epidural catheter placement , induction of anesthesia with fentanyl and propofol , and tracheal intubation facilitated with succinylcholine , anesthesia was maintained with age-adjusted 1 minimum alveolar concentration ( MAC ) desflurane or sevoflurane . Fentanyl IV , morphine or local anesthetics epidurally , and vasoactive drugs as needed were used to maintain arterial blood pressure at ±20 % of baseline value and to keep bispectral index of the electroencephalogram values between 40 to 60 U. Although patients were anesthetized with desflurane for a longer time ( 261 ± 50 min versus 234 ± 37 min , mean ± sd ; P < 0.05 , desflurane versus sevoflurane , respectively ) and for more MAC-hours ( 4.2 ± 0.9 h versus 3.7 ± 0.8 h ; P < 0.05 ) , significantly earlier recovery of response to comm and and tracheal extubation occurred in patients given desflurane than in patients given sevoflurane . The modified Aldrete score was greater in desflurane-anesthetized patients on admission to the postanesthesia care unit ( PACU ) ( P = 0.01 ) but not at discharge ( P = 0.47 ) . On admission to PACU , patients given desflurane had higher oxygen saturations ( 97.0 % ± 2.4 % ) than patients given sevoflurane ( 94.8 % ± 4.4 % , P = 0.035 ) . Overall , the incidence of postoperative nausea and vomiting and the use of antiemetics did not differ between the two anesthetic groups . We conclude that morbidly obese adult patients who underwent major abdominal surgery in a prospect i ve , r and omized study awoke significantly faster after desflurane than after sevoflurane anesthesia and the patients anesthetized with desflurane had higher oxygen saturation on entry to the PACU Background Previous studies have noted a high incidence of adverse outcomes in the postanesthesia care unit ( PACU ) , but few have examined associated factors and patient outcomes . To determine the frequency of acute , unanticipated respiratory problems and to examine the associated patient , surgical , and anesthetic factors , we prospect ively collected preoperative , intraoperative , and postoperative data on 24,157 consecutive PACU patients who received a general anesthetic during a 33-month period . Methods A PACU critical respiratory event ( CRE ) , was defined as any unanticipated hypoxemia ( hemoglobin oxygen saturation < 90 % ) , hypoventilation ( respiratory rate < 8 breaths/min or arterial carbon dioxide tension > 50 mmHg ) or upper-airway obstruction ( stridor or laryngospasm ) requiring an active and specific intervention ( ventilation , tracheal intubation , opioid or muscle relaxant antagonism , insertion of oral/nasal airway or airway manipulation ) . These problems were documented by PACU nurses whereas data on case-mix , surgical factors , and intraoperative management were retrieved from the anesthetic record . Significant patient , surgical , and anesthetic factors were identified by logistic regression analysis . Other morbidity experienced by patients with a CRE was also noted . Results For patients given general anesthesia the risk of a CRE was 1.3 % ( hypoxemia 0.9 % , hypoventilation 0.2 % , airway obstruction 0.2 % ) . Preoperative factors that increase risk were age > 60 yr , male gender , diabetes , and obesity ( P < 0.05 ) . Patients who underwent operative procedures on an emergency basis and whose operation was longer than 4 h were also at increased risk , but those undergoing perineal procedures were at lower risk ( P < 0.05 ) . Anesthetic risk factors ( P < 0.05 ) included opioid premedication ( relative odds 1.8 ) , sedatives preoperatively ( 2.0 ) , fentanyl > 2.0 μg.kg–1.h–1 as the sole opioid ( 1.9 ) , fentanyl used in combination with morphine ( 1.6 ) and atracurium ≥ 0.25 mg.kg–1.h–1 ( 2.2 ) . Patients in whom anesthesia was induced with thiopental ( relative odds 2.5 ) , compared with those who received propofol for induction , were also at increased risk of a CRE . Patients with a CRE stayed longer in PACU , had higher rates of unanticipated admissions to the intensive care unit and were more likely to have PACU cardiac problems ( P < 0.01 ) . Conclusions A CRE is relatively rare . Multiple patient and surgical factors and specific aspects of anesthetic management are associated with the occurrence of a CRE in the PACU Background : The choice of anesthetic technique for general anesthesia in morbidly obese patients remains controversial . We aim ed to compare blood gases , recovery and hemodynamic parameters using TIVA and sevoflurane anesthesia in bariatric surgery . Methods : The study was performed with permission of the ethics committee . We studied 40 morbidly obese patients allocated to 2 groups . The total I.V. anesthesia ( TIVA ) group was named Group T , and the sevoflurane group was named Group S. In Group T , anesthesia induction was achieved with propofol . In Group S , anesthesia induction was achieved by sevoflurane with single breath technique , with maintenance provided with 1 - 2 % volume sevoflurane . Student t , Chi square and ANOVA tests were used for data analysis ; p-value < 0.05 was considered statistically significant . Results : There was no significant difference between the 2 groups in demographic data , blood gas values and recovery characteristic . Hemodynamic values were significantly lower in Group T than Group S , during and after the operative period . Conclusion : While sevoflurane induction and maintenance is a suitable anesthetic modality for obese patients , TIVA can be applied easily in those patients possessing no extra risk factors other than morbid obesity STUDY OBJECTIVE To determine if desflurane results in a faster emergence as measured by time to eye opening compared to sevoflurane in morbidly obese patients undergoing laparoscopic gastroplasty . STUDY DESIGN Prospect i ve , r and omized , double-blinded study . SETTING Tertiary care hospital . PATIENTS 70 patients with a body mass index of 35 or higher undergoing laparoscopic gastroplasty . INTERVENTIONS Patients were r and omized into two groups to receive either desflurane or sevoflurane for maintenance of general anesthesia . MEASUREMENTS Intraoperative measured variables included the time from when the inhalation agent was turned off ( no agent delivered ) to eye opening and the time from when the inhalation agent was turned off to extubation . Postanesthesia care unit (PACU)-measured variables on admission and at 15 minute intervals until discharge included oxygen saturation ( Spo2 ) , blood pressure , heart rate , pain and nausea Visual Analog Scale ( VAS ) scores , emesis , modified Aldrete score , and Mini-Mental Status ( MMS ) examination score . MAIN RESULTS No differences were noted in demographic data , total surgical operative time , times from turning inhalation agent off to eye opening and extubation , or average length of stay in PACU . No differences were noted with respect to pain VAS , treatment for pain , modified Aldrete scores , emesis , or treatment for postoperative nausea or emesis . Differences were noted in PACU nausea VAS at 15 minutes , PACU nausea VAS at discharge , and PACU-MMS score at 45 minutes ; however , multivariate analysis of variance revealed no differences between groups over the repeated PACU measured time periods in nausea VAS ( P=0.17 ) or in MMS ( P=0.34 ) . Higher heart rates in the desflurane group were observed during PACU admission ( 82.3+/-9.8 vs 74.4+/-13.4 bpm , P<0.01 ) and 15 minutes post PACU admission ( 79.4+/-12.1 vs 71.3+/-13.2 bpm , P=0.01 ) . CONCLUSIONS In morbidly obese patients undergoing laparoscopic gastroplasty , emergence , as measured by time to eye opening , did not differ between desflurane and sevoflurane , with similar recovery characteristics Context : Morbidly obese patients are prone for intraoperative hemodynamic disturbances and postoperative airway complications . Aim : Comparison of intraoperative hemodynamics and postoperative recovery characteristics of desflurane versus sevoflurane in morbidly obese patients undergoing laparoscopic bariatric surgery . Setting s and Design : R and omized controlled trial Material s and Methods : After institutional ethics committee approval and written informed consent , 40 morbidly obese patients ( BMI > 35 kg/m2 ) were r and omized to receive desflurane or sevoflurane as part of a st and ardized general anesthesia technique . Volatile anesthetic concentration was titrated to maintain electroencephalographic bispectral index score ( BIS ) in the range of 40 - 60 . Mean arterial pressure ( MAP ) and heart rate ( HR ) were recorded preoperatively , at induction and intubation , then at regular intervals . After extubation , early recovery was recorded by time to emergence and orientation to time and place . In post anesthesia care unit , intermediate recovery was assessed by modified Aldrete Score and Digit Symbol Substitution Test ( DSST ) . Results : Intraoperative MAP and HR did not differ between the two groups ( P > 0.05 ) . The time to response to painful stimuli , obeying verbal comm and s and spontaneous eye opening was shorter ( P = 0.001 ) and modified Aldrete Score was higher after desflurane anesthesia than after sevoflurane anesthesia ( P = 0.049 ) . DSST also returned towards normal faster after desflurane ( 28.50 ± 6.30 min vs. 35.0 ± 5.62 min , P = 0.03 ) . Conclusions : Both desflurane and sevoflurane produce similar hemodynamic changes but the immediate and intermediate recovery was significantly faster after desflurane thus contributing to fast tracking and early discharge of patients STUDY OBJECTIVE Morbid obesity is associated with significant comorbidities . Desflurane has a low fat-blood solubility coefficient and may be better suited in this population to achieve a rapid emergence ; however , sevoflurane has favorable cardiorespiratory properties that might also prove advantageous in the morbidly obese ( MO ) patient . This study used careful drug titration to determine if emergence differences between sevoflurane and desflurane could be minimized in MO patients . DESIGN A r and omized , prospect i ve blinded study to determine the emergence profiles of desflurane and sevoflurane in MO patients when anesthetic drug titration is used . SETTING Operating room of the VA Medical Center , Milwaukee , Wis. PATIENTS Forty American Society of Anesthesiologists II and III , MO patients ( body mass index > or = 35 kg/m2 ) , who were scheduled for elective surgery predicted to last for more than 2 hours , were studied . INTERVENTIONS Patients were induced with fentanyl , midazolam , and propofol and maintained with desflurane or sevoflurane , mixed in air and oxygen . Intraoperative bispectral index ( BIS ) was targeted to 45 to 50 and to 60 in the last 15 minutes of surgery . MEASUREMENTS Intraoperative anesthetic concentration , BIS , and hemodynamics were recorded . During emergence , time to follow comm and and extubation were noted , with assessment s of cognitive function via the Mini-Mental Status Test and psychomotor performance via the Digit Symbol Substitution Test . A blinded observer recorded key recovery events . MAIN RESULTS Demographic data ( age , 61 [ 36 - 83 ] years ; body mass index , 38 [ 35 - 47 ] kg/m2 ) , surgical procedures , length of anesthesia ( approximately 3.5 hours ) , adjuvant drugs , and intraoperative BIS , heart rate , and mean arterial pressure were not significantly different . Hemodynamics , time to follow comm and s and to extubation , and results of Digit Symbol Substitution Test and Mini-Mental Status Test did not differ between anesthetic groups during recovery . CONCLUSIONS There were no differences in emergence and recovery profiles in MO patients receiving desflurane or sevoflurane when anesthetic concentration was carefully titrated BACKGROUND : In this study , we evaluated the influence of propofol versus desflurane anesthesia in overweight patients on postoperative lung function and pulse oximetry values . METHODS : We prospect ively studied 134 patients with body mass indices of 25 to 35 kg/m2 undergoing minor peripheral surgery lasting Output:	Conclusion Postoperative recovery was significantly faster after desflurane than after sevoflurane , isoflurane , or propofol anesthesia in obese patients . No clinical ly relevant differences were observed regarding PACU discharge time , incidence of PONV , or postoperative pain scores . Conclusion La récupération postopératoire a été significativement plus rapide après desflurane qu’après une anesthésie par sévoflurane , isoflurane ou propofol chez des patients obèses . Aucune différence cliniquement pertinente n’a été observée concernant les délais de congé de la salle de réveil , l’incidence des nausées et vomissements postopératoires , ou des scores de douleur postopératoire .
MS213832	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: BACKGROUND AND OBJECTIVES High-dose transarterial technique results in highly effective axillary block . The multiple nerve stimulation technique ( MNS ) requires more time and experience . This prospect i ve study aim ed at comparing onset and success rate of multiple-injection axillary brachial plexus block using two methods of nerve location : transarterial or multiple nerve stimulation technique . METHODS Axillary block was initially induced with 800 mg lidocaine with epinephrine . The transarterial group received deeply injected 30 mL of 1.6 % lidocaine with epinephrine , and 20 mL superficially to the axillary artery . For the multiple nerve stimulation group , three terminal motor nerves were electrolocated and blocked with 20 mL , 20 mL and 10 mL. Blockade was considered effective when analgesia was present in all sensory nerves distal to the elbow . RESULTS Onset ( 8.8 + /- 2.3 min versus 10.2 + /- 2.4 min ; p-value = 0.010 ) was significantly shorter in the transarterial group . Complete sensory block of all four nerves ( median , ulnar , radial and musculocutaneus ) was achieved in 92.5 % versus 83.3 % for multiple nerve stimulation group and transarterial group , respectively , without significant difference ( p = 0.68 ) . Musculocutaneous nerve was significantly easier to be blocked with the aid of peripheral nerve stimulator ( p = 0.034 ) . CONCLUSIONS Both MNS technique for axillary block with nerve stimulator ( 3 injections ) and transarterial technique ( 2 injections ) promote similar results . Musculocutaneous nerve is more easily blocked with the aid of peripheral nerve stimulator . MNS technique has required less supplementary blocks and has delayed beginning of surgery Background and Objectives : A triple-injection technique ( injections at the median , musculocutaneous , and radial nerves ) for axillary block affords a high incidence of complete block ( all the nerves below the elbow ) . However , in certain surgeries , only 1 or 2 nerves are involved in the surgical field . The aim of this prospect i ve r and omized study was to test the effectiveness of surgical anesthesia of a " selective " approach in which only the nerves involved in surgery were electrically located and injected . Methods : Three types of surgery were selected . Type 1 included surgery on the fifth finger , type 2 included superficial surgery ( without bone involvement ) on the palm or on the dorsum of the h and , and type 3 included any surgery on the first 3 fingers . For each type , 138 patients were enrolled and divided into 2 groups : group SEL in which only the nerves involved in the surgical field ( 1 or 2 ) were located and injected and group TNS in which a st and ard triple-nerve stimulation technique was used . Results : A lower rate of surgical anesthesia ( 84 % vs 92 % ; P < 0.05 ) was recorded in group SEL considered as a whole : this was mainly due to the significant difference recorded in type 2 surgery ( 75 % vs 93 % ; P < 0.05 ) . More patients needed intravenous administration of fentanyl for tourniquet pain ( 18 % vs 8 % ; P < 0.005 ) and of midazolam for intraoperative anxiety ( 20 % vs 8 % ; P < 0.005 ) in group SEL considered as a whole . In type 1 , improved patient comfort at block performance ( P < 0.05 ) , a 7-min saving on total anesthetic time ( P < 0.001 ) , and a higher need for midazolam administration ( P < 0.05 ) were recorded in group SEL . In type 2 , a higher need for midazolam administration ( P < 0.05 ) was recorded in group SEL . In type 3 , no clinical ly significant differences between the groups were recorded . Conclusions : A st and ard triple-nerve stimulation technique seems to be preferable to the selective approach even when a limited number of nerves are involved in the surgical field The perivascular technique of axillary brachial plexus block results in incomplete block of radial and musculocutaneous nerves in 10 - 20 % of patients . With the transarterial technique and a large dose of mepivacaine , success rates of 99 % have been reported . We have compared the clinical efficacy of these techniques in 50 patients using 1 % mepivacaine 45 ml with adrenaline . If required , the block was supplemented with additional blocks of single nerves or i.v . alfentanil . Additionally , eight patients in each group were studied with computed tomography after contrast medium was added to 0.5 % bupivacaine 40 ml . There were no statistically significant differences in sensory or motor block between the groups at 20 min or in the plasma concentrations of mepivacaine measured 0 - 45 min after injection . In the CT scans , both proximal and distal spread of the contrast medium were more common after perivascular than after transarterial block . The distribution of the contrast medium was not related to the efficacy of the block Perivascular axillary blockade was performed on 90 patients with the aid of a catheter technique . The patients were r and omly allocated to receive either 40 , 50 or 60 ml of 1 % mepivacaine with adrenaline 1:200,000 . Blood concentrations of mepivacaine were measured up to 90 min after injection in seven , eight and ten of the patients from the three groups . Sensory and motor blockade was evaluated 20 , 30 and 40 min after injection . All groups showed the same temporal development of the blockade , i.e. improval of the blockade during the period from 20 to 40 min after injection , but no difference was found in the sensory or motor blockade between the three groups . However , a further analysis of the incomplete blockades showed a better quality of the sensory blockade in the groups given 50 and 60 ml than in the group given 40 ml . None of the 90 patients showed any signs of systemic toxic reactions . The mean peak values of blood concentrations were 0.5‐1.0 μg/ml higher in the groups A given 50 ml and 60 ml than in the group given 40 ml . On the basis of the present and two previous investigations on the dose response in perivascular axillary blockade , a dose of 50 ml 1 % mepivacaine with adrenaline or I r another equivalent drug with vasoconstrictor is recommended Endoscopic carpal tunnel release has the advantage over open release of reduced tissue trauma and postoperative morbidity . Limited open carpal tunnel release has also been shown to have comparable results , but is easier to perform and is safer . We have compared the results of both techniques in a prospect i ve , r and omised trial . Thirty patients with bilateral carpal tunnel syndrome had simultaneous bilateral release . The technique of release was r and omly allocated to either two-portal endoscopic release ( ECTR ) or limited open release using the Strickl and instrumentation ( LOCTR ) . The results showed that the outcome was similar at follow-up of one year using both techniques . However , the LOCTR group had significantly less tenderness of the scar at the second and fourth postoperative week ( p < 0.01 ) . There was also less thenar and hypothenar ( pillar ) pain after LOCTR . Subjective evaluation showed a preference for LOCTR OBJECTIVE To investigate the clinical effects and safety of the technique of axillary approach brachial plexus blocking by ultrasound-guided four points via one-puncture . METHODS Eighty patients scheduled for elective operation were r and omly divided into 2 equal groups to undergo axillary approach brachial plexus blocking by ultrasound-guided four points via one-puncture technique ( Group U ) or nerve stimulator-guided brachial plexus blocking ( Group N ) . The main branches of brachial plexus ( radial , median , ulnar , and musculocutaneous nerves ) were localized by ultrasound-guided or nerve stimulator-guided techniques . In Group U 8 ml of mixed anesthetic solution containing isovolumetric 0.75 % ropivacaine and 2 % lidocaine was injected into the 4 main branches of brachial plexus , with a total volume of 32 ml . The ultrasonic manifestations of the brachial plexus and its surrounding tissues were observed . The values of diameter and depth of the 4 nerves and the distance of the musculocutaneous nerve to the midpoint of axillary artery were measured . The manipulation time , onset time , maintaining time , efficacy of blocking , and incidence of complication were recorded . RESULTS The manipulation time of Group U was 5.2 + /- 2.1 min , significantly shorter than that of Group N ( 14.6 + /- 3.2 min , P = 0.000 ) , The onset times of the median , radial , and ulnar nerves of Group U were 3.3 + /- 1.9 min , 3.0 + /- 1.7 min , and 3.4 + /- 1.9 min respectively , all significantly shorter than those of Group N ( 4.6 + /- 2.0 min , 7.3 + /- 7.4 min , and 6.4 + /- 6.1 min respectively , P < 0.01 or P < 0.05 ) . The anesthetic success rate of Group U was 100 % , significantly higher than that of Group N ( 77.5 % , P = 0.005 ) . The rate of accidental puncture to blood vessel of Group U was 0 , significantly lower than that of Group N ( 40 % , P = 0.000 ) . CONCLUSION With significantly higher anesthetic success rate , shorter manipulation time and onset time , and lower complication rate , the technique of axillary approach brachial plexus blocking by ultrasound-guided four points via one-puncture is a safe and reliable blocking method in comparison with the nerve stimulator-guided method Perivascular axillary blockade was performed on 90 patients with the aid of a catheter technique . All blockades were performed by the same anaesthetist , who practised perivascular axillary blockade three or four times a day . The patients were r and omly allocated to three groups . The injected volume of local anaesthetic was constant in each group : 40 ml mepivacaine with adrenaline . The concentration and , consequently , the amount ( mg ) were variable factors : ½% ( 200 mg ) , 1 % ( 400 mg ) and 1½% ( 600 mg ) . Sensory and motor blockade were tested 30 min after each injection . All three groups showed a high incidence of analgesia ( 70%‐100 % ) in all cutaneous segments , and none of the blockades showed total failure of the sensory blockade . The lowest incidence of sensory blockade was found in the areas innervated by the axillary , the radial and the musculocutaneous nerves , but no difference was found between the groups . However , the motor blockade was found to improve with increasing concentration of local anaesthetic solution BACKGROUND Axillary plexus blocks are usually guided by ultrasound , but alternative methods may be used when ultrasound equipment is lacking . For a nonultrasound-guided axillary block , the need for three injections has been question ed . OBJECTIVES Could differences in block success between single , double and triple deposits methods be explained by differences in local anaesthetic distribution as observed by MRI ? DESIGN A blinded and r and omised controlled study . SETTING Conducted at Oslo University Hospital , Rikshospitalet , Norway from 2009 to 2011 . PATIENTS Forty-five ASA 1 to 2 patients scheduled for surgery were r and omised to three equally sized groups . All patients completed the study . INTERVENTIONS Patients in the single-deposit group had an injection through a catheter parallel to the median nerve . In the double-deposit group the patients received a transarterial block . In the triple-deposit group the injections of the two other groups were combined . Upon completion of local anaesthetic injection the patients were scanned by MRI , before clinical block assessment . The distribution of local anaesthetic was scored by its closeness to terminal nerves and cords of the brachial plexus , as seen by MRI . The clinical effect was scored by the degree of sensory block in terminal nerve innervation areas . MAIN OUTCOME MEASURES Sensory block effect and MRI distribution pattern . RESULTS The triple-deposit method had a higher success rate ( 100 % ) than the single-deposit method ( 67 % ) and the double-deposit method ( 67 % ) in blocking all cutaneous nerves distal to the elbow ( P = 0.04 ) . The patients in the triple-deposit group most often had the best MRI scores . For any nerve or cord , at least one of the single-deposit or double-deposit groups had a similarly high MRI score as the triple-deposit group . CONCLUSION Distal to the elbow , the triple-deposit method had the highest sensory block success rate . This could be explained to some extent by analysis of the magnetic resonance images . TRIAL REGISTRATION Clinical Trials.gov identifier : NCT01033006 This prospect i ve , r and omized , double-blind study was undertaken to evaluate the success rates of axillary brachial plexus block performed with the help of a peripheral nerve stimulator when either one , two or four of the major nerves of the brachial plexus were located . Seventy-five patients undergoing upper limb surgery were r and omly allocated to one of Output:	Subgroup analysis by method of nerve location showed that the effect size was greater when neurostimulation was used rather than the transarterial technique . Otherwise there were no statistically significant differences between groups in any of the three comparisons on secondary analgesia failure , complications and patient discomfort . AUTHORS ' CONCLUSIONS This review provides evidence that multiple-injection techniques using nerve stimulation for axillary plexus block produce more effective anaesthesia than either double or single-injection techniques . However , there was insufficient evidence to draw any definitive conclusions regarding differences in other outcomes , including safety
MS213833	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: We evaluated the effect of low-frequency rTMS on motor signs in Parkinson 's disease ( PD ) , under a double-blind placebo-controlled trial design . PD patients were r and omly assigned to received either real ( n = 9 ) or sham ( n = 9 ) rTMS for 10 days . Each session comprises two trains of 50 stimuli each delivered at 1 Hz and at 90 % of daily rest motor threshold using a large circular coil over the vertex . The effect of the stimulation , delivered during the ON-period , was evaluated during both ON and OFF periods . Tests were carried out before and after the stimulation period , and again 1 week after . The effect of the stimulation was evaluated through several gait variables ( cadence , step amplitude , velocity , the CV(stride-time ) , and the turn time ) , h and dexterity , and also the total and motor sections of the UPDRS . Only the total and motor section of the UPDRS and the turn time during gait were affected by the stimulation , the effect appearing during either ON or OFF evaluation , and most importantly , equally displayed in both real and sham group . The rest of the variables were not influenced . We conclude the protocol of stimulation used , different from most protocol s that apply larger amount of stimuli , but very similar to some previously reported to have excellent results , has no therapeutic value and should be ab and oned . This contrasts with the positive reported effects using higher frequency and focal coils . Our work also reinforces the need for sham stimulation when evaluating the therapeutic effect of rTMS OBJECTIVE Several studies have shown that repetitive transcranial magnetic stimulation ( rTMS ) over the dorsolateral prefrontal cortex ( DLPFC ) is effective in the treatment of depression in patients with Parkinson disease ( PD ) . However , since research into the effect of this type of rTMS regime on motor function is limited , we studied the effect of rTMS over the DLPFC on the motor functions in PD patients . METHODS Thirteen patients were r and omly assigned into 2 groups , one receiving real-rTMS ( 90 % of resting motor threshold , 10 Hz , 450 pulses-day for 10 consecutive days ) over the DLPFC contralateral to the more affected side , and the other group receiving sham-rTMS . Assessment included a clinical motor evaluation using part III of the Unified Parkinson 's Disease Rating Scale ( UPDRS ) , and several motor tasks . The UPDRS was applied before and after 10 days of rTMS . Finger tapping , reach movement , grip movement and gait were measured in each session before and after the rTMS over the 10 day period . RESULTS Statistical analysis ( ANOVA for repeated measures ; group * day * side * rTMS ) only showed a significant effect for finger tapping , reach movement and gait for the factor day . No significant change was reported for the UPDRS in any group . CONCLUSIONS Application of rTMS over the DLPFC as a 10 day course had no significant effect on motor functions and clinical motor status , and the improvement in performance of motor tasks can be attributed to the effects of practice . SIGNIFICANCE rTMS over the DLPFC did not lead to any motor improvement in PD patients Objective : To investigate the safety and efficacy of intermittent theta-burst stimulation ( iTBS ) in the treatment of motor symptoms in Parkinson disease ( PD ) . Background : Progression of PD is characterized by the emergence of motor deficits , which eventually respond less to dopaminergic therapy and pose a therapeutic challenge . Repetitive transcranial magnetic stimulation ( rTMS ) has shown promising results in improving gait , a major cause of disability , and may provide a therapeutic alternative . iTBS is a novel type of rTMS that may be more efficacious than conventional rTMS . Methods : In this r and omized , double-blind , sham-controlled study , we investigated safety and efficacy of iTBS of the motor and dorsolateral prefrontal cortices in 8 sessions over 2 weeks ( evidence Class I ) . Assessment of safety and clinical efficacy over a 1-month period included timed tests of gait and bradykinesia , Unified Parkinson 's Disease Rating Scale ( UPDRS ) , and additional clinical , neuropsychological , and neurophysiologic measures . Results : We investigated 26 patients with mild to moderate PD : 13 received iTBS and 13 sham stimulation . We found beneficial effects of iTBS on mood , but no improvement of gait , bradykinesia , UPDRS , and other measures . EEG/EMG monitoring recorded no pathologic increase of cortical excitability or epileptic activity . Few reported discomfort or pain and one experienced tinnitus during real stimulation . Conclusion : iTBS of the motor and prefrontal cortices appears safe and improves mood , but failed to improve motor performance and functional status in PD . Classification of evidence : This study provides Class I evidence that iTBS was not effective for gait , upper extremity bradykinesia , or other motor symptoms in PD Objective . To investigate the safety and efficacy of 50-Hz repetitive transcranial magnetic stimulation ( rTMS ) in the treatment of motor symptoms in Parkinson disease ( PD ) . Background . Progression of PD is characterized by the emergence of motor deficits that gradually respond less to dopaminergic therapy . rTMS has shown promising results in improving gait , a major cause of disability , and may provide a therapeutic alternative . Prior controlled studies suggest that an increase in stimulation frequency might enhance therapeutic efficacy . Methods . In this r and omized , double blind , sham-controlled study , the authors investigated the safety and efficacy of 50-Hz rTMS of the motor cortices in 8 sessions over 2 weeks . Assessment of safety and clinical efficacy over a 1-month period included timed tests of gait and bradykinesia , Unified Parkinson ’s Disease Rating Scale ( UPDRS ) , and additional clinical , neurophysiological , and neuropsychological parameters . In addition , the safety of 50-Hz rTMS was tested with electromyography-electroencephalogram ( EMG-EEG ) monitoring during and after stimulation . Results . The authors investigated 26 patients with mild to moderate PD : 13 received 50-Hz rTMS and 13 sham stimulation . The 50-Hz rTMS did not improve gait , bradykinesia , and global and motor UPDRS , but there appeared a short-lived “ on”-state improvement in activities of daily living ( UPDRS II ) . The 50-Hz rTMS lengthened the cortical silent period , but other neurophysiological and neuropsychological measures remained unchanged . EMG/EEG recorded no pathological increase of cortical excitability or epileptic activity . There were no adverse effects . Conclusion . It appears that 50-Hz rTMS of the motor cortices is safe , but it fails to improve motor performance and functional status in PD . Prolonged stimulation or other techniques with rTMS might be more efficacious but need to be established in future research Based on several open-label and case studies , repetitive transcranial magnetic stimulation ( rTMS ) seems to have an antidepressive effect on patients with Parkinson 's disease ( PD ) . However , this hypothesis requires further confirmation . We conducted a r and omized , double-blind placebo-controlled study to evaluate the effect of rTMS over the left dorsolateral prefrontal cortex ( DLPFC ) on depression and various motor and nonmotor features of PD . Twenty-two PD patients with mild or moderate depressive episodes were assigned into two groups , one receiving real-rTMS ( 90 % of resting motor threshold , 5 Hz , 600 pulses-a-day for 10 days ) over the left DLPFC , and another group receiving sham-rTMS . An investigator blinded to the treatment performed three video-taped examinations on each patient : before stimulation ( baseline ) , 1 day ( short term ) , and 30 days after treatment session ended ( long-term effect ) . Mini-Mental State Examination , Unified Parkinson 's Disease Rating Scale ( UPDRS ) , Hoehn-Yahr , Epworth Sleepiness , Visual Analog and Montgomery-Asberg Depression Rating Scales ( MADRS ) , Beck Depression Inventory ( BDI ) , and Trail making and Stroop tests were applied . In the actively treated group , not only depression rating scales showed significant improvement 30 days after treatment ended ( BDI by 44.4 % and MADRS by 26.1 % ) , but also the accuracy of Stroop test ( by 16 % ) . We could also demonstrate an insignificant improvement in UPDRS-III by 7.5 points ( 31.9 % , P = 0.06 ) . In the sham-treated group none of the examined tests and scales improved significantly after sham stimulation . Our study demonstrated the beneficial effect of the left DLPFC rTMS on depression in PD lasting at least 30 days after treatment . However , this result should be confirmed in patients with severe depression by further clinical trials The aim of the present study was to investigate the effects of one session of high-frequency repetitive transcranial magnetic stimulation ( rTMS ) applied over the left dorsal premotor cortex ( PMd ) and left dorsolateral prefrontal cortex ( DLPFC ) on choice reaction time in a noise-compatibility task , and cognitive functions in patients with Parkinson ’s disease ( PD ) . Clinical motor symptoms of PD were assessed as well . Ten patients with PD entered a r and omized , placebo-controlled study with a crossover design . Each patient received 10 Hz stimulation over the left PMd and DLPFC ( active stimulation sites ) and the occipital cortex ( OCC ; a control stimulation site ) in the OFF motor state , i.e. at least after 12 h of dopaminergic drugs withdrawal . Frameless stereotaxy was used to target the optimal position of the coil . For the evaluation of reaction time , we used a noise-compatibility paradigm . A short battery of neuropsychological tests was performed to evaluate executive functions , working memory , and psychomotor speed . Clinical assessment included a clinical motor evaluation using part III of the Unified Parkinson ’s Disease Rating Scale . Statistical analysis revealed no significant effect of rTMS applied over the left PMd and /or DLPFC in patients with PD in any of the measured parameters . In this study , we did not observe any effect of one session of high frequency rTMS applied over the left PMd and /or DLPFC on choice reaction time in a noise-compatibility task , cognitive functions , or motor features in patients with PD . rTMS applied over all three stimulated areas was well tolerated and safe in terms of the cognitive and motor effects Dysfunction of the basal ganglia-thalamocortical motor circuit is a fundamental model to account for motor symptoms in Parkinson 's disease ( PD ) . Using high-frequency repetitive transcranial magnetic stimulation ( rTMS ) over the supplementary motor area ( SMA ) , we investigated whether modulation of SMA excitability engenders therapeutic effects on motor symptoms in PD . In this double-blind placebo-controlled study , 99 patients were enrolled and assigned r and omly to SMA-stimulation and sham-stimulation groups . For SMA stimulation , 20 trains of 50 transcranial magnetic stimuli at 5 Hz were delivered at an intensity of 110 % active motor threshold for leg muscles in one session . The sham stimulation was 20 trains of electric stimuli given through electrodes fixed on the head to mimic the cutaneous sensation during rTMS . Each session of intervention was carried out once a week for the first 8 weeks . The SMA stimulation , in contrast to the sham stimulation , engendered significant improvements in total scores and motor scores of the Unified Parkinson 's Disease Rating Scale . Mean improvements in motor scores were 4.5 points in the SMA-stimulation group and -0.1 points in the sham-stimulation group . Results indicate that 5 Hz rTMS over SMA modestly improves motor symptoms in PD patients ; SMA is a potential stimulation site for PD treatment Dopamine is implicated in movement , learning , and motivation , and in illnesses such as Parkinson 's disease , schizophrenia , and drug addiction . Little is known about the control of dopamine release in humans , but research in experimental animals suggests that the prefrontal cortex plays an important role in regulating the release of dopamine in subcortical structures . Here we used [(11)C]raclopride and positron emission tomography to measure changes in extracellular dopamine concentration in vivo after repetitive transcranial magnetic stimulation ( rTMS ) of the dorsolateral prefrontal cortex in healthy human subjects . Repetitive TMS of the left dorsolateral prefrontal cortex caused a reduction in [(11)C]raclopride binding in the left dorsal cau date nucleus compared with rTMS of the left occipital cortex . There were no changes in binding in the putamen , nucleus accumbens , or right cau date . This shows that rTMS of the prefrontal cortex induces the release of endogenous dopamine in the ipsilateral cau date nucleus . This finding has implication s for the therapeutic and research use of rTMS in neurological and psychiatric disorders The neural mechanisms and circuitry involved in levodopa-induced dyskinesia are unclear . Using repetitive transcranial magnetic stimulation ( rTMS ) over the supplementary motor area ( SMA ) in a group of patients with advanced Parkinson disease , the authors investigated whether modulation of SMA excitability may result in a modification of a dyskinetic state induced by continuous apomorphine infusion . rTMS at 1 Hz was observed to markedly reduce drug-induced dyskinesias , whereas 5-Hz rTMS induced a slight but not significant increase The sequence effect ( SE ) Output:	Subgroup analyses suggest a more prominent effect for M1 stimulation . Meta-regression revealed that a greater number of total stimulation pulses were associated with more UPDRS III improvements over the long-term . The pooled evidence suggests that rTMS improves upper limb function in the short-term , walking performance and UPDRS III in the short- and long-terms in PD sufferers .
MS213834	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Background Breast cancer among women is a relatively common with a more favorable expected survival rates than other forms of cancers . This study aim ed to determine the improved quality of life for post-mastectomy women through peer education . Methods Using pre and post test follow up and control design approach , 99 women with stage I and II of breast cancer diagnosis were followed one year after modified radical mastectomy . To measure the quality of life an instrument design ed by the European organization for research and treatment of cancer , known as the Quality of Life Question ( QLQ-30 ) and it 's breast cancer supplementary measure ( QLQ-BR23 ) at three points in time ( before , immediately and two months after intervention ) for both groups were used . The participant selection was a convenient sampling method and women were r and omly assigned into two experimental and control groups . The experimental group was r and omly assigned to five groups and peer educators conducted weekly educational programs for one month . Tabulated data were analyzed using chi square , t test , and repeated measurement multivariate to compare the quality of life differences over time . Results For the experimental group , the results showed statistically significant improvement in all performance aspects of life quality and symptom reduction ( P < 0.001 ) , while the control group had no significant differences in all aspects of life quality . Conclusion The findings of this study suggest that peer led education is a useful intervention for post-mastectomy women to improves their quality of life OBJECTIVE The aim is to evaluate the effectiveness of a manualized 12-week supportive-expressive group therapy program among primary breast cancer patients treated in community setting s , to determine whether highly distressed patients were most likely to benefit and whether therapist 's training or experience was related to outcome . METHOD Three hundred and fifty-three women within one year of diagnosis with primary breast cancer were r and omly assigned to receive supportive-expressive group therapy or to an education control condition . Participants were recruited from two academic centers and nine oncology practice s , which were members of NCI 's Community Clinical Oncology Program ( CCOP ) and were followed over 2 years . RESULTS A 2x2x19 analysis of variance was conducted with main effects of treatment condition , cohort , and baseline distress and their interactions . There was no main effect for treatment condition after removing one subject with an extreme score . Highly distressed women did not derive a greater benefit from treatment . Therapist training and psychotherapy experience were not associated with a treatment effect . CONCLUSIONS This study provides no evidence of reduction in distress as the result of a brief supportive-expressive intervention for women with primary breast cancer . Future studies might productively focus on women with higher initial levels of distress PURPOSE Evidence suggests that the re-entry phase ( ie , early period after medical treatment completion ) presents distinct challenges for cancer patients . To facilitate the transition to recovery , we conducted the Moving Beyond Cancer ( MBC ) trial , a multisite , r and omized , controlled trial of psychoeducational interventions for breast cancer patients . METHODS Breast cancer patients were registered within 6 weeks after surgery . After medical treatment , they completed baseline measures and were r and omly assigned to st and ard National Cancer Institute print material ( CTL ) ; st and ard print material and peer-modeling videotape ( VID ) ; or st and ard print material , videotape , two sessions with a trained cancer educator , and informational workbook ( EDU ) . Two primary end points were examined : energy/fatigue and cancer-specific distress . Secondary end points were depressive symptoms and post-traumatic growth . Perceived preparedness for re-entry was analyzed as a moderator of effects . RESULTS Of 558 women r and omly assigned to treatment , 418 completed the 6-month assessment and 399 completed the 12-month assessment . In analyses controlling for study site and baseline depressive symptoms , VID produced significant improvement in energy/fatigue at 6 months relative to CTL , particularly among women who felt less prepared for re-entry at baseline . No significant main effect of the interventions emerged on cancer-specific distress , but EDU prompted greater reduction in this outcome relative to CTL at 6 months for patients who felt more prepared for re-entry . Between-group differences in the primary outcomes were not significant at 12 months , and no significant effects emerged on the secondary end points . CONCLUSION A peer-modeling videotape can accelerate the recovery of energy during the re-entry phase in women treated for breast cancer , particularly among those who feel less prepared for re-entry OBJECTIVES Considerable morbidity persists among survivors of breast cancer ( BC ) including high levels of psychological stress , anxiety , depression , fear of recurrence , and physical symptoms including pain , fatigue , and sleep disturbances , and impaired quality of life . Effective interventions are needed during this difficult transitional period . METHODS We conducted a r and omized controlled trial of 84 female BC survivors ( Stages 0-III ) recruited from the H. Lee Moffitt Cancer and Research Institute . All subjects were within 18 months of treatment completion with surgery and adjuvant radiation and /or chemotherapy . Subjects were r and omly assigned to a 6-week Mindfulness-Based Stress Reduction ( MBSR ) program design ed to self-regulate arousal to stressful circumstances or symptoms ( n=41 ) or to usual care ( n=43 ) . Outcome measures compared at 6 weeks by r and om assignment included vali date d measures of psychological status ( depression , anxiety , perceived stress , fear of recurrence , optimism , social support ) and psychological and physical subscales of quality of life ( SF-36 ) . RESULTS Compared with usual care , subjects assigned to MBSR(BC ) had significantly lower ( two-sided p<0.05 ) adjusted mean levels of depression ( 6.3 vs 9.6 ) , anxiety ( 28.3 vs 33.0 ) , and fear of recurrence ( 9.3 vs 11.6 ) at 6 weeks , along with higher energy ( 53.5 vs 49.2 ) , physical functioning ( 50.1 vs 47.0 ) , and physical role functioning ( 49.1 vs 42.8 ) . In stratified analyses , subjects more compliant with MBSR tended to experience greater improvements in measures of energy and physical functioning . CONCLUSIONS Among BC survivors within 18 months of treatment completion , a 6-week MBSR(BC ) program result ed in significant improvements in psychological status and quality of life compared with usual care PURPOSE / OBJECTIVES To find the most effective methods of providing social support for women diagnosed with breast cancer by testing the effectiveness of a telephone social support and education intervention to promote emotional and interpersonal adaptation to breast cancer . DESIGN Multisite , two-group experimental study with repeated measures . SETTING Arkansas and New Jersey . SAMPLE The Arkansas sample consisted of 106 women who entered the study two to four weeks postsurgery for nonmetastatic breast cancer and were r and omly assigned to an experimental or control group . The comparison group consisted of 91 women from New Jersey who had participated in a previously completed study that used the same interventions and found that telephone support result ed in more positive , statistically significant adaptation to the disease . METHODS The experimental group received 13 months of telephone social support and education . Both groups received educational material s via a mailed re source kit . The Profile of Mood States ; Visual Analogue Scale-Worry ; Relationship Change Scale ; University of California , Los Angeles , Loneliness Scale-Version 3 ; and the modified Symptom Distress Scale provided data regarding the variables of interest . Data analysis included descriptive statistics , t tests , and multivariate analysis of variance with repeated measures . MAIN RESEARCH VARIABLES Mood , worry , relationships with significant others , loneliness , and symptoms . FINDINGS Data analysis showed no significant differences between groups , and both improved on some of the outcomes . Significant time-by-location interaction effects were found when comparing the Arkansas and New Jersey sample s , thereby supporting the need to consider regional differences when developing interventions . CONCLUSIONS The mailed educational re source kit alone appeared to be as effective as the telephone social support provided by oncology nurses in conjunction with the mailed re source kit . IMPLICATION S FOR NURSING Mailed educational re source kits may be the most efficient and cost-effective way to provide educational support to newly diagnosed patients with breast cancer , but their effect may differ according to region Abstract Background : This study aims to evaluate the effects of Group Cognitive Behavioral Therapy ( GCBT ) in treating major depression in Chinese women with breast cancer . Methods : Sixty-two breast cancer patients diagnosed with major depression were r and omly assigned to GCBT group ( N = 31 ) or a waiting list control group provided with an educational booklet ( N = 31 ) . The primary outcome measure was the 17-Item Hamilton Depression Rating Scale ( 17-HAMD ) . The second outcome measures were Self-Rating Anxiety Scale , Functional Assessment of Cancer Therapy – Breast and Self-Esteem Scale ( SES ) . Assessment s were carried out at completion of the study and six-month afterwards . Results : Patients in the GCBT group had a significant reduction in the 17-HAMD mean score by 9 points ( p < 0.001 ) , more than any reduction among patients in the control group from baseline to the end of therapy and a significant 7 points ( p < 0.001 ) more reduction from baseline to six-month follow-up . GCBT also yielded significantly greater improvement than the control group with regard to quality of life ( QoL ; p < 0.01 ) and self-esteem ( p < 0.05 ) . No significant differences were found between groups on improving anxiety ( p > 0.05 ) . Conclusion : The results of this trial suggest that GCBT is effective for treating major depression , as well as for improving QoL and self-esteem in breast cancer patients . Trial Registration : Chictr.org Background Among underserved , largely minority women who were breast cancer survivors , this pilot project was design ed to evaluate the quality of life outcomes of a 20 week Contemplative Self-Healing Program . Methods Women previously treated for stage I-III breast cancer were assessed before and after the 20 week program with the FACT-G , FACT-B , FACIT-Spirituality , ECOG , and the Impact of Events Scale . They participated in a 20-week intervention involving guided meditation and cognitive-affective-behavioral learning . Results With an average age of 63 , 62 % of the participants were African-American or Latino . With an average of 5.4 years since the diagnosis of breast cancer , 72 % had an ECOG performance status of 1 . 57 % were currently working . Their baseline FACT-G was 80.5 ± 15.1 , and their baseline Impact of Events Scale was 26.3 ± 18.9 . The within-patient improvement on the FACT-G was 4.6 ± 10.9 ( p = .01 ) ; in parallel the FACT-B improved by 2.8 ± 12.8 points ( p = .03 ) . The Impact of Events Scale improved by 6.6 ± 15.5 points ( p = .01 ) . There was significant within-patient improvement on both the avoidance scale ( 3.8 ± 9.2 ) and on the intrusion scale ( 2.9 ± 7.9 ) . Patients who attended more sessions and conducted more home practice had greater improvements in quality of life . Conclusion Persons receiving a 20-session contemplative self healing intervention showed improved quality of life , with a clinical ly and statistically significant increase in the FACT-G. In addition , this population showed a significant reduction in post-traumatic stress symptoms assessed by the Impact of Events Scale . Trial registration Clinical Trials Gov NCT00278837 A prospect i ve study was conducted to measure anxiety and depression in Iranian breast cancer patients before and after diagnosis using the Hospital Anxiety and Depression Scale ( HADS ) . The HADS was administered at two points in time : before diagnosis and 3 months after . In all , 168 breast cancer patients were interviewed . While 48 % of patients had severe symptoms of anxiety at both baseline and follow-up , more than 60 % of patients had no symptoms of depressive illness at pre- and post-diagnosis assessment s. Comparing anxiety and depression before diagnosis and after 3 months , there were no significant differences between patients ' scores on anxiety ( P = 0.42 ) and depression ( P = 0.98 ) subscales . The results showed that patients with advanced disease and a lower performance status were more anxious and experienced more depression . The study findings suggest that severe symptoms of anxiety are the most frequent symptoms in Iranian breast cancer patients . It seems that during the process of diagnosis and 3 months after psychological morbidity persists in patients who suffer from breast cancer PURPOSE Chronic insomnia is highly prevalent in cancer patients . Cognitive-behavioral therapy ( CBT ) is considered the treatment of choice for chronic primary insomnia . However , no r and omized controlled study has been conducted on its efficacy for insomnia secondary to cancer . Using a r and omized controlled design , this study conducted among breast cancer survivors evaluated the effect of CBT on sleep , assessed both subjectively and objective ly , and on hypnotic medication use , psychological distress , and quality of life . PATIENTS AND METHODS Fifty-seven women with insomnia caused or aggravated by breast cancer were r and omly assigned to CBT ( n = 27 ) or a waiting-list control condition ( n = 30 ) . The treatment consisted of eight weekly sessions administered in a group and combined the use of stimulus control , sleep restriction , cognitive therapy , sleep hygiene , and fatigue management . Follow-up evaluations were carried out 3 , 6 , and 12 months after the treatment . RESULTS Participants who received the insomnia treatment had significantly better subjective sleep indices ( daily sleep diary , Insomnia Severity Index ) , a lower frequency of medicated nights , lower levels of depression and anx Output:	Clear evidence emerged for the efficacy of cognitive behavioral therapy in promoting improvements in anxiety , depression , and quality of life . CONCLUSION This is the first meta- analysis to demonstrate the efficacy of interventions on a range of psychosocial outcomes following breast cancer surgery . The meta- analysis highlighted that cognitive behavioral therapy was consistently the most effective psychosocial intervention promoting improvements in anxiety , depression , and quality of life .
MS213835	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: The purpose of this study was to develop a new two-regression model relating Actigraph activity counts to energy expenditure over a wide range of physical activities . Forty-eight participants [ age 35 yr ( 11.4 ) ] performed various activities chosen to represent sedentary , light , moderate , and vigorous intensities . Eighteen activities were split into three routines with each routine being performed by 20 individuals , for a total of 60 tests . Forty-five tests were r and omly selected for the development of the new equation , and 15 tests were used to cross-vali date the new equation and compare it against already existing equations . During each routine , the participant wore an Actigraph accelerometer on the hip , and oxygen consumption was simultaneously measured by a portable metabolic system . For each activity , the coefficient of variation ( CV ) for the counts per 10 s was calculated to determine whether the activity was walking/running or some other activity . If the CV was < or=10 , then a walk/run regression equation was used , whereas if the CV was > 10 , a lifestyle/leisure time physical activity regression was used . In the cross-validation group , the mean estimates using the new algorithm ( 2-regression model with an inactivity threshold ) were within 0.75 metabolic equivalents ( METs ) of measured METs for each of the activities performed ( P > or= 0.05 ) , which was a substantial improvement over the single-regression models . The new algorithm is more accurate for the prediction of energy expenditure than currently published regression equations using the Actigraph accelerometer BACKGROUND Risk stratification of patients with end-stage congestive heart failure is a critical component of the transplant c and i date selection process . Accurate identification of individuals most likely to survive without a transplant would facilitate more efficient use of scarce donor organs . METHODS AND RESULTS Multivariable proportional hazards survival models were developed with the use of data on 80 clinical characteristics from 268 ambulatory patients with advanced heart failure ( derivation sample ) . Invasive and noninvasive models ( with and without catheterization-derived data ) were constructed . A prognostic score was determined for each patient from each model . Stratum-specific likelihood ratios were used to develop three prognostic-score risk groups . The models were prospect ively vali date d on 199 similar patients ( validation sample ) by calculation of the area under the receiver operating characteristic curve for 1-year event-free survival , the censored c-index for event-free survival , and comparison of event-free survival curves for prognostic-score risk strata . Outcome events were defined as urgent transplant or death without transplant . The noninvasive model performed well in both sample s , and increased performance was not attained by the addition of catheterization-derived variables . Prognostic-score risk groups derived from the noninvasive model in the derivation sample effectively stratified the risk of an outcome event in both sample s ( 1-year event-free survival for derivation and validation sample s , respectively : low risk , 93 % and 88 % ; medium risk , 72 % and 60 % ; high risk , 43 % and 35 % ) . CONCLUSIONS Selection of c and i date s for cardiac transplantation may be improved by use of this noninvasive risk-stratification model PURPOSE The purpose of this study was to use an accelerometer to measure daily walking performance in patients with chronic heart failure ( CHF ) to investigate if this parameter is a determinant of New York Heart Association class and indicative of maximal and functional exercise capacity . METHODS Fifty patients with CHF were instructed to wear an accelerometer for 7 consecutive days while going about their daily business . Maximal and functional exercise capacity was assessed by cardiopulmonary ( VO(2peak ) ) and 6-minute walk testing , respectively . RESULTS Patients in New York Heart Association I , II , and III reached an average total walking time ( TWT ) of 160.6 + /- 35.8 minutes , 133.9 + /- 59.0 minutes , and 76.1 + /- 22.5 minutes per day of which 19 % , 19 % , and 9 % where spent in the fast walking mode ( > 83 m/minute ) , respectively . The TWT correlated strongly with VO(2peak ) ( r = 0.72 ; P < .001 ) and 6-minute walk testing distance ( r = 0.68 ; P < .001 ) . The TWT and time spent in fast walking mode were the strongest determinants in discriminating moderate CHF . CONCLUSION Daily walking performance is a clear determinant of maximal and functional exercise capacities in patients with CHF . Walking intensity in particular is an independent predictor in discriminating patients with advanced heart failure . Monitoring of daily walking performance might aid in detecting disease progression and improve clinical outcome Background Physical activity has not been objective ly measured in prospect i ve cohorts with sufficiently large numbers to reliably detect associations with multiple health outcomes . Technological advances now make this possible . We describe the methods used to collect and analyse accelerometer measured physical activity in over 100,000 participants of the UK Biobank study , and report variation by age , sex , day , time of day , and season . Methods Participants were approached by email to wear a wrist-worn accelerometer for seven days that was posted to them . Physical activity information was extracted from 100Hz raw triaxial acceleration data after calibration , removal of gravity and sensor noise , and identification of wear / non-wear episodes . We report age- and sex-specific wear-time compliance and accelerometer measured physical activity , overall and by hour-of-day , week-weekend day and season . Results 103,712 data sets were received ( 44.8 % response ) , with a median wear-time of 6.9 days ( IQR:6.5–7.0 ) . 96,600 participants ( 93.3 % ) provided valid data for physical activity analyses . Vector magnitude , a proxy for overall physical activity , was 7.5 % ( 2.35 mg ) lower per decade of age ( Cohen ’s d = 0.9 ) . Women had a higher vector magnitude than men , apart from those aged 45 - 54yrs . There were major differences in vector magnitude by time of day ( d = 0.66 ) . Vector magnitude differences between week and weekend days ( d = 0.12 for men , d = 0.09 for women ) and between seasons ( d = 0.27 for men , d = 0.15 for women ) were small . Conclusions It is feasible to collect and analyse objective physical activity data in large studies . The summary measure of overall physical activity is lower in older participants and age-related differences in activity are most prominent in the afternoon and evening . This work lays the foundation for studies of physical activity and its health consequences . Our summary variables are part of the UK Biobank data set and can be used by research ers as exposures , confounding factors or outcome variables in future analyses Reports of studies relating physical activity to stroke and cancer sub-types indicate inconsistent findings . Some are hampered by low statistical power , owing to a low number of events , and a failure to adjust for potential confounding variables . The purpose of this study was to relate physical activity to 12 mortality endpoints in a prospect i ve cohort study of 11,663 men aged 40–64 years who responded to an enquiry about travel activity during a baseline medical examination conducted between 1967 and 1969 . During 25 years of follow-up there were 4672 deaths . Travel activity was inversely related to mortality attributable to all-causes , coronary heart disease , respiratory disease and lung cancer , whereas the association with stroke was positive . There was evidence for attenuation of some of these associations on adjustment for potentially confounding variables . Our simplistic measure of physical activity may , in part , explain the weak associations seen BACKGROUND Previous research demonstrates that participation in light-intensity physical activity ( LIPA ) and moderate-to-vigorous physical activity ( MVPA ) are favorably associated with health-related quality of life ( HRQOL ) . Emerging work demonstrates that sedentary behavior ( SB ) is detrimentally associated with various cardiometabolic biomarkers , with few studies exploring the association of SB on HRQOL , and no studies examining this among congestive heart failure patients . Therefore , the purpose of this study was to examine the potential independent associations of SB on HRQOL among congestive heart failure patients . METHODS Data from the 2003 - 2006 National Health and Nutrition Examination Survey were used . Physical activity was assessed over 7days during all waking hours using the ActiGraph 7164 accelerometer . HRQOL was assessed using the Centers for Disease Control HRQOL index survey . RESULTS 190 participants self-reported a physician-diagnosis of congestive heart failure . After adjustments , SB behavior ( 1-min/day increase ) was associated with worse HRQOL ( β=0.004 ; 95 % CI : 0.0004 - 0.007 ; P=0.03 ) . When MVPA was added as a covariate to this model , SB remained significantly associated with worse HRQOL ( β=0.003 ; 95 % CI : 0.0001 - 0.007 ; P=0.04 ) . However , when adding LIPA to this model that also included MVPA as a covariate , SB was no longer associated with HRQOL ( β=0.0001 ; 95 % CI : -0.003 - 0.004 ; P=0.92 ) . CONCLUSIONS If confirmed by prospect ive/experimental work , this suggests that SB may not have detrimental HRQOL effects among congestive heart failure patients Background Given high rates of obesity , hypertension , and diabetes mellitus , black persons are at risk to develop heart failure . The association of moderate to vigorous physical activity ( MVPA ) and heart failure in black adults is under research ed . The purpose of this study was to explore whether greater MVPA was associated with lower risk of heart failure hospitalizations ( HFHs ) among black adults with normal ejection fractions . Methods and Results We performed a prospect i ve analysis of 4066 black adults who participated in the Jackson Heart Study and who had physical activity measured , had normal ejection fraction on 2‐dimensional echocardiograms , and were followed for 7 years for incident HFH . We used Cox proportional regression analyses adjusted for age , sex , body mass index , smoking status , hypertension , diabetes mellitus , chronic obstructive pulmonary disease , coronary heart disease , atrial fibrillation , and chronic kidney disease and examined effect modification by sex and body mass index . Of the eligible population , 1925 participants , according to the duration of MVPA , had poor health ( 0 minutes/week ) , 1332 had intermediate health ( 1–149 minutes/week ) , and 809 had ideal health ( ≥150 minutes/week ) . There were 168 incident HFHs . MVPA for intermediate and ideal health was associated with decreasing risk of incident HFH ( hazard ratio : 0.70 [ 95 % confidence interval , 49–1.00 ] and 0.35 [ 95 % confidence interval , 0.19–0.64 ] , respectively ; P trend=0.003 ) . The full model revealed hazard ratios of 0.74 [ 95 % confidence interval , 0.52–1.07 ] and 0.41 [ 95 % confidence interval , 0.22–0.74 ] , respectively . There was no effect modification between MVPA and body mass index or sex on incident HFH . Conclusions A dose‐response relationship between increasing levels of MVPA and protection from incident HFH was found in black men and women with normal ejection fractions Purpose : Regular physical activity ( PA ) is recommended for patients with heart failure ( HF ) . However , the clinical and social characteristics of older HF patients with low-level PA and the impact of light-intensity PA on 6-mo postdischarge adverse cardiovascular events are still unclear . Methods : Forty-one older patients who had been admitted because of decompensated HF ( American College of Cardiology [ACC]/American Heart Association [ AHA ] HF classification stage C/D : 76 ± 5 y ) were prospect ively enrolled . Light-intensity ( 1.5 - 2.9 metabolic equivalents [ METs ] ) and moderate-intensity ( ≥3 METs ) PAs were determined by triaxial accelerometry for at least 7 d postdischarge . Six-min walk distance and 36-item Short Form question naire ( SF-36 ) score were evaluated at discharge . HF patients were stratified into either the HFPA-high or HFPA-low group according to median daily PA . Twenty-nine older ACC/AHA stage A/B out patients ( HF-risk ) , who were at risk for HF but no symptoms of HF had developed , also completed these assessment s. Clinical predictors for 6-mo postdischarge HF rehospitalization were assessed . Results : HF patients were anemic and less active . HFPA-low patients were less likely to engage in household work , took fewer steps , and had less light and moderate-intensity PA than HFPA-high patients . There were no differences in 6-min walk distance , SF-36 score , or left ventricular ejection fraction between HFPA-low and HFPA-high patients . Postdischarge PA , especially light-intensity PA , was independently associated with HF rehospitalization . Conclusion : Low volume of PA postdischarge , especially at 1.5 to 2.9 METs , predicts 6-mo postdischarge HF rehospitalization in older HF patients CONTEXT The lifetime risk of heart failure at age 40 years is approximately 1 in 5 in the general population ; however , little is known about the association Output:	Overall , AQPA showed a strong inverse relationship with mortality and predictive utility when combined with established risk scores , and prognostic roles in morbidity , predicting cognitive function , New York Heart Association functional class and intercurrent events ( e.g. hospitalisation ) , but weak relationships with health-related quality of life scores . AQPA has a strong prognostic role in CHF . Big data and machine learning strategies will potentially yield better predictive value of AQPA in CHF patients
MS213836	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: BACKGROUND While the relationship of apolipoprotein E ( APOE ) to behavioral symptoms of dementia ( BSD ) has been studied in community-dwelling persons with AD , it has received limited attention within the nursing home ( NH ) population . The aim of this study was to examine the association between APOE genotype and BSD in NH residents using direct observation . METHODS Thirty-six participants , aged 71 - 102 years , were compared using a non-r and omized two-group design with continuous measures . APOE genotype was obtained by buccal swab . BSD , including restlessness , escape restraint , tapping and banging , search ing and w and ering , pacing and walking , and vocalization , were measured using the Modified Agitated Behavior Rating Scale . Participants were observed every 20 minutes for 12 hours per day for five days . Each participant 's mean behavior scores were compared according to the presence or absence of the APOE epsilon4 allele . RESULTS Resident characteristics included a mean MMSE of 10.44 indicating moderate to severe dementia and a mean of 3.44 medical co-morbidities . Fifty-six percent of the participants had one epsilon4 allele . A significant difference was found between APOE epsilon4+/4- and mean behavioral scores ( F(1,31 ) ) = 4.40 , p = 0.04 ) . Restlessness was significantly inversely correlated with MMSE ( r = -0.367 , p = 0.03 ) , but not APOE genotype . There was no significant correlation between proxy reporting and direct observation ( r = 0.257 , p = 0.13 ) . CONCLUSION Findings indicate that the presence of the APOE epsilon4 + genotype increases the risk for BSD in NH residents with dementia . Direct observation proved a more accurate estimate of BSD than proxy report Purpose To identify correlates of self-rated and caregiver-rated quality of life ( QOL ) in community-residing persons with dementia ( PWD ) for intervention development . Methods Cross-sectional data of 254 PWD and their caregivers participating in a clinical trial were derived from in-home assessment s. Self-rated QOL was measured with the Quality of Life-Alzheimer Disease ( QOL-AD ) scale , and caregiver-rated QOL was measured using the QOL-AD and Alzheimer Disease-Related Quality of Life ( ADRQL ) scales . Multivariate modeling identified correlates of the PWD ’ QOL . Results Self-rated QOL was related significantly to participant race , unmet needs , depression , and total medications . Caregiver-rated QOL-AD scores were significantly associated with participant function , unmet needs , depression , and health problems and with caregiver burden and self-rated health . Significant correlates of ADRQL scores included neuropsychiatric symptom severity , functional and cognitive impairment , and caregiver burden and depression . Conclusions Correlates of QOL in community-residing PWD depend on who rates the PWD ’s QOL and which measure is used . Addressing health problems , medication use , and dementia-related unmet needs , reducing functional dependency , and treating neuropsychiatric symptoms in PWD , while reducing caregiver burden and depression , may maximize QOL in those with dementia Background Psychiatric symptoms occur frequently in the course of AD , are a frequent contributor to institutionalization , predict cognitive decline and death , and often require treatment with psychotropic medications . Previous studies investigating the association between APOE genotype and psychiatric symptomatology in AD have reported contradictory results . Objective To determine whether APOE genotype predicts incident psychiatric symptomatology in patients with AD . Methods Eighty-seven patients with AD at early stages and no psychiatric history were followed semiannually for up to 9.3 years ( mean 5.5 years ) for development of delusions , illusions , hallucinations , behavioral symptoms , and depression . Cox proportional hazards models were used to examine the relative risk for incident psychiatric symptomatology ( outcome ) in relation to APOE genotype ( predictor ) . Results The presence of one & egr;4 allele carried a 2.5-fold risk , whereas the presence of two & egr;4 alleles carried a 5.6-fold risk for development of delusions . The associations remained significant even when age , ethnicity , sex , education , duration of disease , and cognitive and functional performance were controlled for . The presence of two & egr;4 alleles was associated with reduced risk for developing hallucinations in the adjusted analysis only . No significant associations were detected between APOE genotype and the incidence of illusions , behavioral symptoms , or depression . Conclusion The presence of one or more & egr;4 alleles is a significant predictor for the incidence of delusions in the course of AD Objective : The authors aim ed to use baseline data of an ongoing large , prospect i ve study in subjects with mild cognitive impairment ( MCI ) to investigate the impact of APOE genotype on the symptom profile of the condition . Methods : Cognitive assessment s included the AD Assessment Scale cognitive subscale ( ADAS-cog ) , the Mini-Mental State Examination ( MMSE ) , and a cognitive battery for assessment of memory , attention , and executive function . Behavioral assessment s included the Neuropsychiatric Inventory and Beck Depression Inventory . Activities of daily living were assessed by the AD Cooperative Study Activities of Daily Living ( ADCS-ADL ) scale . Hippocampal volumes were measured with MRI . Results : A total of 494 of 1,018 study subjects provided APOE data . Approximately 40 % of the subjects were APOE ε4 carriers . APOE ε4 carriers had lower MMSE ( p = 0.01 ) and higher ADAS-cog ( p < 0.0001 ) scores than noncarriers , indicating worse cognitive impairment . APOE ε4 carriers also had greater deficits on New York University delayed paragraph recall and Buschke free and cued selective reminding tests , and on the ADCS-ADL scale ( p < 0.001 ) . They also had smaller hippocampal volumes ( p = 0.002 ) . Behavioral scores were similar across the subgroups . Conclusion : MCI subjects carrying the APOE ε4 allele showed distinct cognitive and imaging profiles , which appeared to resemble those of early Alzheimer patients . APOE ε4 genotype was associated with greater impairments in memory and functional activities as well as hippocampal atrophy OBJECTIVE The authors conducted a prospect i ve cohort study to estimate the risk of incident mild cognitive impairment in cognitively normal elderly ( aged ≥70 years ) individuals with or without neuropsychiatric symptoms at baseline . The research was conducted in the setting of the population -based Mayo Clinic Study of Aging . METHOD A classification of normal cognitive aging , mild cognitive impairment , and dementia was adjudicated by an expert consensus panel based on published criteria . Hazard ratios and 95 % confidence intervals were computed using Cox proportional hazards model , with age as a time scale . Baseline Neuropsychiatric Inventory Question naire data were available for 1,587 cognitively normal persons who underwent at least one follow-up visit . RESULTS The cohort was followed to incident mild cognitive impairment ( N=365 ) or censoring variables ( N=179 ) for a median of 5 years . Agitation ( hazard ratio=3.06 , 95 % CI=1.89 - 4.93 ) , apathy ( hazard ratio=2.26 , 95 % CI=1.49 - 3.41 ) , anxiety ( hazard ratio=1.87 , 95 % CI=1.28 - 2.73 ) , irritability ( hazard ratio=1.84 , 95 % CI=1.31 - 2.58 ) , and depression ( hazard ratio=1.63 , 95 % CI=1.23 - 2.16 ) , observed initially , increased risk for later mild cognitive impairment . Delusion and hallucination did not . A secondary analysis , limited in significance by the small number of study participants , showed that euphoria , disinhibition , and nighttime behaviors were significant predictors of nonamnestic mild cognitive impairment but not amnestic mild cognitive impairment . By contrast , depression predicted amnestic mild cognitive impairment ( hazard ratio=1.74 , 95 % CI=1.22 - 2.47 ) but not nonamnestic mild cognitive impairment . CONCLUSIONS An increased incidence of mild cognitive impairment was observed in community-dwelling elderly adults who had nonpsychotic psychiatric symptoms at baseline . These baseline psychiatric symptoms were of similar or greater magnitude as biomarkers ( genetic and structural MRI ) in increasing the risk of incident mild cognitive impairment Objective : To investigate the population -based interaction between a biological variable ( APOE & egr;4 ) , neuropsychiatric symptoms , and the risk of incident dementia among subjects with prevalent mild cognitive impairment ( MCI ) . Methods : We prospect ively followed 332 participants with prevalent MCI ( aged 70 years and older ) enrolled in the Mayo Clinic Study of Aging for a median of 3 years . The diagnoses of MCI and dementia were made by an expert consensus panel based on published criteria , after review ing neurologic , cognitive , and other pertinent data . Neuropsychiatric symptoms were determined at baseline using the Neuropsychiatric Inventory Question naire . We used Cox proportional hazards models , with age as a time scale , to calculate hazard ratios ( HRs ) and 95 % confidence intervals ( CIs ) . Models were adjusted for sex , education , and medical comorbidity . Results : Baseline agitation , nighttime behaviors , depression , and apathy significantly increased the risk of incident dementia . We observed additive interactions between APOE & egr;4 and depression ( joint effect HR = 2.21 ; 95 % CI = 1.24–3.91 ; test for additive interaction , p < 0.001 ) ; and between APOE & egr;4 and apathy ( joint effect HR = 1.93 ; 95 % CI = 0.93–3.98 ; test for additive interaction , p = 0.031 ) . Anxiety , irritability , and appetite/eating were not associated with increased risk of incident dementia . Conclusions : Among prevalent MCI cases , baseline agitation , nighttime behaviors , depression , and apathy elevated the risk of incident dementia . There was a synergistic interaction between depression or apathy and APOE & egr;4 in further elevating the risk of incident dementia The apolipoprotein E ( APOE ) locus on chromosome 19 has been shown to modify risk , and age at onset , of Alzheimer 's disease ( AD ) . The authors hypothesized that the phenotypic expression of different psychiatric symptoms in patients with AD would be associated with variability in APOE locus . Neuropsychiatric and genetic testing of 120 probable AD patients revealed 28 % had major depression , 17 % had minor depression , 30 % had delusions , and 14 % had hallucinations ; 69 % were carriers of at least one APOE E4 allele ( 14 % homozygous E4/E4 , 49 % heterozygous E3/E4 , 6 % heterozygous E2/E4 , 29 % homozygous E3/E3 , 2 % heterozygous E2/E3 ) . Prevalence of the various psychiatric disturbances did not differ significantly in AD patients with different APOE genotypes . Apolipoprotein E does not appear to modify the risk of developing AD-associated psychiatric symptomatology The etiology of behavioral and psychological symptoms of dementia ( BPSD ) is complex , including putative biological , psychological , social and environmental factors . Recent years have witnessed accumulation of data on the association between genetic factors and behavioral abnormalities in Alzheimer disease ( AD ) . In this research paper , our aim is to evaluate the association between the APOE , CYP46 , PRNP and PRND genes and the profile of neuropsychiatric symptoms in Polish subjects with AD and mild cognitive impairment ( MCI ) . We studied 99 patients with AD and 48 subjects with MCI . The presence and profile of BPSD were evaluated at baseline and prospect ively with the Neuropsychiatric Inventory ( NPI ) . Patients were dichotomized into those having ever experienced a particular symptom and those who did not over the whole disease period . Genotyping was performed using previously described st and ard protocol s. The prevalence of comorbid behavioral symptoms and the overall level of behavioral burden were significantly greater in AD compared with the MCI group . In AD patients , carrier status of the T allele of the 3′UTR ( untranslated region ) PRND polymorphism was associated with an increased cumulative behavioral load and an elevated risk for delusions , anxiety , agitation/aggression , apathy and irritability/emotional ability . Among MCI subjects , APOE ε4 carriers demonstrated a reduced risk for nighttime behavior change . No other statistically significant genotype-phenotype correlations were observed , including the APOE , CYP46 and PRNP genes . A precise estimation of the exact significance of particular polymorphisms in BPSD etiology requires future studies on large population CONTEXT Little is known about the population -based prevalence of neuropsychiatric symptoms in mild cognitive imp Output:	HighlightsAPOE is not associated with affective symptoms in cognitively impaired subjects . Studies assessing the affect‐APOE relationship show large heterogeneity in design .Contrasting prior findings could not be explained by this variation in study design . No association was found between the individual symptoms and APOE & egr;4 carriership or zygosity . For depression and anxiety , only pooled unadjusted estimates showed positive associations with between‐ study heterogeneity , which could be explained by variation in study design , setting and way of symptom assessment . Conclusions : There is no evidence that APOE & egr;4 carriership or zygosity is associated with the presence of depression , anxiety , apathy , agitation , irritability or sleep disturbances in cognitively impaired subjects .
MS213837	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: This pilot study investigated the effectiveness of Mindfulness-Based Cognitive Therapy ( MBCT ) , a treatment combining mindfulness meditation and interventions taken from cognitive therapy , in patients suffering from chronic-recurrent depression . Currently symptomatic patients with at least three previous episodes of depression and a history of suicidal ideation were r and omly allocated to receive either MBCT delivered in addition to treatment-as-usual ( TAU ; N = 14 completers ) or TAU alone ( N = 14 completers ) . Depressive symptoms and diagnostic status were assessed before and after treatment phase . Self-reported symptoms of depression decreased from severe to mild levels in the MBCT group while there was no significant change in the TAU group . Similarly , numbers of patients meeting full criteria for depression decreased significantly more in the MBCT group than in the TAU group . Results are consistent with previous uncontrolled studies . Although based on a small sample and , therefore , limited in their generalizability , they provide further preliminary evidence that MBCT can be used to successfully reduce current symptoms in patients suffering from a protracted course of the disorder OBJECTIVE To assess the effectiveness of mindfulness-based stress reduction ( MBSR ) for chronic insomnia and combined depressive or anxiety symptoms of older adults aged 75 years and over . DESIGN A r and omized , controlled , single-blind clinical trial . PATIENTS AND METHODS Participants included 60 adults aged 75 years and over with chronic insomnia . Participants were r and omly assigned to the eight-week MBSR group or the wait-list control group . Assessment s using the Pittsburgh Sleep Quality Index ( PSQI ) , Self-rating Anxiety Sale ( SAS ) , and Geriatric Depression Scale ( GDS ) were taken at baseline and post-treatment . For each outcome measure , a repeated measures analysis of variance was used to detect changes across assessment s. RESULTS There was a significant time × group interaction for the PSQI global score ( P = .006 ) ; the MBSR group had a decrease in the PSQI global score ( Cohen׳s d = 1.12 ) , while the control group did not ( Cohen׳s d = -0.06 ) . Among the PSQI components , there was a significant time × group interaction for daytime dysfunction ( P = .048 ) ; Cohen׳s d of the MBSR group was 0.76 , while Cohen׳s d of control group was -0.04 . There was no significant time × group interaction for the SAS score ( P = .116 ) , while for the GDS there was a significant time × group interaction ( P = .039 ) ; the Cohen׳s d value for the MBSR group was 1.20 , and it was 0.12 for the control group . CONCLUSION This study demonstrated that the MBSR program could be a beneficial treatment for chronic insomnia in adults aged 75 years and older OBJECTIVE To determine whether neurocognitive performance and clinical outcomes can be enhanced by a mindfulness intervention in older adults with stress disorders and cognitive complaints . To explore decreased hypothalamic-pituitary-adrenal ( HPA ) axis activity as a possible mechanism . METHODS 103 adults aged 65 years or older with an anxiety or depressive disorder ( diagnosed according to DSM-IV criteria ) and subjective neurocognitive difficulties were recruited in St. Louis , Missouri , or San Diego , California , from September 2012 through August 2013 and r and omly assigned in groups of 5 - 8 to mindfulness-based stress reduction ( MBSR ) or a health education control condition matched for time , attention , and credibility . The primary outcomes were memory ( assessed by immediate and delayed paragraph and list recall ) and cognitive control ( Delis-Kaplan Executive Function System Verbal Fluency Test and Color Word Interference Test ) . Other outcomes included clinical symptoms ( worry , depression , anxiety , and global improvement ) . HPA axis activity was assessed using peak salivary cortisol . Outcomes were measured immediately post-intervention and ( for clinical outcomes only ) at 3- and 6-month follow up . RESULTS On the basis of intent-to-treat principles using data from all 103 participants , the mindfulness group experienced greater improvement on a memory composite score ( P = .046 ) . Groups did not differ on change in cognitive control . Participants receiving MBSR also improved more on measures of worry ( P = .042 ) and depression ( P = .049 ) at posttreatment and on worry ( P = .02 ) , depression ( P = .002 ) , and anxiety ( P = .002 ) at follow-up and were more likely to be rated as much or very much improved as rated by the Clinical Global Impressions-Improvement scale ( 47 % vs 27 % , χ² = 4.5 , P = .03 ) . Cortisol level decreased to a greater extent in the mindfulness group , but only among those participants with high baseline cortisol . CONCLUSIONS In this population of older adults with stress disorders and neurocognitive difficulties , a mindfulness intervention improves clinical outcomes such as excessive worry and depression and may include some forms of immediate memory performance . TRIAL REGISTRATION Clinical Trials.gov identifier : NCT01693874 OBJECTIVES Patients with chronic obstructive lung disease ( COPD ) suffer from significant dyspnea and may benefit from complementary and alternative medicine ( CAM ) therapies aim ed at mitigating symptoms . The objective of this study was to test the efficacy of a mindfulness-based breathing therapy ( MBBT ) on improving symptoms and health-related quality of life in those with COPD . DESIGN We conducted a r and omized controlled trial of 8-week mindfulness-based breathing therapy ( MBBT ) compared to support groups to test efficacy on improving symptoms and health-related quality of life in those with COPD . SETTING The setting for this study was an academic-affiliated veterans healthcare system . SUBJECTS The subjects consisted of 86 patients with COPD . INTERVENTIONS MBBT included weekly meetings practicing mindfulness mediation and relaxation response . OUTCOME MEASURES The main outcome measure was a post 6-minute-walk test ( 6MWT ) Borg dyspnea assessment . Other outcome measures included health-related quality of life measures , 6MWT distance , symptom scores , exacerbation rates , and measures of stress and mindfulness . Analysis of covariance compared differences in outcomes between groups ; paired t test evaluated changes within groups . RESULTS Participants were predominantly elderly men with moderate to severe COPD . We found no improvements in dyspnea ( post 6MWT Borg difference between the MBBT and support group was 0.3 ( 95 % confidence interval [ CI ] : -1.1 , 1.7 ) . We found no differences between groups in almost all other outcome measures by either intention-to-treat analysis or within the subset that completed assigned group sessions . For the physical summary scale of the generic Short Form-36 for Veterans , the difference between outcomes favored the support group ( 4.3 , 95 % CI : 0.4 , 8.1 ) . Participant retention was low compared to mind-body trials that r and omize from CAM wait lists . CONCLUSIONS This trial found no measurable improvements in patients with COPD receiving a mindfulness-based breathing CAM therapy compared to a support group , suggesting that this intervention is unlikely to be an important therapeutic option for those with moderate-to-severe COPD Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more Objectives : To examine the effects of age and depressive symptom severity on changes in positive affect among older adults r and omly assigned to a Mindfulness-Based Stress Reduction ( MBSR ) program or a Waitlist Control group . Drawing from the Motivational Theory of Life-Span Development , we hypothesized that lower levels of depressive symptom severity and older age would be associated with greater positive affect in response to the MBSR intervention . Methods : Data were collected from a sample of community-dwelling English-speaking adults ( n = 200 ) aged ≥ 65 , r and omly assigned to an eight-week MBSR program or a Waitlist Control group . Our main outcome variable was a five-item measure of positive affect , which was measured at study entry as well as eight weeks and six months later . Results : At the six-month follow-up , we observed group by baseline depressive symptom severity ( β = −.17 , p = .02 ) and group by baseline depressive symptom severity by age ( β = −.14 , p = .05 ) interactions . Among MBSR participants , greater baseline depressive symptom severity was also associated with less improvement in positive affect at the six-month follow-up ( β = −.30 , p = .003 ) . Findings were qualified by a significant depressive symptom severity by age interaction ( β = −.25 , p = .01 ) , such that MBSR participants who were 70 and over with lower baseline depressive symptom severity having the greatest improvement in positive affect at the six-month follow-up . Conclusion : MBSR improves positive affect for older adults with lower depressive symptom severity , perhaps because it capitalizes on naturalistic changes in control strategies The cultivation of mindfulness has received increasing attention over the past 2 decades because of its association with increased psychological well-being and reduced stress-related health disorders . Given the robust positive association between perceived stress and cognitive impairment in late life , the current study evaluated the association between trait mindfulness , psychological well-being , and cognitive function in 73 healthy community-dwelling older adults . Controlling for a priori covariates , multivariate regression analyses showed a significant association between trait mindfulness and measures of psychological well-being , including self-reported depressive symptoms , quality of life , and stress profile . Analyses further showed a significant association between trait mindfulness and executive function , namely set shifting . No association was found for declarative memory . Mediation analyses showed that the association between mindfulness and cognitive function is mediated by perceived stress . This research supports the importance of cultivating mindfulness in late life to ensure cognitive and emotional well-being The purpose of this study was to test the feasibility and effectiveness of an adapted 8-week Mindfulness-Based Stress Reduction ( MBSR ) program for elders in a continuing care community . This mixed- methods study used both quantitative and qualitative measures . A r and omized waitlist control design was used for the quantitative aspect of the study . Thirty-nine elderly were r and omized to MBSR ( n = 20 ) or a waitlist control group ( n = 19 ) , mean age was 82 years . Both groups completed pre – post measures of health-related quality of life , acceptance and psychological flexibility , facets of mindfulness , self-compassion , and psychological distress . A subset of MBSR participants completed qualitative interviews . MBSR participants showed significantly greater improvement in acceptance and psychological flexibility and in role limitations due to physical health . In the qualitative interviews , MBSR participants reported increased awareness , less judgment , and greater self-compassion . Study results demonstrate the feasibility and potential effectiveness of an adapted MBSR program in promoting mind – body health for elders In a r and omized controlled trial , we investigated the effects of karate versus a mindfulness-based stress reduction ( MBSR ) intervention on well-being and cognitive functioning in older adults . Fifty-five adults ( 52–81 years old ) participated in twice-weekly karate versus MBSR sessions or no training for 8 weeks . In pre- and post assessment s , subjective well-being , health , cognitive functioning , and chronic stress were measured . Pre assessment hair cortisol served as physiological stress marker . The results showed an improvement for the karate group , but not the MBSR and control group , in subjective mental health and anxiety as well as cognitive processing speed . The MBSR group showed by trend as a decrease in stress . No significant correlation between pre assessment hair cortisol and post assessment outcomes could be established . But the higher the level of baseline self-reported perceived stress , the higher the increase in depression , anxiety , and chronic stress . Generally , it can be assumed that karate and MBSR showed only small training effects concerning the assessed emotional and cognitive parameters Output:	The results of this review provide evidence that the MBSR is more effective than wait-list-control group to reduce depression in older adults with clinical ly significant symptoms immediately following the intervention . However , there is no clear evidence that the intervention reduced the perception of stress and anxiety , or that positive effects are maintained over the longer term .
MS213838	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: PURPOSE This study compared the effects of skill-based and plyometric conditioning ( both performed in addition to regular volleyball training twice a week for 12 wk ) on fitness parameters in female junior volleyball players . METHODS The participants [ n = 47 ; age : 16.6 ( 0.6 ) y ; mass : 59.4 ( 8.1 ) kg ; height : 175.1 ( 3.0 ) cm ] were r and omized into a plyometric ( n = 13 ) , a skill-based ( n = 17 ) , and a control ( n = 17 ) groups . The variables included body height , body mass , calf girth , calf skinfold , corrected calf girth , countermovement jump , 20-m-sprint , medicine ball toss , and sit- and -reach test . RESULTS Two-way analysis of variance ( time × group ) effects for time were significant ( P < .05 ) for all variables except body mass . Significant group × time interactions were observed for calf skinfold [ η2 = .14 ; medium effect size ( ES ) ] , 20-m sprint ( η2 = .09 ; small ES ) , countermovement jump ( η2 = .29 ; large ES ) , medicine ball ( η2 = .58 ; large ES ) , with greater gains ( reduction of skinfold ) for plyometric group , and sit- and -reach ( η2 = .35 ; large ES ) , with greater gains in plyometric and skill-based groups . The magnitude-based inference indicated positive changes in 1 ) medicine ball toss and countermovement jump for all groups ; 2 ) sit- and -reach for the plyometric and skill-based groups ; and 3 ) 20-m sprint , calf girth , calf skinfold , and corrected calf girth for plyometric group only . CONCLUSION Selected variables can be improved by adding 2 plyometric training sessions throughout the period of 12 weeks . Additional skill-based conditioning did not contribute to improvement in the studied variables compared with regular volleyball training OBJECTIVE To compare differences in kinematic and kinetic parameters of knee , hip and ankle joints between male and female college volleyball players . DESIGN Cross-sectional study . BACKGROUND L and ing injuries , which usually involve anterior cruciate ligament injuries , are common in volleyball with a higher incidence in females . L and ing preferences of both male and female players may provide additional background about the mechanisms contributing to the anterior cruciate ligament injuries . METHODS Eight female and eight male college volleyball players performed spike and block l and ings from 40 and 60 cm height platforms . Lower extremity joint kinetics and kinematics , and leg muscle strengths were recorded . RESULTS Females demonstrated significantly lower knee and hip flexion angles compared to their male counterparts in knee flexion at 40 cm spike and hip flexion at 40 cm block l and ings . Group comparison also revealed that male players ' peak knee extensor moment at 60 cm block l and ing was significantly different than female players . Additionally , female players applied significantly higher normalized ground reaction forces and males knee flexion angles and thigh muscle strength results positive and highly correlated but relation could not found in females . It is likely that females may not use their thigh muscles as effective as males in l and ing . CONCLUSION Female volleyball players initiate different lower extremity mechanics during l and ings than that of males . RELEVANCE Identifying the l and ing strategy differences between female and male college volleyball players may provide detailed perspective about the load distribution in lower extremity joints for determining major factors affecting the increased incidence of anterior cruciate ligament injuries in females This study investigated the effects of a plyometric training program and a traditional weight-training program on the onset rate of fatigue in the vertical jump in women . Twenty-five untrained college women ranging in age from 18–35 were r and omly separated into 3 groups : a plyometric group , a traditional weight-training group , and a control ( untrained ) group . For the purpose of this study , the traditional weight-training group was defined as performing 3 sets of 10 repetitions at 70 % of the subject 's 1 repetition maximum ( 1RM ) . Training took place over a 10-week period for both the plyometric and traditional weight-trained groups . The plyometric group prolonged the onset of fatigue by 3.85 seconds as compared with their pretest data . The traditional weight-training group fatigued 0.55 seconds faster after training was implemented as compared with their pretest data . These results showed a significant difference between the groups in their onset rates of fatigue ( p < 0.05 ) . The results of this study show that a plyometric training program prolongs the onset rate of fatigue in the vertical jump in women as compared with a traditional weight-training program OBJECTIVES To compare the impact of short term training with resistance plus plyometric training ( RT+P ) or electromyostimulation plus plyometric training ( EMS+P ) on explosive force production in elite volleyball players . DESIGN Sixteen elite volleyball players of the first German division participated in a training study . METHODS The participants were r and omly assigned to either the RT+P training group ( n=8 ) or the EMS+P training group ( n=8 ) . Both groups participated in a 5-week lower extremity exercise program . Pre and post tests included squat jumps ( SJ ) , countermovement jumps ( CMJ ) , and drop jumps ( DJ ) on a force plate . The three-step reach height ( RH ) was assessed using a custom-made vertec apparatus . Fifteen m straight and lateral sprint ( S15s and S15l ) were assessed using photoelectric cells with interims at 5 m and 10 m. RESULTS RT+P training result ed in significant improvements in SJ ( + 2.3 % ) and RH ( + 0.4 % ) performance . The EMS+P training group showed significant increases in performance of CMJ ( + 3.8 % ) , DJ ( + 6.4 % ) , RH ( + 1.6 % ) , S15l ( -3.8 % ) and after 5 m and 10 m of the S15s ( -2.6 % ; -0.5 % ) . The comparison of training-induced changes between the two intervention groups revealed significant differences for the SJ ( p=0.023 ) in favor of RT+P and for the S15s after 5 m ( p=0.006 ) in favor of EMS+P. CONCLUSIONS The results indicate that RT+P training is effective in promoting jump performances and EMS+P training increases jump , speed and agility performances of elite volleyball players PURPOSE Numerous studies have reported that l and -based plyometrics can improve muscular strength , joint stability , and vertical jump ( VJ ) in athletes ; however , due to the intense nature of plyometric training , the potential for acute muscle soreness or even musculoskeletal injury exists . Performance of aquatic plyometric training ( APT ) could lead to similar benefits , but with reduced risks due to the buoyancy of water . Unfortunately , there is little information regarding the efficacy of APT . Thus , the purpose of this study was to examine the effects of APT on VJ and muscular strength in volleyball players . METHODS Nineteen female volleyball players ( aged 15 + /- 1 yr ) were r and omly assigned to perform 6 wk of APT or flexibility exercises ( CON ) twice weekly , both in addition to traditional preseason volleyball training . Testing of leg strength was performed at baseline and after 6 wk , and VJ was measured at baseline and after 2 , 4 , and 6 wk . RESULTS Similar increases in VJ were observed in both groups after 4 wk ( APT = 3.1 % , CON = 4.9 % ; both P < 0.05 ) ; however , the APT group improved by an additional 8 % ( P < 0.05 ) from week 4 to week 6 , whereas there was no further improvement in the CON group ( -0.9 % ; P = NS ) . After 6 wk , both groups displayed significant improvements in concentric peak torque during knee extension and flexion at 60 and 180 degrees x s(-1 ) ( all P < 0.05 ) . CONCLUSIONS The combination of APT and volleyball training result ed in larger improvements in VJ than in the CON group . Thus , given the likely reduction in muscle soreness with APT versus l and -based plyometrics , APT appears to be a promising training option CONTEXT Plyometric training is credited with providing benefits in performance and dynamic restraint . However , limited prospect i ve data exist quantifying kinematic adaptations such as amortization time , glenohumeral rotation , and scapulothoracic position , which may underlie the efficacy of plyometric training for upper-extremity rehabilitation or performance enhancement . OBJECTIVE To measure upper-extremity kinematics and plyometric phase times before and after an 8-wk upper-extremity strength- and plyometric-training program . DESIGN R and omized pretest-posttest design . SETTING Research laboratory . PARTICIPANTS 40 recreationally active men ( plyometric group , age 20.43 ± 1.40 y , height 180.00 ± 8.80 cm , weight 73.07 ± 7.21 kg ; strength group , age 21.95 ± 3.40 y , height 173.98 ± 11.91 cm , weight 74.79 ± 13.55 kg ) . INTERVENTION Participants were r and omly assigned to either a strength-training group or a strength- and plyometric-training group . Each participant performed the assigned training for 8 wk . MAIN OUTCOME MEASURES Dynamic and static glenohumeral and scapular-rotation measurements were taken before and after the training programs . Dynamic measurement of scapular rotation and time spent in each plyometric phase ( concentric , eccentric , and amortization ) during a ball-toss exercise were recorded while the subjects were fitted with an electromagnetic tracking system . Static measures included scapular upward rotation at 3 different glenohumeral-abduction angles , glenohumeral internal rotation , and glenohumeral external rotation . RESULTS Posttesting showed that both groups significantly decreased the time spent in the amortization , concentric , and eccentric phases of a ball-toss exercise ( P < .01 ) . Both groups also exhibited significantly decreased static external rotation and increased dynamic scapular upward rotation after the training period ( P < .01 ) . The only difference between the training protocol s was that the plyometric-training group exhibited an increase in internal rotation that was not present in the strength-training group ( P < .01 ) . CONCLUSION These findings support the use of both upper-extremity plyometrics and strength training for reducing commonly identified upper-extremity-injury risk factors and improving upper-extremity performance Output:	The included studies indicated that plyometric training seems to increase vertical jump performance , strength , horizontal jump performance , flexibility and agility/speed in volleyball players .
MS213839	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Background Tuberculosis ( TB ) is a major cause of morbidity and mortality among children infected with HIV . Strategies to prevent TB in children include isoniazid preventive therapy ( IPT ) and antiretroviral therapy ( ART ) . IPT and ART have been reported to reduce TB incidence in adults but there are few studies in children . Objective To investigate the combined effect of IPT and ART on TB risk in children infected with HIV . Methods A cohort analysis was done within a prospect i ve , double-blinded , placebo-controlled trial of isoniazid ( INH ) compared with placebo in children infected with HIV in Cape Town , South Africa , a high TB incidence setting . In May 2004 the placebo arm was terminated and all children were switched to INH . ART was not widely available at the start of the study , but children were started on ART following the establishment of the national ART program in 2004 . Data were analysed using Cox proportional hazard regression . Results After adjusting for age , nutritional status and immunodeficiency at enrolment , INH alone , ART alone and INH combined with ART reduced the risk of TB disease by 0.22 ( 95 % CI 0.09 to 0.53 ) , 0.32 ( 95 % CI 0.07 to 1.55 ) and 0.11 ( 95 % CI 0.04 to 0.32 ) respectively . INH reduced the risk of TB disease in children on ART by 0.23 ( 95 % CI 0.05 to 1.00 ) . Conclusions The finding that IPT may offer additional protection in children on ART has significant public health implication s because this offers a possible strategy for reducing TB in children infected with HIV . Widespread use of this strategy will however require screening of children for active TB disease . Trial registration Trial registration — Clinical Trials NCT00330304 BACKGROUND The dual epidemic of human immunodeficiency virus ( HIV ) and tuberculosis is a major cause of sickness and death in sub-Saharan Africa . We conducted a double-blind , r and omized , placebo-controlled trial of preexposure isoniazid prophylaxis against tuberculosis in HIV-infected children and uninfected children exposed to HIV during the perinatal period . METHODS We r and omly assigned 548 HIV-infected and 804 HIV-uninfected infants ( 91 to 120 days of age ) to isoniazid ( 10 to 20 mg per kilogram of body weight per day ) or matching placebo for 96 weeks . All patients received bacille Calmette-Guérin ( BCG ) vaccination against tuberculosis within 30 days after birth . HIV-infected children had access to antiretroviral therapy . The primary outcome measures were tuberculosis disease and death in HIV-infected children and latent tuberculosis infection , tuberculosis disease , and death in HIV-uninfected children within 96 to 108 weeks after r and omization . RESULTS Antiretroviral therapy was initiated in 98.9 % of HIV-infected children during the study . Among HIV-infected children , protocol -defined tuberculosis or death occurred in 52 children ( 19.0 % ) in the isoniazid group and 53 ( 19.3 % ) in the placebo group ( P=0.93 ) . Among HIV-uninfected children , there was no significant difference in the combined incidence of tuberculosis infection , tuberculosis disease , or death between the isoniazid group ( 39 children , 10 % ) and the placebo group ( 45 children , 11 % ; P=0.44 ) . The rate of tuberculosis was 121 cases per 1000 child-years ( 95 % confidence interval [ CI ] , 95 to 153 ) among HIV-infected children as compared with 41 per 1000 child-years ( 95 % CI , 31 to 52 ) among HIV-uninfected children . There were no significant differences in clinical or severe laboratory toxic effects between treatment groups . CONCLUSIONS Primary isoniazid prophylaxis did not improve tuberculosis-disease-free survival among HIV-infected children or tuberculosis-infection-free survival among HIV-uninfected children immunized with BCG vaccine . Despite access to antiretroviral therapy , the burden of tuberculosis remained high among HIV-infected children . ( Funded by the National Institutes of Health and Secure the Future ; Clinical Trials.gov number , NCT00080119 . ) Background Tuberculosis contributes significantly to morbidity and mortality among HIV-infected children in sub-Saharan Africa . Isoniazid prophylaxis can reduce tuberculosis incidence in this population . However , for the treatment to be effective , adherence to the medication must be optimized . We investigated adherence to isoniazid prophylaxis administered daily , compared to three times a week , and predictors of adherence amongst HIV-infected children . Methods We investigated adherence to study medication in a two centre , r and omized trial comparing daily to three times a week dosing of isoniazid . The study was conducted at two tertiary paediatric care centres in Cape Town , South Africa . Over a 5 year period , we followed 324 HIV-infected children aged ≥ 8 weeks . Adherence information based on pill counts was available for 276 children . Percentage adherence was calculated by counting the number of pills returned . Adherence ≥ 90 % was considered to be optimal . Analysis was done using summary and repeated measures , comparing adherence to the two dosing schedules . Mean percentage adherence ( per child during follow-up time ) was used to compare the mean of each group as well as the proportion of children achieving an adherence of ≥ 90 % in each group . For repeated measures , percentage adherence ( per child per visit ) was dichotomized at 90 % . A logistic regression model with generalized estimating equations , to account for within-individual correlation , was used to evaluate the impact of the dosing schedule . Adjustments were made for potential confounders and we assessed potential baseline and time-varying adherence determinants . Results The overall adherence to isoniazid was excellent , with a mean adherence of 94.7 % ( 95 % confidence interval [ CI ] 93.5 - 95.9 ) ; similar mean adherence was achieved by the group taking daily medication ( 93.8 % ; 95 % CI 92.1 - 95.6 ) and by the three times a week group ( 95.5 % ; 95 % CI 93.8 - 97.2 ) . Two-hundred and seventeen ( 78.6 % ) children achieved a mean adherence of ≥ 90 % . Adherence was similar for daily and three times a week dosing schedules in univariate ( odds ratio [ OR ] 0.88 ; 95 % CI 0.66 - 1.17 ; P = 0.38 ) and multivariate ( adjusted OR 0.85 ; 95 % CI 0.64 - 1.11 ; P = 0.23 ) models . Children from overcrowded homes were less adherent ( adjusted OR 0.71 ; 95 % CI 0.54 - 0.95 ; P = 0.02 ) . Age at study visit was predictive of adherence , with better adherence achieved in children older than 4 years ( adjusted OR 1.96 ; 95 % CI 1.16 - 3.32 ; P = 0.01 ) . Conclusion Adherence to isoniazid was excellent regardless of the dosing schedule used . Intermittent dosing of isoniazid prophylaxis can be considered as an alternative to daily dosing , without compromising adherence or efficacy . Trial registration Clinical Trials BACKGROUND Antiretroviral therapy reduces the risk of tuberculosis , but tuberculosis is more common in people with HIV than in people without HIV . We aim ed to assess the effect of isoniazid preventive therapy on the risk of tuberculosis in people infected with HIV-1 concurrently receiving antiretroviral therapy . METHODS For this pragmatic r and omised double-blind , placebo-controlled trial in Khayelitsha , South Africa , we r and omly assigned ( 1:1 ) patients to receive either isoniazid preventive therapy or a placebo for 12 months ( could be completed during 15 months ) . R and omisation was done with r and om number generator software . Participants , physicians , and pharmacy staff were masked to group assignment . The primary endpoint was time to development of incident tuberculosis ( definite , probable , or possible ) . We excluded tuberculosis at screening by sputum culture . We did a modified intention-to-treat analysis and excluded all patients r and omly assigned to groups who withdrew before receiving study drug or whose baseline sputum culture results suggested prevalent tuberculosis . This study is registered with Clinical Trials.gov , number NCT00463086 . FINDINGS 1329 participants were r and omly assigned to receive isoniazid preventive therapy ( n=662 ) or placebo ( n=667 ) between Jan 31 , 2008 , and Sept 31 , 2011 , and contributed 3227 person-years of follow-up to the analysis . We recorded 95 incident cases of tuberculosis ; 37 were in the isoniazid preventive therapy group ( 2·3 per 100 person-years , 95 % CI 1·6 - 3·1 ) , and 58 in the placebo group ( 3·6 per 100 person-years , 2·8 - 4·7 ; hazard ratio [ HR ] 0·63 , 95 % CI 0·41 - 0·94 ) . Study drug was discontinued because of grade 3 or 4 raised alanine transaminase concentrations in 19 of 662 individuals in the isoniazid preventive therapy group and ten of the 667 individuals in the placebo group ( risk ratio 1·9 , 95 % CI 0·90 - 4·09 ) . We noted no evidence that the effect of isoniazid preventive therapy was restricted to patients who were positive on tuberculin skin test or interferon gamma release assay ( adjusted HR for patients with negative tests 0·43 [ 0·21 - 0·86 ] and 0·43 [ 0·20 - 0·96 ] ; for positive tests 0·86 [ 0·37 - 2·00 ] and 0·55 [ 0·26 - 1·24 ] , respectively ) . INTERPRETATION Without a more predictive test or a multivariate algorithm that predicts benefit , isoniazid preventive therapy should be recommended to all patients receiving antiretroviral therapy in moderate or high incidence areas irrespective of tuberculin skin test or interferon gamma release assay status . FUNDING Department of Health of South Africa , the Wellcome Trust , Médecins Sans Frontières , European and Developing Countries Clinical Trials Partnership , Foundation for Innovation and New Diagnostics , the European Union , and Hasso Plattner ( Institute of Infectious Diseases and Molecular Medicine , University of Cape Town ) BACKGROUND There are limited population -based estimates of tuberculosis incidence among human immunodeficiency virus (HIV)-infected and HIV-uninfected infants aged < or = 12 months . We aim ed to estimate the population -based incidence of culture-confirmed tuberculosis among HIV-infected and HIV-uninfected infants in the Western Cape Province , South Africa . METHODS The incidences of pulmonary , extrapulmonary , and disseminated tuberculosis were estimated over a 3-year period ( 2004 - 2006 ) with use of prospect i ve representative hospital surveillance data of the annual number of culture-confirmed tuberculosis cases among infants . The total number of HIV-infected and HIV-uninfected infants was calculated using population -based estimates of the total number of live infants and the annual maternal HIV prevalence and vertical HIV transmission rates . RESULTS There were 245 infants with culture-confirmed tuberculosis . The overall incidences of tuberculosis were 1596 cases per 100,000 population among HIV-infected infants ( 95 % confidence interval [ CI ] , 1151 - 2132 cases per 100,000 population ) and 65.9 cases per 100,000 population among HIV-uninfected infants ( 95 % CI , 56 - 75 cases per 100,000 population ) . The relative risk of culture-confirmed tuberculosis among HIV-infected infants was 24.2 ( 95 % CI , 17 - 34 ) . The incidences of disseminated tuberculosis were 240.9 cases per 100,000 population ( 95 % CI , 89 - 433 cases per 100,000 population ) among HIV-infected infants and 14.1 cases per 100,000 population ( 95 % CI , 10 - 18 cases per 100,000 population ) among HIV-uninfected infants ( relative risk , 17.1 ; 95 % CI , 6 - Output:	Authors ' conclusions Isoniazid prophylaxis given to all children diagnosed with HIV may reduce the risk of active TB and death in HIV‐positive children not on ART in studies from Africa . For children on ART , no clear benefit was detected . .
MS213840	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: This study evaluated the effects of therapeutic horseback riding on social functioning in children with autism . We hypothesized that participants in the experimental condition ( n = 19 ) , compared to those on the wait-list control ( n = 15 ) , would demonstrate significant improvement in social functioning following a 12-weeks horseback riding intervention . Autistic children exposed to therapeutic horseback riding exhibited greater sensory seeking , sensory sensitivity , social motivation , and less inattention , distractibility , and sedentary behaviors . The results provide evidence that therapeutic horseback riding may be a viable therapeutic option in treating children with autism spectrum disorders BACKGROUND Unusual reactions to sensory input now form part of the diagnostic criteria for autism . These features are common and can have an often-devastating impact on autistic individuals and their families . Yet there are few vali date d interventions that help to remediate or support autistic individuals ' adverse sensory experiences . To date , both measurement of sensory experiences and the result ing interventions have been based on assumptions of neurological sensitivities and largely ignored the role of cognition . This study therefore sought to assess the feasibility of a new 8-week CBT-based group intervention for self-regulation of sensory processing difficulties . METHOD Seven cognitively able adolescents diagnosed with autism aged 11 - 16 years from one mainstream secondary school received the 8-week intervention . Measures of sensory reactivity , anxiety and repetitive behaviours were taken at baseline , post-intervention and follow-up , 8 weeks after the intervention had ceased . Semi-structured interviews and focus groups were also conducted with adolescents and their parents to examine further the acceptability of the intervention . RESULTS The results showed that the intervention itself was feasible - both in its implementation and its acceptability to participants . Qualitative analysis clearly showed that the intervention was effective in raising meta-conscious awareness and self-regulation in these autistic adolescents . Analysis of outcome variables showed no significant change over the intervention period , although effect sizes were moderate-to-large . CONCLUSIONS These preliminary results are encouraging and should inform the design of a future pilot r and omized controlled trial to test its efficacy with a larger group of participants ABSTRACT A multiple baseline across participants design was used to evaluate the effects of Social Stories to help preschool-aged children with characteristics of Autism Spectrum Disorders ( ASD ) increase their engagement in functional behaviors and use sensory integrative-based strategies to promote self-regulation . Three children , 3–5 years old , from a self-contained preschool classroom were selected to participate in the study . The intervention package included reading individualized Social Stories that discussed desired behaviors and self-regulation strategies . The research ers measured the percentage of intervals in which participants engaged in desired behaviors . The frequency of desired behaviors increased for all participants . The use of self-regulation strategies varied across participants . These findings suggest that the intervention was successful in increasing desired behaviors of the three children . Further research is recommended on the effectiveness of embedding sensory integrative strategies into Social Stories . Practitioners may consider the use of Social Stories as a tool to increase independence and encourage self-regulated behaviors in children with characteristics of ASD Output:	Synthesis of the articles suggests that self‐regulation ( e.g. , sensory processing , emotional regulation , executive functioning , social function ) improved with cognitive and occupation‐based interventions .
MS213841	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Background Adjuvant endocrine therapy can improve disease-free survival and time before recurrence in breast cancer patients . However , it is associated with considerable side effects that negatively affect patients ’ quality of life and cause non-adherence . The recently demonstrated effect of individual expectations on side-effect development ( nocebo effect ) suggests that psychological factors play a role in the prevention of side effects . The aim of this study is to evaluate cognitive-behavioral side-effect prevention training ( SEPT ) for breast cancer patients . This article describes the study protocol and applied research methods . Methods / Design In a r and omized controlled trial , 184 female breast cancer patients are assigned to receive either SEPT , st and ard medical care or a manualized supportive therapy at the start of adjuvant endocrine treatment . SEPT consists of three sessions of cognitive-behavioral training including psychoeducation to provide a realistic view of endocrine therapy , imagination-training to integrate positive aspects of medication into daily life , and side-effect management to enhance expectations about coping ability . Side effects three months after the start of endocrine therapy serve as primary outcomes . Secondary outcomes include quality of life , coping ability and patients ’ medication adherence . Patients ’ expectations ( i.e. , expectations about side effects , coping ability , treatment and illness ) are analyzed as mediators . Discussion The optimization of expectations might be a potential pathway in health care to improve patients ’ quality of life during long-term medication intake . The results will provide implication s for a possible integration of evidence -based prevention training into clinical practice .Trial registration Clinical Trials.gov , ( NCT01741883 ) We initiated a double-blind , placebo-controlled trial to test the efficacy and safety of branched-chain amino acids ( BCAA ) ( L-leucine 12 g , L-isoleucine 6 g , and L-valine 6 g daily ) in amyotrophic lateral sclerosis ( ALS ) patients . There was an excess mortality in subjects r and omized to active treatment ( 24 BCAA , 13 placebo ) when a total of 126 ALS patients had been recruited . This finding , associated with the lack of efficacy of BCAA ( measured by comparing the disability scales in the two treatment groups ) , led the Data Monitoring Committee to require cessation of the trial BACKGROUND Amyotrophic lateral sclerosis ( ALS ) is a progressive disease with no effective treatment . In an initial study , riluzole decreased mortality and slowed muscle-strength deterioration in ALS patients . We have carried out a double-blind , placebo-controlled , multicentre study to confirm those findings and to assess drug efficacy at different doses . METHODS 959 patients with clinical ly probable or definite ALS of less than 5 years ' duration were r and omly assigned treatment with placebo or 50 mg , 100 mg , or 200 mg riluzole daily ; r and omisation was stratified by centre and site of disease onset ( bulbar or limb ) . The primary outcome was survival without a tracheostomy . Secondary outcomes were rates of change in functional measures ( muscle strength , functional status , respiratory function , patient 's assessment s of fasciculation , cramps , stiffness , and tiredness ) . The primary analysis was the comparison of the 100 mg dose with placebo by intention-to-treat . Drug-effect on survival was assessed before ( log-rank test ) and after adjustment for known prognostic factors ( Cox 's model ) . FINDINGS At the end of the study , after median follow-up of 18 months , 122 ( 50.4 % ) placebo-treated patients and 134 ( 56.8 % ) of those who received 100 mg/day riluzole were alive without tracheostomy ( unadjusted risk 0.79 , p = 0.076 ; adjusted risk 0.65 , p = 0.002 ) . In the groups receiving 50 mg and 200 mg riluzole daily , 131 ( 55.3 % ) and 141 ( 57.8 % ) patients were alive without tracheostomy ( relative to placebo 50 mg adjusted risk 0.76 , p = 0.04 ; 200 mg 0.61 , p = 0.0004 ) . There was a significant inverse dose response in risk of death . No functional scale discriminated between the treatment groups . The most common adverse reactions were asthenia , dizziness , gastrointestinal disorders , and rises in liver enzyme activities ; they were commonest with the 200 mg dose . INTERPRETATION Overall , efficacy and safety results suggest that the 100 mg dose of riluzole has the best benefit-to-risk ratio . This study confirms that riluzole is well tolerated and lengthens survival of patients with ALS BACKGROUND The cause of amyotrophic lateral sclerosis ( ALS ) is not known , and there is no effective treatment . Cell death may be caused by oxidative damage . Selegiline hydrochloride ( Eldepryl ) is a monoamine oxidase-B inhibitor with antioxidant properties . OBJECTIVE To determine if selegiline affects the clinical course of patients with ALS . DESIGN Six-month , double-blind , placebo-controlled study of 133 patients with classical ALS and symptoms for less than 3 years . The primary end point to indicate effectiveness was the rate of change of the Appel ALS total score , an index of disease severity that incorporates strength and function in limbs , respiratory function , and bulbar function . RESULTS Of the 133 patients , 67 were r and omized to receive selegiline and 66 to receive placebo . One hundred four patients ( 53 in the selegiline group and 51 in the placebo group ) completed the 6-month trial . Both groups were comparable for baseline characteristics and mean Appel ALS total score ( 70.5 points for the selegiline group and 70.6 for the placebo group ) . There was no difference in the rate of progression as measured by the Appel ALS total score , showing an average increase of 22 points in 6 months . The monthly rate of change was 3.4 for the selegiline group and 3.5 for the placebo group . There was 1 adverse reaction : worsening depression . Seven patients died during the study ( 4 in the selegiline group and 3 in the placebo group ) . CONCLUSION Selegiline treatment had no significant effect on the rate of clinical progression or outcome of ALS Abstract Treatment with the neuroprotective drug riluzole has previously been shown to increase the probability of survival in patients with amyotrophic lateral sclerosis . This report describes a placebo-controlled , double-blind r and omised clinical trial of riluzole carried out in ALS patients with advanced stage disease or aged over 75 years . The primary objective was to enable access to treatment to patients excluded from the pivotal trial which was run in parallel . Another goal was to assess the safety of riluzole in patients with advanced-stage disease . One hundred and sixty-eight patients were included , r and omised to either riluzole 50 mg b. i. d. or to placebo , and treated for eighteen months . Riluzole was well-tolerated in this patient population , and the adverse events observed were similar in nature and frequency to those observed in previously published clinical trials in patients included in pivotal trials . The study could not include enough patients to reach adequate power to detect differences in survival between the two treatment groups , and no such difference was in fact observed . In conclusion , riluzole is well-tolerated in ALS patients with advanced stage disease Ciliary neurotrophic factor ( CNTF ) is a neuroactive cytokine found in Schwann cells , which appears to be released in response to nerve injury . The ALS CNTF Treatment Study ( ACTS ) clinical trial was a phase II-III r and omized , placebo-controlled , double-blind study design ed to evaluate the safety , tolerability , and efficacy of subcutaneous administration of recombinantly produced human CNTF ( rHCNTF ) in slowing disease progression in 730 patients with amyotrophic lateral sclerosis ( ALS ) . Patients were r and omized to receive 30 micrograms/kg or 15 micrograms/kg rHCNTF or placebo subcutaneously three times a week for 9 months . The primary endpoint of the study , the slope of decline of isometric muscle strength in treated versus placebo patients , showed no statistically significant difference between rHCNTF and placebo-treated patients , and was complicated by an initial statistically significant decrease in strength early in rHCNTF-treated patients . Mortality was similar in all three study arms . There were no statistically significant treatment effects among the secondary measures . Side effects of rHCNTF included anorexia , weight loss , and cough and were sufficient to limit dosing in many patients & NA ; Discovery of the involvement of endogenous opiates in placebo analgesia represents an important step in underst and ing the mechanisms underlying placebo response . In the present study , we investigated the effects of the opiate antagonist naloxone and the cholecystokinin antagonist proglumide on placebo analgesia in a human model of experimentally induced ischemic pain . First , we found that part of the placebo response was reversed by naloxone , confirming previous studies on the role of opioids in the placebo phenomenon . Second , since it was demonstrated that the action of exogenous and endogenous opiates is potentiated by proglumide , we analysed the effects of this cholecystokinin antagonist on placebo response and found that it enhanced placebo analgesia . The placebo effect can thus be modulated in two opposite directions : it can be partially abolished by naloxone and potentiated by proglumide . The fact that placebo potentiation by proglumide occurred only in placebo responders , but not in non‐responders , suggests that activation of an endogenous opiate system is a necessary condition for the action of proglumide . These results suggest an inhibitory role for cholecystokinin in placebo response , although the low affinity of proglumide for cholecystokinin receptors does not rule out the possibility of other mechanisms We design ed a phase II trial to evaluate the efficacy of gabapentin in slowing the rate of decline in muscle strength of patients with amyotrophic lateral sclerosis ( ALS ) and to assess safety and tolerability . Gabapentin ( 800 mg ) or placebo was administered t.i.d . in a r and omized , double-blinded , placebo-controlled , trial for 6 months . We enrolled 152 patients at eight sites in the United States . The primary outcome measure was the slope of the arm megascore , the average maximum voluntary isometric strength from eight arm muscles st and ardized against a reference ALS population . A secondary outcome measure was forced vital capacity . Slopes of arm megascores for patients on gabapentin were compared with slopes of those taking placebo using a two-way ANOVA . We observed a nonstatistically significant trend ( p = 0.057 - 0.08 ) toward slower decline of arm strength in patients taking gabapentin compared with those taking placebo ( mean difference 24 % , median 37 % ) . We observed no treatment effect on forced vital capacity . Gabapentin was well tolerated by patients with ALS . These results suggest that further studies of gabapentin in ALS are warranted Background : Pre clinical and clinical studies of gabapentin in patients with ALS led the authors to undertake a phase III r and omized clinical trial . Methods : Patients were r and omly assigned , in a double-blinded fashion , to receive oral gabapentin 3,600 mg or placebo daily for 9 months . The primary outcome measure was the average rate of decline in isometric arm muscle strength for those with two or more evaluations . Results : Two hundred four patients enrolled , 196 had two or more evaluations , and 128 patients completed the study . The mean rate of decline of the arm muscle strength was not significantly different between the groups . Moreover , there was no beneficial effect upon the rate of decline of other secondary measures ( vital capacity , survival , ALS functional rating scale , timed walking ) nor was there any symptomatic benefit . In fact , analysis of the combined data from the phase II and III trials revealed a significantly more rapid decline of forced vital capacity in patients treated with gabapentin . Conclusion : These data provide no evidence of a beneficial effect of gabapentin on disease progression or symptoms in patients with ALS Calcium channel blocking drugs antagonize excitatory amino acid receptor activation , decrease calcium entry into damaged neurons , and might help to slow or reverse amyotrophic lateral sclerosis ( ALS ) . We enrolled 87 patients with ALS in a r and omized , placebo-controlled , prospect i ve , double-blind crossover study of nimodipine therapy . Monthly measures of isometric muscle strength and respiratory function compared the effects of drug and placebo . No difference in adverse events occurred in placebo vs drug-treated patients , but diarrhoea , nausea , and lightheadedness were more common with nimodipine . There was no significant difference in the rate of decline of pulmonary function or limb strength during treatment with drug or placebo . Nimodipine was ineffective in slowing the progress of ALS BACKGROUND Amyotrophic lateral sclerosis is a progressive motor neuron disease for which there is no adequate treatment . Some research suggests that the excitatory amino acid neurotransmitter glutamate may be involved in the pathogenesis . METHODS To evaluate the efficacy and safety of the antiglutamate agent riluzole , we conducted a prospect i ve , double-blind , placebo-controlled trial in 155 out patients with amyotrophic lateral sclerosis . The dose of riluzole was 10 Output:	Our study indicates significant nocebo in trials for MND treatment , adversely affecting adherence and efficacy of current treatments in clinical practice , with additional implication s for trial design
MS213842	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Aim : To evaluate the efficacy of sweeping of fetal membranes for induction of labor in uncomplicated term pregnancies . Methods : A r and omized controlled trial was performed in 122 pregnant women beyond 39 weeks of gestation with no complications . The women were assigned to have their membranes swept or not ( controls ) for labor induction . The main outcome measures included duration of pregnancy and possible complications of sweeping of membranes , including rupture of membranes , postpartum infections , and vaginal bleeding . Results : Twenty-one patients did not give birth in our hospital and were , therefore , excluded from the study ; 101 women completed the study ( 51 patients in the control group and 50 women in the study group ) . There were no statistically significant differences in maternal age , parity , birth weight , and Bishop score in the two groups . The mean interval between sweeping ( stripping ) and vaginal examination until delivery was 7.7 ± ( SD ) 6.9 and 7.1 ± 5.6 days in the sweeping and in the control group , respectively ( p = 0.61 ) . Of the 101 pregnant women , only 6 patients had premature rupture of membranes ( 2 in the sweeping group and 4 in the control group ) . There were no statistically significant differences between these individuals ( p = 0.68 ) . Significant vaginal bleeding was not observed in the two groups . Meconium-stained amniotic fluid was seen in 13 women : 8 in the sweeping group and 5 in the control group . There were no statistically significant differences among the women who had meconium-stained fluid in case and control groups ( p = 0.39).There were no differences between women who had puerperal fever ( 3 in the sweeping group and 2 in the control group ; p = 0.68).12 of the 101 women ( 6 in each group ) had cesarean section performed , but there was no difference betweeen the two groups . Conclusion : Sweeping of membranes at 39 weeks of gestation has no significant clinical effect on the duration of pregnancy Objective . To compare effectiveness and safety of 25 μg vaginal misoprostol versus Foley catheter and oxytocin for cervical ripening and labor induction in pregnant women with unripe cervices . Design . R and omized controlled trial . Setting . A public maternity in Recife , Brazil . Sample . A total of 240 pregnant women . Methods . Women with a term or post‐term , live , singleton fetus in cephalic presentation , intact membranes , Bishop score < 6 , not in labor , medically indicated for labor induction . They were r and omly divided in Group 1 , where 119 women received 25 μg of intravaginal misoprostol every 6 hours for a maximum of four doses ; and Group 2 , where 121 women had a 14‐F Foley catheter inserted into their cervical canal . Once past the internal os , the balloon was inflated . Intravenous oxytocin was initiated after the balloon was spontaneously extruded from the cervix or after 24 hours . Results . There were no significant differences between the groups regarding baseline characteristics . Misoprostol was more effective in inducing labor than Foley catheter and oxytocin . Mean induction‐to‐vaginal delivery time with misoprostol was shorter ( 17.3 vs. 20.2 hours , p = 0.016 ) . There were more vaginal deliveries in the misoprostol group at 12 ( p < 0.001 ) and 18 ( p = 0.007 ) hours , but the difference was no longer statistically significant at 24 and 48 hours . There were no significant differences in uterine contraction abnormalities , puerperal infection or neonatal outcomes . Conclusions . Vaginal misoprostol is more effective than and as safe as Foley catheter and oxytocin for induction of labor in term and post‐term pregnancy OBJECTIVE : To estimate if membrane sweeping increases the rate of prelabor rupture of membranes . METHODS : This r and omized trial of term , uncomplicated pregnancies included 300 patients . Patients were r and omly assigned into sweep or no-sweep groups , with patients and delivering providers blinded to group allocation . Only the examining provider in the clinic was unblinded to group allocation . Membranes were then swept or not swept at each weekly visit from 38 weeks of gestation onward , depending on the r and omization . Data collected included parity , cervix examination at each visit , estimated gestational age at delivery , rupture of membranes , and maternal or fetal complications . RESULTS : A total of 162 patients were r and omly assigned to the membrane sweep group and 138 to the no-sweep group . There was no difference in baseline characteristics or obstetric and neonatal outcomes between the groups . The average gestational age at delivery and induction rate were not different . The overall prelabor rupture of membranes rate was not significantly higher in the membrane sweep group ( 12 % compared with 7 % ) ( P=.19 ) ; however , patients with a cervix more than 1 cm dilated at time of membrane sweeping were more likely to have prelabor rupture of membranes if they were in the membrane sweep group ( 9.1 % compared with 0 % ; relative risk 1.10 , 95 % confidence interval 1.03–1.18 ) . CONCLUSION : No benefit in gestational age at delivery or reduction of postmaturity occurred from membrane sweeping . Although the overall prelabor rupture of membranes rates were similar , patients with membrane sweeping occurring at more than 1 cm cervical dilation may be at increased risk of prelabor rupture of membranes . CLINICAL TRIAL REGISTRATION : Clinical Trials.gov , www . clinical trials.gov , NCT00294242 LEVEL OF EVIDENCE : Objective . To evaluate the efficacy of acupuncture for labor stimulation . Methods . Nulliparous women at 38 weeks or greater were r and omized to traditional Chinese medicine ( TCM ) acupuncture , sham acupuncture , or usual care only groups . Acupuncture points LI4 , SP6 , BL32 , and BL54 were needled bilaterally . The primary outcome was time from enrollment to delivery . Secondary outcomes included rates of spontaneous labor and cesarean delivery . Medical records were abstract ed for maternal demographic , medical , and delivery outcome data . ANOVA , Student 's t-test , Chi-square , and Kaplan – Meier statistics were used to compare groups . Results . Eighty-nine women were enrolled and r and omized . Maternal age , gestational age , prior acupuncture experience , tobacco , alcohol and drug use , gravida , and history of gynecological surgery were similar among the groups . There were no statistically significant differences among groups for time from enrollment to delivery ( p = 0.20 ) , rates of spontaneous labor ( p = 0.66 ) , or rates of cesarean delivery ( p = 0.37 ) . Rates of maternal and neonatal outcomes were not significantly different . Conclusion . TCM acupuncture was not effective in initiating spontaneous labor or reducing the rate of cesarean delivery compared with sham acupuncture or usual medical care Please cite this paper as : Modlock J , Nielsen B , Uldbjerg N. Acupuncture for the induction of labour : a double‐blind r and omised controlled study . BJOG 2010;117:1255–1261 OBJECTIVE : To estimate the effect of serial membrane sweeping on the onset of labor in women who planned vaginal birth after cesarean ( VBAC ) . METHODS : Women at term with one transverse lower segment cesarean delivery who were suitable for and who planned VBAC were approached to participate . Participants were r and omly assigned to weekly membrane sweeping or weekly vaginal assessment for Bishop score until delivery . Participants and delivery providers were blinded to the allocated treatment . St and ard obstetric care was given to all participants . The primary outcome was onset of labor which was defined as the presence of spontaneous regular and painful contractions that cause cervical dilation to at least 3 cm or prelabor rupture of membranes . Secondary outcomes included induction of labor and repeat cesarean delivery . RESULTS : One hundred eight women were r and omly assigned to membrane sweeping and 105 to control . The spontaneous labor rate was 78.5 % compared with 72.1 % ( relative risk [ RR ] 1.1 , 95 % confidence interval [ CI ] 0.9–1.3 ; P=.34 ) , the induction of labor rate was 12.1 % compared with 9.6 % ( RR 1.3 , 95 % CI 0.6–2.8 ; P=.66 ) , and the all-cause cesarean delivery rate was 40.2 % compared with 44.2 % ( RR 0.9 , 95 % CI 0.7–1.2 ; P=.58 ) for the membrane sweeping and control groups , respectively . Gestational age at delivery ( mean±st and ard deviation ) of 39.6±1.0 weeks for the membrane sweeping group compared with 39.6±0.9 weeks for the control group ( P=.84 ) was no different . CONCLUSION : Serial membrane sweeping at term in women who planned VBAC has no significant effect on the onset of labor , pregnancy duration , induction of labor , or repeat cesarean delivery . CLINICAL TRIAL REGISTRATION : IS RCT N , is rct n.org , IS RCT N55163179 . LEVEL OF EVIDENCE : OBJECTIVE To compare the efficacy and safety of oral misoprostol with intracervical prostagl and in E2 ( PGE2 ) gel for the active management of premature rupture of membranes ( PROM ) at term . METHODS Women with pregnancies between 37 and 42 weeks presenting with PROM at term and a Bishop score of 5 or less were r and omly assigned to receive either a 4-hourly oral dose of 50 microg of misoprostol up to a maximum of 3 doses or 2 applications of intracervical PGE2 gel at a 6-hour interval . Oxytocin was given if labor had not started after 12 hours . RESULTS Twenty women in the misoprostol group ( n=31 ) delivered within 12 hours compared with 5 in the PGE2 group ( n=30 ) ( P<0.001 ) . The induction-to-delivery interval in the misoprostol group was shorter than in the PGE2 gel group ( 615 min vs 1070 min ; P<0.001 ) . The mode of delivery was comparable between the 2 groups ( P=0.821 ) . Abnormalities in uterine contractions and neonatal outcomes were also comparable . The requirement for oxytocin was lower and patient satisfaction was better in the misoprostol group . CONCLUSION Oral misoprostol is a safe and efficacious alternative to intracervical PGE2 gel in the active management of PROM at term OBJECTIVE : To estimate the clinical effectiveness of acupuncture to induce labor . METHODS : This study was a r and omized controlled trial of acupuncture compared with sham acupuncture . Women who were scheduled for a postterm induction with a singleton pregnancy and cephalic presentation were eligible for the study . Women received two acupuncture or sham acupuncture sessions over a 2-day period before the planned medical/pharmacological induction . The principal primary outcomes related to the need for induction methods and time from the administration of the intervention to delivery . RESULTS : Three hundred sixty-four women were r and omly assigned to the trial ( treatment n=181 and control n=183 ) . Women did not differ in their need for induction methods between groups : prostagl and in induction : relative risk ( RR ) 1.20 , 95 % confidence interval ( CI ) 0.96–1.51 , P=.11 ; artificial rupture of membranes only : RR 0.93 , 95 % CI 0.72–1.20 , P=.57 ; oxytocin only : RR 0.89 , 95 % CI 0.60–1.32 , P=.55 ; artificial rupture of membranes plus oxytocin : RR 0.87 , 95 % CI 0.57–1.33 , P=.52 ; prostagl and ins , artificial rupture of membranes , and oxytocin : RR 0.84 , 95 % CI 0.37–1.91 , P=.68 . The median time from acupuncture to delivery was 68.6 hours ( interquartile range 53.9–79.5 ) compared with 65 hours ( interquartile range 49.3–76.3 ) for women in the control group . CONCLUSION : Two sessions of manual acupuncture , using local and distal acupuncture points , administered 2 days before a scheduled induction of labor did not reduce the need for induction methods or the duration of labor for women with a postterm pregnancy . CLINICAL TRIAL REGISTRATION : Australian New Zeal and Clinical Trials Registry , www.anzctr.org.au , ACTRN12606000494538 LEVEL OF EVIDENCE : OBJECTIVE To evaluate the effectiveness of membrane sweeping at 41 weeks for the prevention of post-term pregnancy . DESIGN A multicentre r and omised controlled trial . SETTING Fifty-one primary care midwifery practice s in the Output:	Prostagl and in E2 ( PGE2 ) and vaginal misoprostol were more effective than oxytocin in bringing about vaginal delivery within 24 hours but were associated with more uterine hyperstimulation . Mechanical methods reduced uterine hyperstimulation compared with PGE2 and misoprostol , but increased maternal and neonatal infectious morbidity compared with other methods . Membrane sweeping reduced post-term gestations . Conclusions Research is needed to determine benefits and harms of many induction methods
MS213843	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Background and Purpose — Asymptomatic hemorrhagic transformation of infa rct ion ( AHTI ) is common , but its risk factors and relationship with functional outcome are poorly defined . Methods — The analyses used data from the Tinzapararin in Acute Ischaemic Stroke Trial , a r and omized controlled trial assessing tinzaparin ( low molecular weight heparin ) versus aspirin in 1484 patients with acute ischemic stroke . CT head scans ( baseline , day 10 ) were adjudicated for the presence of hemorrhagic transformation . Stroke subtype was classified according to modified Trial of Org 10172 in Acute Stroke Treatment ( small vessel , large vessel , cardioembolic ) and the Oxfordshire Community Stroke Project ( total anterior , partial anterior , lacunar , and posterior circulatory syndromes ) . Modified Rankin scale and Barthel Index were measured at 3 and 6 months . Analyses were adjusted for age , sex , severity , blood pressure , infa rct volume , and treatment . Symptomatic hemorrhage was excluded . Results — At day 10 , AHTI did not differ between aspirin ( 300 mg ; 32.8 % ) and medium-dose ( 100 IU/kg ; 36.0 % ) and high-dose ( 175 IU/kg ; 31.4 % ) tinzaparin groups ( P=0.44 ) . Relative to lacunar stroke , AHTI on follow-up CT was significantly increased in total anterior circulation syndrome ( odds ratio , 11.5 ; 95 % CI , 7.1 to 18.7 ) and partial anterior circulation syndrome ( odds ratio , 7.2 ; 95 % CI , 4.5 to 11.4 ) stroke . Similarly , relative to small vessel disease , AHTI was increased in large vessel ( odds ratio , 15.1 ; 95 % CI , 9.4 to 24.3 ) and cardioembolic ( odds ratio , 14.1 ; 95 % CI , 8.5 to 23.5 ) stroke . After adjustment for infa rct volume , the presence of AHTI was not associated with outcome at 3 or 6 months as measured by the modified Rankin Scale and Barthel Index . Conclusions — AHTI is increased in ischemic stroke with cortical syndromes and of large vessel or cardioembolic etiology . Heparin does not increase AHTI . AHTI is not associated with functional outcome BACKGROUND Urinary tract infection ( UTI ) is a recognized complication of stroke . We aim ed to determine the incidence of UTI after acute stroke , the risk factors associated with this complication , and its association with outcome . METHODS Prospect i ve study of consecutive acute stroke patients admitted to an urban teaching hospital . Routine clinical assessment included the modified National Institutes of Health Stroke Scale ( mNIHSS ) and modified Rankin scale ( mRS ) . Patients were followed up for 3 months , including recording of clinician diagnosis of UTI . RESULTS We studied 412 patients ; 65 ( 15.8 % ) were diagnosed with UTI , at a median of 14 days ( IQR = 4 - 39 ) post-stroke . In a binomial multivariate regression analysis , UTI was associated with urinary catheterization ( OR = 3.03 , 95 % CI 1.41 - 6.52 ) , higher mRS ( OR = 1.85 , 1.29 - 2.64 ) and increasing age ( OR = 1.51 , 1.13 - 2.00 for each decade ) . UTI was associated with death or disability at 3 months , however , this link was attenuated and became non-significant when measures of stroke severity and pre-stroke morbidity were included in a multivariate analysis . CONCLUSION UTI is common after acute stroke . It is associated with urinary catheterization , post-stroke disability and increasing age . Avoidance of catheterization might reduce the incidence of this common complication We sought to establish the pattern of blood pressure ( BP ) change after hospitalization for acute hemispheric stroke . Methods In 292 patients from the Leicester teaching hospitals with acute hemispheric stroke within the previous 24 hours ( 139 men ; median age , 75 years [ range , 42 to 98 years ] ) , we prospect ively studied BP changes between admission , 24 hours , 1 week , and 4 to 6 weeks . Changes were assessed in relation to the main stroke risk factors , stroke type and severity , and antihypertensive drug treatment . All subjects were followed up for 1 week , with 117 subjects followed up for 4 to 6 weeks . Changes were assessed by repeated- measures ANOVA , and Student 's t tests were used to compare group pairs . Results Systolic and diastolic BP fell by 12 mm Hg ( 95 % confidence interval [ CI ] , 8 to 15 mm Hg ) and 7 mm Hg ( 95 % CI , 5 to 9 mm Hg ) , respectively , in the first 24 hours and 22 mm Hg ( 95 % CI , 18 to 25 mm Hg ) and 12 mm Hg ( 95 % CI , 10 to 14 mm Hg ) , respectively , during the first week ( all changes significant at P<.01 ) but no further thereafter . In those patients receiving no antihypertensive medication before or after stroke , the pattern of change was similar to that of the whole group . Previously diagnosed hypertensive subjects ( n=106 ) had higher initial BP values than did normotensive subjects , although by 1 week the levels were not significantly different . Patients with cerebral hemorrhage confirmed by computed tomography ( n=20 ) had higher systolic BP , but not diastolic BP , throughout the first week than those with cerebral infa rct ion ( n=89 ) . The severity of stroke , age , and previous stroke history did not appear to alter the BP pattern . Stroke patients who were moderate to heavy alcohol consumers had lower convalescent systolic BP levels than lighter drinkers or abstainers . Conclusions We have demonstrated a marked fall in systolic and diastolic BP levels during the first 7 days after acute hemispheric stroke , with little change thereafter . Higher initial systolic BP values were found in patients with cerebral hemorrhage compared with those with cerebral infa rct . Moderate to heavy alcohol consumption before stroke was associated with a greater systolic BP decline in the first week after the event compared with stroke patients who were light drinkers or abstainers BACKGROUND AND PURPOSE Even patients with the most severe strokes sometimes experience a remarkably good recovery . We evaluated possible predictors of a good outcome to search for new therapeutic strategies . METHODS We included the 223 patients ( 19 % ) with the most severe strokes ( Sc and inavian Stroke Scale score < 15 points ) from the 1197 unselected patients in the Copenhagen Stroke Study . Of these , 139 ( 62 % ) died in the hospital and were excluded . The 26 survivors ( 31 % ) with a good functional outcome ( Barthel Index > /=50 points ) were compared with the 58 survivors ( 69 % ) with a poor functional outcome ( Barthel Index < 50 points ) . The predictive value of the following factors was examined in a multivariate logistic regression model : age ; sex ; a spouse ; work ; home care before stroke ; initial stroke severity ; blood pressure , blood glucose , and body temperature on admission ; stroke subtype ; neurological impairment 1 week after onset ; diabetes ; hypertension ; atrial fibrillation ; ischemic heart disease ; previous stroke ; and other disabling disease . RESULTS Decreasing age ( odds ratio [ OR ] , 0.50 per 10-year decrease ; 95 % CI , 0.25 to 0.99 ; P=0.04 ) , a spouse ( OR , 3.1 ; 95 % CI , 1.1 to 8 . 8 ; P=0.03 ) , decreasing body temperature on admission ( OR , 1.8 per 1 degrees C decrease ; 95 % CI , 1.1 to 3.1 ; P=0.01 ) , and neurological recovery after 1 week ( OR , 3.2 per 10-point increase in Sc and inavian Stroke Scale score ; 95 % CI , 1.1 to 7.8 ; P=0.01 ) were all independent predictors of good functional outcome . CONCLUSIONS Patients with the most severe strokes who achieve a good functional outcome are generally characterized by younger age , the presence of a spouse at home , and early neurological recovery . Body temperature was a strong predictor of good functional outcome and the only potentially modifiable factor . We suggest that a r and omized controlled trial be undertaken to evaluate whether active reduction of body temperature can improve the generally poor prognosis of patients with the most severe strokes BACKGROUND AND PURPOSE The great variability of outcome seen in stroke patients has led to an interest in identifying predictors of outcome . The combination of clinical and imaging variables as predictors of stroke outcome in a multivariable risk adjustment model may be more powerful than either alone . The purpose of this study was to determine the multivariable relationship between infa rct volume , 6 clinical variables , and 3-month outcomes in ischemic stroke patients . METHODS Included in the study were 256 eligible patients from the R and omized Trial of Tirilazad Mesylate in Acute Stroke ( RANTTAS ) . Six clinical variables and 1-week infa rct volume were the prespecified predictor variables . The National Institutes of Health Stroke Scale , Barthel Index , and Glasgow Outcome Scale were the outcomes . Multivariable logistic regression techniques were used to develop the model equations , and bootstrap techniques were used for internal validation . Predictive performance of the models was assessed for discrimination with receiver operator characteristic ( ROC ) curves and for calibration with calibration curves . RESULTS The predictive models had areas under the ROC curve of 0.79 to 0.88 and demonstrated nearly ideal calibration curves . The areas under the ROC curves were statistically greater ( P<0.001 ) with both clinical and imaging information combined than with either alone for predicting excellent recovery and death or severe disability . CONCLUSIONS Combined clinical and imaging variables are predictive of 3-month outcome in ischemic stroke patients . Demonstration of this relationship with acute clinical variables and 1-week infa rct information supports future attempts to predict 3-month outcome with all acute variables Objective : To ” nd patient characteristics in the early post stroke phase that could predict three years functional outcome . Design : Prospect i ve study . Setting : In-hospital rehabilitation department ( admission and discharge ) . Outpatient department one and three years post stroke . Subjects : One hundred and forty-two stroke patients ( 56 % women ) , median age 75 years . Main outcome measures : Barthel Index ( BI ) score ; BI score change ; accommodation status ; Rankin scale score ; and Frenchay Activities Index ( FAI ) score , all registered three years post stroke . Results : The percentages of patients still living at home after one and three years were 88 % and 83 % , respectively . Twenty per cent of the patients had deteriorated according to the BI after three years , mostly due to recurrent strokes ( odds ratio ( OR ) 10.3 ; 95 % con”dence interval ( CI ) 3.0–35.5 ) and co-morbidity with other disabling disorders ( OR 3.9 ; CI 1.1–13.5 ) . Co-morbidity also emerged as an important risk factor for dependency according to BI score ( OR 8.8 ; CI 2.4–32.1 ) as well as for a poor FAI score ( OR 4.9 ; CI 1.9–13.0 ) . BI in the early phase was the strongest predictor for long-term functional outcome . Urinary incontinence emerged as a risk factor for nursing home placement after three years ( OR 3.2 ; CI 0.9–11.3 ) . Cognitive dysfunction was a risk factor for poor FAI scoring ( OR 2.7 ; CI 1.0–7.0 ) . Conclusions : After stroke rehabilitation , concomitant chronic disabling disorders and recurrent strokes seem to play an important role regarding dependency , h and icap and long-term functional decline The third most common stroke complication is infection . We studied the rates of aspiration pneumonia and urinary tract infection ( UTI ) , their risk factors and their effect on outcome in the 1455 Glycine Antagonist ( Gavestinel ) in Neuroprotection ( GAIN ) International patients with ischaemic stroke . Forward stepwise logistic regression and Cox proportional hazards modelling identified baseline factors that predicted events and the independent effect of events up to day 7 on poor stroke outcome at 3 months in patients alive at day 7 , after correcting for prognostic factors . Higher baseline National Institute of Health Stroke Scale ( NIHSS ) and age , male gender , history of diabetes and stroke subtype predicted pneumonia , which occurred in 13.6 % of patients . Female gender and higher baseline NIHSS and age predicted UTI , which occurred in 17.2 % of patients . Pneumonia was associated with poor outcome by mortality ( hazard ratio , 2.2 ; 95 % confidence interval , 1.5 - 3.3 ) , Barthel index ( < 60 ) ( odds ratio , 3.8 ; 2.2 - 6.7 ) , NIHSS ( 4.9 ; 1.7 - 14 ) and Rankin scale ( > /=2 ) ( 3.4 ; 1.4 - 8.3 ) . UTI was associated with Barthel index ( 1.9 ; 1.2 - 2.9 ) , NI Output:	There are rather consistent findings that greater age , a more severe stroke ( measured through a clinical evaluation scale ) , the presence of urinary incontinence ( with impaired awareness ) and a larger stroke volume ( measured through brain imaging techniques ) predict poor stroke outcome . Studies using a selected group of stroke patients tended to identify different predictors . The current evidence is insufficient for the development of a clinical prediction tool that is better than physicians ' informal predictions .
MS213844	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: BACKGROUND Lanthanum carbonate ( LC ) , an effective non-calcium phosphate binder is widely used to manage hyperphosphatemia in patients with chronic kidney disease ( CKD ) on dialysis . Recently , the additional indication for control of hyperphosphatemia in CKD patients not on dialysis has been approved . METHODS A multicenter , r and omized , double-blind , placebo-controlled trial to confirm the efficacy and safety of LC in Japanese hyperphosphatemic stage 4 - 5 CKD patients not on dialysis . After a 4-week run-in period , 143 eligible subjects with serum phosphate levels of 5.6 - 11.0 mg/dL were r and omized ( 2 : 1 ) to receive LC or placebo ( 88 vs. 55 ) for 8 weeks ; 119 subjects completed the study ( 76 vs. 43 ) . The starting LC dose was 750 mg/day , which was then up-titrated to 2,250 mg/day as needed while tolerated . Primary efficacy analysis was performed on the intent-to-treat ( ITT ) population of 141 patients ( 86 vs. 55 ) . RESULTS LC produced a significantly greater reduction in serum phosphate level compared with placebo after 8 weeks of treatment ( difference , 0.97 ( 95 % CI : 0.58 , 1.37 ) mg/ dL ; p < 0.0001 ) . The cumulative proportion of subjects with controlled phosphate levels ≤ 4.6 mg/dL was higher in the LC group than the placebo group ( 59.56 % vs. 10.46 % ) . LC caused significantly greater reductions in serum Ca × P product and urinary phosphate excretion compared with placebo . The safety profile of LC was similar to that of placebo . CONCLUSIONS This study demonstrated the effectiveness of LC to control hyperphosphatemia in pre-dialysis CKD patients BACKGROUND JTT-751 is a novel phosphate binder containing ferric citrate as the active ingredient . METHODS In this Phase 3 , multicenter , r and omized , open-label , parallel-group study , we compared the efficacy and safety of JTT-751 and sevelamer hydrochloride in patients undergoing hemodialysis . A total of 230 patients with a serum phosphate ≥1.97 and < 3.23 mmol/L were r and omized to JTT-751 ( dose adjusted between 1.5 and 6.0 g/day ) or sevelamer hydrochloride ( dose adjusted between 3.0 and 9.0 g/day ) for 12 weeks . The primary outcome was change in serum phosphate from baseline to end of treatment . Secondary outcomes included the changes in corrected serum calcium and intact parathyroid hormone ( PTH ) . The changes in ferritin , transferrin saturation and erythropoiesis-stimulating agent dose were additional outcomes . RESULTS Changes in serum phosphate at the end of treatment were -0.82 mmol/L in the JTT-751 group and -0.78 mmol/L in the sevelamer group , establishing non-inferiority of JTT-751 compared with sevelamer ( least squares mean , -0.03 mmol/L ; 95 % confidence interval , -0.13 to 0.07 mmol/L ) . Corrected serum calcium increased and PTH decreased from baseline within both groups ; changes between groups were similar . Gastrointestinal disorders were the most common adverse events in both groups ; the incidence of diarrhea was higher in the JTT-751 group , while constipation occurred frequently in the sevelamer group . Treatment with JTT-751 result ed in significant relative increases in serum ferritin and transferrin saturation . CONCLUSIONS Efficacy and safety of JTT-751 was comparable to sevelamer in patients on hemodialysis with hyperphosphatemia . Differential adverse effects were observed ; biochemical markers of iron status increased in patients treated with JTT-751 . TRIAL REGISTRATION NUMBER CTI-111433 ( The Japan Pharmaceutical Information Center at : http//www . clinical trials.jp ) . Date of registration : 7 March 2011 Background and Aims : Calcium-containing phosphate binders have been shown to increase the progression of vascular calcification in hemodialysis patients . This is a prospect i ve study that compares the effects of calcium acetate and sevelamer on coronary calcification ( CAC ) and bone histology . Methods : 101 hemodialysis patients were r and omized for each phosphate binder and su bmi tted to multislice coronary tomographies and bone biopsies at entry and 12 months . Results : The 71 patients who concluded the study had similar baseline characteristics . On follow-up , the sevelamer group had higher levels of intact parathyroid hormone ( 498 ± 352 vs. 326 ± 236 pg/ml , p = 0.017 ) , bone alkaline phosphatase ( 38 ± 24 vs. 28 ± 15 U/l , p = 0.03 ) and deoxypyridinoline ( 135 ± 107 vs. 89 ± 71 nmol/l , p = 0.03 ) and lower LDL cholesterol ( 74 ± 21 vs. 91 ± 28 mg/dl , p = 0.015 ) . Phosphorus ( 5.8 ± 1.0 vs. 6 ± 1.0 mg/dl , p = 0.47 ) and calcium ( 1.27 ± 0.07 vs. 1.23 ± 0.08 mmol/l , p = 0.68 ) levels did not differ between groups . CAC progression ( 35 vs. 24 % , p = 0.94 ) and bone histological diagnosis at baseline and 12 months were similar in both groups . Patients of the sevelamer group with a high turnover at baseline had an increase in bone resorption ( eroded surface , ES/BS = 9.0 ± 5.9 vs. 13.1 ± 9.5 % , p = 0.05 ) , whereas patients of both groups with low turnover at baseline had an improvement in bone formation rate ( BFR/BS = 0.015 ± 0.016 vs. 0.062 ± 0.078 , p = 0.003 for calcium and 0.017 ± 0.016 vs. 0.071 ± 0.084 μm3/μm2/day , p = 0.010 for sevelamer ) . Conclusions : There was no difference in CAC progression or changes in bone remodeling between the calcium and the sevelamer groups Background High levels of circulating fibroblast growth factor 23 ( FGF23 ) are associated with chronic kidney disease ( CKD ) progression and high mortality . In the Phosphate Reduction Evaluation of FGF23 in Early CKD Treatment ( PREFECT ) study , we assessed the effect of reducing intestinal phosphate absorption using lanthanum carbonate on FGF23 levels in normophosphatemic patients with CKD stage 3 . Methods Thirty-five individuals were r and omized to lanthanum carbonate 3000 mg/day ( n = 23 ) or placebo ( n = 12 ) for 12 weeks . Levels of intact FGF23 ( iFGF23 ) , C-terminal FGF23 , serum and urinary phosphate and calcium , intact parathyroid hormone and 1,25-dihydroxyvitamin D were assessed . Results The median age was 65 years in the lanthanum group and 73 years in the placebo group ; 58.8 % and 41.7 % were men , respectively . No significant difference was seen in mean iFGF23 between groups at week 12 . There was , however , a transient reduction from baseline in iFGF23 in the lanthanum group at week 1 , from 70.5 pg/ml to 51.9 pg/ml , which was not seen in the placebo group ; this between-group difference in percentage change from baseline was significant in post hoc analyses ( p = 0.0102 ) . Urinary phosphate decreased after 1 week of lanthanum treatment and remained low at week 12 . Conclusions Reducing intestinal phosphate absorption with lanthanum carbonate did not lead to sustained reductions in iFGF23 in patients with CKD stage 3 , although phosphaturia decreased . This suggests that factors other than phosphate burden may be responsible for driving increases in circulating FGF23 in patients with CKD.Trial registration Clinical Trials.gov NCT01128179 , 20 May 2010 BACKGROUND Iron deficiency anemia and serum phosphate levels > 4.0mg/dL are relatively common in chronic kidney disease stages 3 to 5 and are associated with higher risks of progressive loss of kidney function , cardiovascular events , and mortality . STUDY DESIGN Double-blind , placebo-controlled , r and omized trial . SETTING & PARTICIPANTS 149 patients with estimated glomerular filtration rates < 60 mL/min/1.73 m(2 ) , iron deficiency anemia ( hemoglobin , 9.0 - 12.0 g/dL ; transferrin saturation [TSAT]≤ 30 % , serum ferritin ≤ 300 ng/mL ) , and serum phosphate levels ≥ 4.0 to 6.0mg/dL. Use of intravenous iron or erythropoiesis-stimulating agents was prohibited . INTERVENTION R and omization to treatment for 12 weeks with ferric citrate coordination complex ( ferric citrate ) or placebo . OUTCOMES & MEASUREMENTS Co primary end points were change in TSAT and serum phosphate level from baseline to end of study . Secondary outcomes included change from baseline to end of treatment in values for ferritin , hemoglobin , intact fibroblast growth factor 23 ( FGF-23 ) , urinary phosphate excretion , and estimated glomerular filtration rate . RESULTS Ferric citrate treatment increased mean TSAT from 22 % ± 7 % ( SD ) to 32 % ± 14 % and reduced serum phosphate levels from 4.5 ± 0.6 to 3.9 ± 0.6 mg/dL , while placebo exerted no effect on TSAT ( 21 % ± 8 % to 20 % ± 8 % ) and less effect on serum phosphate level ( 4.7 ± 0.6 to 4.4 ± 0.8 mg/dL ; between-group P<0.001 for each ) . Ferric citrate increased hemoglobin levels ( from 10.5 ± 0.8 to 11.0 ± 1.0 g/dL ; P<0.001 vs placebo ) , reduced urinary phosphate excretion 39 % ( P<0.001 vs placebo ) , and reduced serum intact FGF-23 levels from a median of 159 ( IQR , 102 - 289 ) to 105 ( IQR , 65 - 187 ) pg/mL ( P=0.02 vs placebo ) . The incidence and severity of adverse effects were similar between treatment arms . LIMITATIONS The study is limited by relatively small sample size and short duration and by having biochemical rather than clinical outcomes . CONCLUSIONS Short-term use of ferric citrate repletes iron stores , increases hemoglobin levels , and reduces levels of serum phosphate , urinary phosphate excretion , and FGF-23 in patients with chronic kidney disease stages 3 to 5 BACKGROUND AND OBJECTIVES Ferric citrate hydrate is a novel iron-based phosphate binder being developed for hyperphosphatemia in patients with CKD . DESIGN , SETTING , PARTICIPANTS , & MEASUREMENTS A phase 3 , multicenter , r and omized , double blind , placebo-controlled study investigated the efficacy and safety of ferric citrate hydrate in nondialysis-dependent patients with CKD . Starting in April of 2011 , 90 CKD patients ( eGFR=9.21±5.72 ml/min per 1.73 m(2 ) ) with a serum phosphate≥5.0 mg/dl were r and omized 2:1 to ferric citrate hydrate or placebo for 12 weeks . The primary end point was change in serum phosphate from baseline to the end of treatment . Secondary end points included the percentage of patients achieving target serum phosphate levels ( 2.5 - 4.5 mg/dl ) and change in fibroblast growth factor-23 at the end of treatment . RESULTS The mean change in serum phosphate was -1.29 mg/dl ( 95 % confidence interval , -1.63 to -0.96 mg/dl ) in the ferric citrate hydrate group and 0.06 mg/dl ( 95 % confidence interval , -0.20 to 0.31 mg/dl ) in the placebo group ( P<0.00 Output:	DISCUSSION / CONCLUSIONS Use of calcium results in higher mortality than either sevelamer in particular and NCBPBs in general ( moderate quality evidence ) . Our results raise questions about whether administration of calcium as an intervention for CKD- MBD remains ethical .
MS213845	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Abstract 1680 participants were r and omized over the recruitment period in MAPT study . A total of 1290 participants were recruited in the 7 University Hospital centers , and 390 participants in the 6 memory clinics around Toulouse Gerontopole / Alzheimer Disease research clinical center . The first r and omization was on May 30 , 2008 , and the targeted number of r and omized participants was reached on February 24 , 2011 ; 2595 subjects were finally screened , of which 1680 fulfilled the eligibility criteria which represents 64.8 % . Approximately , one quarter of screened people refused to participate after the detailed presentation of the study and 4.3 % were still interested in participating but missed for unknown reasons the baseline visit even after repeated contacts . Of the 1810 subjects who signed the consent for participating to the study at the baseline visit , 130 ( 7.1 % ) were excluded because one of the eligibility criteria was not satisfied . Interestingly , the higher percentage of r and omizations compared to screened participants is the personal contact source ; almost 85 % of screened participants entered in the study . In an equivalent way , Medias and conferences are efficient recruiting sources to enrol volunteers in the study . Unexpectedly , only about 60 % of screened participants from the hospital and GP sources were r and omized and 33.2 % from health care services . Almost a quarter of the r and omized participants come from the hospital out patients clinics and approximately 20 % from public conferences . A total of 1128 contacts yielded to 556 screened volunteers and 345 r and omized participants in the coordinating center of Toulouse . Thus , 30 % of contacts were recruited Purpose To assess the effects of creatine supplementation , associated or not with strength training , upon emotional and cognitive measures in older woman . Methods This is a 24-week , parallel-group , double-blind , r and omized , placebo-controlled trial . The individuals were r and omly allocated into one of the following groups ( n=14 each ) : 1 ) placebo , 2 ) creatine supplementation , 3 ) placebo associated with strength training or 4 ) creatine supplementation associated with strength training . According to their allocation , the participants were given creatine ( 4 x 5 g/d for 5 days followed by 5 g/d ) or placebo ( dextrose at the same dosage ) and were strength trained or not . Cognitive function , assessed by a comprehensive battery of tests involving memory , selective attention , and inhibitory control , and emotional measures , assessed by the Geriatric Depression Scale , were evaluated at baseline , after 12 and 24 weeks of the intervention . Muscle strength and food intake were evaluated at baseline and after 24 weeks . Results After the 24-week intervention , both training groups ( ingesting creatine supplementation and placebo ) had significant reductions on the Geriatric Depression Scale scores when compared with the non-trained placebo group ( p = 0.001 and p = 0.01 , respectively ) and the non-trained creatine group ( p < 0.001 for both comparison ) . However , no significant differences were observed between the non-trained placebo and creatine ( p = 0.60 ) groups , or between the trained placebo and creatine groups ( p = 0.83 ) . Both trained groups , irrespective of creatine supplementation , had better muscle strength performance than the non-trained groups . Neither strength training nor creatine supplementation altered any parameter of cognitive performance . Food intake remained unchanged . Conclusion Creatine supplementation did not promote any significant change in cognitive function and emotional parameters in apparently healthy older individuals . In addition , strength training per se improved emotional state and muscle strength , but not cognition , with no additive effects of creatine supplementation . Trial Registration Clinical trials.gov BACKGROUND Research indicates that the chronic consumption of flavonoids is associated with cognitive benefits in adults with mild cognitive impairment and neurodegenerative disease , although to our knowledge , there have been no such studies in healthy older adults . Furthermore , the effects of commonly consumed orange juice flavanones on cognitive function remain unexplored . OBJECTIVE We investigated whether 8 wk of daily flavanone-rich orange juice consumption was beneficial for cognitive function in healthy older adults . DESIGN High-flavanone ( 305 mg ) 100 % orange juice and an equicaloric low-flavanone ( 37 mg ) orange-flavored cordial ( 500 mL ) were consumed daily for 8 wk by 37 healthy older adults ( mean age : 67 y ) according to a crossover , double-blind , r and omized design separated by a 4-wk washout . Cognitive function , mood , and blood pressure were assessed at baseline and follow-up by using st and ardized vali date d tests . RESULTS Global cognitive function was significantly better after 8-wk consumption of flavanone-rich juice than after 8-wk consumption of the low-flavanone control . No significant effects on mood or blood pressure were observed . CONCLUSIONS Chronic daily consumption of flavanone-rich 100 % orange juice over 8 wk is beneficial for cognitive function in healthy older adults . The potential for flavanone-rich foods and drinks to attenuate cognitive decline in aging and the mechanisms that underlie these effects should be investigated IMPORTANCE Oxidative stress and vascular impairment are believed to partly mediate age-related cognitive decline , a strong risk factor for development of dementia . Epidemiologic studies suggest that a Mediterranean diet , an antioxidant-rich cardioprotective dietary pattern , delays cognitive decline , but clinical trial evidence is lacking . OBJECTIVE To investigate whether a Mediterranean diet supplemented with antioxidant-rich foods influences cognitive function compared with a control diet . DESIGN , SETTING , AND PARTICIPANTS Parallel-group r and omized clinical trial of 447 cognitively healthy volunteers from Barcelona , Spain ( 233 women [ 52.1 % ] ; mean age , 66.9 years ) , at high cardiovascular risk were enrolled into the Prevención con Dieta Mediterránea nutrition intervention trial from October 1 , 2003 , through December 31 , 2009 . All patients underwent neuropsychological assessment at inclusion and were offered retesting at the end of the study . INTERVENTIONS Participants were r and omly assigned to a Mediterranean diet supplemented with extravirgin olive oil ( 1 L/wk ) , a Mediterranean diet supplemented with mixed nuts ( 30 g/d ) , or a control diet ( advice to reduce dietary fat ) . MAIN OUTCOMES AND MEASURES Rates of cognitive change over time based on a neuropsychological test battery : Mini-Mental State Examination , Rey Auditory Verbal Learning Test ( RAVLT ) , Animals Semantic Fluency , Digit Span subtest from the Wechsler Adult Intelligence Scale , Verbal Paired Associates from the Wechsler Memory Scale , and the Color Trail Test . We used mean z scores of change in each test to construct 3 cognitive composites : memory , frontal ( attention and executive function ) , and global . RESULTS Follow-up cognitive tests were available in 334 participants after intervention ( median , 4.1 years ) . In multivariate analyses adjusted for confounders , participants allocated to a Mediterranean diet plus olive oil scored better on the RAVLT ( P = .049 ) and Color Trail Test part 2 ( P = .04 ) compared with controls ; no between-group differences were observed for the other cognitive tests . Similarly adjusted cognitive composites ( mean z scores with 95 % CIs ) for changes above baseline of the memory composite were 0.04 ( -0.09 to 0.18 ) for the Mediterranean diet plus olive oil , 0.09 ( -0.05 to 0.23 ; P = .04 vs controls ) for the Mediterranean diet plus nuts , and -0.17 ( -0.32 to -0.01 ) for the control diet . Respective changes from baseline of the frontal cognition composite were 0.23 ( 0.03 to 0.43 ; P = .003 vs controls ) , 0.03 ( -0.25 to 0.31 ) , and -0.33 ( -0.57 to -0.09 ) . Changes from baseline of the global cognition composite were 0.05 ( -0.11 to 0.21 ; P = .005 vs controls ) for the Mediterranean diet plus olive oil , -0.05 ( -0.27 to 0.18 ) for the Mediterranean diet plus nuts , and -0.38 ( -0.57 to -0.18 ) for the control diet . All cognitive composites significantly ( P < .05 ) decreased from baseline in controls . CONCLUSIONS AND RELEVANCE In an older population , a Mediterranean diet supplemented with olive oil or nuts is associated with improved cognitive function . TRIAL REGISTRATION is rct n.org Identifier : IS RCT N35739639 Recent epidemiological studies have indicated numerous associations between vascular and lifestyle related risk factors and incident dementia . However , evidence from r and omised controlled trials ( RCT ) showing effectiveness of interventions aim ed at these risk factors in preventing or postponing dementia onset is still lacking . Three large RCTs on multi-component interventions to prevent dementia ( preDIVA , FINGER , MAPT ) have been initiated in Europe to address these issues . Irrespective of some method ological differences , all three studies target cardiovascular and lifestyle related risk factors . Collaboration within the newly founded ' European Dementia Prevention Initiative ' ( EDPI ) will allow for a comprehensive exploration of optimal target population , intervention and outcome measures , which are currently unknown . Combining data of the ongoing studies and running simulation analyses will facilitate determining the optimal design including accurate sample -size calculations for future multi-national clinical trials on dementia prevention . Interventions aim ing at dementia prevention should be pragmatic and easy to implement on a large scale in different health care systems , without generating high additional costs or burden on participants or physicians . As the optimal age for intervention precedes the optimal age for outcome assessment , traditional trial design s might lead to suboptimal timing of either of the two . Separation of intervention and outcome assessment in time is a potential solution , but requires studies with very long follow-up . International collaboration of research groups with experience in dementia prevention studies and well-organised logistics for these major projects is pivotal to success for future large-scale dementia prevention studies . Founding of EDPI is an important first step in this direction Background and Purpose Cardiovascular risk factors are associated with an increased risk of dementia . Treatment of hypertension and hypercholesterolemia is associated with a decrease in incident dementia . Whether interventions aim ed at cardiovascular risk factors in late life also reduce dementia risk is unknown . Here , we report the outline of a pragmatic study that will attempt to answer this question and we describe the prevalence of cardiovascular risk factors in the target population . Methods We design ed a large cluster-r and omized trial with a 6-year follow-up in 3700 elderly subjects ( 70 to 78 y ) to assess whether nurse-led intensive vascular care in primary care decreases the incidence of dementia and reduces disability . Secondary outcome parameters are mortality , incidence of vascular events , and cognitive functioning . Intensive vascular care comprises treatment of hypertension , hypercholesterolemia , diabetes and reducing overweight , smoking cessation , and stimulating physical exercise . Results Baseline data of 1004 subjects show that 87 % of the subjects have 1 or more cardiovascular risk factors and 44 % have even 2 or more risk factors amenable to treatment . Seventy-nine percent of the subjects receiving antihypertensive medication still have a systolic pressure of > 140 mm Hg . Conclusions In this older age group , the very high percentage of elderly subjects with cardiovascular risk factors illustrates the large window of opportunity for therapies directed to lower the cardiovascular risk and potentially also the risk for dementia BACKGROUND Modifiable vascular and lifestyle-related risk factors have been associated with dementia risk in observational studies . In the Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability ( FINGER ) , a proof-of-concept r and omised controlled trial , we aim ed to assess a multidomain approach to prevent cognitive decline in at-risk elderly people from the general population . METHODS In a double-blind r and omised controlled trial we enrolled individuals aged 60 - 77 years recruited from previous national surveys . Inclusion criteria were CAIDE ( Cardiovascular Risk Factors , Aging and Dementia ) Dementia Risk Score of at least 6 points and cognition at mean level or slightly lower than expected for age . We r and omly assigned participants in a 1:1 ratio to a 2 year multidomain intervention ( diet , exercise , cognitive training , vascular risk monitoring ) , or a control group ( general health advice ) . Computer-generated allocation was done in blocks of four ( two individuals r and omly allocated to each group ) at each site . Group allocation was not actively disclosed to participants and outcome assessors were masked to group allocation . The primary outcome was change in cognition as measured through comprehensive neuropsychological test battery ( NTB ) Z score . Analysis was by modified intention to treat ( all participants with at least one post-baseline observation ) . This trial is registered at Clinical Trials.gov , number NCT Output:	Overall , most of the nutritional interventions tested by the selected RCTs were found to produce statistically significant cognitive benefits ( defined as improved neuropsychological test scores ) . Results of the present review suggest that several dietary patterns and nutritional components may constitute promising strategies in postponing , slowing , and preventing cognitive decline .
MS213846	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: OBJECTIVE To test the hypothesis that there is a review er bias against publication of a test of an unconventional drug . DESIGN R and omized , controlled , double-blind study of peer review . PARTICIPANTS Convenience sample of 291 medical doctors from a wide variety of specialties drawn from a list of conference participants . METHODS Review ers were r and omly assigned to receive one of two versions of a manuscript . Version M related to an in-vitro experiment on a mainstream drug ( Metoprolol ) . The otherwise identical version V used a highly unconventional drug ( beef spleen cell extract ) for the same experiment . Review ers were asked to complete a st and ardised evaluation sheet including visual analogue scales ( VASs ) on a set of predefined quality criteria . All participants were debriefed after completion of the study . RESULTS The response rate was 61 % . There were no significant differences in VAS ratings between the two versions of the manuscript . Ratings covered the entire range of the VASs . CONCLUSION In the present setting , there was no evidence for a review er-bias against testing an unconventional drug . The low inter-rater reliability , however , suggested inadequate validity of peer review Publication of medical research has high stakes : the communication and legitimization of medical research , the advancement of authors ' careers , priorities in funding decisions , the direction of future research , and the visibility and prestige of journals themselves . Peer review and editing play central roles in the publication process , affecting the acceptance of a manuscript and the form in which it appears . The most commonly heard justification of peer review is that it is an indispensable aid to an editor in assessing the importance of a scientific question and in assessing how well that question has been answered [ 1 , 2 ] . However , it has also been criticized as being inherently conservative , censorial , and , perhaps worst of all , arbitrary [ 3 ] . A frequently heard charge is that peer review delays the dissemination of crucial medical information without commensurate benefit [ 4 - 7 ] . During the last several years , some medical journal editors decided that the value of peer- review and editing practice s should be examined with the same rigor dem and ed for testing medical hypotheses [ 8 , 9 ] . The First International Congress on Peer Review was organized in 1989 [ 10 ] , bringing together medical journal editors and other interested scholars to present and discuss research on peer review ; a second Congress was held in 1993 . The peer- review process has two components : the assessment s by external review ers and the decisions and actions taken by editors , which are partially affected by comments from the review ers . To our knowledge , no study has evaluated the effects of peer review and editing on manuscript quality once the decision to accept has been made , and a computerized search of Index Medicus back to 1966 failed to locate any such studies . In this paper , we present the results of such a study , assessing the change in a manuscript between the times of provisional acceptance and final publication . We studied whether the quality of accepted manuscripts was improved by peer- review and editorial processes and , if it was , which aspects were most improved . Methods Setting The study was conducted at the editorial offices of Annals of Internal Medicine . Annals , a specialty journal in internal medicine , is published twice monthly and has a circulation of approximately 100 000 . Annals receives approximately 2400 manuscripts annually , of which half are reports of original research . During the period of this study , the investigators included the editors of Annals ( RHF and SWF ) and a statistical associate editor ( SNG ) . The Review Process No change was noted in the usual review and editing procedures at Annals during the time of this study . All manuscripts received at Annals were initially review ed by one of two full-time editors or one of two half-time deputy editors , as well as by one of seven associate editors , all of whom are faculty members of medical schools in Philadelphia and have subspecialty interests ( for example , infectious disease , gastroenterology ) . Half of the su bmi ssions were returned to authors without further review and half were sent to at least 2 outside review ers , selected by the associate editor from a data base of about 7000 review ers . After comments from the review ers were received , the original editor and associate editor reassessed each manuscript and chose which ones would be discussed at a weekly editorial conference of editors , deputy editors , medical associate editors , and two statistical associate editors . Factors that affected acceptance decisions included the quality of the research , the importance of the question , the contribution of the finding to its field , the utility and interest for Annals readers , the quality of the presentation , the priority relative to other articles , and available space . Authors were notified either that the editors would not accept the paper , that the editors were willing to reconsider the paper after major revisions , or that the paper was provisionally accepted , pending satisfactory revision . Approximately one third of the articles evaluated by outside review ers were accepted , 15 % of su bmi tted original research articles . Papers to be considered further were sent to authors , along with the comments of the two outside review ers , comments of one of the statistical editors , and a letter from one of the editors or deputy editors ( which summarized the discussion at the weekly conference , the ideas of the associate editor , and suggestions from the editor ) . In addition , each manuscript was review ed by a production editor , and directions for changes in manuscript wording or layout of figures and tables were included . All revised manuscripts were review ed by the editor or deputy editor in charge of the manuscript , the appropriate associate editor , the statistical editor , and the production editor . Some revised manuscripts were also reassessed by the original outside review ers . Approximately half of the revised manuscripts were returned to authors for further revision . Most revised manuscripts ( > 95 % ) were ultimately published . The time taken by this process was approximately 2 weeks for the initial decision to review or reject , 8 additional weeks to review and make an acceptance decision , 8 weeks until final acceptance , and about 4 months until publication . More than 95 % of manuscripts su bmi tted to Annals had a provisional acceptance or rejection decision sent to the authors within 3 months . The average time from su bmi ssion to publication was about 7 months , with initial peer review accounting for approximately 6 weeks . Manuscript Selection and Study Design All original research manuscripts ( articles ) accepted for publication by Annals from March 1992 to March 1993 were entered into the study after obtaining the author 's consent . Commentaries , review s , expository pieces , editorials , and brief reports were not included . This study had a beforeafter design , in which two versions of each manuscript were evaluated : the version originally su bmi tted and the version sent to the printer for publication after all modifications based on peer review , editors ' comments , and copyediting . All before and after manuscripts were in electronic form and were reformatted to make the appearance of the two versions identical . Authors ' names and affiliations were removed . The design of the study was approved by the Institutional Review Board of the University of Pennsylvania School of Medicine . Definition of Quality Manuscript quality can be separated conceptually into two components : the quality of the research itself , and the quality of the research report . The quality of the research report was evaluated in this study . It was defined as follows on the cover sheet of the quality assessment instrument : Whether the authors have described their research in enough detail and with sufficient clarity so a reader could make an independent judgment about the strengths and weaknesses of their data and conclusions . Manuscript Quality Assessment Instrument A 34- question instrument was developed to structure the assessment of the quality of a manuscript ( Appendix ) . Items were derived from published checklists [ 11 - 14 ] , articles about the contents of journal articles [ 15 - 18 ] , the authors ' editorial experience , and the comments of journal editors and method ologists who review ed drafts of the instrument . Each question could be answered on a 5-point ordinal scale , where 1 was worst and 5 was best . The instrument was organized along the same dimensions as a st and ard journal article : Title and Abstract ( 2 items ) , Introduction ( 2 items ) , Methods ( 7 items ) , Results ( 15 items ) , Discussion and Conclusions ( 4 items ) , and General Evaluation ( 4 items ) . An additional question asked for a subjective assessment of the manuscript 's overall quality on a 10-point scale . The instrument differed from previously published quality scoring schemes in several ways . It was not a checklist but rather was a set of structured judgments , grade d ordinally , allowing users the discretion not to penalize a manuscript if a detail was omitted that was not critical to the study 's interpretation . Also , in keeping with the definition of quality given above , each question was about the adequacy of the reporting rather than the quality of the research itself . Assessment A panel of 44 physicians and epidemiologists with training in research methods and in critically assessing the medical literature was recruited to serve as an independent panel of expert assessors ( experts ) . They did not receive any formal training in the use of the assessment instrument , although general guidelines were given on the cover sheet ( Appendix ) . The panel was masked to the design and aims of the study ; they were told only that they were participating in a study of manuscript quality for Annals . Before and after versions of each manuscript were r and omly assigned to different experts to prevent the bias that might have been introduced if they could infer the design of the study and thereby which manuscript had been through the editorial process . Thirty-two manuscript versions were given to two or three experts to assess the reliability of the instrument ; all others were assessed by only one expert . Statistical Analyses The study was design ed to have 90 % power to detect a 0.5 unit change in average score , assuming a within-manuscript st and ard deviation of 1 scale unit , using = 0.05 . The main outcome measure was the percentage of items that were scored 3 or higher on the 5-point scales ( percentage score ) . The average of all score components ( average score ) was also analyzed . Linear regression was used to assess the effect of revision on each of these outcome measures , with terms controlling for manuscript and review er . Item-specific analyses were done on dichotomized item scores ( 0 for ratings 2 and 1 for ratings 3 ) . The change from before revision to after revision in individual items was statistically assessed with conditional logistic regression , which allowed for variable group CONTEXT The quality of a process can only be tested against its agreed objectives . Editorial peer- review is widely used , yet there appears to be little agreement about how to measure its effects or processes . METHODS To identify outcome measures used to assess editorial peer review as performed by biomedical journals , we analyzed studies identified from 2 systematic review s that measured the effects of editorial peer review on the quality of the output ( ie , published articles ) or of the process itself ( eg , review ers ' comments ) . RESULTS Ten studies used a variety of instruments to assess the quality of articles that had undergone peer review . Only 1 , nonr and omized study compared the quality of articles published in peer- review ed and non-peer- review ed journals . The others measured the effects of variations in the peer- review process or used a before- and -after design to measure the effects of st and ard peer review on accepted articles . Eighteen studies measured the quality of review ers ' reports under different conditions such as blinding or after training . One study compared the time and cost of different review processes . CONCLUSIONS Until we have properly defined the objectives of peer- review , it will remain almost impossible to assess or improve its effectiveness . The research needed to underst and the broader effects of peer review poses many method ologic problems and would require the cooperation of many parts of the scientific community CONTEXT Anxiety about bias , lack of accountability , and poor quality of peer review has led to questions about the imbalance in anonymity between review ers and authors . OBJECTIVE To evaluate the effect on the quality of peer review of blinding review ers to the authors ' identities and requiring review ers to sign their reports . DESIGN R and omized controlled trial . SETTING A general medical journal . PARTICIPANTS A total of 420 review ers from the journal 's data base . INTERVENTION We modified a paper accepted for publication introducing 8 areas of weakness . Review ers were r and omly allocated to 5 groups . Groups 1 and 2 received manuscripts from which the authors ' names and affiliations had been removed , while groups 3 and 4 were aware of the authors ' identities . Groups 1 and 3 were asked to sign their reports , while groups 2 and 4 were asked to return their reports unsigned . The fifth group was sent the paper in the usual manner of the journal , with authors ' identities revealed and a request to comment anonymously . Group 5 differed from group 4 only in that its members were unaware that they were taking part in a study . MAIN OUTCOME MEASURE The number of weaknesses in the paper that were commented on by the review ers . RESULTS Reports were received from 221 review ers ( 53 % ) . The mean number of weaknesses commented on was 2 ( 1.7 , 2.1 , 1.8 , and 1.9 for groups 1 , 2 , 3 , and 4 and 5 combined , respectively ) . There were no statistically significant differences between groups in their performance . Review ers who were blinded to authors ' dentities were less likely to recommend rejection than those who were aware of the authors ' identities ( odds ratio , 0.5 ; 95 % confidence interval , 0.3 - 1.0 ) . CONCLUSIONS Neither blinding review ers to the authors and origin of the paper nor requiring them to sign their reports had any effect on rate of detection of errors . Such measures are unlikely to improve the quality of peer review reports OBJECTIVE To study whether review ers aware of author identity are biased in favor of authors with more previous publications . DESIGN R and omized controlled trial . SETTING Editorial office of the Journal of Developmental and Behavioral Pediatrics . PARTICIPANTS Two " blinded " and two " nonblinded " review ers assigned to 57 consecutive manuscripts su bmi tted between September 1991 and March 1992 . OUTCOME MEASURES Spearman rank correlation coefficients were used to compare the sum of rating scores of 1 to 5 ( 1 , accept ; 5 , reject ) given by the two blinded review ers , the two nonblinded review ers , and the editors to the number of articles published previously by the first and senior authors ( as determined from requested curricula vitae ) . Blinded review ers were sent a question naire asking whether they could determine the identity of the authors , how they knew , and whether they thought binding changed the quality or difficulty of their Output:	Editorial peer review , although widely used , is largely untested and its effects are uncertain
MS213847	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: BACKGROUND Subjects with a mild cognitive impairment ( MCI ) have a memory impairment beyond that expected for age and education yet are not demented . These subjects are becoming the focus of many prediction studies and early intervention trials . OBJECTIVE To characterize clinical ly subjects with MCI cross-sectionally and longitudinally . DESIGN A prospect i ve , longitudinal inception cohort . SETTING General community clinic . PARTICIPANTS A sample of 76 consecutively evaluated subjects with MCI were compared with 234 healthy control subjects and 106 patients with mild Alzheimer disease ( AD ) , all from a community setting as part of the Mayo Clinic Alzheimer 's Disease Center/Alzheimer 's Disease Patient Registry , Rochester , Minn. MAIN OUTCOME MEASURES The 3 groups of individuals were compared on demographic factors and measures of cognitive function including the Mini-Mental State Examination , Wechsler Adult Intelligence Scale-Revised , Wechsler Memory Scale-Revised , Dementia Rating Scale , Free and Cued Selective Reminding Test , and Auditory Verbal Learning Test . Clinical classifications of dementia and AD were determined according to the Diagnostic and Statistical Manual of Mental Disorders , Revised Third Edition and the National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer 's Disease and Related Disorders Association criteria , respectively . RESULTS The primary distinction between control subjects and subjects with MCI was in the area of memory , while other cognitive functions were comparable . However , when the subjects with MCI were compared with the patients with very mild AD , memory performance was similar , but patients with AD were more impaired in other cognitive domains as well . Longitudinal performance demonstrated that the subjects with MCI declined at a rate greater than that of the controls but less rapidly than the patients with mild AD . CONCLUSIONS Patients who meet the criteria for MCI can be differentiated from healthy control subjects and those with very mild AD . They appear to constitute a clinical entity that can be characterized for treatment interventions One of the defining differences between mild cognitive impairment ( MCI ) and dementia is the degree of independence in everyday activities . Effecting memory-related behavioural change in MCI could help maintain daily function and prolong the time before onset of dependency . However , it is well known that changing previously well-established behaviours is difficult to achieve . We conducted a r and omised controlled trial to evaluate the effectiveness of a multidisciplinary group-based intervention programme in changing everyday memory behaviour in individuals with amnestic MCI . The intervention provided evidence d-based memory training and lifestyle education to optimise memory behaviour . Fifty-four participants were r and omly assigned to treatment or waitlist-control conditions . Consistent with our primary goal , treatment participants showed an increase in memory- strategy knowledge and use from pre-test to immediate post-test , and these gains were maintained at three-month post-test relative to waitlist controls . There were no group differences in memory beliefs or on laboratory tests of objective memory performance . The increase in memory- strategy knowledge and use was associated with the degree of participation in the programme . Individuals with MCI , therefore , can acquire and maintain knowledge about memory strategies and , importantly , can change their everyday memory behaviour by putting this knowledge into practice . This incorporation of practical memory strategies into daily routines could potentially provide the means for maintaining functional independence by individuals with MCI , an issue to be addressed in future research OBJECTIVES This article describes results of a r and omized controlled trial comparing a time-limited early-stage memory loss ( ESML ) support group program conducted by a local Alzheimer 's Association chapter to a wait-list ( WL ) control condition . METHODS One hundred and forty-two dyads were r and omized in blocks to ESML ( n = 96 ) or WL ( n = 46 ) . Mean age of participants was 74.9 years , and mean Mini-Mental State Examination was 23.4 . The primary outcome was participant 's quality of life ; secondary outcomes included mood , family communication , and perceived stress . RESULTS On the intent-to-treat ( ITT ) pre-post analysis , significant differences were seen in participant quality of life ( p < .001 ) , depression ( p < .01 ) , and family communication ( p < .05 ) . Within the care partner groups , there was no significant difference between ESML and WL in the ITT analysis . A post hoc exploratory examination of changes that were associated with improved quality of life in ESML participants revealed significant reductions of depressive symptoms and behavior problems ( p < .05 ) , improved family communication ( p < .05 ) , self-efficacy ( p < .01 ) , Medical Outcomes Study short form ( SF-36 ) role-emotional ( p < .05 ) , SF-36 social functioning ( p < .05 ) , and SF-36 mental health components ( p < .01 ) in improvers . DISCUSSION These results support the efficacy of ESML support groups for individuals with dementia Background : Patients with mild cognitive impairment ( MCI ) have to deal with an uncertain prognosis and also face a multitude of memory-related problems and psychosocial consequences . A newly developed group programme proved to be feasible , however , it needed confirmation by a controlled study . Aim : This controlled study evaluates this group therapy for MCI patients aim ed to help them accept and manage the memory problems and the psychosocial consequences . The programme combines elements from psychoeducation , cognitive rehabilitation and cognitive-behavioural therapy . Patients and Methods : Ninety-three MCI patients received treatment , with 30 patients being first assigned to a waiting list , thus serving as their own control group . Pre- and post-treatment acceptance and helplessness were assessed using subscales of the Illness Cognition Question naire , while distress and general well-being were gauged with the Geriatric Depression Scale and subscales of the R AND -36 . Results : Linear mixed model analyses showed that , relative to the controls , acceptance had increased more in the intervention group compared to the waiting-list period ( p = 0.034 ) . Distress and general well-being showed no changes . Treatment responders demonstrating a clinical ly significant effect on acceptance and two of three secondary outcome measures had higher baseline levels of helplessness and fewer self-reported memory complaints in daily life than patients who did not improve . Conclusion : The intervention helped the patients deal better with their uncertain future in that they were overall better able to accept their condition , with especially the female patients showing a decrease in helplessness cognitions , although the effects were relatively small Objectives : The Enriched Opportunities Programme ( EOP ) is a multi-level intervention focussing on improved quality of life for people with dementia . This study compared the experience of people living with dementia and other mental health problems in extra care housing schemes that utilised EOP with schemes that employed an active control intervention . Method : Ten extra care housing schemes were cluster r and omised to receive either the EOP intervention or an active control intervention for an 18-month period . Residents with dementia or other significant mental health problems ( 20–30 per scheme ) were assessed on a number of outcome measures at baseline , six months , one year and 18 months . The primary outcome measure was quality of life . Self-reported depression was an important secondary outcome . Results : The EOP-participating residents rated their quality of life more positively over time ( 4.0 ( SE 0.6 ) units ; 14 % p < 0.001 ) than the active control ( 1.3 ( SE 0.6 ) units ; 4 % p = 0.003 ) . There was also a significant group – time interaction for depressive symptoms ( p = 0.003 ) . The EOP-participating residents reported a reduction of 25 % at both six and 12 months and a 37 % reduction at 18 months ( all p 's < 0.001 ) . EOP residents were less likely than residents in the active control sites to move to a care home or to be admitted to a hospital inpatient bed . They were more likely to be seen by a range of community health professionals . Conclusion : The EOP had a positive impact on the quality of life of people with dementia in well-staffed extra care housing schemes Background After diagnosis of a dementing illness , patients and their spouses have many concerns related to the disease and their future . This often leads to poor psychological well-being and reduced health-related quality of life ( HRQoL ) of the family . Support for self-management skills has been proven to be an effective method to improve prognosis of asthma , heart failure and osteoarthritis . However , self-management interventions have not been studied in dementia . Therefore , our aim was to examine , in an objective -oriented group intervention , the efficacy of self-management support program ( SMP ) on the HRQoL of dementia patients and their spousal caregivers as well as on the sense of competence and psychological well-being of caregivers . Methods During the years 2011 to 12 , 160 dementia patients and their spouses will be recruited from memory clinics and r and omized into two arms : 80 patients for group-based SMP sessions including topics selected by the participants , 80 patients will serve as controls in usual community care . Sessions may include topics on dementia , community services , active lifestyle and prevention for cognitive decline , spousal relationship , future planning and emotional well-being . The patients and spouses will have their separate group sessions ( ten participants per group ) once a week for eight weeks . Main outcome measures will be patients ’ HRQoL ( 15D ) and spousal caregivers ’ HRQoL ( R AND -36 ) , and sense of competence ( SCQ ) . Secondary measures will be caregivers ’ psychological well-being ( GHQ-12 ) and coping re sources , patients ’ depression , cognition and signs of frailty . Data concerning admissions to institutional care and the use and costs of health and social services will be collected during a two-year follow-up . Discussion This is a ‘ proof-of-concept ’ study to explore the efficacy of group support for self-management skills among dementia families . It will also provide data on cost-effectiveness of the intervention . Trial registration Background Social support is important in daily activities of the elderly . This study tests the hypothesis that there is an association between social support and cognitive function among the elderly in a community setting . Methods Face-to-face interviews were conducted in a cross-sectional stratified r and om sample of 4,993 elderly ( ≥65 years ) city residents . Using multiple regression analysis , we investigated the influence of social support on cognitive function . Results 12 % were over 80 years old . 53.28 % were men . 67.14 % were married . Higher Short Portable Mental Status Question naire ( SPMSQ ) scores ( higher score means better cognitive function ) were associated with strong social support , as measured by marital status and perceived positive support from friends . Lower cognitive function was associated with older and with female respondents . Only instrumental activities of daily living ( IADL ) were statistically and negatively related to SPMSQ . Lower functional status was associated with lower cognitive function . Elders with grade school educations had lower SPMSQ scores than did elders with high school educations . Conclusions In Taiwan , higher cognitive function in community-living elderly was associated with increased social support . Life-style management should provide social activities for the elderly to promote a better quality of life BACKGROUND Relatives and caregivers of patients with dementia are often insecure about the impact of their efforts . This study examines whether and to what extent social support in the form of regular visits is increasing the well-being of demented aged . PROCEDURE A field experiment with slightly to seriously demented institutionalized aged persons ( MMS 5 - 25 ) was carried out to assess the effect of increased social support upon their well-being . Voluntary helpers , who were willing to visit their patients on a regular basis , were recruited by appeals at the senior university and by advertisements . The volunteers were trained to deal with the demented and were looked after regularly . The test subjects were r and omly assigned to one of two test groups . The first group was visited regularly for ten weeks , whereas the second group served as a control group . The participants of the experimental group received a visiting card with a photo of the volunteer and the next appointment date to remember their visitors and to increase the effect of predictability . RESULTS The effect of visits on the well-being of the institutionalized aged persons was significantly positive ( F(1,39 ) = 11.16 , p < 0.002 ) . The psychological , physiological and social well-being of the participants was improved . Additionally , visits moderated the pain result ing from physical illness and seemed to decrease the effects of mental decline on their performance . Furthermore , it was most impressive to find that the demented aged really took notice of the visits and seemed to remember them in one way or an other . The study pointed out that demented aged persons are still very sensitive in an emotional respect and that they are still able to give astonishing good and differentiated information about their feelings even in an advanced state of dementia . Even the volunteers gained from their visits , which was shown by their higher well-being after their visits Accurate clinical staging of dementia in older subjects has not previously been achieved despite the use of such methods as psychometric testing , behavioural rating , and various combinations of simpler psychometric and behavioural evaluations . The Clinical Dementia Rating ( CRD ) , a global rating device , was developed for a prospect i ve study of mild senile dementia -- Alzheimer type ( SDAT ) . Reliability , validity , and correlational data are discussed . The CRD was found to distinguish unambiguously among older subjects with a wide range of cognitive function , from healthy to severely impaired OBJECTIVES To determine whether community care of demented patients can be prolonged by means of a 2-year support program based on nurse case management . DESIGN R and omized controlled intervention study with 2-year follow-up . SETTING Demented patients entitled to payments from the Social Insurance Institution for community care , in five municipalities in eastern Finl and . PARTICIPANTS One hundred demented patients , age 65 and older , living at home with the primary support of Output:	CONCLUSIONS Limited data from two studies suggest that support groups may be of psychological benefit to people with dementia by reducing depression and improving quality of life and self-esteem .
MS213848	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: We have evaluated the anaesthetic effect of tetracaine gel 1 g , applied for 45 min , compared with EMLA cream 2 g , applied for 60 min , in a r and omized , double-blind study in 60 children aged 3 - 15 yr . Venous cannulation was performed 15 min after removal of the EMLA cream ( n = 20 ) and tetracaine gel ( n = 20 ) . Cannulation was performed up to 215 min after removal of the tetracaine gel in another 20 patients . Significantly lower pain scores were recorded by the children treated with tetracaine gel compared with EMLA cream ( P < 0.02 ) . Forty to 45 % of children in the tetracaine groups reported no pain compared with only 10 % in the EMLA group . Only minor adverse effects were observed . We conclude that tetracaine gel provided effective , rapid , long-lasting and safe local anaesthesia , and was significantly better than EMLA cream in reducing pain during venous cannulation in children using the recommended application periods for both formulations OBJECTIVES Children view needle sticks as the worst source of pain and fear in the hospital setting . In an effort to minimize the pain of needle sticks , the use of eutectic mixture of lidocaine and prilocaine ( EMLA ) has become st and ard practice in many children 's hospitals . Unfortunately , EMLA requires at least 60 minutes to be fully effective and reportedly may cause vasoconstriction , leading to difficult vein cannulation . A newly available local anesthetic ( ELA-Max ) may require less time and cause less vasoconstriction . The purpose of this r and omized crossover study was to investigate the anesthetic equivalence of EMLA and ELA-Max . METHODS Thirty well children ( 14 girls and 16 boys ) who were between the ages of 7 and 13 years volunteered to have EMLA applied to the dorsal aspect of 1 h and for 60 minutes and ELA-Max applied to the other h and for 30 minutes . Right and left h and s were r and omized to treatment type and order of intravenous ( IV ) insertion . Clinical Research Center nurses , blind to the anesthetic r and omization , attempted to insert a 22-gauge Teflon IV catheter into a vein in each h and . The children rated pain during IV insertion on the Oucher scale , and the nurse rated the difficulty of the insertion . RESULTS There was no significant difference in pain ratings for h and s that were treated with EMLA ( mean : 20.5 ) or with ELA-Max ( mean : 24 ) , and there was no difference for the difficulty of vein cannulation . Children 's preprocedure state anxiety was positively associated with pain ratings . CONCLUSIONS ELA-Max , applied for 30 minutes before IV cannulation , has an anesthetic effectiveness similar to EMLA applied for 60 minutes . Some children rated IV insertion pain fairly high for both h and s ( eg , 60 on a 0- to 100-point scale ) despite anesthetic treatment . Preprocedural anxiety may affect the perception and /or rating of pain . There were no differences between h and s that were treated with EMLA or with ELA-Max for success of IV insertion background . Liposomes are microscopic phospholipid vessels that have been utilized to extend the action of topical medications . Previous studies have demonstrated that liposomal vehicles can prolong the action of a variety of medications , including antifungals , anesthetics , interferon , and antineoplastic agents . objective . The purpose of this study was to examine the degree and duration of anesthesia produced by lidocaine in a liposomal vehicle compared with lidocaine in a nonliposomal vehicle and compared with EMLA . The topical preparations in this study were allowed to contact the skin for a 30‐minute period prior to evaluation of anesthetic effectiveness . Unoccluded and Tegaderm‐occluded topical preparations were evaluated in two separate arms of the study . material s and methods . Thirteen healthy volunteers ( three male , 10 female ) were recruited for the nonocclusion arm of the study . Six healthy volunteers ( two male , four female ) were recruited for the occlusion arm of the study . Subjects with a history of allergy to lidocaine , a history of seizures , cardiac or respiratory difficulty , pregnant patients , and patients less than 18 years old were excluded . Written informed consent was obtained from all patients prior to testing . The volar forearms of the volunteers were swabbed with isopropyl alcohol and allowed to dry . A template was then utilized to mark 2 × 2‐cm squares with a skin marker on both volar forearms . In total , nine squares corresponding to nine test areas were marked . The nine test preparations were applied to the test areas in a double‐blinded fashion using a clean swab stick . The test preparations were then allowed to remain on the skin for 30 minutes in either occluded or nonoccluded form depending upon the arm of the study . Following the 30‐minute application period , the test preparations were wiped off with clean gauze . Testing for anesthesia was performed by following a previously published method utilizing gentle pinpricks . A new pinprick apparatus was used for each patient . Pinprick testing was performed at 0 , 15 , 30 , 60 , and 90 minutes following the end of the 30‐minute application period . Patients ' responses to the pinprick were recorded in a binary fashion , as being either : 1 ) totally painless or 0 ) painfully sharp to any degree . Ten applications of the pinprick were applied r and omly across each 2 × 2‐cm test area . The number of painless applications of the pinprick out of a total of 10 applications of the pinprick was then recorded for each test area at every particular test time . In total , nine test preparations were evaluated . Analysis of the data was performed by a PhD statistical faculty consultant from the UCLA Mathematics Department . results . Liposomal lidocaine preparations evidence d longer duration s of anesthesia than lidocaine preparations in nonliposomal vehicles . Five percent liposomal lidocaine preparations were statistically equivalent to EMLA in anesthetic effectiveness . conclusion . Five percent liposomal lidocaine is an effective alternative topical agent for use in the attainment of temporary local anesthesia of the skin A r and omized double-blind study was conducted in 83 women scheduled for elective caesarean section to determine the efficacy of EMLA and lignocaine infiltration for epidural insertion . The patients were r and omly allocated to one of three groups : Group A ( EM/LIG ) received EMLA and intradermal and subdermal 1 % lignocaine infiltration , Group B ( EM/SAL ) EMLA and saline while Group C ( PL/LIG ) received placebo cream and 1 % lignocaine . Assessment s using a 100 mm pain score were performed on skin infiltration and after subsequent insertion of a 16 gauge Tuohy needle into the supraspinous ligament . Skin changes under the applied cream and nursing rating of patients ’ response were also noted . Statistical analyses were performed using Kruskal-Wallis and Fisher 's Exact Tests . Groups were comparable for age , weight , parity and EMLA application time ( interquartile range 105 - 150 minutes ) There were significantly higher pain scores for skin infiltration in Group C ( PL/LIG ) ( P<0.01 ) and for epidural needle insertion in Group B ( EM/SAL ) ( P<0.05 ) . We concluded that in this patient population , the application of EMLA cream for at least 90 minutes plus 1 % lignocaine infiltration optimized patient comfort for epidural insertion Background The eutectic mixture of local anaesthetics ( EMLA ) provides effective topical anaesthesia after a minimum of 60 to 90 mm application . Since liposome-encapsulated tetracaine ( LET ) can provide rapid dermal penetration , the goal of this study was to compare the local anaesthetic effects of EMLA and LET in human volunteers after 60 mm application . Methods After obtaining institutional approval and informed consent , healthy volunteers were recruited in a double blind , crossover , r and omized trial . The study creams ( 0.5 ml EMLA and 0.5 ml LET 5 % ) were applied r and omly to opposite arms for 60 min . The discomfort of iv cathetenzation was assessed using a visual analogue pain score ( VAS ) . Cutaneous side effects of the creams were recorded . Results Sixty-one subjects were studied . Twenty-one were excluded because of technical difficulties . Forty subjects completed the study and were included in the data analysis . The mean ( ±SD ) VAS was lower for LET than for EMLA ( 10.9 ± 9.0 mm vs 22.7 ± 17.1 mm , P < 0.001 ) . Erythema secondary to vasodilatation occurred more frequent in the LET group than in the EMLA group ( 33 vs 3 . P < 0.001 ) . One subject with a history of atopy developed a rash at the LET application site . Conclusion Liposome-encapsulated tetracaine can provide a more effective topical anaesthesia than EMLA for intravenous catheterization after 60 min application . Clinical evaluations are necessary to determine the efficacy and safety of LET in providing topical anaesthesia for vanous invasive percutaneous procedures in other patient population s . RésuméObjectifLe mélange eutectique d’anesthésique local ( EMLA ) appliqué pendant 60 à 90 minutes procure une anesthésie topique efficace . On sait que tétracaïne encapsulée dans les liposomes ( LET ) pénètre le derme rapidement . Cette étude a été entreprise pour comparer les effets anesthésiques locaux de l’EMLA et du LET chez des volontaires humains après 60 mm d’application . MéthodesAprès obtention de l’approbation des instances appropriées et du consentement éclairé , des volontaires ont été recrutés dans une étude aléatoire croisée à double insu . Les crèmes ( EMLA 0.5 ml et LET 5 % 0,5 ml ) ont été appliquées aléatoirement sur des bras opposés pendant 60 min . L’inconfort de la canulation veineuse a été évalué sur une échelle visuelle analogique ( ÉVA ) . Les effets secondaires ont été notés . RésultatsSoixante et un sujets ont participé à l’étude do nt vingt et un ont été rejetés à cause de problèmes techniques . Quarante sujets ont complété l’étude et ont été conservés pour l’analyse des données . L’ÉVA moyenne ( ±ÉT ) du LET était inférieure à celle de l’EMLA ( 10.9 ± 9.0 mm vs 22,7 ± 17.1 . P < 0,001 ) . L’érythème secondaire à la vasodilatation était plus fréquent dans le groupe LET que dans le groupe EMLA ( 33 vs 3 , P < 0.001 ) . Un des sujets considéré comine atopique a présenté de l’érythème au site d’application du LET . Conclusion La tétracaïne encapsulée dans les liposomes peut procurer une anesthésie topique plus efficace que l’EMLA pour la canulation veineuse après 60 min d’application . Des évaluations cliniques sont nécessaires pour déterminer l’efficacité et l’innocuité du LET pour l’anesthésie topique pendant des manipulations percutanées diverses chez d’autres groupes de patients In a double-blind , double-dummy study , the efficacy of topical 5 % EMLA cream was compared with that of lignocaine infiltration in alleviating the pain of arterial cannulation . Forty unpremedicated adults were allocated r and omly to four groups to receive EMLA cream alone , EMLA and 0.9 % saline infiltration , EMLA and 1 % lignocaine infiltration or placebo cream and 1 % lignocaine infiltration . Following arterial cannulation , pain was assessed by the patient using a visual analogue score and by an independent observer using a four-category verbal rating score . Significantly lower pain scores were observed in all patients receiving EMLA compared with those receiving placebo cream and lignocaine infiltration by both patient ( P less than 0.01 ) and observer ( P less than 0.001 ) assessment s. There were no significant differences between the three EMLA groups In this r and omized , double-blind study , we have compared the ability of 5 % liposome-encapsulated tetracaine ( amethocaine ) ( LET ) vs 5 % eutectic mixture of local anaesthetics ( EMLA ) to produce local anaesthesia of intact skin in 40 healthy volunteers . Volunteers had both preparations applied to their forearms under an occlusive dressing for 1 h. Superficial anaesthesia was measured by a total of nine 1-mm pinpricks on each arm . Deeper anaesthesia was assessed by single insertion of a sterile 22-gauge needle to a depth of 3 mm and pain was reported on a visual analogue scale ( VAS ) . If the volunteer perceived greater than four of the 1-mm pinpricks , the 3-mm insertion was not performed . Results showed that the number of pinpricks perceived was significantly less ( P < 0.01 ) for LET ( median 1.0 ; range 0 - 9 ) vs EMLA ( 1. Output:	EMLA may be an effective , noninvasive means of analgesia before dermal procedures . However , we identified 3 topical anesthetics that are at least as efficacious as EMLA : tetracaine , liposome-encapsulated tetracaine , and liposome-encapsulated lidocaine . Liposomal lidocaine is commercially available in the United States and offers a more rapid onset and less expensive alternative to EMLA
MS213849	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: BACKGROUND Involvement of family in bedside rounds is one strategy to implement family-centered care to help families get clear information about their child , and be actively involved in decision-making about care . However in developing countries such as Pakistan , daily bedside rounds include the physician , residents , medical students and a nurse/technician . Parents are not currently a part of these rounds . OBJECTIVE To assess whether family-centered rounds improve parents ' and health care professionals ' satisfaction , decrease patient length of stay , and improve time utilization when compared to traditional practice rounds in a population with a low literacy rate , socioeconomic status , and different cultural values and beliefs . DESIGN A non-r and omized before-after study design . SETTING A private hospital in Karachi , Pakistan . PARTICIPANTS A convenience sample of 82 parents , whose children were hospitalized for a minimum of 48h , and 25 health care professionals able to attend two consecutive rounds . METHODS During the before phase , traditional bedside rounds were practice d ; and during after phase , family-centered rounds were practice d. Parents and health care professionals completed a question naire on the second day of rounds . An observational form facilitated data collection on length of stay and time utilization during . RESULTS Parents ' ratings during the family-centered rounds were significantly higher for some parental satisfaction items : evidence of team work ( p=0.007 ) , use of simple language during the rounds ( p=0.002 ) , feeling of inclusion in discussion at rounds ( p=0.03 ) , decision making ( p=0.01 ) , and preference for family-centered rounds ( p=<0.001 ) . No significant differences were found in health care professionals ' satisfaction between rounds . Patient length of stay was significantly reduced in the family-centered rounds group , while no significant difference was found in the duration of rounds . Family-centered rounds served as an opportunity for parents to correct/add to patient history or documentation . CONCLUSION Parents were satisfied with both forms of rounds ; however , they appeared to have a greater preference for family-centered rounds than health care professionals . Family-centered rounds were a re source for Pakistani parents , enabling direct communication with the medical team without impacting on the time required to complete rounds . Family-centered rounds may improve quality of care such as decreasing length of stay or preventing critical incidents OBJECTIVE It was hypothesized that parents exposed to a communication skills intervention would participate ( e.g. , ask questions , express concerns ) in a pre-surgical consultation more than parents in the control group . METHODS Sixty-five parents of prospect i ve pediatric surgery patients were r and omly assigned to either a communication skills intervention ( booklet mailed prior to the consultation ) or control group . Only initial consultation parents were included , no follow-ups . Audio-recordings of the medical consultations were obtained and the transcripts analyzed utilizing a content-coding system to determine patient participation . Also , parents were given a health literacy test ( s-TOFHLA ) and a post-interview question naire to gather demographic data . RESULTS Intervention parents participated overall significantly more than control parents . Follow-up analyses revealed that intervention parents asked significantly more questions , and engaged in significantly more information verifying and expressing of concerns . There were no significant differences for parents ' assertive statements or information provision . Other significant predictors of parents ' participation were consultation length and parents ' income . CONCLUSION The intervention tested in this study promoted parents ' participation in a pre-surgical consultation . As such , it has the potential to improve information exchange between parents and physicians with positive implication s for informed consent . PRACTICE IMPLICATION S Providing parents with communication guidelines prior to a surgical consultation may improve physician-patient communication OBJECTIVE Problems with clinician-patient communication negatively impact newborn screening , genetics , and all of healthcare . Training programs teach communication , but educational methods are not feasible for entire population s of clinicians . To address this healthcare quality gap , we developed a Communication Quality Assurance intervention . METHODS Child health providers volunteered for a r and omized controlled trial of assessment and a report card . Participants provided telephone counseling to a st and ardized parent regarding a newborn screening result showing heterozygous status for cystic fibrosis or sickle cell disease . Our rapid-throughput timeline allows individualized feedback within a week . Two encounters were recorded ( baseline and after a r and om sample received the report card ) and abstract ed for four groups of communication quality indicators . RESULTS 92 participants finished both counseling encounters within our rapid-throughput time limits . Participants r and omized to receive the report card improved communication behaviors more than controls , including request for teach-back ( p<0.01 ) , opening behaviors ( p=0.01 ) , anticipate/vali date emotion ( p<0.001 ) and the ratio of explained to unexplained jargon words ( p<0.03 ) . CONCLUSION The rapid-throughput report card is effective at improving specific communication behaviors . PRACTICE IMPLICATION S Communication can be taught , but this project shows how healthcare organizations can assure communication quality everywhere . Further implementation could improve newborn screening , genetics , and healthcare in general OBJECTIVE . We evaluated the effectiveness of a continuing medical education program , Physician Asthma Care Education , in improving pediatricians ’ asthma therapeutic and communication skills and patients ’ health care utilization for asthma . METHODS . We conducted a r and omized trial in 10 regions in the United States . Primary care providers were recruited and r and omly assigned by site to receive the program provided by local faculty . The program included 2 interactive seminar sessions ( 2.5 hours each ) that review ed national asthma guidelines , communication skills , and key educational messages . Format included short lectures , case discussion s , and a video modeling communication techniques . We collected information on parent perceptions of physicians ’ communication , the child ’s asthma symptoms , and patients ’ asthma health care utilization . We used multivariate regression models to determine differences between control and intervention groups . RESULTS . A total of 101 primary care providers and a r and om sample of 870 of their asthma patients participated . After 1 year , we completed follow-up telephone interviews with the parents of 731 of the 870 patients . Compared to control subjects , parents reported that physicians in the intervention group were more likely to inquire about patients ’ concerns about asthma , encourage patients to be physically active , and set goals for successful treatment . Patients of physicians that attended the program had a greater decrease in days limited by asthma symptoms ( 8.5 vs 15.6 days ) , as well as decreased emergency department asthma visits ( 0.30 vs 0.55 visits per year ) . CONCLUSIONS . The Physician Asthma Care Education program was used in a range of locations and was effective in improving parent-reported provider communication skills , the number of days affected by asthma symptoms , and asthma health care use . Patients with more frequent asthma symptoms and higher health care utilization at baseline were more likely to benefit from their physician ’s participation in the program OBJECTIVE To determine whether augmenting st and ard feedback on resident performance with a multi source feedback intervention improved pediatric resident communication skills and professionalism . DESIGN R and omized controlled trial . SETTING Children 's Hospital Medical Center , Cincinnati , Ohio , from June 21 , 2004 , to July 7 , 2005 . PARTICIPANTS Thirty-six first-year pediatric residents . INTERVENTIONS Residents assigned to the multi source feedback group ( n = 18 ) completed a self- assessment , received a feedback report about baseline parent and nurse evaluations , and participated in a tailored coaching session in addition to receiving st and ard feedback . Residents in the control group ( n = 18 ) received st and ard feedback only . The control group and their residency directors were blinded to parent and nurse evaluations until the end of the study . MAIN OUTCOME MEASURES Residents ' specific communication skills and professional behaviors were rated by parents and nurses of pediatric patients . Both groups were evaluated at baseline and after 5 months . Scores were calculated on each item as percentage in the highest response category . RESULTS Both groups had comparable baseline characteristics and ratings . Parent ratings increased for both groups . While parent ratings increased more for the multi source feedback group , differences between groups were not statistically significant . In contrast , nurse ratings increased for the multi source feedback group and decreased for the control group . The difference in change between groups was statistically significant for communicating effectively with the patient and family ( 35 % ; 95 % confidence interval , 11.0%-58.0 % ) , timeliness of completing tasks ( 30 % ; 95 % confidence interval , 7.9%-53.0 % ) , and demonstrating responsibility and accountability ( 26 % ; 95 % confidence interval , 2.9%-49.0 % ) . CONCLUSION A multi source feedback intervention positively affected communication skills and professional behavior among pediatric residents Background To assess the student perspective on acceptability , realism , and perceived effect of communication training with peer role play ( RP ) and st and ardised patients ( SP ) . Methods 69 prefinal year students from a large German medical faculty were r and omly assigned to one of two groups receiving communication training with RP ( N = 34 ) or SP ( N = 35 ) in the course of their paediatric rotation . In both groups , training addressed major medical and communication problems encountered in the exploration and counselling of parents of sick children . Acceptability and realism of the training as well as perceived effects and applicability for future parent-physician encounters were assessed using six-point Likert scales . Results Both forms of training were highly accepted ( RP 5.32 ± .41 , SP 5.51 ± .44 , n.s . ; 6 = very good , 1 = very poor ) and perceived to be highly realistic ( RP 5.60 ± .38 , SP 5.53 ± .36 , n.s . ; 6 = highly realistic , 1 = unrealistic ) . Regarding perceived effects , participation was seen to be significantly more worthwhile in the SP group ( RP 5.17 ± .37 , SP 5.50 ± .43 ; p < .003 ; 6 = totally agree , 1 = do n't agree at all ) . Both training methods were perceived as useful for training communication skills ( RP 5.01 ± .68 , SP 5.34 ± .47 ; 6 = totally agree ; 1 = do n't agree at all ) and were considered to be moderately applicable for future parent-physician encounters ( RP 4.29 ± 1.08 , SP 5.00 ± .89 ; 6 = well prepared , 1 = unprepared ) , with usefulness and applicability both being rated higher in the SP group ( p < .032 and p < .009 ) . Conclusions RP and SP represent comparably valuable tools for the training of specific communication skills from the student perspective . Both provide highly realistic training scenarios and warrant inclusion in medical curricula . Given the expense of SP , deciding which method to employ should be carefully weighed up . From the perspective of the students in our study , SP were seen as a more useful and more applicable tool than RP . We discuss the potential of RP to foster a greater empathic appreciation of the patient perspective To determine whether st and ardized instructions enhance communication of discharge information , we provided 197 parents of children in whom otitis media was diagnosed with one of three types of instruction at the time of discharge from a pediatric emergency department : ( 1 ) instruction by individual housestaff and medical students after consultation with an attending physician ( control group ) ; ( 2 ) st and ardized verbal instructions given by housestaff and students trained in their use ( verbal group ) ; or ( 3 ) the same instructions given to the verbal group , together with a type-written copy of the information to take home ( verbal + written group ) . Prior to leaving the emergency department and , again , by phone , 1 and 3 days later , parents were question ed concerning the prescribed medication 's name , dose , frequency , and duration of administration ( medication data ) , three signs of improvement , and eight signs indicating the need for medical advice ( worrisome signs ) . The mean percentage of correct responses per parent in each group was computed for each information category . Both at exit interview and at follow-up , parents receiving either form of st and ardized instructions showed significantly greater knowledge of information related to their child 's illness than did controls . Information regarding medication data was more likely to be communicated to parents in all groups than were signs of improvement or worrisome signs . The addition of written instructions to st and ardized verbal instructions did not improve parental recall of discharge information The Physician Asthma Care Education ( PACE ) program significantly improved asthma prescribing and communication behaviours of primary care paediatricians in the USA . We tested the feasibility and acceptability of a modified PACE program with Australian general practitioners ( GP ) and measured its impact on self-reported consulting behaviours in a pilot study . Recruitment took place through a local GP division . Twenty-five GP completed two PACE Australia workshops , which incorporated paediatric asthma management consistent with Australian asthma guidelines and focussed on effective communication strategies . Program feasibility , usefulness and perceived benefit were measured by question naires before the workshop and 1 month later , and an evaluation question naire after each workshop . GP were universally enthusiastic and supportive of the workshops . The most useful elements they reported were communication skills , case studies , device demonstrations and the toolkit provided . GP self reports of the perceived helpfulness of the key communication strategies and their confidence in their application and reported frequency of use increased significantly after the workshops . The PACE program shows promise in improving the way in which Australian GP manage asthma consultations , particularly with regard to doctor-patient communication . The impact ofthe modified PACE Australia program on the processes and outcomes ofGP care ofchildren with asthma is now being measured in a r and omised controlled trial INTRODUCTION Following the recent amendment to the Medical Education Act in Germany ( Approbationsordnung 2002 ) and the abolition of the prelim Output:	Most interventions improved providers ' interpersonal , patient-centered interviewing skills . Interventions that targeted parents involved booklets and role-playing to encourage questions . They improved parents ' satisfaction and communication . An intervention that targeted youth used a video portraying how children can communicate better with physicians . Once the children aged 5 - 15 years watched the video , they wrote questions for their physicians prior to the medical visit . The experimental group of children had better rapport with physicians and could recall recommendations about medications more often than the control group .
MS213850	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: OBJECTIVE To determine the effect of routine intravenous ( IV ) administration set changes on central venous catheter ( CVC ) colonization and catheter-related bacteremia . DESIGN Prospect i ve , r and omized , controlled trial . SETTING Eighteen-bed intensive care unit ( ICU ) in a large metropolitan hospital . PARTICIPANTS Two hundred fifty-one patients with 404 chlorhexidine gluconate and silver sulfadiazine-coated multi-lumen CVCs . INTERVENTIONS CVCs inserted in the ICU and in situ on day 4 were r and omized to have their IV administration sets changed on day 4 ( n = 203 ) or not at all ( n = 201 ) . Use of fluid containers and blood product administration sets was limited to 24 hours . CVCs were removed when not required , infection was suspected , or in place on day 7 . Catheter cultures were performed on removal by blinded laboratory staff . Catheter-related bacteremia was diagnosed by a blinded intensivist using strict definitions . Data were collected regarding catheter duration , site , Acute Physiology and Chronic Health Evaluation ( APACHE ) II score , patient age , diagnosis , hyperglycemia , hypoalbuminemia , immune status , number of fluid containers and IV injections , and administration of propofol , blood , total parenteral nutrition , or lipid infusion . RESULTS There were 10 colonized CVCs in the group receiving a set change and 19 in the group not receiving one . This difference was not statistically significant on Kaplan-Meier survival analysis . There were 3 cases of catheter-related bacteremia per group . Logistic regression found that burns diagnosis and increased ICU stay significantly predicted colonization . CONCLUSION IV administration sets can be used for 7 days in patients with short-term , antiseptic-coated CVCs In a prospect i ve study , 218 cardiothoracic patients , in whom ' Abbocath-T ' cannulae had been inserted preoperatively into the internal jugular vein , were r and omized to receive skin preparation of the insertion site with tincture of iodine ( 108 controls ) or tincture of iodine followed by application of sterile 2 % calcium mupirocin ointment ( 110 test patients ) . Cannulae were usually removed within 48 h of the operation . Patients receiving mupirocin were less likely to develop significant colonization of one or more of their cannulae as judged by Maki 's criterion of a yield of greater than 15 colony forming units ( cfu ) from a cannula segment rolled on an agar plate ( 17 % of mupirocin treated patients compared with 54 % of the controls , P less than 0.001 ) . Coagulase-negative staphylococci , micrococci , or both , were the commonest isolates and were cultured from 70 % of the 186 control cannulae compared with 24 % of 172 cannulae inserted through mupirocin-treated skin ( P less than 0.001 ) . A count of more than 15 cfu was found on the tips of 25 % control cannulae compared with 5 % of the cannulae from mupirocin-treated patients , an effect which was independent of in-situ time ( P less than 0.001 ) . For cannulae with colonized tips , the same species was isolated from the skin of the insertion site in 67 % , from the exterior of the hub in 61 % and from the lumen in only 15 % . There were no side effects attributed to mupirocin or superinfection with resistant organisms . We conclude that in cardiothoracic patients the application of mupirocin after st and ard skin preparation with tincture of iodine significantly reduces the colonization of central venous cannulae by organisms derived from the skin insertion site The objective of this study was to assess the risk of bacteremia , estimate the cost and evaluate the quality of life by using a transparent dressing ( TD ) versus ( vs ) a dry gauze ( DG ) on the exit site of long term central I.V. catheters ( LTCC ) of hemodialysis patients . This 6-months preliminary study was conducted on 58 patients ( pts ) r and omized to receive DG replaced 3 times/week ( 29 pts ) or TD replaced every 7 days ( 29 pts ) . Data on patients , conditions of the exit site , local infection , bacteremia , quality of life and cost related to each type of dressing were collected . Two pts in the DG group experienced bacteremia related to their LTCC vs 1 pt in the group TD . A total of 7 ( DG ) vs 13 ( TD ) pts experienced skin condition changes at the catheter exit site . Some skin reactions , erythema and pruritus , did occur initially in the group TD and was due in part to insufficient drying time of the skin preparation solution . The estimated individual , weekly costs for using the DG was $ 7.60 vs $ 4.72 Canadian dollars for the TD . The SF-36 ™ scores did not show a significant difference between the 2 groups during the study ( 3.8 ( PCS ) , 6.4 ( MCS ) at study end ) . Although this study was statistically underpowered , it suggests that the incidence of bacteremia was not increased with the use of a TD . Moreover , the use of a TD allowed fewer dressing changes , lowered total treatment costs , with no observed unfavorable impact on the quality of life and without significant local complications of the exit site . Based on the positive results observed in this pilot study , further study is warranted to examine the cost effectiveness of long-term use of TD dressings on dialysis catheter exit sites BACKGROUND Intravascular-catheter-related infections are frequent life-threatening events in health care , but incidence can be decreased by improvements in the quality of care . Optimisation of skin antisepsis is essential to prevent short-term catheter-related infections . We hypothesised that chlorhexidine-alcohol would be more effective than povidone iodine-alcohol as a skin antiseptic to prevent intravascular-catheter-related infections . METHODS In this open-label , r and omised controlled trial with a two-by-two factorial design , we enrolled consecutive adults ( age ≥18 years ) admitted to one of 11 French intensive-care units and requiring at least one of central -venous , haemodialysis , or arterial catheters . Before catheter insertion , we r and omly assigned ( 1:1:1:1 ) patients via a secure web-based r and om-number generator ( permuted blocks of eight , stratified by centre ) to have all intravascular catheters prepared with 2 % chlorhexidine-70 % isopropyl alcohol ( chlorhexidine-alcohol ) or 5 % povidone iodine-69 % ethanol ( povidone iodine-alcohol ) , with or without scrubbing of the skin with detergent before antiseptic application . Physicians and nurses were not masked to group assignment but microbiologists and outcome assessors were . The primary outcome was the incidence of catheter-related infections with chlorhexidine-alcohol versus povidone iodine-alcohol in the intention-to-treat population . This study is registered with Clinical Trials.gov , number NCT01629550 and is closed to new participants . FINDINGS Between Oct 26 , 2012 , and Feb 12 , 2014 , 2546 patients were eligible to participate in the study . We r and omly assigned 1181 patients ( 2547 catheters ) to chlorhexidine-alcohol ( 594 patients with scrubbing , 587 without ) and 1168 ( 2612 catheters ) to povidone iodine-alcohol ( 580 patients with scrubbing , 588 without ) . Chlorhexidine-alcohol was associated with lower incidence of catheter-related infections ( 0·28 vs 1·77 per 1000 catheter-days with povidone iodine-alcohol ; hazard ratio 0·15 , 95 % CI 0·05 - 0·41 ; p=0·0002 ) . Scrubbing was not associated with a significant difference in catheter colonisation ( p=0·3877 ) . No systemic adverse events were reported , but severe skin reactions occurred more frequently in those assigned to chlorhexidine-alcohol ( 27 [ 3 % ] patients vs seven [ 1 % ] with povidone iodine-alcohol ; p=0·0017 ) and led to chlorhexidine discontinuation in two patients . INTERPRETATION For skin antisepsis , chlorhexidine-alcohol provides greater protection against short-term catheter-related infections than does povidone iodine-alcohol and should be included in all bundles for prevention of intravascular catheter-related infections . FUNDING University Hospital of Poitiers , CareFusion OBJECTIVE To compare the effectiveness for prevention of central venous and arterial catheter colonization of 3 skin antisepsis with 1 of 3 antiseptic solutions : 10 % aqueous povidone iodine ( aqueous PI ) , 2 % aqueous chlorhexidine gluconate ( aqueous CG ) , and 0.5 % alcoholic chlorhexidine gluconate ( alcoholic CG ) . DESIGN Prospect i ve , r and omized controlled trial . SETTING Intensive care unit in a teaching hospital . METHODS Patients were r and omly assigned to 1 of the 3 skin antisepsis groups . The distal tips of catheters were semiquantitatively cultured when the catheters were no longer necessary or if there was a suspicion of catheter-related infection . Rates of catheter colonization , catheter-related sepsis , and catheter-related bacteremia were compared among the 3 groups . RESULTS A total of 631 catheters were included in the study ( 194 from the aqueous PI group , 211 from the aqueous CG group , and 226 from the alcoholic CG group ) . The incidence of catheter colonization was significantly lower in the alcoholic CG than in the aqueous PI group ( 14.2 % vs 24.7 % ; relative risk , 0.5 [ 95 % confidence interval , 0.3 - 0.8 ; P < .01 ] ) ; it was also significantly lower in the aqueous CG group than in the aqueous PI group ( 16.1 % vs 24.7 % ; relative risk , 0.6 [ 95 % confidence interval , 0.4 - 0.9 ; P = .03 ] ) . There were no significant differences between the aqueous CG and the alcoholic CG groups . Incidences of catheter-related bacteremia were similar for all 3 groups . The aqueous and alcoholic CG solutions were superior to the aqueous PI solution in preventing catheter colonization due to gram-positive bacteria . CONCLUSIONS The aqueous and alcoholic CG solutions for cutaneous antisepsis were similarly effective in preventing colonization of central venous catheters and arterial catheters . Both had significantly lower incidences of colonization than did the aqueous PI solution ; this effect seems to be related to the CG solutions ' more efficacious prevention of colonization with gram-positive bacteria OBJECTIVE To examine the extent to which US acute care hospitals have adopted recommended practice s to prevent central venous catheter-related bloodstream infections ( CR-BSIs ) . PARTICIPANTS AND METHODS Between March 16 , 2005 , and August 1 , 2005 , a survey of infection control coordinators was conducted at a national r and om sample of nonfederal hospitals with an intensive care unit and more than 50 hospital beds ( n=600 ) and at all Department of Veterans Affairs ( VA ) medical centers ( n=119 ) . Primary outcomes were regular use of 5 specific practice s and a composite approach for preventing CR-BSIs . RESULTS The overall survey response rate was 72 % ( n=516 ) . A higher percentage of VA compared to non-VA hospitals reported using maximal sterile barrier pre caution s ( 84 % vs 71 % ; P=.01 ) ; chlorhexidine gluconate for insertion site antisepsis ( 91 % vs 69 % ; P<.001 ) ; and a composite approach ( 62 % vs 44 % ; P=.003 ) combining concurrent use of maximal sterile barrier pre caution s , chlorhexidine gluconate , and avoidance of routine central line changes . Those hospitals having a higher safety culture score , having a certified infection control professional , and participating in an infection prevention collaborative were more likely to use CR-BSI prevention practice s. CONCLUSION Most US hospitals are using maximal sterile barrier pre caution s and chlorhexidine gluconate , 2 of the most strongly recommended practice s to prevent CR-BSIs . However , fewer than half of non-VA US hospitals reported concurrent use of maximal sterile barrier pre caution s , chlorhexidine gluconate , and avoidance of routine central line changes . Wider use of CR-BSI prevention practice s by hospitals could be encouraged by fostering a culture of safety , participating in infection prevention collaboratives , and promoting infection control professional certification BACKGROUND Long-term central venous catheterization is associated with a higher rate of catheter-related blood stream infections ( CR-BSI ) . It is unclear whether there is a difference in the CR-BSI rate associated with central venous catheters Output:	None of the individual subgroup comparisons of aqueous chlorhexidine versus aqueous povidone-iodine , alcoholic chlorhexidine versus aqueous povidone-iodine and alcoholic chlorhexidine versus alcoholic povidone-iodine showed clear differences for catheter-related BSI or mortality ( and were generally underpowered ) . AUTHORS ' CONCLUSIONS It is not clear whether cleaning the skin around CVC insertion sites with antiseptic reduces catheter related blood stream infection compared with no skin cleansing . Skin cleansing with chlorhexidine solution may reduce rates of CRBSI and catheter colonisation compared with cleaning with povidone iodine . Moreover these results may be influenced by the nature of the antiseptic solution ( i.e. aqueous or alcohol-based ) .
MS213851	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: A structured question naire consisting of two parts was used to evaluate the impact of ovarian cancer and its management on quality of life in 28 patients with advanced disease . The first part rated their perceptions of behavioral disruption and emotional distress in five life areas , i.e. , activity , daily living , health , support , and outlook as set out by the interviewer-rated Spitzer question naire " Quality of Life Index of Cancer Patients . " The second part rated their response in the domain of sexual activity . Data were collected prospect ively at three monthly intervals during the 2-year descriptive study . In 12 patients ovarian cancer persisted despite surgery and chemotherapy result ing in the demise of 8 women within 2 years . During the first year of study these patients described a similar deterioration in quality of life as those who had a complete response to treatment . However , after 1 year , patients with persistent disease rated their quality of life much lower . Diagnosis of persistent disease after conventional treatment proved more stressful than the diagnosis of the primary disease . Treatment of ovarian cancer will produce behavioral disruption and emotional distress , with lasting affects seen even in patients with complete response 2 years after commencing therapy Background Women with platinum-resistant ovarian cancer are a heterogeneous group whose median overall survival is 12 months . We hypothesized that their quality of life ( QoL ) scores would be prognostic . Patients and methods Data from AURELIA ( n = 326 ) , a r and omized trial of chemotherapy with or without bevacizumab , were used to identify baseline QoL domains [ EORTC ( European Organisation for Research and Treatment of Cancer ) QLQ-C30 and OV28 ] that were significantly associated with overall survival in multivariable Cox regression analyses . Patients were classified as having good , medium , or poor risk . Cutpoints were vali date d in an independent data set , CARTAXHY ( n = 136 ) . Multivariable analyses of significant QoL domains on survival were adjusted for clinicopathological prognostic factors . The additional QoL information was assessed using C statistic . Results In AURELIA , all domains , except cognitive function , predicted overall survival in univariable analyses . Physical function ( P < 0.001 ) and abdominal/gastrointestinal symptom ( P < 0.001 ) scores remained significant in multivariable models . In high ( score < 67 ) , medium ( 67 - 93 ) , and low ( > 93 ) risk categories for physical function , median overall survival was 11.0 , 14.7 , and 19.3 months , respectively ( P < 0.001 ) . In CARTAXHY , median overall survival was 7.9 , 16.2 , and 23.9 months ( P < 0.001 ) , respectively . For high- ( > 44 ) , medium- ( 13 - 44 ) , and low- ( < 13 ) risk categories for abdominal/gastrointestinal symptoms , median overall survival was 11.9 , 14.3 , and 19.7 months in AURELIA ( P < 0.001 ) and 10.5 , 19.6 , and 24.1 months in CARTAXHY ( P = 0.02 ) . Physical function ( P = 0.02 ) and abdominal/gastrointestinal symptoms ( P = 0.03 ) remained independent prognostic factors after adjustment for clinicopathological factors . The C statistic of the full model was 0.71 . For QoL factors alone , patient factors alone and disease factors alone , the C statistics were 0.61 , 0.61 , and 0.67 respectively . Conclusions Physical function and abdominal/gastrointestinal symptom scores improved predictions of overall survival over clinicopathological factors alone in platinum-resistant ovarian cancer . This additional prognostic information could improve trial stratification , patient-doctor communication about prognosis , and clinical decision-making . Clinical trial registration NCT00976911 PURPOSE Although patient-reported cancer symptoms and quality -of-life issues ( SQLIs ) have been promoted as essential to a comprehensive assessment , efficient and efficacious methods have not been widely tested in clinical setting s. The purpose of this trial was to determine the effect of the Electronic Self-Report Assessment -Cancer ( ESRA-C ) on the likelihood of SQLIs discussed between clinicians and patients with cancer in ambulatory clinic visits . Secondary objectives included comparison of visit duration between groups and usefulness of the ESRA-C as reported by clinicians . PATIENTS AND METHODS This r and omized controlled trial was conducted in 660 patients with various cancer diagnoses and stages at two institutions of a comprehensive cancer center . Patient-reported SQLIs were automatically displayed on a graphical summary and provided to the clinical team before an on-treatment visit ( n = 327 ) ; in the control group , no summary was provided ( n = 333 ) . SQLIs were scored for level of severity or distress . One on-treatment clinic visit was audio recorded for each participant and then scored for discussion of each SQLI . We hypothesized that problematic SQLIs would be discussed more often when the intervention was delivered to the clinicians . RESULTS The likelihood of SQLIs being discussed differed by r and omized group and depended on whether an SQLI was first reported as problematic ( P = .032 ) . Clinic visits were similar with regard to duration between groups , and clinicians reported the summary as useful . CONCLUSION The ESRA-C is the first electronic self-report application to increase discussion of SQLIs in a US r and omized clinical trial Main purpose The objective of this study was to determine the relationship between clinician- grade d symptoms based on the common toxicity criteria ( CTC ) and patient-reported quality of life ( QoL ) . We hypothesized that toxicity symptoms that are objective or observable would have a higher correlation with QoL than subjective data . Material and methods A retrospective analyses of data from three closed r and omized chemotherapy trials was performed . A total of 2,110 patients with ovarian cancer ( stage IIB – IV ) who had complete toxicity and QoL data at cycles 3 and 6 were included . Toxicities were grade d according to the National Cancer Institute Common Toxicity Criteria . Quality of life was assessed every other cycle by using the European Organization for Research and Treatment of Cancer Quality of Life Question naire ( EORTC QLQ-C30).Main results Correlations between CTC grading and the QLQ-C30 functioning scales were weak ( < 0.30 ) ; correlation coefficients between CTC ratings and the QLQ-C30 symptom scales including nausea , vomiting , constipation , pain , and dyspnea ranged from 0.32 to 0.49 except for constipation ( 0.55 ) . On a symptom level exact agreement between clinician and patient reporting ranged from 54.2 % ( pain ) to 80.8 % ( emesis/vomiting ) . When symptom grading differed , patients reported greater severity for pain , constipation , and dyspnea , whereas clinicians grade d emesis/vomiting and nausea as more severe than the grading by patients . Conclusion Patient experience is not routinely captured by CTC toxicity scales . Therefore , clinicians should not entirely rely on the CTC grading but consider patient-reported outcomes as well PURPOSE There is growing interest to enhance symptom monitoring during routine cancer care using patient-reported outcomes , but evidence of impact on clinical outcomes is limited . METHODS We r and omly assigned patients receiving routine outpatient chemotherapy for advanced solid tumors at Memorial Sloan Kettering Cancer Center to report 12 common symptoms via tablet computers or to receive usual care consisting of symptom monitoring at the discretion of clinicians . Those with home computers received weekly e-mail prompts to report between visits . Treating physicians received symptom printouts at visits , and nurses received e-mail alerts when participants reported severe or worsening symptoms . The primary outcome was change in health-related quality of life ( HRQL ) at 6 months compared with baseline , measured by the EuroQol EQ-5D Index . Secondary endpoints included emergency room ( ER ) visits , hospitalizations , and survival . RESULTS Among 766 patients allocated , HRQL improved among more participants in the intervention group than usual care ( 34 % v 18 % ) and worsened among fewer ( 38 % v 53 % ; P < .001 ) . Overall , mean HRQL declined by less in the intervention group than usual care ( 1.4- v 7.1-point drop ; P < .001 ) . Patients receiving intervention were less frequently admitted to the ER ( 34 % v 41 % ; P = .02 ) or hospitalized ( 45 % v 49 % ; P = .08 ) and remained on chemotherapy longer ( mean , 8.2 v 6.3 months ; P = .002 ) . Although 75 % of the intervention group was alive at 1 year , 69 % with usual care survived the year ( P = .05 ) , with differences also seen in quality -adjusted survival ( mean of 8.7 v. 8.0 months ; P = .004 ) . Benefits were greater for participants lacking prior computer experience . Most patients receiving intervention ( 63 % ) reported severe symptoms during the study . Nurses frequently initiated clinical actions in response to e-mail alerts . CONCLUSION Clinical benefits were associated with symptom self-reporting during cancer care BACKGROUND Serum CA125 concentration often rises several months before clinical or symptomatic relapse in women with ovarian cancer . In the MRC OV05/EORTC 55955 collaborative trial , we aim ed to establish the benefits of early treatment on the basis of increased CA125 concentrations compared with delayed treatment on the basis of clinical recurrence . METHODS Women with ovarian cancer in complete remission after first-line platinum-based chemotherapy and a normal CA125 concentration were registered for this r and omised controlled trial . Clinical examination and CA125 measurement were done every 3 months . Patients and investigators were masked to CA125 results , which were monitored by coordinating centres . If CA125 concentration exceeded twice the upper limit of normal , patients were r and omly assigned ( 1:1 ) by minimisation to early or delayed chemotherapy . Patients and clinical sites were informed of allocation to early treatment , and treatment was started as soon as possible within 28 days of the increased CA125 measurement . Patients assigned to delayed treatment continued masked CA125 measurements , with treatment commencing at clinical or symptomatic relapse . All patients were treated according to st and ard local practice . The primary outcome was overall survival . Analysis was by intention to treat . This study is registered , IS RCT N87786644 . FINDINGS 1442 patients were registered for the trial , of whom 529 were r and omly assigned to treatment groups and were included in our analysis ( 265 early , 264 delayed ) . With a median follow-up of 56·9 months ( IQR 37·4 - 81·8 ) from r and omisation and 370 deaths ( 186 early , 184 delayed ) , there was no evidence of a difference in overall survival between early and delayed treatment ( HR 0·98 , 95 % CI 0·80 - 1·20 , p=0·85 ) . Median survival from r and omisation was 25·7 months ( 95 % CI 23·0 - 27·9 ) for patients on early treatment and 27·1 months ( 22·8 - 30·9 ) for those on delayed treatment . INTERPRETATION Our findings showed no evidence of a survival benefit with early treatment of relapse on the basis of a raised CA125 concentration alone , and therefore the value of routine measurement of CA125 in the follow-up of patients with ovarian cancer who attain a complete response after first-line treatment is not proven . FUNDING UK Medical Research Council and the European Organisation for Research and Treatment of Cancer OBJECTIVES To document levels of and changes in physical activity before and after ovarian cancer diagnosis and explore associations with psychosocial outcomes . METHODS Of 1207 eligible Australian Ovarian Cancer Study ( AOCS ) participants , 798 participated in an additional prospect i ve Quality of Life ( QoL ) Study which measured anxiety , depression and QoL at 3 - 6 monthly intervals for 2 years beginning 3 - 48 months after diagnosis . AOCS asked about physical activity before diagnosis and 530 women also completed a one-off lifestyle question naire 7 - 64 months after diagnosis which assessed activity during their first and , if relevant , second-to-third and fourth-to-sixth years following diagnosis . Analysis of variance was used to relate physical activity to psychosocial outcomes . RESULTS Almost 40 % of women decreased their physical activity in the first year after diagnosis . Approximately 25 % still had lower levels after 2 - 3 and 4+years . Recent physical activity level was inversely associated with depression and positively associated with QoL ( P<0.05 ) . Also , women who maintained or increased their physical activity after diagnosis had better mean depression and QoL scores than women who decreased physical activity or remained inactive ( P<0.05 ) . Among women who received chemotherapy shortly prior to completing the lifestyle question naire , high versus low or medium physical activity was associated with significantly lower mean depression scores during both periods of treatment and non-treatment ( P<0.05 ) . CONCLUSIONS Many women did not regain their pre-morbid physical activity levels several years after ovarian cancer diagnosis . Low physical activity may simply be a consequence of poor well-being but , alternatively , physical activity may improve psychosocial health of this group The objective of this study was to determine current practice with regards to follow- Output:	ConclusionS tudies have shown that PROMs can identify otherwise undetected symptoms . Using PROMs proactively during the consultation has been shown to improve symptom management for patients with some other types of cancer .
MS213852	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Background and Aims Cognitive behavioral group therapy ( CBGT ) is an effective , well-established , but not widely available treatment for social anxiety disorder ( SAD ) . Internet-based cognitive behavior therapy ( ICBT ) has the potential to increase availability and facilitate dissemination of therapeutic services for SAD . However , ICBT for SAD has not been directly compared with in-person treatments such as CBGT and few studies investigating ICBT have been conducted in clinical setting s. Our aim was to investigate if ICBT is at least as effective as CBGT for SAD when treatments are delivered in a psychiatric setting . Methods We conducted a r and omized controlled non-inferiority trial with allocation to ICBT ( n = 64 ) or CBGT ( n = 62 ) with blinded assessment immediately following treatment and six months post-treatment . Participants were 126 individuals with SAD who received CBGT or ICBT for a duration of 15 weeks . The Liebowitz Social Anxiety Scale ( LSAS ) was the main outcome measure . The following non-inferiority margin was set : following treatment , the lower bound of the 95 % confidence interval ( CI ) of the mean difference between groups should be less than 10 LSAS-points . Results Both groups made large improvements . At follow-up , 41 ( 64 % ) participants in the ICBT group were classified as responders ( 95 % CI , 52%–76 % ) . In the CBGT group , 28 participants ( 45 % ) responded to the treatment ( 95 % CI , 33%–58 % ) . At post-treatment and follow-up respectively , the 95 % CI of the LSAS mean difference was 0.68–17.66 ( Cohen ’s d between group = 0.41 ) and −2.51–15.69 ( Cohen ’s d between group = 0.36 ) favoring ICBT , which was well within the non-inferiority margin . Mixed effects models analyses showed no significant interaction effect for LSAS , indicating similar improvement across treatments ( F = 1.58 ; df = 2 , 219 ; p = .21 ) . Conclusions ICBT delivered in a psychiatric setting can be as effective as CBGT in the treatment of SAD and could be used to increase availability to CBT . Trial Registration Clinical Trials.gov In web-based health promotion programs , large variations in participant engagement are common . The aim was to investigate determinants of high use of a worksite self-help web-based program for stress management . Two versions of the program were offered to r and omly selected departments in IT and media companies . A static version of the program including health screening tool , diary and information about stress was offered to the control group . Additional material s , i.e. interactive , cognitive-based and classical stress management exercises and a chat room , were offered to the intervention group . Baseline data regarding participants ' demographics , health ( self-ratings and biological measures ) , lifestyle , work-related factors and group membership were analyzed to study determinants of employees ' participation in the program during a period of 12 months . Multiple logistic regression analysis was used and found intervention group membership , being a woman , having at most a secondary education , regular physical exercise habits and having positive expectations of the program were significant predictors of high use . The findings demonstrate that the interactivity of a web-based program is an important factor for determining participation in a web-based worksite stress management program . Implication s for those developing and implementing future web-based health promotion activities are discussed Background Social anxiety disorder ( SAD ) is one of the most common anxiety disorders and is associated with marked impairments . However , a small proportion of individuals with SAD seek and receive treatment . Internet-administrated cognitive behavior therapy ( iCBT ) has been found to be an effective treatment for SAD . This trial will be the first Internet-delivered guided self-help intervention for SAD in Romania . Methods Participants with social anxiety disorder ( N = 96 ) will be recruited via newspapers , online banners and Facebook . Participants will be r and omized to either : a ) an active treatment , or b ) a waiting list control group . The treatment will have a guided iCBT format and will last for nine weeks . Self-report question naires on social phobia , anxiety , depression , treatment credibility and irrational thinking will be used . All assessment s will be collected pre , post and at follow-up ( six months after intervention ) . Liebowitz Social Anxiety Scale – Self-Report version ( LSAS-SR ) will be the primary outcome measure and will be administrated on a weekly basis in both conditions . Discussion The present r and omized controlled trial investigates the efficacy of an Internet-administered intervention in reducing social anxiety symptoms in a culture where this form of treatment has not been tested . This trial will add to the body of knowledge on the efficacy of iCBT , and the results might lead to an increase of the accessibility of evidence -based psychological treatment in Romania . Trial registration Clinical Trials.gov : The mental health challenges of some vocations present a challenge for current intervention models . Bibliotherapy focused on transdiagnostic processes that might both prevent and alleviate a range of mental health distress could be an effective and practical approach . K-12 school personnel ( N = 236 ; 91 % female ; 30 - 60 years old ) responding to a wellness-oriented program announcement were r and omized to receive an Acceptance and Commitment Therapy ( ACT ) self-help volume or to a waitlist . Three-fourths were above clinical cutoffs in general mental health , depression , anxiety , or stress . Participants read the book for two months , completed exercises and quizzes , and after post assessment were followed for 10 weeks ; waitlist participants were then also given the book with two months to complete it . Overall , participants showed significant improvement in psychological health . Significant preventive effects for depression and anxiety were observed along with significant ameliorative effects for those in the clinical ranges of depression , anxiety and stress . Follow up general mental health , depression , and anxiety outcomes were related to the manner in which participants used the workbook and to post levels of psychological flexibility Bibliotherapy is potentially effective in the treatment of panic disorder ( PD ) . A still unanswered question is whether pacing is important . This study was design ed to test whether there is a difference between being assigned a full book as therapy and receiving one individual chapter every week ( i.e. pacing ) . A total of 28 participants were r and omized to either 10 paced chapters or one book with 10 chapters . To maximize compliance , short weekly telephone calls were added in both conditions ( M = 17.8 min , SD = 4.2 ) . Both treatments showed promising results , with effects maintained up to 2 years and with within-group effect sizes ( Cohen 's d ) between 0.95 and 1.11 . Pretreatment ratings of credibility were positively correlated with the change scores at both posttest and 2-year follow-up for three panic measures . Pacing of text material in bibliotherapy for PD is not needed , and all material can be provided at once when the treatment is guided by a therapist BACKGROUND Although effective therapies for social phobia exist , many individuals refrain from seeking treatment owing to the embarrassment associated with help-seeking . Internet-based cognitive-behavioural self-help can be an alternative , but adherence is a problem . AIMS To evaluate a 9-week programme of internet-based therapy design ed to increase treatment adherence by the addition of short weekly telephone calls , nine in all , with a total duration of 95 min . METHOD In a r and omised controlled trial the effects of internet-based cognitive-behavioural therapy in the treatment group ( n=29 ) were compared with a waiting-list control group ( n=28 ) . RESULTS Compared with the control group the treated participants experienced greater reductions on measures of general and social anxiety , avoidance and depression . Adherence to treatment was high , with 93 % finishing the complete treatment package . One year later all improvements were maintained . CONCLUSIONS This study provides evidence to support the use of internet-based treatment supplemented by short , weekly telephone calls Objective : This study aim ed to compare the effectiveness of computerised cognitive behaviour therapy ( CCBT ) with a wait list control ( WLC ) for the treatment of patients with an anxiety disorder ( social phobia , panic disorder , generalised anxiety disorder ) referred to a specialist , publically funded , outpatient anxiety service . Method : Patients with social phobia ( n = 37 ) , panic disorder ( n = 32 ) or generalised anxiety disorder ( n = 14 ) were r and omised to treatment with either CCBT ( n = 40 ) or WLC ( n = 43 ) . Self-report rating scale assessment s were conducted at baseline , 12 and 24 weeks . Results : Compared with WLC , the CCBT group improved significantly on approximately half of the self-report primary ( the Work and Social Adjustment Scale ) and approximately half of the secondary measures at both 12 and 24 weeks ( the Liebowitz Social Anxiety Scale , the Penn State Worry Question naire , the Generalised Anxiety inventory and the Fear Question naire ) . Effect sizes in this study were moderate . Conclusion : This is one of the few studies to investigate CCBT for anxiety disorders in patients in a secondary care service . The results show that CCBT in this secondary care setting has the potential to be beneficial and confirms and extends the findings from previous studies of self-referral or primary care setting Background Phobic disorders are highly prevalent and constitute a considerable burden for patients and society . As patients wait for face-to-face psychotherapy for phobic disorders in outpatient clinics , this time can be used for guided self-help interventions . The aim of this study is to investigate a five week internet-based guided self-help programme of exposure therapy in terms of clinical effectiveness and impact on speed of recovery in psychiatric out patients , as well as the cost-effectiveness of this pre-treatment waiting list intervention . Methods / design A r and omised controlled trial will be conducted among 244 Dutch adult patients recruited from waiting lists of outpatient clinics for face-to-face psychotherapy for phobic disorders . Patients suffering from at least one DSM-IV classified phobic disorder ( social phobia , agoraphobia or specific phobia ) are r and omly allocated ( at a 1:1 ratio ) to either a five-week internet-based guided self-help program followed by face-to-face psychotherapy , or a control group followed by face-to-face psychotherapy . Waiting list status and duration are unchanged and actual need for further treatment is evaluated prior to face-to-face psychotherapy . Clinical and economic self- assessment measurements take place at baseline , post-test ( five weeks after baseline ) and at 3 , 6 , 9 and 12 months after baseline . Discussion Offering pre-treatment internet-based guided self-help efficiently uses time otherwise lost on a waiting list and may increase patient satisfaction . Patients are expected to need fewer face-to-face sessions , reducing total treatment cost and increasing speed of recovery . Internet-delivered treatment for phobias may be a valuable addition to psychotherapy as dem and for outpatient treatment increases while budgets decrease . Trial registration Netherl and s Trial Register Background Internet support groups ( ISGs ) are popular , particularly among people with depression , but there is little high quality evidence concerning their effectiveness . Aim The study aim ed to evaluate the efficacy of an ISG for reducing depressive symptoms among community members when used alone and in combination with an automated Internet-based psychotherapy training program . Method Volunteers with elevated psychological distress were identified using a community-based screening postal survey . Participants were r and omised to one of four 12-week conditions : depression Internet Support Group ( ISG ) , automated depression Internet Training Program ( ITP ) , combination of the two ( ITP+ISG ) , or a control website with delayed access to e-couch at 6 months . Assessment s were conducted at baseline , post-intervention , 6 and 12 months . Results There was no change in depressive symptoms relative to control after 3 months of exposure to the ISG . However , both the ISG alone and the combined ISG+ITP group showed significantly greater reduction in depressive symptoms at 6 and 12 months follow-up than the control group . The ITP program was effective relative to control at post-intervention but not at 6 months . Conclusions ISGs for depression are promising and warrant further empirical investigation . Trial Registration Controlled-Trials.com IS RCT BRUCE BAKERHarvard UniversityPhobic Ss were r and omly assigned to 1 of 2 treatment groups : ( 1 ) a " conven-tional desensitization " group , which was treated by a therapist in the labora-tory , or ( 2 ) a " do-it-yourself " group , which carried out the desensitizationprocess at home . For the latter , the only therapist contact was an initialinterview and a weekly progress-check phone call . According to Ss ' reportsof success , both groups did equally well . These results are discussed withrespect to the relative importance of relationship and content in the therapeuticprocess Background Interventions to promote mental well-being can bring benefits to the individual and to society . The Internet can facilitate the large-scale and low-cost delivery of individually targeted health promoting interventions . Objective To evaluate the effectiveness of a self-directed Internet-delivered cognitive-behavioral skills training tool in improving mental well-being in a population sample . Methods This was a r and omized trial with a waiting-list control . Using advertisements on a national health portal and through its mailing list , we recruited 3070 participants aged 18 or over , resident in Engl and , and willing to give their email address and access a fully automated Web-based intervention . The intervention ( MoodGYM ) consisted of 5 interactive modules that teach cognitive-behavioral principles . Participants in the intervention arm received weekly email reminders to access the intervention Output:	Self-help may be useful for people who are not able or are not willing to use other services for people with anxiety disorders ; for people who can access it , face-to-face cognitive behavioural therapy is probably clinical ly superior . Recent interventions for specific problems that incorporate clinician support may be more effective than transdiagnostic interventions ( i.e. interventions for multiple disorders ) provided with no guidance , but these issues are confounded in the available trials .
MS213853	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: BACKGROUND AND PURPOSE This prospect i ve , multicenter study was performed to determine the frequency of symptomatic complications up to 30 months after stroke using prespecified definitions of complications . METHODS We recruited 311 consecutive stroke patients admitted to hospital . Research nurses review ed their progress on a weekly basis until hospital discharge and again at 6 , 18 , and 30 months after stroke . RESULTS Complications during hospital admission were recorded in 265 ( 85 % ) of stroke patients . Specific complications were as follows : neurological-recurrent stroke ( 9 % of patients ) , epileptic seizure ( 3 % ) ; infections-urinary tract infection ( 24 % ) , chest infection ( 22 % ) , others ( 19 % ) ; mobility related-falls ( 25 % ) , falls with serious injury ( 5 % ) , pressure sores ( 21 % ) ; thromboembolism-deep venous thrombosis ( 2 % ) , pulmonary embolism ( 1 % ) ; pain-shoulder pain ( 9 % ) , other pain ( 34 % ) ; and psychological-depression ( 16 % ) , anxiety ( 14 % ) , emotionalism ( 12 % ) , and confusion ( 56 % ) . During follow-up , infections , falls , " blackouts , " pain , and symptoms of depression and anxiety remained common . Complications were observed across all 3 hospital sites , and their frequency was related to patient dependency and duration after stroke . CONCLUSIONS Our prospect i ve cohort study has confirmed that poststroke complications , particularly infections and falls , are common . However , we have also identified complications relating to pain and cognitive or affective symptoms that are potentially preventable and may previously have been underestimated Background and Purpose — Drop foot after stroke may be addressed using an ankle foot orthosis ( AFO ) or a foot drop stimulator ( FDS ) . The Functional Ambulation : St and ard Treatment versus Electric Stimulation Therapy ( FASTEST ) trial was a multicenter , r and omized , single-blinded trial comparing FDS and AFO for drop foot among people ≥3 months after stroke with gait speed ⩽0.8 m/s . Methods — Participants ( n=197 ; 79 females and 118 males ; 61.14±11.61 years of age ; time after stroke 4.55±4.72 years ) were r and omized to 30 weeks of either FDS or a st and ard AFO . Eight dose-matched physical therapy sessions were provided to both groups during the first 6 weeks of the trial . Results — There was significant improvement within both groups from baseline to 30 weeks in comfortable gait speed ( 95 % confidence interval for mean change , 0.11–0.17 m/s for FDS and 0.12–0.18 m/s for AFO ) and fast gait speed . However , no significant differences in gait speed were found in the between-group comparisons . Secondary outcomes ( st and ard measures of body structure and function , activity , and participation ) improved significantly in both groups , whereas user satisfaction was significantly higher in the FDS group than in the control group . Conclusions — Using either an FDS or an AFO for 30 weeks yielded clinical ly and statistically significant improvements in gait speed and other functional outcomes . User satisfaction was higher in the FDS group . Although both groups did receive intervention , this large clinical trial provides evidence that FDS or AFO with initial physical therapy sessions can provide a significant and clinical ly meaningful benefit even years after stroke . Clinical Trial Registration Information— URL : http://www . clinical trials.gov . Unique Identifier : NCT01138995 Background Falls are common in stroke survivors returning home after rehabilitation , however there is currently a lack of evidence about preventing falls in this population . This paper describes the study protocol for the FLASSH ( FaLls prevention After Stroke Survivors return Home ) project . Methods and design This r and omised controlled trial aims to evaluate the effectiveness of a multi-factorial falls prevention program for stroke survivors who are at high risk of falling when they return home after rehabilitation . Intervention will consist of a home exercise program as well as individualised falls prevention and injury minimisation strategies based on identified risk factors for falls . Additionally , two sub- studies will be implemented in order to explore other key areas related to falls in this population . The first of these is a longitudinal study evaluating the relationship between fear of falling , falls and function over twelve months , and the second evaluates residual impairment in gait stability and obstacle crossing twelve months after discharge from rehabilitation . Discussion The results of the FLASSH project will inform falls prevention practice for stroke survivors . If the falls prevention program is shown to be effective , low cost strategies to prevent falls can be implemented for those at risk around the time of discharge from rehabilitation , thus improving safety and quality of life for stroke survivors . The two sub- studies will contribute to the overall underst and ing and management of falls risk in stroke survivors . Trial registration This trial is registered with the Australian and New Zeal and Clinical Trials Registry ( ACTRN012607000398404 ) Objectives To investigate if repeated verbal instructions about physical activity to patients with ischaemic stroke could increase long term physical activity . Design Multicentre , multinational , r and omised clinical trial with masked outcome assessment . Setting Stroke units in Denmark , China , Pol and , and Estonia . Participants 314 patients with ischaemic stroke aged ≥40 years who were able to walk—157 ( mean age 69.7 years ) r and omised to the intervention , 157 ( mean age 69.4 years ) in the control group . Interventions Patients r and omised to the intervention were instructed in a detailed training programme before discharge and at five follow-up visits during 24 months . Control patients had follow-up visits with the same frequency but without instructions in physical activity . Main outcome measures Physical activity assessed with the Physical Activity Scale for the Elderly ( PASE ) at each visit . Secondary outcomes were clinical events . Results The estimated mean PASE scores were 69.1 in the intervention group and 64.0 in the control group ( difference 5.0 ( 95 % confidence interval −5.8 to 15.9 ) , P=0.36 . The intervention had no significant effect on mortality , recurrent stroke , myocardial infa rct ion , or falls and fractures . Conclusion Repeated encouragement and verbal instruction in being physically active did not lead to a significant increase in physical activity measured by the PASE score . More intensive strategies seem to be needed to promote physical activity after ischaemic stroke . Trial registration Clinical Trials Background and Purpose — The optimal organization of rehabilitation services after discharge from a stroke unit has not been determined . This study sought to evaluate the effect of early supported discharge and continued rehabilitation at home ( ESD ) , in terms of patient outcome 5 years after stroke and changes in selected data over time . Methods — Eighty-three patients from Southwest Stockholm , mildly or moderately impaired 5 to 7 days after acute stroke , were enrolled in a r and omized controlled trial . The core components of the ESD service were initial treatment in a stroke unit and the involvement of an outreach team to deliver and coordinate home-based rehabilitation in partnership with the patient . At the 5-year follow-up , measures used to assess patient outcome included survival , motor capacity , dysphasia , activities of daily living ( ADL ) , social activities , subjective dysfunction , and self-reported falls . Results — Fifty-four patients ( 30 in the intervention group and 24 in the control group ) were evaluated 5 years after stroke , at which time a significantly larger proportion of patients in the intervention group were independent in extended ADL and active in household activities . Conclusions — This ESD service has a beneficial effect on extended ADL 5 years after stroke for mildly to moderately impaired patients BACKGROUND Locomotor training , including the use of body-weight support in treadmill stepping , is a physical therapy intervention used to improve recovery of the ability to walk after stroke . The effectiveness and appropriate timing of this intervention have not been established . METHODS We stratified 408 participants who had had a stroke 2 months earlier according to the extent of walking impairment -- moderate ( able to walk 0.4 to < 0.8 m per second ) or severe ( able to walk < 0.4 m per second)-- and r and omly assigned them to one of three training groups . One group received training on a treadmill with the use of body-weight support 2 months after the stroke had occurred ( early locomotor training ) , the second group received this training 6 months after the stroke had occurred ( late locomotor training ) , and the third group participated in an exercise program at home managed by a physical therapist 2 months after the stroke ( home-exercise program ) . Each intervention included 36 sessions of 90 minutes each for 12 to 16 weeks . The primary outcome was the proportion of participants in each group who had an improvement in functional walking ability 1 year after the stroke . RESULTS At 1 year , 52.0 % of all participants had increased functional walking ability . No significant differences in improvement were found between early locomotor training and home exercise ( adjusted odds ratio for the primary outcome , 0.83 ; 95 % confidence interval [ CI ] , 0.50 to 1.39 ) or between late locomotor training and home exercise ( adjusted odds ratio , 1.19 ; 95 % CI , 0.72 to 1.99 ) . All groups had similar improvements in walking speed , motor recovery , balance , functional status , and quality of life . Neither the delay in initiating the late locomotor training nor the severity of the initial impairment affected the outcome at 1 year . Ten related serious adverse events were reported ( occurring in 2.2 % of participants undergoing early locomotor training , 3.5 % of those undergoing late locomotor training , and 1.6 % of those engaging in home exercise ) . As compared with the home-exercise group , each of the groups receiving locomotor training had a higher frequency of dizziness or faintness during treatment ( P=0.008 ) . Among patients with severe walking impairment , multiple falls were more common in the group receiving early locomotor training than in the other two groups ( P=0.02 ) . CONCLUSIONS Locomotor training , including the use of body-weight support in stepping on a treadmill , was not shown to be superior to progressive exercise at home managed by a physical therapist . ( Funded by the National Institute of Neurological Disorders and Stroke and the National Center for Medical Rehabilitation Research ; LEAPS Clinical Trials.gov number , NCT00243919 . ) QUESTIONS Is treadmill walking with body weight support during inpatient rehabilitation detrimental to walking quality compared with assisted overground walking ? Does it result in better walking capacity , perception of walking or community participation ? DESIGN Analysis of secondary outcomes of a r and omised trial with concealed allocation , assessor blinding and intention-to-treat analysis . PARTICIPANTS 126 patients unable to walk within 4 weeks of a stroke who were undergoing inpatient rehabilitation . INTERVENTION The experimental group undertook up to 30 minutes of treadmill walking with body weight support via an overhead harness per day while the control group undertook up to 30 minutes of overground walking . OUTCOME MEASURES The secondary outcomes were walking quality and capacity , walking perception , community participation and falls . RESULTS Six months after entering the study , there was no difference between the groups of independent walkers in terms of speed ( MD 0.10 m/s , 95 % CI -0.06 to 0.26 ) or stride ( MD 6 cm , 95 % CI -7 to 19 ) . The independent walkers in the experimental group walked 57 m further ( 95 % CI 1 to 113 ) in the 6 min walk than those in the control group . The experimental group ( walkers and non-walkers ) rated their walking 1 point out of 10 ( 95 % CI 0.1 to 1.9 ) higher than the control group . There was no difference between the groups in community participation or number of falls . CONCLUSION Treadmill training with body weight support results in better walking capacity and perception of walking compared to overground walking without deleterious effects on walking quality BACKGROUND AND PURPOSE This study describes the methodology , patient outcome , and use of hospital and rehabilitation services at 3 months of a population -based r and omized controlled trial . The purpose was to evaluate rehabilitation at home after early supported discharge from the Department of Neurology , Huddinge Hospital , for moderately disabled stroke patients in southwest Stockholm . METHODS The patients were eligible if they were continent , independent in feeding , had mental function within normal limits , and had impaired motor function and /or aphasia 1 week after stroke . Patients were r and omized either to early supported discharge with continuity of rehabilitation at home for 3 to 4 months or to routine rehabilitation service in a hospital , day care , and /or outpatient care . The home rehabilitation team consisted of two physical therapists , two occupational therapists , and one speech therapist ; one of the therapists was assigned as case manager for the patient . The rehabilitation program at home emphasized a task- and context -oriented approach . The activities were chosen on the basis of the patient 's personal interests . Spouses were offered education and individual counseling . A total of 81 patients were followed up for a minimum of 3 months . Patient outcome was assessed by the Frenchay Social Activity Index , Extended Katz Index , Barthel Index , Lindmark Motor Capacity Assessment , Nine-Hole Peg Test , walking speed over 10 m , reported falls , and subjective dysfunction according to the Sickness Impact Profile . Patient use of hospital and home rehabilitation service and patient satisfaction with care were studied . RESULTS Overall there were no statistical significant differences in outcome . Multivariate logistic regression analysis suggested a systematic positive effect for the home rehabilitation group in social activity , activities of daily living , motor capacity , manual dexterity , and walking . A considerable difference Output:	There is currently insufficient evidence that exercises or prescription of single lens glasses to multifocal users prevent falls or decrease the number of people falling after being discharged from rehabilitation following their stroke .
MS213854	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Background : Evidence -based pharmacological treatment options for patients with persistent inguinal postherniorrhaphy pain are lacking . Methods : Twenty-one male patients , with severe , unilateral , persistent inguinal postherniorrhaphy pain , participated in a r and omized , double-blind , placebo-controlled crossover trial , receiving lidocaine patch ( 5 % ) and placebo patch treatments in periods of 14 days separated by a 14-day wash-out period . Pain intensities ( at rest , during movement , and pressure evoked [ Numerical Rating Scale ] ) were assessed before treatment and on the last 3 days of each treatment period . Patients were a priori divided into two subgroups based on quantitative sensory testing ( + /− thermal “ hyposensitivity ” ) . Skin biopsies for intraepidermal nerve fiber density assessment were taken at baseline , and quantitative sensory testing was performed before and after each treatment period . The primary outcome was change in pain intensity assessed as the difference in summed pain intensity differences between lidocaine and placebo patch treatments . Results : There was no difference in summed pain intensity differences between lidocaine and placebo patch treatments in all patients ( mean difference 6.2 % [ 95 % CI = −6.6 to 18.9 % ] ; P = 0.33 ) or in the two subgroups ( + /− thermal “ hyposensitivity ” ) . The quantitative sensory testing ( n = 21 ) demonstrated an increased pressure pain thresholds after lidocaine compared with placebo patch treatment . Baseline intraepidermal nerve fiber density ( n = 21 ) was lower on the pain side compared with the nonpain side ( −3.8 fibers per millimeter [ 95 % CI = −6.1 to −1.4 ] ; P = 0.003 ) . One patient developed mild erythema in the groin during both treatments . Conclusions : Lidocaine patch treatment did not reduce combined resting and dynamic pain ratings compared with placebo in patients with severe , persistent inguinal postherniorrhaphy pain Objective Oral amitriptyline , a tricyclic antidepressant , is effective for treating neuropathic pain . We conducted a double-blind , r and omized , placebo-controlled crossover study to evaluate the efficacy of topical 5 % amitriptyline and 5 % lidocaine in treating patients with neuropathic pain . Methods Thirty-five patients with postsurgical neuropathic pain , postherpetic neuralgia , or diabetic neuropathy with allodynia or hyperalgesia were assigned to receive 3 topical creams ( 5 % amitriptyline , 5 % lidocaine , or placebo ) in r and om sequence . The primary outcome measure was change in pain intensity ( baseline vs. posttreatment average pain ) using a 0 to 100 mm Visual Analog Scale . Secondary outcome measures included the McGill Pain Question naire , requirement for rescue medication , and patient satisfaction . Primary statistical comparisons were made with paired t tests or signed-rank tests . Results A reduction in pain intensity was observed with topical lidocaine ( P<0.05 ) . No significant change in pain intensity was found with topical amitriptyline or placebo . In pairwise comparison of treatments , topical lidocaine and placebo each reduced pain more than topical amitriptyline ( P<0.05 ) . Discussion This r and omized , placebo-controlled crossover study examining topical 5 % amitriptyline and 5 % lidocaine in the treatment of neuropathic pain showed that topical lidocaine reduced pain intensity but the clinical improvement is minimal and that topical 5 % amitriptyline was not effective Abstract Variability in patients ' response to interventions in pain and other clinical setting s is large . Many explanations such as trial methods , environment or culture have been proposed , but this paper sets out to show that the main cause of the variability may be r and om chance , and that if trials are small their estimate of magnitude of effect may be incorrect , simply because of the r and om play of chance . This is highly relevant to the questions of ‘ How large do trials have to be for statistical accuracy ? ’ and ‘ How large do trials have to be for their results to be clinical ly valid ? ’ The true underlying control event rate ( CER ) and experimental event rate ( EER ) were determined from single‐dose acute pain analgesic trials in over 5000 patients . Trial group size required to obtain statistically significant and clinical ly relevant ( 0.95 probability of number‐needed‐to‐treat within ±0.5 of its true value ) results were computed using these values . Ten thous and trials using these CER and EER values were simulated using varying group sizes to investigate the variation due to r and om chance alone . Most common analgesics have EERs in the range 0.4–0.6 and CER of about 0.19 . With such efficacy , to have a 90 % chance of obtaining a statistically significant result in the correct direction requires group sizes in the range 30–60 . For clinical relevance nearly 500 patients are required in each group . Only with an extremely effective drug ( EER>0.8 ) will we be reasonably sure of obtaining a clinical ly relevant NNT with commonly used group sizes of around 40 patients per treatment arm . The simulated trials showed substantial variation in CER and EER , with the probability of obtaining the correct values improving as group size increased . We contend that much of the variability in control and experimental event rates is due to r and om chance alone . Single small trials are unlikely to be correct . If we want to be sure of getting correct ( clinical ly relevant ) results in clinical trials we must study more patients . Credible estimates of clinical efficacy are only likely to come from large trials or from pooling multiple trials of conventional ( small ) size Objective Current therapies often have limited efficacy and untenable side effects when used to treat persistent incisional pain following cancer-related surgery . Lidocaine patches reduce neuropathic pain from herpes zoster but their benefits for persistent cancer-related postsurgical incisional pain remain unclear . Study design Multicenter , double-blind , r and omized , two-period crossover trial . Material s and methods Twenty-eight cancer patients with postsurgical incisional pain were r and omly assigned to receive either lidocaine patches followed by placebo patches or the reverse . Each study period lasted 4 weeks . Patches were applied daily upon waking and left in place for a maximum of 18 h. The primary outcome measure , an 11-point pain intensity rating scale , was administered weekly . Secondary outcomes were administered weekly ( Brief Pain Inventory-Short Form(BPI-SF ) , Subject Global Impression of Change ) and at the end of each study period ( Short Form-Magill Pain Question naire , Linear Analogue Self Assessment Scale , Neuropathy Pain Scale , Pain Catastrophizing Scale , Profile of Mood States Short Form ) . Results Twenty-one patients completed the first period and 18 completed their crossover second phase . No significant intergroup differences were detected in pain intensity ratings . Few secondary end points were significantly different when subjects used the lidocaine versus placebo patches . BPI-SF interference scores were lower in patients using the lidocaine patch during the first study period , including several scores that achieved statistical significance , general activity ( p = 0.02 ) , work ( p = 0.04 ) , and relations with others ( p = 0.02 ) . Conclusion Lidocaine patch use did not significantly reduce pain intensity ratings or the majority of related secondary end points in cancer patients with persistent incisional pain & NA ; Post‐herpetic neuralgia ( PHN ) is a common and often intractable neuropathic pain syndrome predominantly affecting the elderly . Topical local anesthetics have shown promise in both uncontrolled and controlled studies . Thirty‐five subjects with established PHN affecting the torso or extremities completed a four‐session , r and om order , double‐blind , vehicle‐controlled study of the analgesic effects of topically applied 5 % lidocaine in the form of a non‐woven polyethylene adhesive patch . All subjects had allodynia on examination . Up to 3 patches , covering a maximum of 420 cm2 , were applied to cover the area of greatest pain as fully as possible . Lidocaine containing patches were applied in two of the four 12‐h‐long sessions , in one session vehicle patches were applied , and one session was a no‐treatment observation session . Lidocaine containing patches significantly reduced pain intensity at all time points 30 min to 12 h compared to no‐treatment observation , and at all time points 4–12 h compared to vehicle patches . Lidocaine patches were superior to both no‐treatment observation and vehicle patches in averaged category pain relief scores . The highest blood Lidocaine level measured was 0.1 & mgr;g/ ml , indicating minimal systemic absorption of Lidocaine . Patch application was without systemic side effects and well tolerated when applied on allodynic skin for 12 h. This study demonstrates that topical 5 % Lidocaine in patch form is easy to use and relieves post‐herpetic neuralgia BACKGROUND Traditional and largely qualitative review s of evidence are now giving way to much more structured systematic overviews that use a quantitative method to calculate the overall effect of treatment . The latter approach is dependent on the quality of primary studies , which may introduce bias if they are of poor method ologic quality . OBJECTIVE To test the hypothesis that the inclusion of poor- quality trials in meta-analyses would bias the conclusions and produce incorrect estimates of treatment effect . METHODS An overview of r and omized trials of antiestrogen therapy in subfertile men with oligospermia was performed to test the hypothesis . Data sources included online search ing of MEDLINE and Science Citation Index data bases between 1966 and 1994 , scanning the bibliography of known primary studies and review articles , and contacting experts in the field . After independent , blind assessment , nine of 149 originally identified studies met the inclusion criteria and were selected . We assessed study quality independently . Outcome data from each study were pooled and statistically summarized . RESULTS There was a marginal improvement in pregnancy rate with antiestrogen treatment ( odds ratio , 1.6 ; 95 % confidence interval , 0.9 to 2.6 ) . Sensitivity analyses on the basis of method ologic quality demonstrated that poor- quality studies produced a positive effect with treatment , whereas no benefit was observed with high- quality studies . CONCLUSION The results of a meta- analysis are influenced by the quality of the primary studies included . Method ologically , poor studies tend to exaggerate the overall estimate of treatment effect and may lead to incorrect inferences Postherpetic neuralgia ( PHN ) following herpes zoster is a common and disabling neuropathic pain syndrome . In a double‐blind , three‐session study , 5 % lidocaine gel or vehicle was applied simultaneously to both the area of pain and to the contralateral mirror‐image unaffected skin . In the local session , lidocaine gel was applied to the painful skin area . In the remote session , lidocaine gel was applied to mirror‐image skin . In the placebo session , vehicle was applied bilaterally . For cranial PHN , gel was applied without occlusion for 8 hours . For limb or torso PHN , gel was applied under occlusion for 24 hours . The 16 subjects with cranial PHN reported pain relief significantly favoring local drug application at 30 minutes , 2 , 4 , and 8 hours . The 23 subjects with torso or limb PHN reported significantly lower pain intensity with local drug application at 8 hours and both pain relief and reduced pain intensity at 24 hours . Remote lidocaine application to mirror‐image skin was no different from placebo . No systemic adverse effects were reported and blood levels did not exceed 0.6 μg/ml . Topical application of 5 % lidocaine gel relieves PHN pain by a direct drug action on painful skin BACKGROUND Trigeminal nerve block has been widely used for trigeminal neuralgia . This may induce paraesthesia . The second division of the trigeminal nerve passes through the sphenopalatine ganglion , which is located posterior to the middle turbinate and is covered by a mucous membrane . We examined the effectiveness of intranasal lidocaine 8 % spray on paroxysmal pain in second-division trigeminal neuralgia . METHODS Twenty-five patients with second-division trigeminal neuralgia were r and omized to receive two sprays ( 0.2 ml ) of either lidocaine 8 % or saline placebo in the affected nostril using a metered-dose spray . After a 7 day period , patients were crossed over to receive the alternative treatment . The paroxysmal pain triggered by touching or moving face was assessed with a 10 cm visual analogue scale ( VAS ) before and 15 min after treatment . Patients used a descriptive scale to grade pain outcome , and were asked to note whether the pain returned and how long after therapy it recurred . RESULTS Intranasal lidocaine 8 % spray significantly decreased VAS [ baseline : 8.0 ( 2.0 ) cm , 15 min postspray : 1.5 ( 1.9 ) cm , mean ( SD ) ] , whereas the placebo spray did not [ 7.9 ( 2.0 ) cm , 7.6 ( 2.0 ) cm ] . Moreover , pain was described as moderate or better by 23 patients of the lidocaine spray and 1 of the placebo group . The effect of treatment persisted for 4.3 h ( range 0.5 - 24 h ) . CONCLUSIONS Intranasal lidocaine 8 % administered by a metered-dose spray produced prompt but temporary analgesia without serious adverse reactions in patients with second-division trigeminal neuralgia BACKGROUND : A topical lidocaine patch is effective in the treatment of posttraumatic peripheral neuropathy ( PTPN ) , but it is not suited for breakthrough pain because of difficulty with an additional application . Here , we examined the effect of 8 % lidocaine pump spray ( Xylocaine pump spray ® , XPS ) on peripher Output:	In all but one study , third tier ( very low quality ) evidence indicated that lidocaine was better than placebo for some measure of pain relief . Pooling multiple-dose studies across conditions demonstrated no clear evidence of an effect of lidocaine on the incidence of adverse events or withdrawals , but there were few events and the withdrawal phase of enriched enrolment design s is not suitable to assess the true impact of adverse events ( very low quality evidence ) . This review found no evidence from good quality r and omised controlled studies to support the use of topical lidocaine to treat neuropathic pain , although individual studies indicated that it was effective for relief of pain . Clinical experience also supports efficacy in some patients .
MS213855	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: We describe the development of a cognitive therapy intervention for chronic insomnia . The therapy is based on a cognitive model which suggests that the processes that maintain insomnia include : ( 1 ) worry and rumination , ( 2 ) attentional bias and monitoring for sleep-related threat , ( 3 ) unhelpful beliefs about sleep , ( 4 ) misperception of sleep and daytime deficits and ( 5 ) the use of safety behaviors that maintain unhelpful beliefs . The aim of cognitive therapy for insomnia is to reverse all five maintaining processes during both the night and the day . In an open trial 19 patients meeting diagnostic criteria for primary insomnia were treated with cognitive therapy for insomnia . Assessment s were completed pretreatment , posttreatment and at 3- , 6- and 12-month followup . The significant improvement in both nighttime and daytime impairment evident at the posttreatment assessment was retained up to the 12 month followup The aim of this study was to identify indicators of non-functional overreaching ( NFOR ) in team sport athletes undertaking intensive training loads . Eighteen semi-professional rugby league players were r and omly assigned into two pair matched groups . One group completed 6 weeks of normal training ( NT ) whilst the other group was deliberately overreached through intensified training ( IT ) . Both groups then completed the same 7-day stepwise training load reduction taper . Multistage fitness test ( MSFT ) performance , $ $ \ifmmode\exp and after\dot\else\exp and after\.\fi{V}{\text{O}}_{{2\max } } $ $ , peak aerobic running velocity ( Vmax ) , maximal heart rate , vertical jump , 10-s cycle sprint performance and body mass were measured pre- and post-training period and following the taper . Hormonal , haematological and immunological parameters were also measured pre-training and following weeks 2 , 4 and 6 of training and post-taper . MANOVA for repeated measures with contrast analysis indicated that MSFT performance and $ $ \ifmmode\exp and after\dot\else\exp and after\.\fi{V}{\text{O}}_{{2\max } } $ $ were significantly reduced in the IT group over time and condition , indicating that a state of overreaching was attained . However , the only biochemical measure that was significantly different between the IT and NT group was the glutamine to glutamate ( Gln/Glu ) ratio even though testosterone , testosterone to cortisol ( T/C ) ratio , plasma glutamate , and CK activity were significantly changed after training in both groups . Positive endurance and power performance changes were observed post-taper in the IT group confirming NFOR . These changes were associated with increases in the T/C ratio and the Gln/Glu ratio and decreases in plasma glutamate and CK activity . These results indicate that although there was no single reliable biochemical marker of NFOR in these athletes , the Gln/Glu ratio and MSFT test may be useful measures for monitoring responses to IT in team sport athletes BACKGROUND Chronic insomnia is a common health problem with substantial consequences in older adults . Cognitive behavioral treatments are efficacious but not widely available . The aim of this study was to test the efficacy of brief behavioral treatment for insomnia ( BBTI ) vs an information control ( IC ) condition . METHODS A total of 79 older adults ( mean age , 71.7 years ; 54 women [ 70 % ] ) with chronic insomnia and common comorbidities were recruited from the community and 1 primary care clinic . Participants were r and omly assigned to either BBTI , consisting of individualized behavioral instructions delivered in 2 intervention sessions and 2 telephone calls , or IC , consisting of printed educational material . Both interventions were delivered by a nurse clinician . The primary outcome was categorically defined treatment response at 4 weeks , based on sleep question naires and diaries . Secondary outcomes included self-report symptom and health measures , sleep diaries , actigraphy , and polysomnography . RESULTS Categorically defined response ( 67 % [ n = 26 ] vs 25 % [ n = 10 ] ; χ(2 ) = 13.8 ) ( P < .001 ) and the proportion of participants without insomnia ( 55 % [ n = 21 ] vs 13 % [ n = 5 ] ; χ(2 ) = 15.5 ) ( P < .001 ) were significantly higher for BBTI than for IC . The number needed to treat was 2.4 for each outcome . No differential effects were found for subgroups according to hypnotic or antidepressant use , sleep apnea , or recruitment source . The BBTI produced significantly better outcomes in self-reported sleep and health ( group × time interaction , F(5,73 ) = 5.99 , P < .001 ) , sleep diary ( F(8,70 ) = 4.32 , P < .001 ) , and actigraphy ( F(4,74 ) = 17.72 , P < .001 ) , but not polysomnography . Improvements were maintained at 6 months . CONCLUSION We found that BBTI is a simple , efficacious , and durable intervention for chronic insomnia in older adults that has potential for dissemination across medical setting s. TRIAL REGISTRATION clinical trials.gov Identifier : NCT00177203 We determined the effect of coingestion of caffeine ( Caff ) with carbohydrate ( CHO ) on rates of muscle glycogen re synthesis during recovery from exhaustive exercise in seven trained subjects who completed two experimental trials in a r and omized , double-blind crossover design . The evening before an experiment subjects performed intermittent exhaustive cycling and then consumed a low-CHO meal . The next morning subjects rode until volitional fatigue . On completion of this ride subjects consumed either CHO [ 4 g/kg body mass ( BM ) ] or the same amount of CHO + Caff ( 8 mg/kg BM ) during 4 h of passive recovery . Muscle biopsies and blood sample s were taken at regular intervals throughout recovery . Muscle glycogen levels were similar at exhaustion [ approximately 75 mmol/kg dry wt ( dw ) ] and increased by a similar amount ( approximately 80 % ) after 1 h of recovery ( 133 + /- 37.8 vs. 149 + /- 48 mmol/kg dw for CHO and Caff , respectively ) . After 4 h of recovery Caff result ed in higher glycogen accumulation ( 313 + /- 69 vs. 234 + /- 50 mmol/kg dw , P < 0.001 ) . Accordingly , the overall rate of re synthesis for the 4-h recovery period was 66 % higher in Caff compared with CHO ( 57.7 + /- 18.5 vs. 38.0 + /- 7.7 mmol x kg dw(-1 ) x h(-1 ) , P < 0.05 ) . After 1 h of recovery plasma Caff levels had increased to 31 + /- 11 microM ( P < 0.001 ) and at the end of the recovery reached 77 + /- 11 microM ( P < 0.001 ) with Caff . Phosphorylation of CaMK(Thr286 ) was similar after exercise and after 1 h of recovery , but after 4 h CaMK(Thr286 ) phosphorylation was higher in Caff than CHO ( P < 0.05 ) . Phosphorylation of AMP-activated protein kinase (AMPK)(Thr172 ) and Akt(Ser473 ) was similar for both treatments at all time points . We provide the first evidence that in trained subjects coingestion of large amounts of Caff ( 8 mg/kg BM ) with CHO has an additive effect on rates of postexercise muscle glycogen accumulation compared with consumption of CHO alone INTRODUCTION Elite athletes frequently undergo periods of intensified training ( IT ) within their normal training program . These periods can lead athletes into functional overreaching , characterized by high perceived fatigue , impaired sleep , and performance . Because whole-body cryostimulation ( WBC ) has been proven to be an effective recovery method in the short term ( < 76 h ) , we investigated whether daily WBC sessions during IT could prevent exercise and sleep-related signs of overreaching . METHODS After a normal training week ( BASE ) , 10 elite synchronized swimmers performed two 2-wk IT periods in a r and omized crossover fashion using WBC daily ( ITWBC ) or not ( ITCON ) , separated by 9 d of light training . Swim time trials ( 400 m ) were performed at BASE and after each IT to quantify blood lactate ( [La]B ) , HR ( HR400 ) , salivary alpha amylase ( [α-amylase]s400 ) , and cortisol ( [cortisol]s400 ) responses . Swimmers wore a wrist actigraph nightly to monitor sleep patterns . RESULTS Swim speed ( 400 m ) , [La]B400 , and [α-amylase]s400 decreased from BASE to ITCON , although no significant changes were found after ITWBC . Decreased swim speed was correlated to decreased HR400 and [cortisol]s400 . During ITCON , significant decreases in actual sleep duration ( -21 ± 7 min ) and sleep efficiency ( -1.9 % ± 0.8 % ) were observed , with increased sleep latency ( + 11 ± 5 min ) and fatigue compared with BASE , although these variables did not change during ITWBC . Using a qualitative statistical analysis , we observed that daily WBC use result ed in a 98 % , 59 % , 66 % , and 78 % chance of preserving these respective variables compared with ITCON . CONCLUSION WBC use during IT helped mitigate the signs of functional overreaching observed during ITCON , such as reduced sleep quantity , increased fatigue , and impaired exercise capacity . These results support the daily use of WBC by athletes seeking to avoid functional overreaching during key periods of competition preparation Abstract Objectives : To improve well-being and performance indicators in a group of Australian Football League ( AFL ) players via a six-week sleep optimisation programme . Design : Prospect i ve intervention study following observations suggestive of reduced sleep and excessive daytime sleepiness in an AFL group . Methods : Athletes from the Adelaide Football Club were invited to participate if they had played AFL senior-level football for 1–5 years , or if they had excessive daytime sleepiness ( Epworth Sleepiness Scale [ ESS ] > 10 ) , measured via ESS . An initial education session explained normal sleep needs , and how to achieve increased sleep duration and quality . Participants ( n = 25 ) received ongoing feedback on their sleep , and a mid-programme education and feedback session . Sleep duration , quality and related outcomes were measured during week one and at the conclusion of the six-week intervention period using sleep diaries , actigraphy , ESS , Pittsburgh Sleep Quality Index , Profile of Mood States , Training Distress Scale , Perceived Stress Scale and the Psychomotor Vigilance Task . Results : Sleep diaries demonstrated an increase in total sleep time of approximately 20 min ( 498.8 ± 53.8 to 518.7 ± 34.3 ; p < .05 ) and a 2 % increase in sleep efficiency ( p < 0.05 ) . There was a corresponding increase in vigour ( p < 0.001 ) and decrease in fatigue ( p < 0.05 ) . Conclusions : Improvements in measures of sleep efficiency , fatigue and vigour indicate that a sleep optimisation programme may improve athletes ’ well-being . More research is required into the effects of sleep optimisation on athletic performance ABSTRACT The concept of recovery strategies includes various ways to achieve a state of well-being , prevent underrecovery syndromes from occurring and re-establish pre-performance states . A systematic application of individualised relaxation techniques is one of those . Following a counterbalanced cross-over design , 27 sport science students ( age 25.22 ± 1.08 years ; sports participation 8.08 ± 3.92 h/week ) were r and omly assigned to series of progressive muscle relaxation , systematic breathing , power nap , yoga , and a control condition . Once a week , over the course of five weeks , their repeated sprint ability was tested . Tests ( 6 sprints of 4 s each with 20 s breaks between them ) were executed on a non-motorised treadmill twice during that day intermitted by 25 min breaks . RM-ANOVA revealed significant interaction effects between the relaxation conditions and the two sprint sessions with regard to average maximum speed over all six sprints , F(4,96 ) = 4.06 , P = 0.004 , = 0.15 . Post-hoc tests indicated that after systematic breathing interventions , F(1,24 ) = 5.02 , P = 0.033 , = 0.18 , participants performed significantly better compared to control sessions . As the focus of this study lied on basic mechanisms of relaxation techniques in sports , this r and omised controlled trial provides us with distinct knowledge on their effects , i.e. , systematic breathing led to better performances , and therefore , seems to be a suited relaxation method during high-intensity training ABSTRACT Elite soccer players are at risk of reduced recovery following periods of sleep disruption , particularly following late-night matches . It remains unknown whether improving sleep quality or quantity in such scenarios can improve post-match recovery . Therefore , the aim of this study was to investigate the effect of an acute sleep hygiene strategy ( SHS ) on physical and perceptual recovery of players following a late-night soccer match . In a r and omised cross-over design , two highly-trained amateur teams ( 20 players ) played two late-night ( 20:45 ) friendly matches against each other seven days apart . Players completed an SHS after the match or proceeded with their normal post-game routine ( NSHS ) . Over the ensuing Output:	Evidence suggests that sleep extension had the most beneficial effects on subsequent performance . Consistent with previous research , these results suggest that sleep plays an important role in some , but not all , aspects of athletes ’ performance and recovery .
MS213856	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Cluster immunotherapy represents an interesting alternative to conventional up‐dosing schedules because it allows achieving the maintenance dose within a shorter time interval . In this study , the efficacy and safety of cluster immunotherapy with a high polymerized allergen extract of a grass/rye pollen mixture have been evaluated in a r and omized , double‐blind , placebo‐controlled , multicenter study Although many patients with allergic rhinoconjunctivitis have symptoms due to sensitization with more than one pollen allergen , and mixed pollen extracts are widely used for allergen immunotherapy in practice , there are few published trials Background and Objectives : Allergy to house dust mite is one of the most common causes of allergic rhinitis ( AR ) in China . We sought to compare the efficacy and safety of a 6-week cluster schedule of specific immunotherapy with that of a 14-week conventional schedule for the treatment of subjects with persistent AR . Methods : The trial was a prospect i ve and r and omized study involving 96 patients with persistent AR , aged 14–60 years , who were allergic to Dermatophagoides pteronyssinus . While 48 patients were r and omly assigned to the cluster schedule reaching the maintenance dose within 6 weeks , the other 48 were r and omly assigned to the conventional schedule reaching the maintenance dose within 14 weeks . Eighty-nine patients completed a 1-year treatment course . While kinetic changes in clinical efficacy and adverse reactions were observed during the treatment , quality of life , cutaneous reactivity and serum-specific immunoglobulin E to Dermatophagoides pteronyssinus were measured before and after treatment . Results : The cluster schedule reduced the time to reach the maintenance dose by 57 % and caused mild systemic adverse reactions after 1.0 % of injections ( 6.7 % of patients ) , with no differences in comparison with the conventional schedule . Cluster specific immunotherapy led to decreases in clinical symptoms and earlier use of medication than did the conventional schedule . Similar improvements in quality of life and reduced cutaneous reactivity without significant changes in specific immunoglobulin E were observed in both groups after 1 year . Conclusions : The cluster schedule is a safe alternative to the conventional schedule with the advantage of achieving clinical effectiveness sooner BACKGROUND Few studies have investigated the use of specific immunotherapy ( SIT ) for childhood seasonal allergic asthma . OBJECTIVE We sought to examine the efficacy and safety of SIT with Alutard SQ grass pollen ( Phleum pratense Alutard SQ ; ALK-Abelló , Hørsholm , Denmark ) in children with seasonal allergic asthma . METHODS A r and omized , double-blind , placebo-controlled study assessing the efficacy of grass pollen SIT over 2 pollen seasons was performed . Children ( 3 - 16 years ) with a history of seasonal allergic asthma sensitized to grass pollen ( P pratense ) and requiring at least 200 microg of inhaled beclomethasone equivalent per day were enrolled . Subjects with symptomatic asthma or rhinoconjunctivitis outside the grass pollen season were excluded . The primary outcome measure was a combined asthma symptom-medication score during the second pollen season . Secondary outcome measures included end-point titration skin prick testing and conjunctival and bronchial provocation testing to allergen , sputum eosinophilia , exhaled nitric oxide , and adverse events . RESULTS Thirty-nine subjects were enrolled . Thirty-five subjects provided data for analysis . The use of SIT was associated with a substantial reduction in asthma symptom-medication score compared with that after placebo ( P = .04 ) . There were also significant reductions in cutaneous ( P = .002 ) , conjunctival ( P = .02 ) , and bronchial ( P = .01 ) reactivity to allergen after SIT compared with that after placebo . The 2 groups had similar levels of airway inflammation , despite a trend toward less inhaled steroid use in the active group . No serious adverse events were reported , and no subjects withdrew because of adverse events . CONCLUSION The study has shown that SIT is effective and well tolerated in children with seasonal allergic asthma to grass pollen BACKGROUND The clinical efficacy of allergen immunotherapy using therapeutic vaccines containing modified allergen extracts has been previously shown . OBJECTIVE To evaluate the clinical efficacy of a vaccine containing depigmented , polymerized extract of Dermatophagoides pteronyssinus in asthmatic children , monosensitized to mites , after 4 months of treatment . MATERIAL AND METHODS A total of 30 mite-allergic , asthmatic children ( age range , 8 - 16 years ) were entered in the study ; 15 were treated with the modified allergen extract ( active group ) and 15 received only pharmacologic treatment ( control group ) . The study was open , controlled and parallel with r and om allocation of the patients to each of the groups . Efficacy was evaluated using allergen-specific bronchial challenge tests , dose-response skin-prick tests , and symptom and medication scores . The results of the bronchial challenges and dose-response skin-prick tests were compared at baseline and after 4 months of treatment . The build up phase consisted of 4 injections in 2 days , followed by 4 injections of the maintenance dose . RESULTS All patients of the active group concluded the study , whereas 2 of the control group did not . In the active group , there was a significant difference in the PC20FEV1 ( P < .01 ) after 4 months . The mean allergen quantity needed was 26 microg at baseline vs. 309 microg after 4 months ( a 12.8-fold increase ) . There was no difference in the control group ( 5 tg at baseline vs 8 microg at the end ) . A significant reduction in the number of cases with dual bronchial response was observed in the treated group ( P < .05 ) . Two treated patients of this group experienced a negative bronchial challenge after 4 months of treatment . The group of active patients also experienced significant improvement in skin reactivity and symptom and medication scores . CONCLUSIONS Vaccines containing depigmented polymerized extracts of D pteronyssinus are safe and effective in the treatment of mite allergic asthmatic children , and provide clinical benefit after 4 months of treatment To cite this article : Pfaar O , Urry Z , Robinson DS , Sager A , Richards D , Hawrylowicz CM , Bräutigam M , Klimek L. A r and omized placebo‐controlled trial of rush preseasonal depigmented polymerized grass pollen immunotherapy . Allergy 2012 ; 67 : 272–279 BACKGROUND The inhalation of Salsola kali pollen is a common cause of respiratory diseases in Europe and North America . OBJECTIVE To evaluate the efficacy and safety of a depigmented and glutaraldehyde-polymerized therapeutic vaccine of S kali . METHODS The trial was r and omized , double-blind , and placebo-controlled using a rush protocol in the build-up phase . Sixty patients with rhinoconjunctivitis ( 19 also had mild asthma ) were r and omly allocated to receive either active treatment ( polymerized extract ) or placebo . The final distribution was 41 patients in the active and 19 in the placebo group . Side effects were registered . Symptom and medication scores and the number of days free of symptoms during the pollen season were assessed to evaluate the clinical efficacy . A Rhinoconjunctivitis Quality of Life Question naire was completed in the previous pollen season ( before treatment ) and during the pollen season 1 year later ( in the trial ) . Dose-response skin tests were performed at baseline and at the end of the trial . RESULTS There was a significant difference ( P < .05 ) in symptom and medication scores between both groups during the pollen season , with the active group the one that had fewer symptoms and lower intake of medication . The number of days without symptoms was higher in the active group ( P < .05 ) . This group also had a significant improvement in the Rhinoconjunctivitis Quality of Life Question naire and a reduction in skin sensitivity . No moderate or severe systemic reactions were registered . CONCLUSION Immunotherapy with this modified vaccine of S kali pollen is safe and efficacious to treat patients clinical ly sensitive to this pollen . CLINICAL IMPLICATION S Patients allergic to S kali ( Russian thistle ) can be successfully treated with immunotherapy to improve symptoms of allergic rhinitis and asthma , reduce medication use , and improve quality of life parameters We investigated the effects of cluster specific immunotherapy ( SIT ) with Dermatophagoides pteronyssinus ( Der p ) on CD4(+ ) CD25(+ ) Foxp3(+ ) Treg cells and IL-10-secreting type I T regulatory ( Tr1 ) cells in Der p-sensitized children with allergic rhinitis ( AR ) . We performed a prospect i ve r and omized study involving 46 children ( aged 8 - 13 yr ) , of whom 25 children received Der p-SIT + pharmacotherapy and 21 received only pharmacotherapy , over a period of 1 yr . Prior to and at end of treatment , CD4(+ ) CD25(+ ) Foxp3(+ ) Treg cells and allergen-specific IL-10(+ ) IL-4(- ) , IFN-γ(+ ) IL-4(- ) , and IL-4(+ ) IFN-γ-CD4(+ ) T cells were measured by flow cytometry . Similarly , IL-4 , IFN-γ , and IL-10 in supernatants from allergen-stimulated peripheral blood mononuclear cell ( P BMC ) cultures were measured by ELISA , and the suppressive effect of CD4(+ ) CD25(high ) T cells on cell proliferation and cytokine release was estimated from both groups . Allergen-specific serum IgE and IgG4 were also assessed at the beginning and end of treatment by RAST and ELISA , respectively . The levels of allergen-specific Tr1 cells , IgG4 , and allergen-induced IL-10 synthesis from P BMC cultures were significantly increased after SIT for 1 yr compared with baseline levels ( p < 0.001 for all ) , with significant correlation between increased levels of Tr1 cells and improvements in nasal symptoms ( r = 0.48 , p < 0.05 ) . In contrast , the levels of CD4(+ ) CD25(+ ) Foxp3(+ ) T cells , allergen-specific Th1 and Th2 cells , the production of IL-4 and IFN-γ , and the function of CD4(+ ) CD25(high ) T cells were not altered in either group at the end of treatment . These data suggest that the up-regulation of Tr1 cells may play an important role in SIT and be a useful marker of successful SIT in AR patients Output:	This review demonstrated that rush and cluster schedules are clinical ly and immunological efficacious , with faster effect than conventional schedules . No relevant difference with respect to clinical outcomes was noticed between subgroups ( pediatric , adult and mixed population s ) . Regarding safety , most local adverse reactions were mild and there were neither life-threatening systemic reactions nor fatal events . No relevant differences in the incidence and severity of either local or systemic reactions between the accelerated schedule group and control group were registered . Accelerated SCIT build-up schedules are effective in the treatment of respiratory allergy in pediatric patients , representing a safe alternative to the conventional schedules with the advantage of achieving clinical effectiveness sooner
MS213857	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Objectives : To evaluate the effect of hormonal contraception including combined oral contraceptives ( COCs ) , and the injectable progestins depo-medroxyprogesterone acetate ( DMPA ) and norethisterone enanthate ( Net-En ) on the risk of HIV acquisition among women in South Africa . Design / methods : We analyzed data from 5567 women aged 16–49 years participating in the Carraguard Phase 3 Efficacy Trial . Participants were interviewed about contraceptive use and sexual behaviors and underwent pelvic examinations and HIV testing quarterly . We used marginal structural Cox regression models to estimate the effect of hormonal contraception exposure on HIV acquisition risk among women overall and among young women ( 16–24 years ) in particular . Results : Two hundred and seventy participants became HIV-infected ( 3.7 per 100 woman-years ) ; HIV incidence was 2.8 , 4.6 , 3.5 and 3.4 per 100 woman-years in the COC , DMPA , Net-En and nonhormonal contraceptive groups , respectively ( P = 0.09 ) . The adjusted hazard ratios ( AHRs ) were 0.84 [ 95 % confidence interval ( CI ) 0.51–1.39 ] , 1.28 ( 95 % CI 0.92–1.78 ) and 0.92 ( 95 % CI 0.64–1.32 ) among COC , DMPA and Net-En users , respectively , compared with the nonhormonal group controlling for covariates . Age modified the effect of hormonal contraception on HIV acquisition risk ; among young women , the AHRs were 1.02 ( 95 % CI 0.46–2.28 ) for COCs , 1.68 ( 95 % CI 0.96–2.94 ) for DMPA and 1.36 ( 95 % CI0.78–2.35 ) for Net-En users . Conclusions : In this study conducted among South African women , hormonal contraception did not significantly increase the risk of HIV acquisition . However , the effect estimate does not rule out a moderate increase in HIV risk associated with DMPA use found in some other recent studies With two million new HIV infections annually , ongoing investigations of risk factors for HIV acquisition is critical to guide ongoing HIV prevention efforts . We conducted a prospect i ve cohort analysis of HIV uninfected female sex workers enrolled at an HIV prevention clinic in Nairobi ( n = 1640 ) . In the initially HIV uninfected cohort ( 70 % ) , we observed 34 HIV infections during 1514 person-years of follow-up , i.e. an annual incidence of 2.2 % ( 95 % CI 1.6–3.1 % ) . In multivariable Cox Proportional Hazard analysis , HIV acquisition was associated with a shorter baseline duration of sex work ( aHR 0.76 , 95 % CI 0.63–0.91 ) , minimum charge/sex act ( aHR 2.74 , 0.82–9.15 , for low vs. intermediate ; aHR 5.70 , 1.96–16.59 , for high vs. intermediate ) , N. gonorrhoeae infection ( aAHR 5.89 , 95 % CI 2.03–17.08 ) , sex with casual clients during menses ( aHR 6.19 , 95 % CI 2.58–14.84 ) , Depo Provera use ( aHR 5.12 , 95 % CI 1.98–13.22 ) , and estimated number of annual unprotected regular partner contacts ( aHR 1.004 , 95 % CI 1.001–1.006 ) . Risk profiling based on baseline predictors suggested that substantial heterogeneity in HIV risk is evident , even within a key population . These data highlight several risk factors for HIV acquisition that could help to re-focus HIV prevention messages BACKGROUND Hormonal contraceptives are used widely but their effects on HIV-1 risk are unclear . We aim ed to assess the association between hormonal contraceptive use and risk of HIV-1 acquisition by women and HIV-1 transmission from HIV-1-infected women to their male partners . METHODS In this prospect i ve study , we followed up 3790 heterosexual HIV-1-serodiscordant couples participating in two longitudinal studies of HIV-1 incidence in seven African countries . Among injectable and oral hormonal contraceptive users and non-users , we compared rates of HIV-1 acquisition by women and HIV-1 transmission from women to men . The primary outcome measure was HIV-1 seroconversion . We used Cox proportional hazards regression and marginal structural modelling to assess the effect of contraceptive use on HIV-1 risk . FINDINGS Among 1314 couples in which the HIV-1-seronegative partner was female ( median follow-up 18·0 [ IQR 12·6 - 24·2 ] months ) , rates of HIV-1 acquisition were 6·61 per 100 person-years in women who used hormonal contraception and 3·78 per 100 person-years in those who did not ( adjusted hazard ratio 1·98 , 95 % CI 1·06 - 3·68 , p=0·03 ) . Among 2476 couples in which the HIV-1-seronegative partner was male ( median follow-up 18·7 [ IQR 12·8 - 24·2 ] months ) , rates of HIV-1 transmission from women to men were 2·61 per 100 person-years in couples in which women used hormonal contraception and 1·51 per 100 person-years in couples in which women did not use hormonal contraception ( adjusted hazard ratio 1·97 , 95 % CI 1·12 - 3·45 , p=0·02 ) . Marginal structural model analyses generated much the same results to the Cox proportional hazards regression . INTERPRETATION Women should be counselled about potentially increased risk of HIV-1 acquisition and transmission with hormonal contraception , especially injectable methods , and about the importance of dual protection with condoms to decrease HIV-1 risk . Non-hormonal or low-dose hormonal contraceptive methods should be considered for women with or at-risk for HIV-1 . FUNDING US National Institutes of Health and the Bill & Melinda Gates Foundation Vaginal Gel Versus HIV HIV prevention technologies for women are urgently needed , especially in sub-Saharan Africa where young women bear the greatest burden of the HIV epidemic . Abdool Karim et al. ( p. 1168 ; published online 19 July ) present the results of the CAPRISA 004 r and omized control trial . The nearly 3-year-long trial , conducted in urban and rural South African women , tested the efficacy of a vaginal gel containing the antiretroviral drug tenofovir in preventing HIV infection . The dosing strategy required application of the gel both before and after coitus , and with this regime HIV infection was reduced by approximately 39 % overall , by 54 % in women with high adherence to the protocol , and with no increase in overall adverse event rates . Tenofovir in a vaginal gel formulation shows significant protection against HIV infection in a r and omized control trial . The Centre for the AIDS Program of Research in South Africa ( CAPRISA ) 004 trial assessed the effectiveness and safety of a 1 % vaginal gel formulation of tenofovir , a nucleotide reverse transcriptase inhibitor , for the prevention of HIV acquisition in women . A double-blind , r and omized controlled trial was conducted comparing tenofovir gel ( n = 445 women ) with placebo gel ( n = 444 women ) in sexually active , HIV-uninfected 18- to 40-year-old women in urban and rural KwaZulu-Natal , South Africa . HIV serostatus , safety , sexual behavior , and gel and condom use were assessed at monthly follow-up visits for 30 months . HIV incidence in the tenofovir gel arm was 5.6 per 100 women-years ( person time of study observation ) ( 38 out of 680.6 women-years ) compared with 9.1 per 100 women-years ( 60 out of 660.7 women-years ) in the placebo gel arm ( incidence rate ratio = 0.61 ; P = 0.017 ) . In high adherers ( gel adherence > 80 % ) , HIV incidence was 54 % lower ( P = 0.025 ) in the tenofovir gel arm . In intermediate adherers ( gel adherence 50 to 80 % ) and low adherers ( gel adherence < 50 % ) , the HIV incidence reduction was 38 and 28 % , respectively . Tenofovir gel reduced HIV acquisition by an estimated 39 % overall , and by 54 % in women with high gel adherence . No increase in the overall adverse event rates was observed . There were no changes in viral load and no tenofovir resistance in HIV seroconverters . Tenofovir gel could potentially fill an important HIV prevention gap , especially for women unable to successfully negotiate mutual monogamy or condom use BACKGROUND Preexposure prophylaxis with antiretroviral drugs has been effective in the prevention of human immunodeficiency virus ( HIV ) infection in some trials but not in others . METHODS In this r and omized , double-blind , placebo-controlled trial , we assigned 2120 HIV-negative women in Kenya , South Africa , and Tanzania to receive either a combination of tenofovir disoproxil fumarate and emtricitabine ( TDF-FTC ) or placebo once daily . The primary objective was to assess the effectiveness of TDF-FTC in preventing HIV acquisition and to evaluate safety . RESULTS HIV infections occurred in 33 women in the TDF-FTC group ( incidence rate , 4.7 per 100 person-years ) and in 35 in the placebo group ( incidence rate , 5.0 per 100 person-years ) , for an estimated hazard ratio in the TDF-FTC group of 0.94 ( 95 % confidence interval , 0.59 to 1.52 ; P=0.81 ) . The proportions of women with nausea , vomiting , or elevated alanine aminotransferase levels were significantly higher in the TDF-FTC group ( P=0.04 , P<0.001 , and P=0.03 , respectively ) . Rates of drug discontinuation because of hepatic or renal abnormalities were higher in the TDF-FTC group ( 4.7 % ) than in the placebo group ( 3.0 % , P=0.051 ) . Less than 40 % of the HIV-uninfected women in the TDF-FTC group had evidence of recent pill use at visits that were matched to the HIV-infection window for women with seroconversion . The study was stopped early , on April 18 , 2011 , because of lack of efficacy . CONCLUSIONS Prophylaxis with TDF-FTC did not significantly reduce the rate of HIV infection and was associated with increased rates of side effects , as compared with placebo . Despite substantial counseling efforts , drug adherence appeared to be low . ( Supported by the U.S. Agency for International Development and others ; FEM-PrEP Clinical Trials.gov number , NCT00625404 . ) The use of hormonal contraception has been associated with an increased risk of HIV-1 in some studies but not in others . We analysed data from a 10-year prospect i ve cohort study of female sex workers in Mombasa , Kenya . In multivariate analysis , women using the injectable contraceptive depot medroxyprogesterone acetate and women using oral contraceptive pills were at increased risk of HIV-1 acquisition compared with women using no contraceptive method Objective : To evaluate the effect of oral and injectable hormonal contraception on the risk of HIV acquisition among women in South Africa and Zimbabwe . Design : Secondary data analysis of 4913 sexually active women aged 18–49 years followed for up to 24 months in the Methods for Improving Reproductive Health in Africa ( MIRA ) phase III effectiveness trial of the diaphragm and lubricant gel for HIV prevention . Methods : Participants were interviewed quarterly about contraception and sexual behavior and were tested for pregnancy , HIV , and other sexually transmitted infections . We used a Cox proportional hazards marginal structural model , weighted by the inverse probability of hormonal contraception use , to compare the risk of HIV acquisition among nonpregnant women reporting use of combined oral contraceptive pills ( COC ) , progestin-only pills ( POP ) , and /or injectable hormonal contraception to women not using these methods . Results : During the study , 283 participants seroconverted . Use of oral contraceptives ( POP or COC ) was not associated with HIV risk [ adjusted hazard ratio ( HRa ) = 0.86 , 95 % confidence interval ( CI ) 0.32 , 1.78 ] . Injectable hormonal contraception was associated with a small nonsignificant risk of HIV infection ( HRa = 1.34 , 95 % CI 0.75 , 2.37 ) . The effect of injectable horm Output:	The preponderance of data for oral contraceptive pills , injectable norethisterone enanthate , and levonorgestrel implants do not suggest an association with HIV acquisition , though data for implants are limited . Although confounding in these observational data can not be excluded , new information increases concerns about DMPA and HIV acquisition risk in women .
MS213858	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Some studies have found that prospect i ve memory ( PM ) cues which are emotionally valenced influence age effects in prospect i ve remembering , but it remains unclear whether this effect reflects the operation of processes implemented at encoding or retrieval . In addition , none of the prior ageing studies of valence on PM function have examined potential costs of engaging in different valence conditions , or re source allocation trade-offs between the PM and the ongoing task . In the present study , younger , young-old and old-old adults completed a PM task in which the valence of the cues varied systematic ally ( positive , negative or neutral ) at encoding , but was kept constant ( neutral ) at retrieval . The results indicated that PM accuracy did not vary as a function of affect at encoding , and that this effect did not interact with age group . There was also no main or interaction effect of valence on PM reaction time in PM cue trials , indicating that valence costs across the three encoding conditions were equivalent . Old-old adults ’ PM accuracy was reduced relative to both young-old and younger adults . Prospect i ve remembering incurred dual-task costs for all three groups . Analyses of reaction time data suggested that for both young-old and old-old , these costs were greater , implying differential re source allocation cost trade-offs . However , when reaction time data were expressed as a proportional change that adjusted for the general slowing of the older adults , costs did not differ as a function of group Event-based prospect i ve memory tasks entail detecting cues or reminders in our environment related to previously established intentions . If they are detected at an opportune time , then the intention can be fulfilled . In Experiments 1a-1c , we gave people 3 different nonfocal intentions ( e.g. , respond to words denoting animals ) and discovered that negatively valenced cues delivered the intention to mind less frequently than positively valenced cues . In Experiment 2 , this effect was extended to valenced and neutral sentential context s with convergent results that cues embedded in negatively valenced sentences evoked remembering the intention less often than in positive context s. In addition , both classes of valence caused the intention to be forgotten more often than a more neutral context . We propose that valence has the ability to usurp attentional re sources that otherwise would have supported successful prospect i ve memory performance Prospect i ve memory ( PM ) describes the ability to execute a previously planned action at the appropriate point in time . Although behavioral studies clearly showed that prospect i ve memory performance is affected by the emotional significance attributed to the intended action , no study so far investigated the brain mechanisms subserving the modulatory effect of emotional salience on PM performance . The general aim of the present study was to explore brain regions involved in prospect i ve memory processes when PM cues are associated with emotional stimuli . In particular , based on the hypothesised critical role of the prefrontal cortex in prospect i ve memory in the presence of emotionally salient stimuli , we expected a stronger involvement of aPFC when the retrieval and execution of the intended action is cued by an aversive stimulus . To this aim BOLD responses of PM trials cued by aversive facial expressions were compared to PM trials cued by neutral facial expressions . Whole brain analysis showed that PM task cued by aversive stimuli is differentially associated with activity in the right lateral prefrontal area ( BA 10 ) and in the left cau date nucleus . Moreover a temporal shift between the response of the cau date nucleus that preceded that of aPFC was observed . These findings suggest that the cau date nucleus might provide an early analysis of the affective properties of the stimuli , whereas the anterior lateral prefrontal cortex ( BA10 ) would be involved in a slower and more deliberative analysis to guide goal -directed behaviour This study examined the cue detection in the non-focal event-based prospect i ve memory ( PM ) of individuals with and without a major depressive disorder using behavioural and eye tracking assessment s. The participants were instructed to search on each trial for a different target stimulus that could be present or absent and to make prospect i ve responses to the cue object . PM tasks included cue only and target plus cue , whereas ongoing tasks included target only and distracter only . The results showed that a ) participants with depression performed more poorly than those without depression in PM ; b ) participants with depression showed more fixations and longer total and average fixation duration s in both ongoing and PM conditions ; c ) participants with depression had lower scores on accuracy in target-plus-cue trials than in cue-only trials and had a higher gaze rate of targets on hits and misses in target-plus-cue trials than did those without depression . The results indicate that the state of depression may impair top-down cognitive control function , which in turn results in particular deficits in the engagement of monitoring for PM cues Rationale Prospect i ve memory involves remembering to do something in the future and has a prospect i ve component ( remembering that something must be done ) and a retrospective component ( remembering what must be done and when it must be done ) . Initial studies reported an impairment in prospect ive-memory performance due to acute alcohol consumption . Retrospective-memory studies demonstrated that alcohol effects vary depending on the emotionality of the information that needs to be learned . Objectives The aim of the present study was to investigate possible differential effects of a mild acute alcohol dose ( 0.4 g/kg ) on the prospect i ve and retrospective components of prospect i ve memory depending on cue valence . MethodS eventy-five participants were allocated to an alcohol or placebo group and performed a prospect ive-memory task in which prospect ive-memory cue valence was manipulated ( negative , neutral , positive ) . The multinomial model of event-based prospect i ve memory ( Smith and Bayen 2004 ) was used to measure alcohol and valence effects on the two prospect ive-memory components separately . Results Overall , no main effect of alcohol or valence on prospect ive-memory performance occurred . However , model-based analyses demonstrated a significantly higher retrospective component for positive compared with negative cues in the placebo group . In the alcohol group , the prospect i ve component was weaker for negative than for neutral cues and the retrospective component was stronger for positive than for neutral cues . Group comparisons showed that the alcohol group had a significantly lower prospect i ve component for negative cues and a lower retrospective component for neutral cues . Conclusion This is the first study to demonstrate selective alcohol effects on prospect ive-memory components depending on prospect ive-memory cue valence Obsessive-compulsive disorder can result in a variety of deficits to cognitive performance , including negative consequences for attention and memory performance . The question addressed in the current study concerned whether this disorder influenced performance in an event-based prospect i ve memory task . The results from a sub clinical population indicated that , relative to non-anxious controls and mildly depressed controls , people with obsessive-compulsive tendencies ( washing compulsions ) incur decrements in remembering to respond to cues related to a neutral intention ( respond to animals ) . This deficit was ameliorated by giving the sub clinical group an intention about a threat-related category ( respond to bodily fluids ) and cueing them with concepts that they had previously rated as particularly disturbing to them . Thus , their normal attentional bias for extended processing of threat-related information overcame their natural deficit in event-based prospect i ve memory This study examined the separate influence and joint influences on event-based prospect i ve memory task performance due to the valence of cues and the valence of context s. We manipulated the valence of cues and context s with pictures from the International Affective Picture System . The participants , undergraduate students , showed higher performance when neutral compared to valenced pictures were used for cueing prospect i ve memory . In addition , neutral pictures were more effective as cues when they occurred in a valenced context than in the context of neutral pictures , but the effectiveness of valenced cues did not vary across context s that differed in valence . The finding of an interaction between cue and context valence indicates that their respective influence on event-based prospect i ve memory task performance can not be understood in isolation from each other . Our findings are not consistent with by the prevailing view which holds that the scope of attention is broadened and narrowed , respectively , by positively and negatively valenced stimuli . Instead , our findings are more supportive of the recent proposal that the scope of attention is determined by the motivational intensity associated with valenced stimuli . Consistent with this proposal , we speculate that the motivational intensity associated with different retrieval cues determines the scope of attention , that context s with different valence values determine participants ’ task engagement , and that prospect i ve memory task performance is determined jointly by attention scope and task engagement Prospect i ve memory involves the formation and execution of intended actions and is essential for autonomous living . In this study ( N=32 ) , the effect of the nature of PM cues ( semantic versus perceptual ) on established event-related potentials ( ERPs ) elicited in PM tasks ( N300 and prospect i ve positivity ) was investigated . PM cues defined by their perceptual features clearly elicited the N300 and prospect i ve positivity whereas PM cues defined by semantic relatedness elicited prospect i ve positivity . This calls into question the view that the N300 is a marker of general processes underlying detection of PM cues , but supports existing research showing that prospect i ve positivity represents general post-retrieval processes that follow detection of PM cues . Continued refinement of ERP paradigms for underst and ing the neural correlates of PM is needed So far , little is known about the neurocognitive mechanisms associated with emotion effects on prospect i ve memory ( PM ) performance . Thus , this study aim ed at disentangling possible mechanisms for the effects of emotional valence of PM cues on the distinct phases composing PM by investigating event-related potentials ( ERPs ) . Participants were engaged in an ongoing N-back task while being required to perform a PM task . The emotional valence of both the ongoing pictures and the PM cues was manipulated ( pleasant , neutral , unpleasant ) . ERPs were recorded during the PM phases , such as encoding , maintenance , and retrieval of the intention . A recognition task including PM cues and ongoing stimuli was also performed at the end of the sessions . ERP results suggest that emotional PM cues not only trigger an automatic , bottom-up , capture of attention , but also boost a greater allocation of top-down processes . These processes seem to be recruited to hold attention toward the emotional stimuli and to retrieve the intention from memory , likely because of the motivational significance of the emotional stimuli . Moreover , pleasant PM cues seemed to modulate especially the prospect i ve component , as revealed by changes in the amplitude of the ERP correlates of strategic monitoring as a function of the relevance of the valence for the PM task . Unpleasant pictures seemed to modulate especially the retrospective component , as revealed by the largest old/new effect being elicited by unpleasant PM pictures in the recognition task Theoretically , prospect i ve memory retrieval can be accomplished either by controlled monitoring of the environment for a target event or by a more reflexive process that spontaneously responds to the presence of a target event . These views were evaluated in Experiments 1 - 4 by examining whether performing a prospect i ve memory task produced costs on the speed of performing the ongoing task . In Experiment 5 , the authors directly tested for the existence of spontaneous retrieval . The results supported the multiprocess theory ( M. A. McDaniel & G. O. Einstein , 2000 ) predictions that ( a ) spontaneous retrieval can occur and can support good prospect i ve memory and ( b ) depending on task dem and s and individual differences , people rely to different degrees on monitoring versus spontaneous retrieval for prospect i ve remembering The present study investigated the effect of Parkinson ’s disease ( PD ) on prospect i ve memory ( PM ) tasks by varying the emotional content of the PM actions . Twenty-one older adults with PD and 25 healthy older adults took part in the present study . Participants performed three virtual days in the Virtual Week task . On each virtual day , participants performed actions with positive , negative or neutral content . Immediately following each virtual day , participants completed a recognition task to assess their retrospective memory for the various PM tasks . PD patients were less accurate than the control group at both PM accuracy and recognition task accuracy . The effect of emotional valence was also evident , indicating that all participants were more accurate on positive PM tasks than both negative and neutral . This study confirmed PM impairment in PD patients and extended previous research showing how positive emotional stimuli can influence PM performance We investigated whether focal/nonfocal effects ( e.g. , Einstein et al. , 2005 ) in prospect i ve memory ( PM ) are explained by cue differences in monitoring difficulty . In Experiment 1 , we show that syllable cues ( used in Einstein et al. , 2005 ) are more difficult to monitor for than are word cues ; however , initial-letter cues ( in words ) are similar in monitoring difficulty to word cues ( Experiments 2a and 2b ) . Accordingly , in Experiments 3 and 4 , we design ated either an initial letter or a particular word as a PM cue in the context of a lexical decision task , a task that presumably directs attention to focal processing of words but not initial letters . We found that the nonfocal condition was more likely than the focal condition to produce costs to the lexical decision task ( task interference ) . Furthermore , when task interference was minimal or absent , focal PM performance remained relatively high , whereas nonfocal PM performance was near floor ( Experiment 4 ) . Collectively , these results suggest that qualitatively different retrieval processes can support prospect i ve remembering for focal versus nonfocal cues Converging experimental operations and several prospect i ve memory tasks were used across three experiments to determine the extent to which prospect i ve remembering is supported by data driven versus conceptually driven processes . In all experiments , subjects were asked to perform an action when a target item later occurred . When the semantic context changed from encoding to test , prospect i ve memory significantly declined ( Experiment 1 ) . When the target event ( the item , which in its subsequent appearance in the experiment was the signal to perform the action ) was presented as a word ( relative to picture presentation , Experiment 2 ) or was encoded nonsemantically ( relative to semantic encoding , Experiment 3 ) , there was a decline in prospect i ve memory performance . Dividing attention during prospect i ve memory retrieval substantially reduced prospect i ve memory performance ( Experiment 3 ) . The results of this research indicated that prospect i ve memory is largely conceptually driven , and it behaves more similarly to direct rather than indirect conceptual tests . We suggest that prospect i ve remembering of the type studied here is mediated by a reflexive episodic associative memory system as proposed by Moscovitch ( 1994 ) The present study reports test – retest consist Output:	Moderating effects were also found for cue-focality and whether studies controlled for the arousal level of the cues . The principal finding is that positively-valenced cues improve prospect i ve memory performance and that timing of the manipulation can moderate emotional effects on prospect i ve memory .
MS213859	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Acute pyelonephritis remains a frequent complication of pregnancy . Prevention of the potential complications of this disease requires aggressive in-hospital management . However , the high frequency of positive outpatient cultures following discharge has cast doubt on the adequacy of in-hospital care and , at the same time , has concentrated attention on follow-up care . In a r and omized , prospect i ve study , we evaluated the effects of in-hospital management and outpatient nitrofurantoin on subsequent urine cultures . The overall frequency of positive cultures following discharge from the hospital was 38 % . However , appropriate antibiotic selection , a negative follow-up in-hospital culture and nitrofurantoin suppression reduced the rate to 8 % ( P less than .01 ) . Nitrofurantoin did not reduce the rate of positive cultures if antibiotic selection was inappropriate or if the in-hospital follow-up culture was positive . These results suggest that more aggressive management of acute pyelonephritis in pregnancy may be indicated and that suppressive therapy can not compensate for inappropriate in-hospital management Today , it is widely accepted that a short-course or single-dose treatment with antimicrobial agents in pregnancy is the optimal therapy to minimize the risk of toxicity both for the mother and the fetus . A r and omized trial comparing single-dose ( 3 g ) treatment with fosfomycin trometamol ( FT ) versus pipemidic acid ( 200-gram doses b.i.d . for 7 days ) in bacteriuric pregnant women is presented . The preliminary results show that single-dose FT has the same cure effect as conventional therapy with pipemidic acid A total of 120 patients , including 53 pregnant women with significant bacteriuria , received 163 7-day courses of oral antimicrobial agents allocated in a r and omised manner . The cure rates after 6 weeks ' follow-up ranged from 73 % to 86 % , and there was no statistical difference between preparations of ampicillin , carbenicillin indanyl easter , and 2 different formulations of nifuratel . Side-effects occurred in 30 % to 40 % of the courses of penicillin drugs , but in under 15 % of the course of nifuratel . It is concluded that the new oral preparation of carbenicillin is a useful addition to the list of antimicrobial agents which are effective in the treatment of urinary infections in domiciliary patients . Furthermore , nifuratel has been confirmed as a highly active non-toxic drug which is valuable in the treatment of urinary infections Summary The clinical and bacteriological efficacy and adverse reactions of ofloxacin vs trimethoprim-sulphamethoxazole were investigated in a double-blind , r and omised study in 250 female patients ( 125 in each group ) with acute , uncomplicated lower urinary tract infections . The dosages of ofloxacin and trimethoprim-sulphamethoxazole were 100 mg and 160 mg + 800 mg twice daily , respectively . The duration of therapy was 3 days . 81 % of the patients had significant bacteriuria . Escherichia coli was isolated in 76 % and Staphylococcus saprophyticus in 11 % of the infections . The bacteriological elimination , clinical cure and improvement rates of the evaluable patients on ofloxacin treatment were 92 and 95 % , respectively . The corresponding figures on trimethoprim-sulphamethoxazole therapy were 88 and 90 % . Adverse reactions were clinical ly unimportant , and none of the patients had to stop treatment . Mild and transient side effects , mainly from the gastrointestinal tract , central nervous system and skin , were reported by 19 and 22 % of the patients in the ofloxacin and trimethoprim-sulphamethoxazole groups , respectively . None of the differences in clinical and bacteriological efficacy and side effects of ofloxacin vs trimethoprim-sulphamethoxazole were statistically significant . Ofloxacin appears to be an appropriate antibiotic for short term therapy of acute , uncomplicated , lower urinary , tract infections , comparing favourably with trimethoprim-sulphamethoxazole treatment in this study Output:	In most of the comparisons there were no significant differences between the treatments under study with regard to cure rates , recurrent infection , incidence of preterm delivery , admission to neonatal intensive care unit , need for change of antibiotic and incidence of prolonged pyrexia . Although antibiotic treatment is effective for the cure of urinary tract infections , there are insufficient data to recommend any specific drug regimen for treatment of symptomatic urinary tract infections during pregnancy . All the antibiotics studied were shown to be very effective in decreasing the incidence of the different outcomes . Complications were very rare .
MS213860	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Background The median age of newly diagnosed patients with non-small cell lung cancer ( NSCLC ) is 67 years , and one-third of patients are older than 75 years . Elderly patients are more vulnerable to the adverse effects of chemotherapy , and targeted therapy might thus be a relevant alternative . The objective of this study was to assess the cost-effectiveness of erlotinib followed by chemotherapy after progression , compared to the reverse strategy , in fit elderly patients with advanced NSCLC participating in a prospect i ve r and omized phase 2 trial ( GFPC0504 ) . Methods Outcomes ( PFS and overall survival ) and costs ( limited to direct medical costs , from the third-party payer perspective ) were prospect ively collected until second progression . Costs after progression and health utilities ( based on disease states and grade 3–4 toxicities ) were derived from the literature . Results Median overall survival , QALY and total costs for the erlotinib-first strategy were respectively 7.1 months , 0.51 and 27 734 € , compared to 9.4 months , 0.52 and 31 688 € for the chemotherapy-first strategy . The Monte Carlo simulation demonstrates that the two strategies do not differ statistically . Conclusion In terms of cost effectiveness , in fit elderly patients with NSCLC , erlotinib followed by chemotherapy compares well with the reverse strategy OBJECTIVES A recent r and omized study showed switch maintenance with pemetrexed after nonpemetrexed-containing first-line chemotherapy in patients with advanced nonsmall-cell lung cancer to prolong overall survival by 2.8 months . We examined the cost-effectiveness of pemetrexed in this indication , from the perspective of the Swiss health care system , and assessed the influence of the costs of best supportive care ( BSC ) on overall cost-effectiveness . METHODS A Markov model was constructed based on the pemetrexed maintenance study , and the incremental cost-effectiveness ratio ( ICER ) of adding pemetrexed until disease progression was calculated as cost per quality -adjusted life-year gained . Uncertainties concerning the costs of BSC on the ICER were addressed . RESULTS The base case ICER for maintenance therapy with pemetrexed plus BSC compared to BSC alone was € 106,202 per quality -adjusted life-year gained . Varying the costs for BSC had a marked effect . Assuming a reduction of the costs for BSC by 25 % in the pemetrexed arm result ed in an ICER of € 47,531 per quality -adjusted life-year , which is below predefined criteria for cost effectiveness in Switzerl and . CONCLUSIONS Switch maintenance with pemetrexed in patients with advanced nonsquamous-cell lung cancer after st and ard first-line chemotherapy is not cost-effective . Uncertainties on the re source use and costs for BSC have a large influence on the cost-effectiveness calculation and should be reported in more detail BACKGROUND / OBJECTIVE Non-platinum-based chemotherapy is a potential alternative to platinum doublet therapy for advanced non-small cell lung cancer in selected patients . We determined the cost-effectiveness of gemcitabine/vinorelbine ( GEMVIN ) , versus cisplatin/gemcitabine ( PG ) or cisplatin/vinorelbine ( PV ) , from a government payer perspective . METHODS Results from a r and omized trial of GEMVIN versus PG or PV demonstrated no significant difference in global quality of life ( primary endpoint ) or overall survival between regimens , but superior progression-free survival for platinum-based regimens . A cost analysis was conducted using direct medical costs of treatment , grade 3 or 4 toxicity management , and investigations for the mean number of cycles per study arm . Costs were calculated using Canadian dollars in 2005 , and then in 2013 after drug patent expiry . RESULTS In 2005 , GEMVIN was the most expensive regimen ( $ 6868 ) , and PV the least expensive ( $ 4650 ) , with an incremental cost of GEMVIN over PV of $ 2218 . Diagnostic and administration costs did not differ significantly among regimens ; GEMVIN had the lowest toxicity costs . The principal cost driver in 2005 was the cost of chemotherapy . In 2013 , toxicity and administration costs emerged as major drivers ; GEMVIN was less costly than PV and PG , ( cost savings of $ 413 over PV ) . CONCLUSION Despite similar outcomes , GEMVIN was more expensive than PV or PG in 2005 because of higher chemotherapy costs . By 2013 , after chemotherapy drug patent expiry , GEMVIN became the least costly regimen . Economic considerations in oncology change over time , and should be revisited in policy decisions based on cost Background Platinum-doublet , first-line treatment of locally advanced or metastatic non-small cell lung cancer ( NSCLC ) is limited to 4–6 cycles . An alternative strategy used to prolong the duration of first-line treatment and extend survival in metastatic NSCLC is first-line maintenance therapy . Erlotinib was approved for first-line maintenance in a stable disease population following results from a r and omized , controlled Phase III trial comparing erlotinib with best supportive care . We aim ed to estimate the incremental cost-effectiveness of erlotinib 150 mg/day versus best supportive care when used as first-line maintenance therapy for patients with locally advanced or metastatic NSCLC and stable disease . Methods An economic decision model was developed using patient-level data for progression-free survival and overall survival from the SATURN ( SequentiAl Tarceva in UnResectable NSCLC ) study . An area under the curve model was developed ; all patients entered the model in the progression-free survival health state and , after each month , moved to progression or death . A time horizon of 5 years was used . The model was conducted from the perspective of national health care payers in France , Germany , and Italy . Probabilistic sensitivity analyses were performed . Results Treatment with erlotinib in first-line maintenance result ed in a mean life expectancy of 1.39 years in all countries , compared with a mean 1.11 years with best supportive care , which represents 0.28 life-years ( 3.4 life-months ) gained with erlotinib versus best supportive care . In the base-case analysis , the cost per life-year gained was € 39,783 , € 46,931 , and € 27,885 in France , Germany , and Italy , respectively . Conclusion Erlotinib is a cost-effective treatment option when used as first-line maintenance therapy for locally advanced or metastatic NSCLC Introduction Lung cancer , the most prevalent malignant cancer in the world , remains a serious threat to public health . Recently , a large number of studies have shown that an epidermoid growth factor receptor-tyrosine kinase inhibitor ( EGFR TKI ) , Erlotinib , has significantly better efficacy and is better tolerated in advanced non-small cell lung cancer ( NSCLC ) patients with a positive EGFR gene mutation . However , access to this drug is severely limited in China due to its high acquisition cost . Therefore , we decided to conduct a study to compare cost-effectiveness between erlotinib monotherapy and carboplatin-gemcitabine ( CG ) combination therapy in patients with advanced EGFR mutation-positive NSCLC . Methods A Markov model was developed from the perspective of the Chinese health care system to evaluate the cost-effectiveness of the two treatment strategies ; this model was based on data from the OPTIMAL trial , which was undertaken at 22 centres in China . The 10-year quality -adjusted life years ( QALYs ) , direct costs , and incremental cost-effectiveness ratio ( ICER ) were estimated . To allow for uncertainties within the parameters and to estimate the model robustness , one-way sensitivity analysis and probabilistic sensitivity analysis were performed . Results The median progression-free survival ( PFS ) obtained from Markov model was 13.2 months ( 13.1 months was reported in the trial ) in the erlotinib group while and 4.64 months ( 4.6 months was reported in the trial ) in the CG group . The QALYs were 1.4 years in the erlotinib group and 1.96 years in the CG group , indicating difference of 0.56 years . The ICER was most sensitive to the health utility of DP ranged from $ 58,584.57 to $ 336,404.2 . At a threshold of $ 96,884 , erlotinib had a 50%probability of being cost-effective . Conclusions Erlotinib monotherapy is more cost-effective compared with platinum-based doublets chemotherapy as a first-line therapy for advanced EGFR mutation- positive NSCLC patients from within the Chinese health care system OBJECTIVE To compare the effectiveness and cost-effectiveness of erlotinib versus gefitinib as first-line treatment of epidermal growth factor receptor-activating mutation-positive non-small-cell lung cancer patients . DESIGN . Indirect treatment comparison and a cost-effectiveness assessment . SETTING Hong Kong . PATIENTS Those having epidermal growth factor receptor-activating mutation-positive non-small-cell lung cancer . INTERVENTIONS Erlotinib versus gefitinib use was compared on the basis of four relevant Asian phase-III r and omised controlled trials : one for erlotinib ( OPTIMAL ) and three for gefitinib ( IPASS ; NEJGSG ; WJTOG ) . The cost-effectiveness assessment model simulates the transition between the health states : progression-free survival , progression , and death over a lifetime horizon . The World Health Organization criterion ( incremental cost-effectiveness ratio <3 times of gross domestic product/capita : < US$ 102 582 ; approximately < HK$798 078 ) was used to rate cost-effectiveness . RESULTS The best fit of study characteristics and prognostic patient characteristics were found between the OPTIMAL and IPASS trials . Comparing progression-free survival hazard ratios of erlotinib versus gefitinib using only these r and omised controlled trials in an indirect treatment comparison result ed in a statistically significant progression-free survival difference in favour of erlotinib ( indirect treatment comparison hazard ratio=0.33 ; 95 % confidence interval , 0.19 - 0.58 ; P=0.0001 ) . The cost-effectiveness assessment model showed that the cost per progression-free life year gained and per quality -adjusted life year gained was at acceptable values of US$ 39 431 ( approximately HK$306 773 ) and US$ 62 419 ( approximately HK$485 619 ) for erlotinib versus gefitinib , respectively . CONCLUSION The indirect treatment comparison of OPTIMAL versus IPASS shows that erlotinib is significantly more efficacious than gefitinib . Furthermore , the cost-effectiveness assessment indicates that the incremental cost-effectiveness ratios are well within an acceptable range in relation to the survival benefits obtained . In conclusion , erlotinib is cost-effective compared to gefitinib for first-line epidermal growth factor receptor-activating mutation-positive non-small-cell lung cancer patients Abstract Background : During the 1990s , a number of new cytotoxic agents with clinical ly relevant activity in non-small-cell lung cancer ( NSCLC ) , and with a more favourable therapeutic index than drugs already in use , became available . Given the high prices of these new drugs and the large number of patients affected , it is important to compare the relative benefits and costs of these treatments with the existing regimens before treatment policy decisions are changed . Purpose : An economic evaluation of three different regimens of chemotherapy in patients with advanced NSCLC was performed from the perspective of the Dutch health insurance system using tariffs valid for 2002 . The economic evaluation was integrated into a phase III clinical trial in which the reference regimen cisplatinpaclitaxel was compared with two experimental regimens : cisplatin-gemcitabine and gemcitabine-paclitaxel . Material s and methods : Unit costs were applied to re source use data collected prospect ively on case report forms during the trial . The average total ( uncensored ) cost per patient was determined for each of the treatment groups . The principal outcome measure for the economic evaluation was the estimated mean survival time per treatment group . This outcome was then incorporated into incremental cost-effectiveness ratios based on costs corrected for censoring . The impact of uncertainty was assessed by bootstrap techniques , and the analysis and interpretation of the data focused on the bivariate density of differences in outcomes and costs in the incremental cost-effectiveness plane . The final results were summarised by the derivation of cost-effectiveness acceptability curves . Results : The estimated mean survival time was equivalent in the two cisplatinbased regimens with largely overlapping confidence intervals . There was a 99 % probability that cisplatin-gemcitabine is the least costly regimen of the two and a 72 % probability that this regimen reduces costs while at the same time improving survival . Compared with cisplatin-paclitaxel , the gemcitabine-paclitaxel regimen engendered a borderline significant reduction in mean survival time combined with an almost 90 % probability of an increase in costs . Conclusion : The two cisplatin-based regimens are equivalent in terms of survival , but cisplatin-gemcitabine may reduce costs by approximately € 2000 per patient compared with cisplatin-paclitaxel . Gemcitabine-paclitaxel is a dominated option with higher costs and a reduction in mean survival time compared with cisplatinpaclitaxel BACKGROUND A large proportion of elderly patients ( > 70 years ) with newly diagnosed NSCLC are shown to be frail by a comprehensive geriatric assessment . This population is more vulnerable to adverse effects of chemotherapy and might thus benefit more from targeted therapy . The objective of this study was to assess the cost-effectiveness of erlotinib followed by chem Output:	For all primary chemotherapy agents , use of carboplatin is associated with slightly higher costs than cisplatin .
MS213861	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Objective : To assess the efficacy of an innovative smoking cessation intervention targeted to a multiethnic , economically disadvantaged HIV-positive population . Design : A two-group r and omized clinical trial compared a smoking cessation intervention delivered by cellular telephone with usual care approach . Methods : Current smokers from a large , inner city HIV/AIDS care center were recruited and r and omized to receive either usual care or a cellular telephone intervention . The usual care group received brief physician advice to quit smoking , targeted self-help written material s and nicotine replacement therapy . The cellular telephone intervention received eight counseling sessions delivered via cellular telephone in addition to the usual care components . Smoking-related outcomes were assessed at a 3-month follow-up . Results : The trial had 95 participants and 77 ( 81.0 % ) completed the 3-month follow-up assessment . Analyses indicated biochemically verified point prevalence smoking abstinence rates of 10.3 % for the usual care group and 36.8 % for the cellular telephone group ; participants who received the cellular telephone intervention were 3.6 times ( 95 % confidence interval , 1.3 - 9.9 ) more likely to quit smoking compared with participants who received usual care ( P = 0.0059 ) . Conclusions : These results suggest that individuals living with HIV/AIDS are receptive to , and can be helped by , smoking cessation treatment . In addition , smoking cessation treatment tailored to the special needs of individuals living with HIV/AIDS , such as counseling delivered by cellular telephone , can significantly increase smoking abstinence rates over that achieved by usual care Background Advances in technology allowed the development of a novel smoking cessation program delivered by video messages sent to mobile phones . This social cognitive theory-based intervention ( called “ STUB IT ” ) used observational learning via short video diary messages from role models going through the quitting process to teach behavioral change techniques . Objective The objective of our study was to assess the effectiveness of a multimedia mobile phone intervention for smoking cessation . Methods A r and omized controlled trial was conducted with 6-month follow-up . Participants had to be 16 years of age or over , be current daily smokers , be ready to quit , and have a video message-capable phone . Recruitment targeted younger adults predominantly through radio and online advertising . Registration and data collection were completed online , prompted by text messages . The intervention group received an automated package of video and text messages over 6 months that was tailored to self-selected quit date , role model , and timing of messages . Extra messages were available on dem and to beat cravings and address lapses . The control group also set a quit date and received a general health video message sent to their phone every 2 weeks . Results The target sample size was not achieved due to difficulty recruiting young adult quitters . Of the 226 r and omized participants , 47 % ( 107/226 ) were female and 24 % ( 54/226 ) were Maori ( indigenous population of New Zeal and ) . Their mean age was 27 years ( SD 8.7 ) , and there was a high level of nicotine addiction . Continuous abstinence at 6 months was 26.4 % ( 29/110 ) in the intervention group and 27.6 % ( 32/116 ) in the control group ( P = .8 ) . Feedback from participants indicated that the support provided by the video role models was important and appreciated . Conclusions This study was not able to demonstrate a statistically significant effect of the complex video messaging mobile phone intervention compared with simple general health video messages via mobile phone . However , there was sufficient positive feedback about the ease of use of this novel intervention , and the support obtained by observing the role model video messages , to warrant further investigation . Trial registration Australian New Zeal and Clinical Trials Registry Number : ACTRN12606000476538 ; http://www.anzctr.org.au/trial_view.aspx?ID=81688 ( Archived by WebCite at http://www.webcitation.org/5umMU4sZi Summary We evaluated the effectiveness of a mobile phone text-messaging based smoking cessation intervention package among Chinese adolescent smokers . Students aged 16–19 years were recruited from six vocational high schools located in Shanghai . We assigned the six schools to an intervention group or a control group by cluster r and omization . The 92 participants in the intervention group were given tailored information via mobile phone text-messaging for 12 weeks . The 87 participants in the control group were provided with a self-help pamphlet about smoking cessation instead . After the intervention , attitudes towards the disadvantages of smoking were significantly improved , and the level of nicotine dependence and cigarette dependence significantly decreased in the intervention group . The intervention group had a relatively higher self-reported 7-day abstinence compared to the control group and 30-day abstinence , but the differences were not significant . However , the intervention group had a significantly higher rate of smoking reduction ( 66 % vs. 35 % ) and moving forward in quitting stages ( 52 % vs. 18 % ) compared to the control group . The interactive and tailored assistance provided by the mobile phone text-messaging was effective in smoking behaviour intervention in Chinese adolescent smokers Mounting evidence suggests that smokers living with HIV/AIDS have a significantly increased risk of numerous adverse health outcomes ( both AIDS- and non-AIDS-related ) compared with HIV-positive nonsmokers . Therefore , efforts to design and implement effective cessation programs for this ever-growing special population are warranted . The present study assessed the effects of a cell phone intervention ( CPI ) on hypothesized mediators ( i.e. , changes in depression , anxiety , social support , and self-efficacy ) demonstrated to influence cessation outcomes in other population s. Ninety-five participants from an inner-city AIDS clinic were r and omized to receive either the CPI or recommended st and ard of care ( RSOC ) smoking cessation treatment . Participants r and omized to the RSOC group ( n=47 ) received brief advice to quit , a 10-week supply of nicotine patches , and self-help material s. Participants r and omized to the CPI group ( n=48 ) received RSOC components plus a series of eight proactive counseling sessions delivered via cell phones . A series of regression analyses ( linear and logistic ) was used to assess the relationships between treatment group , the hypothesized mediators , and biochemically confirmed smoking cessation outcomes . Results indicated that the CPI group experienced greater reductions in anxiety and depression , and increases in self-efficacy compared with the RSOC group . Further , changes in depression , anxiety , and self-efficacy weakened the association between treatment group and cessation outcome . The mediator hypothesis , however , for social support was rejected , as the difference score was not significantly associated with treatment group . These results suggest that the efficacy of the CPI is at least partially mediated by its ability to decrease symptoms of distress while increasing self-efficacy Background Although supporting lifestyle change is an effective way of preventing further events in people with cardiovascular disease , providing access to such interventions is a major challenge . This study aims to investigate whether simple reminders about behaviour change sent via mobile phone text message decrease cardiovascular risk . Methods and analysis R and omised controlled trial with 6 months of follow-up to evaluate the feasibility , acceptability and effect on cardiovascular risk of repeated lifestyle reminders sent via mobile phone text messages compared to usual care . A total of 720 patients with coronary artery disease will be r and omised to either st and ard care or the TEXT ME intervention . The intervention group will receive multiple weekly text messages that provide information , motivation , support to quit smoking ( if relevant ) and recommendations for healthy diets and exercise . The primary end point is a change in plasma low-density lipoprotein cholesterol at 6 months . Secondary end points include a change in systolic blood pressure , smoking status , quality of life , medication adherence , waist circumference , physical activity levels , nutritional status and mood at 6 months . Process outcomes related to acceptability and feasibility of TEXT ME will also be collected . Ethics and dissemination Primary ethics approval was received from Western Sydney Local Health Network Human Research Ethics Committee — Westmead . Results will be disseminated via the usual scientific forums including peer- review ed publications and presentations at international conferences . Clinical trials registration number ACTRN12611000161921 INTRODUCTION Substantial evidence indicates that cigarette smoking among people living with HIV/AIDS ( PLWHA ) represents a significant public health concern . However , few efforts to assess smoking cessation interventions targeting this population have been reported . In this brief report , 3-month outcomes from an ongoing treatment trial for PLWHA who smoke are described . METHODS Study participants were recruited from a large HIV care center serving a diverse population of PLWHA . A two-group r and omized design was used to compare the efficacy of usual-care ( UC ) smoking cessation treatment versus a cell phone intervention ( CPI ) . Follow-ups were conducted at the HIV clinic 3 months postenrollment . Using an intent-to-treat approach , a series of multiple regression models were used to compare smoking outcomes in the 2 groups . RESULTS Four hundred and seventy-four participants were enrolled and r and omized , UC ( n = 238 ) and CPI ( n = 236 ) . Mean age in the sample was 44.8 ( SD = 8.1 ) years , and the majority were male ( 70.0 % ) , Black ( 76.6 % ) , and had an education level of high school or less ( 77.5 % ) . At follow-up , participants in the CPI group were 4.3 ( 95 % CI = 1.9 , 9.8 ) times more likely to be abstinent ( 7 day ) compared with those in the UC group . Similarly , significant point estimates were observed for the other smoking outcomes of interest . CONCLUSIONS Findings from this preliminary report indicate that a smoking cessation intervention for PLWHA consisting of cell phone-delivered proactive counseling results in significantly higher abstinence rates compared with a st and ard care approach . Evaluation of the long-term ( 6-month and 12-month ) efficacy of the CPI approach is ongoing Background The study aims to test the differential effects of a web-based text and a web-based video-driven computer-tailored approach for lower socio-economic status ( LSES ) and higher socio-economic status ( HSES ) smokers which incorporate multiple computer-tailored feedback moments . The two programs differ only in the mode of delivery ( video- versus text-based messages ) . The paper aims to describe the development and design of the two computer-tailored programs . Methods / design Respondents who smoked at the time of the study inclusion , who were motivated to quit within the following six months and who were aged 18 or older were included in the program . The study is a r and omized control trial with a 2 ( video/text ) * 2(LSES/HSES ) design . Respondents were assigned either to one of the intervention groups ( text versus video tailored feedback ) or to the control group ( non-tailored generic advice ) . In all three conditions participants were asked to fill in the baseline question naire based on the I-Change model . The question naire assessed socio-demographics , attitude towards smoking , knowledge , self-efficacy , social influence , depression , level of addiction , action planning , goal actions , intention to quit smoking , seven-day point prevalence and continued abstinence . Follow-up measurements were conducted at six and twelve months after baseline . Discussion The present paper describes the development of the two computer-tailored smoking cessation programs , their components and the design of the study . The study results reveal different working mechanisms of multiple tailored smoking cessation interventions and will help us to gain more insight into effective strategies to target different subgroups , especially smokers with a lower socio-economic status . Trial registration Dutch Trial Register Background Despite promising data in Western countries , there is a dearth of research into the efficacy of text messaging-based smoking cessation programs in other setting s , including the Middle East , where smoking prevalence rates are higher . Objective This paper reports cessation rates observed in SMS Turkey , a text messaging-based smoking cessation program for adult smokers in Ankara , Turkey . Methods This study was a small-scale , parallel-group r and omized controlled trial ( RCT ) conducted in Ankara , Turkey . Participants were adult daily smokers who were seriously thinking about quitting in the next 15 days and living in Ankara , Turkey . The text messaging intervention , SMS Turkey , provided 6 weeks of daily messages aim ed at giving participants skills to help them quit smoking . Messages were sent in an automated fashion , except 2 days and 7 days after the initial quit day . On days 2 and 7 , the research assistant manually assigned participants to content “ paths ” based on whether they were still not smoking or had relapsed . The control arm received a brochure that provided similar information about smoking cessation . The main outcome measure was self-reported 3-month sustained abstinence , verified by carbon monoxide ( CO ) readings . Neither participants nor research ers were blinded to arm assignment . Results The 151 participants were r and omly assigned to 1 of 2 groups : 76 to the SMS Turkey intervention group and 75 to the brochure control group . Using intention to treat , all 151 participants were included in analyses . Three-month cessation trends were not significantly higher in the intervention group : 11 % intervention vs 5 % control had quit ( χ2 1=1.4 , P=.24 ; R2=2.0 , 95 % CI 0.62 - 6.3 ) . When the sample was stratified by sex , female intervention participants ( 14 % , n=5 ) were significantly Output:	The current evidence supports a beneficial impact of mobile phone-based smoking cessation interventions on six-month cessation outcomes .
MS213862	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Background : Nonsteroidal antiinflammatory drugs are commonly used to treat postoperative and chronic pain . Animal studies suggest that these drugs act , in part , by blocking prostagl and in production in the spinal cord . The authors tested intrathecal ketorolac in patients with chronic or postoperative pain . Methods : After approval of the institutional review board and the Food and Drug Administration , three clinical studies were performed . First , 15 patients receiving chronic intrathecal morphine received 0.5–2.0 mg of intrathecal ketorolac . Second , 12 patients receiving chronic intrathecal morphine received , in a double-blinded , r and omized , cross-over design , intrathecal saline or 2.0 mg of ketorolac , with pain intensity as the primary outcome measure . Third , 30 patients undergoing total vaginal hysterectomy received , in a double-blinded , r and omized , controlled design , intrathecal saline or 2.0 mg of ketorolac , with bupivacaine with time to first morphine dose after surgery as the primary outcome measure . Results : Patients with chronic pain had many symptoms before intrathecal injection , without worsening of these symptoms from ketorolac . Pain intensity was reduced by intrathecal ketorolac , but this did not differ from placebo . In the first study , pain was reduced by intrathecal ketorolac in patients with high cerebrospinal fluid prostagl and in E2 concentrations but not in those with normal concentrations . Intrathecal ketorolac did not alter time to first morphine after surgery . Conclusions : Intrathecal ketorolac did not relieve chronic pain or extend anesthesia or analgesia from intrathecal bupivacaine administered at the beginning of surgery . Under the conditions of these studies , it seems that spinal cylcooxygenase activity does not contribute to chronic or postoperative pain The efficacy of bupivacaine instillation into preperitoneal space following laparoscopic herniorrhaphy for postoperative pain reduction is still in controversy . A r and omized controlled trial was conducted to determine the efficacy of bupivacaine instillation . The 40 patients , who had an inguinal hernia with no complication , unilateral or bilateral and recurrence or no recurrence after previous hernia repair , were r and omly assigned to receive bupivacaine ( n = 19 ) and normal saline ( n = 21 ) . The intervention or placebo was instilled into the preperitoneal space after total extraperitoneal laparoscopic herniorrhaphy . Pain intensity was assessed by using a visual analogue scale and verbal rating scale after the 1st , 2nd , 6th , 12th , and 24th hour postoperatively . For the bupivacaine and placebo group , mean pain scores were 3.5 versus 5.2 ( P = .059 ) , 2.9 versus 4.5 ( P = .117 ) , 2.1 versus 3.2 ( P = .101 ) , 1.5 versus 2.7 ( P = .145 ) , and 1.6 versus 2.0 ( P = .672 ) after the 1st , 2nd , 6th , 12th , and 24th hour , respectively . Complications developed in 4 patients in the bupivacaine group and 7 patients in the placebo group after 3 months follow-up time . There is no strong evidence to confirm that bupivacaine instillation into preperitoneal space after laparoscopic herniorrhaphy can reduce postoperative pain Objective : To characterize the beneficial effects of perioperative systemic lidocaine on length of hospital stay , gastrointestinal motility , and the inflammatory response after colorectal surgery . Summary Background Data : Surgery-induced stimulation of the inflammatory response plays a major role in the development of several postoperative disorders . Local anesthetics possess anti-inflammatory activity and are thought to positively affect patients ' outcome after surgery . This double-blinded , r and omized , and placebo-controlled trial aim ed to evaluate beneficial effects of systemic lidocaine and to provide insights into underlying mechanisms . Methods : Sixty patients undergoing colorectal surgery , not willing or unable to receive an epidural catheter , were r and omly assigned to lidocaine or placebo treatment . Before induction of general anesthesia , an intravenous lidocaine bolus ( 1.5 mg/kg ) was administered followed by a continuous lidocaine infusion ( 2 mg/min ) until 4 hours postoperatively . Length of hospital stay , gastrointestinal motility , and pain scores were recorded and plasma levels or expression of pro- and anti-inflammatory mediators determined . Results : Lidocaine significantly accelerated return of bowel function and shortened length of hospital stay by one day . No difference could be observed in daily pain ratings . Elevated plasma levels of IL-6 , IL-8 , complement C3a , and IL-1ra as well as expression of CD11b , l- and P-selectin , and platelet-leukocyte aggregates were significantly attenuated by systemic lidocaine . Conclusions : Perioperative intravenous lidocaine not only improved gastrointestinal motility but also shortened length of hospital stay significantly . Anti-inflammatory activity modulating the surgery-induced stress response may be one potential mechanism . Systemic lidocaine may thus provide a convenient and inexpensive approach to improve outcome for patients not suitable for epidural anesthesia OBJECTIVES To test the hypotheses that lidocaine 5 % patches decrease the severity of acute pain and incidence of persistent incisional pain after robotic cardiac valve surgery . DESIGN A r and omized , placebo-controlled , double-blind trial . SETTING Tertiary care academic medical center . SUBJECTS Patients having robotic cardiac valve surgery . METHODS Patients having robotic cardiac valve surgery were r and omly assigned to 5 % lidocaine patches or identical-appearing placebo patches . Patches were applied around each incision 12 hours/day until pain resolved , or for 6 months . Supplemental opioid was provided by patient-controlled analgesia or orally . Pain was initially evaluated with a Visual Analog Scale , and subsequently by telephone with a Verbal Response Scale and the Pain Disability Index ( our primary outcome ) after 1 week , 1 month , 3 months , and 6 months . Global Perceived Effect , a measure of patient satisfaction , was simultaneously recorded . Repeated- measures analysis of variance and generalized estimating equations were our primary statistical tools . RESULTS Acute pain scores and opioid use were low , as was the incidence of persistent pain . Lidocaine 5 % patches did not influence any measure of acute or persistent incisional pain . Estimated difference ( 95 % CI ) in mean Pain Disability Index for Lidocaine patch minus placebo was -2.5 ( 95 % CI -7.1 , 2.1 ) , P = 0.28 . CONCLUSIONS Lidocaine 5 % patches did not reduce acute or persistent pain in patients having robotic thoracic surgery , though pain scores were low in both treatment groups . Clinicians should choose alternative analgesic approaches in these patients Iliac crest bone graft remains the gold st and ard in achieving spinal arthrodesis , but chronic pain from graft harvest occurs in up to 39 % of patients . Studies have shown that a single administration of local anesthetic reduces short-term pain , but they have not adequately investigated possible longer-term benefits . The goal of this study was to determine whether local administration of bupivacaine after iliac crest bone graft harvesting reduces pain and improves patient-reported outcomes . In this prospect i ve , r and omized , controlled , and blinded clinical study , 40 patients were identified who underwent posterior spine fusion with iliac crest bone graft and were r and omized to receive either bupivacaine ( treatment group , n=20 ) or saline ( control group , n=20 ) at the iliac crest bone graft site . Pain at the harvest site was determined by a series of 12 visual and numeric pain scale assessment s. Short Form-12 mental and physical component scores , EuroQol-5D , and Oswestry Disability Index assessment s were made , along with determination of patient satisfaction and self-reported outcome of surgery . Baseline pain and outcome assessment s were statistically similar ( P>.05 ) . Average pain scores were lower for all 12 assessment s in the treatment group at mean follow-up of 5 weeks ( significant differences in 6 assessment s ) and 20 weeks ( significant differences in 2 assessment s ) . No significant differences were found in Short Form-12 and EuroQol-5D scores . For patients who underwent lumbar fusion , the treatment group had significantly improved Oswestry Disability Index scores ( mean±SD=10.8±7.1 vs 18.7±5.9 , P=.012 ) . Significantly more patients in the treatment group reported that surgery met all expectations ( 90 % vs 50 % , P=.016 ) . This study is the 1st to show that a single administration of bupivacaine at the iliac crest bone graft harvest site during posterior spine fusion surgery can result in improved outcomes and reduced pain far beyond the anesthetic duration of activity Summary Background . A r and omized prospect i ve double-blinded study was conducted in 100 patients suffering from mono- or bisegmental cervical retrospondylosis or disc herniation . Method . In group I , 50 patients were treated by injection of 10 ml Ropivacaine 7,5 % at the iliac crest bonegraft donorsite . Local anaesthetic ( LA ) was injected through the wound drainage after closure of the muscle fascia , the suction drainage was opened after closure of the skin . Group II was treated with 0,9 % saline . Operator and patient were blinded to the injected substance . Daily controls of pain intensity were made with the 10 cm visual analog scale from 0 ( no pain ) to 10 ( severe pain ) for 5 days . All patients were question ed regarding pain character and movement provoking pain . Additional pain medication was st and arized . Findings . Statistical analysis of mean pain intensity over the whole hospital stay showed a significant difference in pain intensity between the two groups ( p = 0,017 , Chi-Square test ) . The comparison between pain intensity with LA and without LA showed a gradual increase in statistical significance from day 1 to day 5 ( day 1 : p = 0,54 , not significant ; day 2 : p = 0,026 ; day 3 : p = 0,008 ; day 4 : p = 0,004 ; day 5 : p = 0,002).Interpretation . This data shows that intra-operative blockage of peripheral nociceptive structures results in decreased pain at later time points . We conclude that wound infiltration with 7,5 % Ropivacaine after bonegraft removal at the iliac crest is effective in reducing postoperative pain Surgical field infiltration with adrenaline is common practice for quality surgical field during cleft lip and palate repair in children . Intravascular absorption of adrenaline infiltration often leads to adverse haemodynamic responses . In this prospect i ve , double-blinded , r and omised study the haemodynamic effects , quality of surgical field and postoperative analgesia following surgical field infiltration with different concentrations of adrenaline with and without lignocaine were compared in 100 American Society of Anesthesiologists physical status I children aged six months to seven years undergoing cleft lip/palate surgery . A st and ard anaesthesia protocol was used and they were r and omised into four groups based on solution for infiltration : adrenaline 1:400000 ( group A ) , adrenaline 1:200,000 ( group B ) , lignocaine + adrenaline 1:400,000 ( group C ) and lignocaine + adrenaline 1:200,000 ( group D ) . Statistically significant tachycardia and hypertension occurred only in group B as compared to other groups ( P < 0.001 ) . The peak changes in heart rate and mean arterial pressure following infiltration occurred at 4.3±2.4 , 3.8±1.5 , 5.7±3.2 and 5.9±4.9 minutes in groups A , B , C and D respectively . Surgical field was comparable among all groups . Postoperative pain scores and rescue analgesic requirements were lesser in the groups where lignocaine was added to the infiltrating solution ( P < 0.05 ) . We found that 1:400000 or 1:200000 adrenaline with lignocaine 0.5 to 0.7 % is most suitable for infiltration in terms of stable haemodynamics , quality of surgical field and good postoperative analgesia in children Background : Postoperative pain mostly results from sensitization of afferent fibers at injury sites driving central sensitization . Recently , peripheral processes have gained attention as mechanisms of hyperalgesia , and prostagl and ins are among highly sensitizing agents . To date , perioperative administration of a single local dose of nonsteroidal antiinflammatory drugs has shown inconclusive efficacy . Rather than a single bolus , the current study evaluates the postoperative analgesic effect of diclofenac continuous intrawound infusion after elective cesarean delivery . Methods : Ninety-two parturients were r and omly allocated to receive a 48-h continuous intrawound infusion with 240 ml containing 300 mg diclofenac , 0.2 % ropivacaine , or saline . In the ropivacaine and sal Output:	We conclude that there is moderate- quality evidence that regional anaesthesia may reduce the risk of developing PPP after three to 18 months after thoracotomy and three to 12 months after caesarean section . There is low- quality evidence that regional anaesthesia may reduce the risk of developing PPP three to 12 months after breast cancer surgery . On a caution ary note , we can not extend our conclusions to other surgical interventions or regional anaesthesia techniques , for example we can not conclude that paravertebral block reduces the risk of PPP after thoracotomy .
MS213863	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: STUDY OBJECTIVE Emergency department ( ED ) -based clinical research has the potential to include patient population s that are typically underrepresented in clinical research . The objective of this study is to assess how emergency clinical care and research processes , informed consent , and patient demographic factors ( age , sex , and ethnicity/race ) affect enrollment and consent in clinical research in the ED . METHODS This was an analysis of prospect ively collected data of all patients ( aged 2 to 101 years ) eligible for one of 7 clinical research studies from February 2005 to April 2007 in an academic ED . We measured rates of enrollment and consent in the clinical studies . RESULTS One thous and two hundred two of the 4418 patients screened for participation in 7 clinical studies were clinical ly eligible for enrollment . Of the 868 patients who were able to provide a voluntary decision regarding consent , 639 ( 73.6 % ) agreed to participate ; an overall enrollment rate of 53.2 % . The mean age of patients enrolled was 51.8 years ( range 3 to 98 years ) . Black patients ( 49.2 % enrollment ) and Latino patients ( 18.4 % enrollment ) were less likely to be enrolled in comparison with white patients ( 58.3 % enrollment ) ( adjusted odds ratio [ OR ] of enrollment for blacks=0.64 ; 95 % confidence interval [ CI ] 0.50 to 0.82 ; adjusted OR of enrollment for Latinos=0.16 ; 95 % CI 0.08 to 0.33 ) . Enrollment rates were lower among pediatric ( 40.0 % ) and geriatric patients ( 49.1 % ) in comparison with adult patients ages 18 to 64 years ( 55.5 % ) ( adjusted OR of enrollment for pediatric patients = 0.70 , 95 % CI 0.34 to 1.43 ; adjusted OR of enrollment for geriatric patients = 0.69 , 95 % CI 0.53 to 0.90 ) . Unique issues contributing to underenrollment included challenges in consent among pediatric and elderly patients , language issues in Latino patients , reduced voluntary consent rates among black patients , and perhaps underuse of minimal risk waivers . CONCLUSION In a large academic ED , minority , pediatric , and geriatric patients were less likely to be enrolled in acute care clinical research studies than middle-aged whites . Enrollment and consent strategies design ed to enhance research participation in these important patient population s may be necessary to address disparities in the development and application of evidence -based emergency and acute care Background Concerns have been raised about low participation rates of people from minority ethnic groups in clinical trials . However , the evidence is unclear as many studies do not report the ethnicity of participants and there is insufficient information about the reasons for in eligibility by ethnic group . Where there are data , there remains the key question as to whether ethnic minorities more likely to be ineligible ( e.g. due to language ) or decline to participate . We have addressed these questions in relation to the Birmingham Rehabilitation Uptake Maximisation ( BRUM ) study , a r and omized controlled trial ( RCT ) comparing a home-based with a hospital-based cardiac rehabilitation programme in a multi-ethnic population in the UK . Methods Analysis of the ethnicity , age and sex of presenting and recruited subjects for a trial of cardiac rehabilitation in the West-Midl and s , UK . Participants : 1997 patients presenting post-myocardial infa rct ion , percutaneous transluminal coronary angioplasty or coronary artery bypass graft surgery . Data collected : exclusion rates , reasons for exclusion and reasons for declining to participate in the trial by ethnic group . Results Significantly more patients of South Asian ethnicity were excluded ( 52 % of ' South Asian ' v 36 % ' White European ' and 36 % ' Other ' , p < 0.001 ) . This difference in eligibility was primarily due to exclusion on the basis of language ( i.e. the inability to speak English or Punjabi ) . Of those eligible , similar proportions were recruited from the different ethnic groups ( white , South Asian and other ) . There was a marked difference in eligibility between people of Indian , Pakistani or Bangladeshi origin . Conclusion Once eligible for this trial , people from different ethnic groups were recruited in similar proportions . The reason for in eligibility in the BRUM study was the inability to support the range of minority language PURPOSE Well-conducted cancer clinical trials are essential for improving patient outcomes . Unfortunately , only 3 % of new cancer patients participate in clinical trials . Barriers to patient accrual in cancer clinical trials must be identified and overcome to increase patient participation . MATERIAL S AND METHODS We prospect ively tracked factors that potentially affected patient accrual into cancer clinical trials at the University of California Davis Cancer Center . Oncologists seeing new out patients were asked to complete question naires regarding patient characteristics and the physician 's decision-making on patient eligibility , protocol availability , and patient opinions on participation . Statistical analysis was performed to correlate these parameters with subsequent protocol accrual . RESULTS There were 276 assessable patients . At the initial visits , physicians did not consider clinical trials in 38 % ( 105/276 ) of patients principally because of a perception of protocol unavailability and poor performance status . Physicians considered 62 % ( 171/276 ) of patients for participation in clinical trials . Of these , only 53 % ( 91/171 ) had an appropriate protocol available for site and stage of disease . Seventy-six of 90 patients ( 84 % ) with available protocol s met eligibility criteria for a particular study . Only 39 of 76 patients ( 51 % ) agreed to participate in cancer clinical trials , for an overall accrual rate of 14 % ( 39/276 ) . The remainder ( 37/76 , 49 % ) declined trial participation despite meeting eligibility criteria . The most common reasons were a desire for other treatment ( 34 % ) , distance from the cancer center ( 13 % ) , patient refusal to disclose reason ( 11 % ) , and insurance denial ( 8 % ) . Patients with private insurance were less likely to enroll in clinical trials compared to those with government-funded insurance ( OR , 0.34 ; P = .03 ; 95 % CI , 0.13 to 0.9 ) . CONCLUSION Barriers to cancer clinical trial accrual can be prospect ively identified and addressed in the development and conduct of future studies , which may potentially lead to more robust clinical trials enrollment . Investigation of patient perceptions regarding the clinical trials process and the role of third party-payers is warranted Background / Aims : Asian Americans have been underrepresented in cancer research . The purpose of this study was to evaluate the efficacy of a multiple arm recruitment approach in improving Asian recruitment into the Cancer Genetics Network ( CGN ) . Methods : 1,096 potential participants , identified through cancer registries located at University of California , Irvine ( UCI ) and Fred Hutchinson Cancer Research Center ( FHCRC ) , were r and omly assigned to receive one of four recruitment approaches . Results : A 6.2 % gain in Asian participation into the CGN was achieved over a 2-year period at FHCRC and UCI , which contributed a 2 % CGN-wide increase in overall Asian enrollment . Site-specific differences in recruitment success by study arm were observed . Conclusion : Novel recruitment approaches can assist in improving recruitment of Asian population s into cancer genetic research studies PURPOSE R and om assignment to clinical trials involving different treatment modalities can be difficult . We describe our experience with the Surgical Prostatectomy Versus Interstitial Radiation Intervention Trial ( SPIRIT ; ACOSOG Z0070 NCIC PR10 ) , a r and omized trial for early-stage prostate cancer comparing radical prostatectomy ( RP ) , and brachytherapy ( BT ) . A multidisciplinary educational session was developed to improve patient underst and ing of treatment options and to facilitate accrual . PATIENTS AND METHODS Prostate cancer referrals were screened and men who met favorable risk criteria ( T1c/T2a , prostate-specific antigen [ PSA ] < 10 ng/mL , Gleason < or = 6 ) were invited to a structured education session before a specialty consultation . Men and their partners viewed the SPIRIT informed-consent video and heard from a cancer patient who described his participation in a r and omized trial . Then , a urologist and radiation oncologist together compared and contrasted RP and BT to establish the rationale for the trial . RESULTS In May 2002 , SPIRIT opened for accrual and was endorsed by the University Health Network urologists and radiation oncologists . The first 27 eligible patients were approached about SPIRIT , consulted both specialties , and viewed an educational video . No patients consented . The multidisciplinary education session was then introduced . Forty-seven education sessions with 263 patients result ed in 34 consents . Of 203 patients who were suitable for the study but declined r and om assignment , 62 chose surgery , 94 chose brachytherapy , three patients chose external radiotherapy , and 11 chose no treatment . Consent rates for eligible and suitable patients were one in six . CONCLUSION Men who underst and their treatment options and trial rationale as presented jointly by representative specialists from competing treatment modalities may be better equipped to make an informed decision and are more likely to consent to r and om assignment Purpose Writing scientific articles is a daunting task for novice research ers . In this qualitative study carried out in 2007 , the authors evaluated the experiences of a group of novice research ers engaged in the writing process , to eluci date the main difficulties and sources of encouragement they encountered . Method Sixteen novice research ers were interviewed . Most were women ( 10 ) , and most were enrolled in programs of medicine ( 9 ) , followed by nursing ( 4 ) and physical therapy ( 3 ) . These were drawn via convenience sampling from a r and omized control trial in which 48 of them were equally assigned to either an online or a face-to-face course of instruction . On completion , interviews were conducted in focus groups of four students each . The interviews were transcribed and read independently by two of the authors , who then encoded the material based on the principles of grounded theory . Initial categories were converted to major emerging themes , which were vali date d when participants were asked to review the findings . Triangulation of results was carried out by discussing the emerging themes in an online forum with five specialists in college writing education . Results Classifying the diverse responses of participants led to the emergence of four major themes : cognitive burden , group support and mentoring , difficulty in distinguishing between content and structure , and backward design of manuscripts . Conclusions The themes produced by this study provide some insight into the challenges faced by novice research ers in their early attempts at scientific writing . Remedies that address these challenges are needed to substantially improve scientific writing instruction PURPOSE To investigate patients ' willingness to participate ( WTP ) in a r and omized controlled trial ( RCT ) comparing intensity-modulated radiotherapy ( IMRT ) with proton beam therapy ( PBT ) for prostate cancer ( PCa ) . METHODS AND MATERIAL S We undertook a qualitative research study in which we prospect ively enrolled patients with clinical ly localized PCa . We used purposive sampling to ensure a diverse sample based on age , race , travel distance , and physician . Patients participated in a semi-structured interview in which they review ed a description of a hypothetical RCT , were asked open-ended and focused follow-up questions regarding their motivations for and concerns about enrollment , and completed a question naire assessing characteristics such as demographics and prior knowledge of IMRT or PBT . Patients ' stated WTP was assessed using a 6-point Likert scale . RESULTS Forty-six eligible patients ( 33 white , 13 black ) were enrolled from the practice s of eight physicians . We identified 21 factors that impacted patients ' WTP , which largely centered on five major themes : altruism/desire to compare treatments , r and omization , deference to physician opinion , financial incentives , and time dem and s/scheduling . Most patients ( 27 of 46 , 59 % ) stated they would either " definitely " or " probably " participate . Seventeen percent ( 8 of 46 ) stated they would " definitely not " or " probably not " enroll , most of whom ( 6 of 8) preferred PBT before their physician visit . CONCLUSIONS A substantial proportion of patients indicated high WTP in a RCT comparing IMRT and PBT for PCa Study objectives The emergency department ( ED ) provides an arena for patient enrolment into a variety of research studies even for non-critically ill patients . Given the types of illness , time constraints and sense of urgency that exists in the ED environment , concern exists about whether research subjects in the ED can provide full consent for participation . We sought to identify enrolled research subjects ' perspectives on the informed consent process for research conducted in the ED . Methods This was a prospect i ve , observational study of ED subjects , 18 years or older , who had been approached to participate in research in the ED and who were judged to have decision-making capacity . Exclusions were critical illness and refusal to participate . Subjective were followed up within 1 week after enrolling using structured phone interviews by trained interviewers . Results During the study period , 229 eligible patients were approached to participate in both a target study and this study . Of these , 66 % ( 150/229 ) agreed to participate in this study , at least to the extent of allowing us access to their demographic data . The study participant group was similar in terms of gender to this particular ED 's patient population but had significantly more African-Americans and persons older than 45 . Conclusion Despite rigorous time constraints and rapid throughput times , the Output:	Conclusions / Significance Chinese heritage clinical research participants value personal benefit , financial incentives , the ability to help others , recommendations of others , advertisements , and convenience when considering clinical research participation .
MS213864	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: PURPOSE To determine if photodynamic therapy with verteporfin ( Visudyne ; Novartis AG , Bülach , Switzerl and ) , termed verteporfin therapy , can safely reduce the risk of vision loss compared with a placebo ( with sham treatment ) in patients with subfoveal choroidal neovascularization caused by age-related macular degeneration who were identified with a lesion composed of occult with no classic choroidal neovascularization , or with presumed early onset classic choroidal neovascularization with good visual acuity letter score . METHODS This was a double-masked , placebo-controlled ( sham treatment ) , r and omized , multicenter clinical trial involving 28 ophthalmology practice s in Europe and North America . The study population was patients with age-related macular degeneration , with subfoveal choroidal neovascularization lesions measuring no greater than 5400 microm in greatest linear dimension with either 1 ) occult with no classic choroidal neovascularization , best-corrected visual acuity score of at least 50 ( Snellen equivalent approximately 20/100 ) , and evidence of hemorrhage or recent disease progression ; or 2 ) evidence of classic choroidal neovascularization with a best-corrected visual acuity score of at least 70 ( better than a Snellen equivalent of approximately 20/40 ) ; assigned r and omly ( 2:1 ) to verteporfin therapy or placebo therapy . Verteporfin ( 6 mg per square meter of body surface area ) or placebo ( 5 % dextrose in water ) was administered by means of intravenous infusion of 30 ml over 10 minutes . Fifteen minutes after the start of the infusion , a laser light at 689 nm delivered 50 J/cm(2 ) by application of an intensity of 600 mW/cm(2 ) over 83 seconds using a spot size with a diameter 1000 microm larger than the greatest linear dimension of the choroidal neovascularization lesion on the retina . At follow-up examinations every 3 months , retreatment with the same regimen was applied if angiography showed fluorescein leakage . The main outcome measure was at least moderate vision loss , that is , a loss of at least 15 letters ( approximately 3 lines ) , adhering to an intent-to-treat analysis with the last observation carried forward to impute for missing data . RESULTS Two hundred ten ( 93 % ) and 193 ( 86 % ) of the 225 patients in the verteporfin group compared with 104 ( 91 % ) and 99 ( 87 % ) of the 114 patients in the placebo group completed the month 12 and 24 examinations , respectively . On average , verteporfin-treated patients received five treatments over the 24 months of follow-up . The primary outcome was similar for the verteporfin-treated and the placebo-treated eyes through the month 12 examination , although a number of secondary visual and angiographic outcomes significantly favored the verteporfin-treated group . Between the month 12 and 24 examinations , the treatment benefit grew so that by the month 24 examination , the verteporfin-treated eyes were less likely to have moderate or severe vision loss . Of the 225 verteporfin-treated patients , 121 ( 54 % ) compared with 76 ( 67 % ) of 114 placebo-treated patients lost at least 15 letters ( P = .023 ) . Likewise , 67 of the verteporfin-treated patients ( 30 % ) compared with 54 of the placebo-treated patients ( 47 % ) lost at least 30 letters ( P = .001 ) . Statistically significant results favoring verteporfin therapy at the month 24 examination were consistent between the total population and the subgroup of patients with a baseline lesion composition identified as occult choroidal neovascularization with no classic choroidal neovascularization . This subgroup included 166 of the 225 verteporfin-treated patients ( 74 % ) and 92 of the 114 placebo-treated patients ( 81 % ) . In these patients , 91 of the verteporfin-treated group ( 55 % ) compared with 63 of the placebo-treated group ( 68 % ) lost at least 15 letters ( P = .032 ) , whereas 48 of the verteporfin-treated group ( 29 % ) and 43 of the placebo-treated group ( 47 % ) lost at least 30 letters ( P = .004 ) . Other secondary outcomes , including visual acuity letter score worse than 34 ( approximate Snellen equivalent of 20/200 or worse ) , mean change in visual acuity letter score , development of classic choroidal neovascularization , progression of classic choroidal neovascularization and size of lesion , favored the verteporfin-treated group at both the month 12 and month 24 examination for both the entire study group and the subgroup of cases with occult with no classic choroidal neovascularization at baseline . Subgroup analyses of lesions composed of occult with no classic choroidal neovascularization at baseline suggested that the treatment benefit was greater for patients with either smaller lesions ( 4 disc areas or less ) or lower levels of visual acuity ( letter score less than 65 , an approximate Snellen equivalent of 20/50(-1 ) or worse ) at baseline . Prospect ively planned multivariable analyses confirmed that these two baseline variables affected the magnitude of treatment benefit . ( ABSTRACT TRUNCATED OBJECTIVE To report 24-month vision and fluorescein angiographic outcomes from trials evaluating photodynamic therapy with verteporfin ( Visudyne ; CIBA Vision Corp , Duluth , Ga ) in patients with subfoveal choroidal neovascularization ( CNV ) caused by age-related macular degeneration ( AMD ) . DESIGN Two multicenter , double-masked , placebo-controlled , r and omized clinical trials . SETTING Twenty-two ophthalmology practice s in Europe and North America . PARTICIPANTS Patients with subfoveal CNV lesions caused by AMD with greatest linear dimension on the retina measuring 5400 micrometer or less , with evidence of classic CNV and best-corrected visual acuity ( approximate Snellen equivalent ) between 20/40 and 20/200 . METHODS The methods were similar to those described in our 1-year results , with follow-up examinations beyond 1 year continuing every 3 months ( except for Photograph Reading Center evaluations , which occurred only at month 18 and month 24 examinations ) . During the second year , the same regimen ( with verteporfin or placebo as applied at baseline ) was used if angiography showed fluorescein leakage from CNV . The primary outcome was the proportion of eyes with fewer than 15 letters ( approximately 3 lines ) of visual acuity loss at the month 24 examination , adhering to an intent-to-treat analysis . The last observation was carried forward to impute for any missing data . RESULTS Three hundred fifty-one ( 87 % ) of 402 patients in the verteporfin group compared with 178 ( 86 % ) of 207 patients in the placebo group completed the month 24 examination . Beneficial outcomes with respect to visual acuity and contrast sensitivity noted at the month 12 examination in verteporfin-treated patients were sustained through the month 24 examination . At the month 24 examination for the primary outcome , 213 ( 53 % ) of 402 verteporfin-treated patients compared with 78 ( 38 % ) of 207 placebo-treated patients lost fewer than 15 letters ( P<.001 ) . In subgroup analyses for predominantly classic lesions ( in which the area of classic CNV makes up at least 50 % of the area of the entire lesion ) at baseline , 94 ( 59 % ) of 159 verteporfin-treated patients compared with 26 ( 31 % ) of 83 placebo-treated patients lost fewer than 15 letters at the month 24 examination ( P<.001 ) . For minimally classic lesions ( in which the area of classic CNV makes up < 50 % but > 0 % of the area of the entire lesion ) at baseline , no statistically significant differences in visual acuity were noted . Few additional photosensitivity adverse reactions and injection site adverse events were associated with verteporfin therapy in the second year of follow-up . CONCLUSIONS The visual acuity benefits of verteporfin therapy for AMD patients with predominantly classic CNV subfoveal lesions are safely sustained for 2 years , providing more compelling evidence to use verteporfin therapy for these cases . For AMD patients with subfoveal lesions that are minimally classic , there is insufficient evidence to warrant routine use of verteporfin therapy OBJECTIVE To report vision and safety outcomes from an extension of a 2-year investigation evaluating verteporfin photodynamic therapy in patients with age-related macular degeneration with subfoveal choroidal neovascularization ( CNV ) . DESIGN AND SETTING Open-label extension of selected patients from 2 multicenter , double-masked , placebo-controlled , r and omized clinical trials , the Treatment of Age-Related Macular Degeneration With Photodynamic Therapy ( TAP ) Investigation , at 22 ophthalmology practice s in Europe and North America . PARTICIPANTS Patients enrolled in the TAP Investigation and followed up for at least 24 months in whom verteporfin therapy to CNV might reduce the risk of further vision loss . METHODS Before receiving verteporfin therapy in the extension , eligible patients signed a written informed consent form accompanied by an oral consent process approved by local institutional review boards . Methods were similar to those described for 1- and 2-year results , with follow-up examinations beyond 2 years continuing at 3-month intervals with a few exceptions , including that extension patients with fluorescein leakage from CNV were to receive open-label verteporfin therapy irrespective of their original treatment assignment . RESULTS Of 402 patients in the verteporfin group , 351 ( 87.3 % ) completed the month 24 examination ; 320 ( 91.2 % ) of these enrolled in the extension study . The enrolled participants included 124 ( 78.0 % ) of the 159 verteporfin-treated patients with lesions composed of predominantly classic CNV at baseline , of whom 105 ( 84.7 % ) completed the month 36 examination . Verteporfin-treated patients with this lesion composition at baseline who participated in the extension study , with or without a month 36 examination , appeared more likely to have a younger age , better level of visual acuity , absence of fluorescein leakage from classic CNV , or no progression of classic CNV beyond the baseline boundaries of the lesion at the month 24 examination compared with those who did not enroll in the extension . For the 105 patients with a predominantly classic baseline lesion composition who completed the month 36 examination , an average of 1.3 treatments were given from the month 24 examination up to , but not including , the month 36 examination . A letter score loss in the study eye of at least 15 from baseline for these patients occurred in 39 ( 37.5 % ) at the month 24 examination compared with 44 ( 41.9 % ) of these patients at the month 36 examination . Visual acuity changed little from the month 24 examination ( mean , -1.9 lines ) to the month 36 examination ( mean , -2.0 lines ) for these eyes . Verteporfin-treated patients had little change in the mean visual acuity lost and few or no additional instances of infusion-related back pain or photosensitivity reactions from month 24 to month 36 . Two patients originally assigned to placebo had acute severe vision decrease within 7 days after verteporfin treatment during the extension . One patient originally assigned to verteporfin had acute severe vision decrease after verteporfin treatment of the fellow eye during the extension . CONCLUSIONS Vision outcomes for verteporfin-treated patients with predominantly classic lesions at baseline remained relatively stable from month 24 to month 36 , although only approximately one third of the verteporfin-treated patients originally enrolled with this lesion composition had a month 36 examination . From these results , the TAP Study Group identified no safety concerns to preclude repeating photodynamic therapy with verteporfin . Additional treatment was judged likely to reduce the risk of further vision loss . Caution appears warranted in the absence of comparison with an untreated group during the extension and since not all patients in the TAP Investigation participated in the TAP Extension OBJECTIVE To determine if photodynamic therapy with verteporfin ( Visudyne ; CIBA Vision Corp , Duluth , GA ) can improve the chance of stabilizing or improving vision ( < 8 letter loss ) safely in patients with subfoveal choroidal neovascularization ( CNV ) caused by pathologic myopia . DESIGN Multicenter , double-masked , placebo-controlled , r and omized clinical trial at 28 ophthalmology practice s in Europe and North AMERICA : PARTICIPANTS One hundred twenty patients with subfoveal CNV caused by pathologic myopia with a greatest linear dimension no more than 5400 microM and best-corrected visual acuity ( Snellen equivalent ) of approximately 20/100 or better . INTERVENTION Patients were r and omly assigned ( 2:1 ) to verteporfin ( 6 mg per square meter of body surface area ; n = 81 ) or placebo ( 5 % dextrose in water ; n = 39 ) Output:	Subgroup analyses suggest that the benefits may be confined to people with no occult choroidal neovascularisation . REVIEW ER 'S CONCLUSIONS Photodynamic therapy in people with classic choroidal neovascularisation due to age-related macular degeneration is effective in preventing visual loss . There is no evidence that photodynamic therapy is beneficial for people with evidence of occult choroidal neovascularisation .
MS213865	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Abstract Objectives : To examine the cost of providing hospital at home in place of some forms of inpatient hospital care . Design : Cost minimisation study within a r and omised controlled trial . Setting : District general hospital and catchment area of neighbouring community trust . Subjects : Patients recovering from hip replacement ( n=86 ) , knee replacement ( n=86 ) , and hysterectomy ( n=238 ) ; elderly medical patients ( n=96 ) ; and patients with chronic obstructive airways disease ( n=32 ) . Interventions : Hospital at home or inpatient hospital care . Main outcome measures : Cost of hospital at home scheme to health service , to general practitioners , and to patients and their families compared with hospital care . Results : No difference was detected in total healthcare costs between hospital at home and hospital care for patients recovering from a hip or knee replacement , or elderly medical patients . Hospital at home significantly increased healthcare costs for patients recovering from a hysterectomy ( ratio of geometrical means 1.15 , 95 % confidence interval 1.04 to 1.29 , P=0.009 ) and for those with chronic obstructive airways disease ( Mann-Whitney U test , P=0.01 ) . Hospital at home significantly increased general practitioners ' costs for elderly medical patients ( Mann-Whitney U test , P<0.01 ) and for those with chronic obstructive airways disease ( P=0.02 ) . Patient and carer expenditure made up a small proportion of total costs . Conclusion : Hospital at home care did not reduce total healthcare costs for the conditions studied in this trial , and costs were significantly increased for patients recovering from a hysterectomy and those with chronic obstructive airways disease . There was some evidence that costs were shifted to primary care for elderly medical patients and those with chronic obstructive airways disease . Key messages Hospital at home schemes are a popular alternative to st and ard hospital care , but there is uncertainty about their cost effectiveness In our r and omised controlled trial we compared the cost of hospital at home care with that of inpatient hospital care for patients recovering from hip replacement , knee replacement , and hysterectomy ; elderly medical patients ; and those with chronic obstructive airways disease There were no major differences in health service costs between the two arms of the trial for patients recovering from hip or knee replacement and elderly medical patients Hospital at home care increased healthcare costs for patients recovering from hysterectomy and for those with chronic obstructive airways disease Hospital at home care result ed in some costs shifting to general practitioners for elderly medical patients and those with chronic obstructive airways OBJECTIVE : To test the cost effectiveness of Hospital in the Home compared to hospital admission for acute medical conditions BACKGROUND We have previously reported the use of a hospital based respiratory nurse service ( Acute Respiratory Assessment Service , ARAS ) to support home treatment of patients with exacerbations of chronic obstructive pulmonary disease ( COPD ) . A controlled trial was undertaken to compare early discharge with home treatment supported by respiratory nurses with conventional hospital management of patients admitted with exacerbations of COPD . METHODS Patients with COPD admitted as emergencies were identified the next working day . They were eligible for inclusion in the study if the differential diagnosis included an exacerbation of COPD , but were excluded if other medical conditions or acidotic respiratory failure required inpatient investigation or management . Of 360 patients review ed , 209 were being assessed for other active medical problems and were excluded , 33 potential participants were already involved in research studies and so were ineligible , and 37 did not wish to participate in the study . Eighty one patients were r and omised to receive conventional inpatient care ( n=40 ) or to planned early discharge the next working day ( n=41 ) . Those discharged early continued treatment at home under the supervision of specialist respiratory nurses . Outcome measures were readmission , additional hospital days , and deaths within 60 days of initial admission . Process measures included number of visits , duration of follow up by the respiratory nurse , and additional treatment provided to support early discharge . RESULTS On an intention to treat basis , a policy of early discharge reduced inpatient stay from a mean of 6.1 ( range 1–13 ) days with conventional management to 3.2 ( 1–16 ) days with an early discharge policy . Twelve patients ( 30 % conventional management , 29.3 % early discharge ) were readmitted in each group giving a mean difference in readmission of 0.7 % ( 95 % CI of the difference –19.2 to 20.6 ) . In the conventional management group readmitted patients spent a mean of 8.75 additional days in hospital compared with 7.83 days in the early discharge group , giving a mean difference of 0.92 days ( 95 % CI of the difference –6.5 to 8.3 ) . There were two deaths ( 5 % ) in the conventional management group and one ( 2.4 % ) in the early discharge group , a mean difference of 2.6 % ( 95 % CI of the difference –5.7 to 10.8 ) . CONCLUSIONS Patients with acute exacerbations of COPD uncomplicated by acidotic respiratory failure or other medical problems can be discharged home earlier than is current practice with support by visiting respiratory nurses . No difference was found in the subsequent need for readmission BACKGROUND Patients with acute proximal deep-vein thrombosis are usually treated first in the hospital with intravenous st and ard ( unfractionated ) heparin . However , the longer plasma half-life , better bioavailability after subcutaneous administration , and more predictable anticoagulant response of low-molecular-weight heparins make them attractive for possible home use . We compared these two approaches . METHODS Patients with acute proximal deep-vein thrombosis were r and omly assigned to receive either intravenous st and ard heparin in the hospital ( 253 patients ) or low-molecular-weight heparin ( 1 mg of enoxaparin per kilogram of body weight subcutaneously twice daily ) administered primarily at home ( 247 patients ) . The study design allowed out patients taking low-molecular-weight heparin to go home immediately and hospitalized patients taking low-molecular-weight heparin to be discharged early . All the patients received warfarin starting on the second day . RESULTS Thirteen of the 247 patients receiving low-molecular-weight heparin ( 5.3 percent ) had recurrent thromboembolism , as compared with 17 of the 253 patients receiving st and ard heparin ( 6.7 percent ; P=0.57 ; absolute difference , 1.4 percentage points ; 95 percent confidence interval , -3.0 to 5.7 ) . Five patients receiving low-molecular-weight heparin had major bleeding , as compared with three patients receiving st and ard heparin . After r and omization , the patients who received low-molecular-weight heparin spent a mean of 1.1 days in the hospital , as compared with 6.5 days for the st and ard-heparin group ; 120 patients in the low-molecular-weight- heparin group did not need to be hospitalized at all . CONCLUSIONS Low-molecular-weight heparin can be used safely and effectively to treat patients with proximal deep-vein thrombosis at home A r and omised controlled trial has been conducted into the effects of discharging patients from hospital either 48 hours or six to seven days after operations for inguinal hernia and varicose veins . There was no statistically significant difference in major postoperative complications between the two lengths of stay for either of the two conditions . Similarly there was no difference between the two groups of hernia patients in relation to eventual recurrences . There was no significant difference in length of convalescence between long-stay and short-stay patients in full-time occupations . The savings to the statutory services of discharging patients early were estimated at 25.72 pounds per patient . Patients appeared to approve of the type of care they experienced , regardless of length of stay . However , the families of short-stay patients were significantly less enthusiastic in their attitudes towards the policy of early discharge than the families of long-stay patients BACKGROUND AND PURPOSE This study describes the methodology , patient outcome , and use of hospital and rehabilitation services at 3 months of a population -based r and omized controlled trial . The purpose was to evaluate rehabilitation at home after early supported discharge from the Department of Neurology , Huddinge Hospital , for moderately disabled stroke patients in southwest Stockholm . METHODS The patients were eligible if they were continent , independent in feeding , had mental function within normal limits , and had impaired motor function and /or aphasia 1 week after stroke . Patients were r and omized either to early supported discharge with continuity of rehabilitation at home for 3 to 4 months or to routine rehabilitation service in a hospital , day care , and /or outpatient care . The home rehabilitation team consisted of two physical therapists , two occupational therapists , and one speech therapist ; one of the therapists was assigned as case manager for the patient . The rehabilitation program at home emphasized a task- and context -oriented approach . The activities were chosen on the basis of the patient 's personal interests . Spouses were offered education and individual counseling . A total of 81 patients were followed up for a minimum of 3 months . Patient outcome was assessed by the Frenchay Social Activity Index , Extended Katz Index , Barthel Index , Lindmark Motor Capacity Assessment , Nine-Hole Peg Test , walking speed over 10 m , reported falls , and subjective dysfunction according to the Sickness Impact Profile . Patient use of hospital and home rehabilitation service and patient satisfaction with care were studied . RESULTS Overall there were no statistical significant differences in outcome . Multivariate logistic regression analysis suggested a systematic positive effect for the home rehabilitation group in social activity , activities of daily living , motor capacity , manual dexterity , and walking . A considerable difference in re source use during such a 3-month period was seen . A 52 % reduction in hospitalization was observed : from 29 days in the routine rehabilitation group to 14 days in the home rehabilitation group . Patient satisfaction was in favor of the latter group . CONCLUSIONS Early supported discharge with continuity of home rehabilitation services for the majority of moderately disabled stroke patients during the first 3-month period after acute stroke is not less beneficial than routine rehabilitation and can be a rehabilitation service of choice if follow-up at 6 and 12 months confirms the suggested effectiveness and considerable reduction in use of health care It was postulated that home hospitalisation ( HH ) of selected chronic obstructive pulmonary disease ( COPD ) exacerbations admitted at the emergency room ( ER ) could facilitate a better outcome than conventional hospitalisation . To this end , 222 COPD patients ( 3.2 % female ; 71±10 yrs ( mean±sd ) ) were r and omly assigned to HH ( n=121 ) or conventional care ( n=101 ) . During HH , integrated care was delivered by a specialised nurse with the patient 's free-phone access to the nurse ensured for an 8‐week follow-up period . Mortality ( HH : 4.1 % ; controls : 6.9 % ) and hospital readmissions ( HH : 0.24±0.57 ; controls : 0.38±0.70 ) were similar in both groups . However , at the end of the follow-up period , HH patients showed : 1 ) a lower rate of ER visits ( 0.13±0.43 versus 0.31±0.62 ) ; and 2 ) a noticeable improvement of quality of life ( Δ St George 's Respiratory Question naire ( SGRQ ) , −6.9 versus −2.4 ) . Furthermore , a higher percentage of patients had a better knowledge of the disease ( 58 % versus 27 % ) , a better self-management of their condition ( 81 % versus 48 % ) , and the patient 's satisfaction was greater . The average overall direct cost per HH patient was 62 % of the costs of conventional care , essentially due to fewer days of inpatient hospitalisation ( 1.7±2.3 versus 4.2±4.1 days ) . A comprehensive home care intervention in selected chronic obstructive pulmonary disease exacerbations appears as cost effective . The home hospitalisation intervention generates better outcomes at lower costs than conventional care To compare the results of home and hospital treatment in men aged under 70 years who had suffered acute myocardial infa rct ion within 48 hours 1895 patients were considered for study in four centres in south-west Engl and . Four-hundred- and -fifty patients were r and omly allocated to receive care either at home by their family doctor or in hospital , initially in an intensive care unit . The r and omised treatment groups were similar in age , history of cardiovascular disease , and incidence of hypotension when first examined . They were followed up for up to a year after onset . The mortality rate at 28 days was 12 % for the r and om home group and 14 % for the r and om hospital group ; the corresponding figures at 330 days were 20 % and 27 % . On average , older patients and those without initial hypotension fared rather better under home care . The patients who underwent r and omisation were similar to those whose place of care was not r and omised , except that the non-r and omised group contained a higher proportion of initially hypotensive patients , whose prognosis was poor wherever treated . These results confirm and extend our preliminary findings . Home care is a proper form of treatment for many patients with acute myocardial infa rct ion , particularly those over 60 years and those with an uncomplicated attack seen by general practitioners BACKGROUND An intravenous course of st and ard ( unfractionated ) heparin with the dose adjusted to prolong the activated partial-thromboplastin time to a desired length is the st and ard initial in-hospital treatment for patients with deep-vein thrombosis , but fixed Output:	Allocation to hospital at home result ed in a small reduction in hospital length of stay , but hospital at home increased overall length of care . Patients allocated to hospital at home expressed greater satisfaction with care than those in hospital , while the view of carers was mixed . Early discharge schemes for patients recovering from elective surgery and elderly patients with a medical condition may have a place in reducing the pressure on acute hospital beds , providing the views of the carers are taken into account . For these clinical groups hospital length of stay is reduced , although this is offset by the provision of hospital at home .
MS213866	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: The complete treatment of anogenital warts has not been obtained with any combination of methods ; therefore , new methods are still under investigation . In this study the activity and side effects of imiquimod 5 % cream were investigated . The study group consisted of 23 male and 11 female volunteers and the control group of 9 male and 2 female volunteers . Patients applied the cream three times a week , every other day in the evenings for a period of 12 weeks . After the treatment , patients were regularly monitored for six months for recurrences . At the end of the study , 23 ( 69.7 % ) patients ( all of females and 54.5 % of males ) in the study group displayed a complete clearance , 9 patients displayed 50 - 90 % clearance and 1 patient displayed less than 50 % clearance . In the control group , only 1 patient displayed a complete clearance , 1 patient displayed 50 - 90 % clearance , and the other 8 patients showed no alteration in the lesions . These results were statistically significantly different ( p<0.01 ) . In 15 patients in the study group , no side effects were reported ; the most frequently seen side effects were erythema and erosion . In six patients that were observed for a period of six months , recurrences occurred . Imiquimod 5 % cream is a topically applied medicament that should be considered as an effective and reliable medical option in the treatment of anogenital warts Objective . To evaluate if new imiquimod formulations using a shorter treatment duration are safe and efficacious to treat anogenital warts . Methods . In two studies 534 women ≥12 years of age ( mean 33.4 ) with 2–30 warts ( mean 7.9 ) and total wart area ≥10 mm2 ( mean 166.3 ) were r and omized ( 1 : 2 : 2 ) to placebo ( 106 ) , imiquimod 2.5 % ( 212 ) or 3.75 % ( 216 ) creams applied once daily until complete clearance or a maximum of 8 weeks . Results . For placebo , imiquimod 2.5 % and 3.75 % , respectively , complete clearance of all warts was achieved in 14.2 % , 28.3 % , and 36.6 % of women ( intent-to-treat , P = 0.008 imiquimod 2.5 % , and P < 0.001 3.75 % versus placebo ) . Mean changes in wart counts were −10.7 % , −50.9 % , and −63.5 % ( per- protocol , P < 0.001 each active versus placebo ) and safety-related discontinuation rates 0.9 % , 1.4 % , and 2.3 % . Conclusions . Imiquimod 3.75 % applied daily for up to 8 weeks was well tolerated and superior to placebo in treating women with external anogenital warts OBJECTIVES The objectives of this study were to estimate the incidence of genital warts and treatment costs in women consulting gynaecologists in France in 2005 . PATIENTS AND METHODS A prospect i ve observational study was performed through a representative sample of gynaecologists . Investigators enrolled all patients seen with genital warts during a 2-month period . A question naire detailing socio-demographic characteristics , case description , patient 's clinical profile , past/ current management , and treatment of genital warts was completed by the investigators . RESULTS 212 gynaecologists participated in the study . Question naires were completed for 263 patients including 198 ( 75.3 % ) new cases , 53 ( 20.2 % ) recurrent cases and 12 ( 4.5 % ) resistant cases . The overall incidence was estimated at 228.9/100,000 ( female 15 - 65year old population ) corresponding to 47,755 cases annually managed by gynaecologists in France . The average treatment cost was 482.70euro for society and 342.40 euro for third-party payers . The annual direct cost of genital warts management was estimated at 23,051,339euro , of which 16,351,312euro was funded by the French health care system . DISCUSSION AND CONCLUSION The costs of treating genital warts are considerable . The introduction of a quadrivalent ( type 6,11,16,18 ) Human Papillomavirus vaccine including types responsible for 90 % of genital warts could potentially substantially reduce these costs The purpose of this double-blind , placebo-controlled , comparative study was to evaluate the specific clinical efficacy and tolerance of human leukocyte interferon-α ( 2 × l06 IU/g ) and podophyllotoxin 0.5 % incorporated in a hydrophilic cream to cure genital warts . Preselected Asian women ( n=60 ) aged 18–40 years ( mean 22.9 ) , with a clinical and biopsy-confirmed diagnosis of genital warts , harboring 322 lesions ( mean 5.36 ) were r and omly assigned to three parallel groups to receive one of the two test drugs or placebo . Each patient received a preceded tube ( 40 g ) containing either human leukocyte interferon-α , podophyllotoxin , or identically appearing placebo cream for 3 days ' usage . In addition to written instructions , each subject was shown how to apply a minimal amount of trial medication on their lesions thrice daily for 3 consecutive days per week ( maximum nine topical applications per week ) . Patients were examined on a weekly basis , and a cure was considered to be a biopsy-confirmed , total elimination of a lesion . Moreover , patients cured during the study period were spared further therapy , and were requested to return in 16 weeks to monitor for the occurrence of a relapse . The remaining patients ' empty tubes were collected , and similarly precoded replacement tubes were given to continue the treatment ; a total of 214 tubes were used . The study was scheduled for 16 weeks with 4 weeks of active treatment . Individuals were excluded from the study due to pregnancy , breast feeding , or the receiving of any type of antiviral therapy during the 4 weeks preceding enrollment . Better results were obtained with leukocyte interferon-α cream than with podophyllotoxin both in terms of the number of cured patients ( 18/20 vs. 12/20 , or 90 % vs. 60 % ; P<0.0285 ) and the number of eliminated lesions ( 105/110 ) vs. 87/108 , or 95.5 % vs. 80.5 % ; P<0.001 . In the placebo group 4/20 ( 20 % ) patients were cured , indicating lower results . Out of the 60 patients 51 ( 85 % ) complained of no drug-related symptomatic side effects . However , the most frequent non objective adverse symptoms experienced by the patients were mild tenderness 4/60 ( 6.6 % ) , burning sensation 3/60 ( 5 % ) , and transitory increase in body temperature ( > 38 ° C ) accompanied by headache and itching 2/60 ( 3.3 % ) . None of the patients suffering from these side effects elected to discontinue the study . The patients were evaluated for 1 year after the initial visit , and among the 34/60 ( 56.6 % ) cured patients two had a relapse after 9 months . In conclusion , the clinical results of this study demonstrate that leukocyte interferon-α ( 2 × l06 IU/g ) is more efficacious than 0.5 % podophyllotoxin and placebo in hydrophilic cream , and substantiates that along with mild , non objective , transient , localized , adverse symptoms , human leukocyte α-interferon therapy is more effective and better than podophyllotoxin in cream for curing genital warts in PURPOSE Genital warts are a highly prevalent and chronic sexually transmitted disease for which there is no completely satisfactory therapy . Conventional ablative therapy requires repeated treatment , often for months or years . This study was undertaken to evaluate the safety and efficacy of 0.5 % podofilox in patient-administered treatment of penile warts . PATIENTS AND METHODS Thirty-eight men with penile warts were r and omly assigned to double-blind , self-administration of 0.5 % podofilox solution or placebo , twice daily for 3 days per week for 4 weeks . Eleven podofilox and 15 placebo recipients with residual warts then received an additional 4 weeks of open-label treatment . RESULTS By the end of treatment , podofilox recipients had their mean wart number and area reduced to 15.9 % and 5.1 % of baseline values , compared to 97.4 % and 92.9 % in the placebo group ( p = 0.0001 ) . Local adverse reactions were more common in the podofilox group , but were transient . Complete disappearance of warts was observed in 25 ( 53.3 % ) of 45 treatment courses , including open-label treatment . Recurrences of warts after therapy were frequent . Only 21 % of patients remained free of warts 2 weeks after completing treatment , and subsequent recurrences were noted in all patients available for long-term follow-up , which is a common limitation of ablative therapy for genital warts . CONCLUSION Podofilox 0.5 % solution is effective in treating penile warts and is well tolerated in a self-administered regimen . Podofilox 0.5 % offers potential advantages in safety and cost over podophyllin resin therapy of genital warts BACKGROUND Genital warts are a well-recognized clinical entity and a disease of great antiquity that differ from skin warts both histologically and antigenically . It is a common sexually transmitted disease of high prevalence all over the world . Women are more likely to be unaware of such warts because it is harder for them to examine their genitalia . OBJECTIVE The purpose of this multicenter , double-blind , placebo-controlled study was to compare the clinical efficacy and tolerance of 0.3 % and 0.5 % podophyllotoxin in a cream emulsion ( castor oil , BP as vehicle ) to cure genital condylomata in women . METHODS Preselected ( n = 80 ) Asian females ( mean age 23.6 years ) , harboring 544 warts ( mean 6.8 in number ) , ranging from 1 to 9 mm in size ( mean 2.1 mm ) with biopsy-proven diagnosis of condylomata acuminata were r and omly allocated to three groups ( 30 + 30 + 20 ) . At home the patients applied the given trial medication themselves ( using the finger ) twice a day , for 3 consecutive days per week , and if not cured the same course was extended to 3 more weeks , in total 24 topical applications for 4 weeks . The patients were examined on a weekly basis , and a total regression of warts ( biopsy-proven ) was evaluated as complete cure . RESULTS By the end of the study , the placebo group ( 20 patients , bearing 124 warts ) did not show any regression or clinical efficacy , while 41/60 patients ( 68.3 % ) and 349/420 warts ( 83 % ) were cured in the 0.3 % and 0.5 % treatment groups ( placebo vs. active groups p < 0.001 ) . Patients using the 0.5 % active medication had substantially more eliminated warts ( 205/349 , 95.8 % ) than the 0.3 % group ( 70 % ) . Localized adverse symptoms were mild to moderate and were well tolerated by the patients with no dropout . Forty-three patients ( 53.8 % ) did not show any adverse reaction . The most frequent adverse symptoms were tenderness ( 23/80 , 28.8 % ) and burning sensation ( 14/80 , 17.5 % ) . Among 41/80 ( 51.25 % ) cured patients 4 had a relapse after 16 weeks . CONCLUSION Along with mild , tolerable side effects the study demonstrates that 0.5 % podophyllotoxin cream is more efficacious than 0.3 % ( p < 0.01 ) and can be considered as a reliable home-based treatment Background The approximately 1100 medical journals now active in China are publishing a rapidly increasing number of research reports , including many studies identified by their authors as r and omized controlled trials . It has been noticed that these reports mostly present positive results , and their quality and authenticity have consequently been called into question . We investigated the adequacy of r and omization of clinical trials published in recent years in China to determine how many of them met acceptable st and ards for allocating participants to treatment groups . Methods The China National Knowledge Infrastructure electronic data base was search ed for reports of r and omized controlled trials on 20 common diseases published from January 1994 to June 2005 . From this sample , a subset of trials that appeared to have used r and omization methods was selected . Twenty-one investigators trained in the relevant knowledge , communication skills and quality control issues interviewed the original authors of these trials about the participant r and omization methods and related quality -control features of their trials . Results From an initial sample of 37,313 articles identified in the China National Knowledge Infrastructure data base , we found 3137 apparent r and omized controlled trials . Of these , 1452 were studies of conventional medicine ( published in 411 journals ) and 1685 were studies of traditional Chinese medicine ( published in 352 journals ) . Interviews with the authors of 223 Output:	Analysis by MTC indicated that ablative techniques were typically more effective than topical interventions at completely clearing AGWs at the end of treatment . The results generated by the MTC are in agreement with consensus opinion that ablative techniques are clinical ly more effective at completely clearing AGWs after treatment . The results of the economic analysis suggest that podophyllotoxin 0.5 % solution is likely to represent a cost-effective first-line treatment option . No treatment and podophyllin are unlikely to be considered cost-effective treatment options .
MS213867	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Because fruits and vegetables are rich in bioactive compounds with potential cancer-preventive actions , increased consumption may reduce the risk of ovarian cancer . Evidence on the association between fruit and vegetable intake and ovarian cancer risk has not been consistent . We analyzed and pooled the primary data from 12 prospect i ve studies in North America and Europe . Fruit and vegetable intake was measured at baseline in each study using a vali date d food-frequency question naire . To summarize the association between fruit and vegetable intake and ovarian cancer , study -specific relative risks ( RR ) were estimated using the Cox proportional hazards model , and then combined using a r and om-effects model . Among 560,441 women , 2,130 cases of invasive epithelial ovarian cancer occurred during a maximum follow-up of 7 to 22 years across studies . Total fruit intake was not associated with ovarian cancer risk — the pooled multivariate RR for the highest versus the lowest quartile of intake was 1.06 [ 95 % confidence interval ( 95 % CI ) , 0.92 - 1.21 ; P value , test for trend = 0.73 ; P value , test for between- studies heterogeneity = 0.74 ] . Similarly , results for total vegetable intake indicated no significant association ( pooled multivariate RR , 0.90 ; 95 % CI , 0.78 - 1.04 , for the highest versus the lowest quartile ; P value , test for trend = 0.06 ; P value , test for between- studies heterogeneity = 0.31 ) . Intakes of botanically defined fruit and vegetable groups and individual fruits and vegetables were also not associated with ovarian cancer risk . Associations for total fruits and vegetables were similar for different histologic types . These results suggest that fruit and vegetable consumption in adulthood has no important association with the risk of ovarian cancer Background A series of recent reports from large-scale cohort studies involving more than 100,000 subjects reported no or only very small inverse associations between fruit and vegetable intake and overall cancer incidence , despite having sufficient power to do so . To date , however , no such data have been reported for Asian population s. Objective To provide some indication of the net impact of fruit and vegetable consumption on overall cancer prevention , we examined these associations in a pooled analysis of large-scale cohort studies in Japanese population s. Methods We analyzed original data from four cohort studies that measured fruit and vegetable consumption using vali date d question naires at baseline . Hazard ratios ( HRs ) in the individual studies were calculated , with adjustment for a common set of variables , and combined using a r and om-effects model . Results During 2,318,927 person-years of follow-up for a total of 191,519 subjects , 17,681 cases of overall cancers were identified . Consumption of fruit or vegetables was not associated with decreased risk of overall cancers : corresponding HRs for the highest versus lowest quartiles of intake for men and women were 1.03 ( 95 % CI , 0.97–1.10 ; trend p = 1.00 ) and 1.03 ( 95 % CI , 0.95–1.11 ; trend p = 0.97 ) , respectively , for fruit and 1.07 ( 95 % CI , 1.01–1.14 ; trend p = 0.18 ) and 0.98 ( 95 % CI , 0.91–1.06 ; trend p = 0.99 ) , respectively , for vegetables , even in analyses stratified by smoking status and alcohol drinking . Conclusions The results of this pooled analysis do not support inverse associations of fruit and vegetable consumption with overall cancers in the Japanese population Abstract Objective To assess the prospect i ve associations between consumption of ultra-processed food and risk of cancer . Design Population based cohort study . Setting and participants 104 980 participants aged at least 18 years ( median age 42.8 years ) from the French NutriNet-Santé cohort ( 2009 - 17 ) . Dietary intakes were collected using repeated 24 hour dietary records , design ed to register participants ’ usual consumption for 3300 different food items . These were categorised according to their degree of processing by the NOVA classification . Main outcome measures Associations between ultra-processed food intake and risk of overall , breast , prostate , and colorectal cancer assessed by multivariable Cox proportional hazard models adjusted for known risk factors . Results Ultra-processed food intake was associated with higher overall cancer risk ( n=2228 cases ; hazard ratio for a 10 % increment in the proportion of ultra-processed food in the diet 1.12 ( 95 % confidence interval 1.06 to 1.18 ) ; P for trend<0.001 ) and breast cancer risk ( n=739 cases ; hazard ratio 1.11 ( 1.02 to 1.22 ) ; P for trend=0.02 ) . These results remained statistically significant after adjustment for several markers of the nutritional quality of the diet ( lipid , sodium , and carbohydrate intakes and /or a Western pattern derived by principal component analysis ) . Conclusions In this large prospect i ve study , a 10 % increase in the proportion of ultra-processed foods in the diet was associated with a significant increase of greater than 10 % in risks of overall and breast cancer . Further studies are needed to better underst and the relative effect of the various dimensions of processing ( nutritional composition , food additives , contact material s , and neoformed contaminants ) in these associations . Study registration Clinical trials.gov NCT03335644 OBJECTIVE Assumptions have linked orange juice ( OJ ) consumption with weight gain and adverse effects on health due to its sugar content ; however , epidemiologic studies have not shown increased risk for overweight or obesity with the consumption of 100 % OJ . The aim of this study was to verify whether the combination of a reduced-calorie diet ( RCD ) and 100 % OJ contribute to weight loss , promote changes in glucose and lipid metabolism , and improve diet quality in obese individuals . METHODS A r and omized controlled trial with 78 obese patients ( age 36 ± 1 y , body mass index [ BMI ] 33 ± 3 kg/m2 ) were enrolled in two groups : Individuals in the OJ group su bmi tted to an RCD that included OJ ( 500 mL/d ) , and individuals in the control group su bmi tted to an RCD without OJ . Body composition , biochemical biomarkers , and dietary intake were analyzed over a 12-wk period . RESULTS Both treatments had similar outcomes regarding body weight ( -6.5 kg ; P = 0.363 ) , BMI ( -2.5 kg/m2 ; P = 0.34 ) , lean mass ( -1 kg ; P = 0.29 ) , fat mass ( -5 kg ; P = 0.58 ) , body fat ( -3 % ; P = 0.15 ) , and waist-to-hip ratio ( -0.1 ; P = 0.79 ) . Insulin levels in the OJ group decreased by 18 % ( P = 0.05 ) , homeostasis model assessment -insulin resistance by 33 % ( P = 0.04 ) , total cholesterol by 24 % ( P = 0.004 ) , low-density lipoprotein cholesterol by 24 % ( P ≤ 0.001 ) , and high-sensitivity C-reactive protein levels by 33 % ( P = 0.001 ) compared with the control group . Consumption of energy and nutrients was similar between the two groups , but vitamin C and folate increased by 62 % ( P ≤ 0.015 ) and 39 % ( P = 0.033 ) , respectively , after OJ intervention . CONCLUSION When consumed concomitantly with an RCD , OJ does not inhibit weight loss ; ameliorate the insulin sensitivity , lipid profile , or inflammatory status , or contribute nutritionally to the quality of the diet The association between drinking 100 % fruit juice and long-term weight gain is controversial and has been investigated in few studies . We examined whether 100 % fruit juice consumption was associated with weight change in a large prospect i ve cohort of postmenopausal women . We analyzed data from 49,106 postmenopausal women in the United States enrolled in the Women 's Health Initiative between 1993 and 1998 . Food frequency question naires at baseline and year 3 assessed food and beverage intake . Body weight was measured at in-person clinic visits . We used linear mixed effects modeling to determine the association between change in 100 % fruit juice consumption and 3-year weight change over the same time period . Covariates of interest included age , demographic factors , smoking , body mass index , hormone replacement therapy , lifestyle factors , change in whole fruit intake , and change in sugar-sweetened beverage intake . The mean weight change was 3.2 lbs . over 3 years . In multivariable adjusted analyses , each 1 serving/day increase in 100 % fruit juice intake was associated with a 3-year weight gain of 0.39 lbs . ( 95 % confidence interval : 0.10 , 0.69 ) . In conclusion , an increase in 100 % fruit juice consumption was associated with a small amount of long-term weight gain in postmenopausal women The importance of vegetable and fruit intakes for the prevention of fracture in older women is not well understood . Few studies have explored vegetable and fruit intakes separately , or the associations of specific types of vegetables and fruits with fracture hospitalisations . The objective of this study was to examine the associations of vegetable and fruit intakes , separately , and specific types of vegetables and fruits with fracture-related hospitalisations in a prospect i ve cohort of women aged ≥70 years . Vegetable and fruit intakes were assessed at baseline ( 1998 ) in 1468 women using a food frequency question naire . The incidence of fracture-related hospitalisations over 14.5 years of follow-up was determined using the Hospital Morbidity Data Collection , linked via the Western Australian Data Linkage System . Fractures were identified in 415 ( 28.3 % ) women , of which 158 ( 10.8 % ) were hip fractures . Higher intakes of vegetables , but not fruits , were associated with lower fracture incidence . In multivariable-adjusted models for vegetable types , cruciferous and allium vegetables were inversely associated with all fractures , with a hazard ratio ( HR ) ( 95 % confidence interval ) of 0.72 ( 0.54 , 0.95 ) and 0.66 ( 0.49 , 0.88 ) , respectively , for the highest vs. lowest quartiles . Increasing vegetable intake , with an emphasis on cruciferous and allium vegetables , may prevent fractures in older postmenopausal women Dietary recommendations to promote health include fresh , frozen and tinned fruit , but few studies have examined the health benefits of tinned fruit . We therefore studied the association between tinned fruit consumption and mortality . We followed up participants from three prospect i ve cohorts in the United Kingdom : 22,421 participants from the European Prospect i ve Investigation into Cancer and Nutrition (EPIC)-Norfolk cohort ( 1993–2012 ) , 52,625 participants from the EPIC-Oxford cohort ( 1993–2012 ) , and 7440 participants from the Whitehall II cohort ( 1991–2012 ) , all reporting no history of heart attack , stroke , or cancer when entering these studies . We estimated the association between frequency of tinned fruit consumption and all cause mortality ( primary outcome measure ) using Cox regression models within each cohort , and pooled hazard ratios across cohorts using r and om-effects meta- analysis . Tinned fruit consumption was assessed with vali date d food frequency question naires including specific questions about tinned fruit . During 1,305,330 person years of follow-up , 8857 deaths occurred . After adjustment for lifestyle factors and risk markers the pooled hazard ratios ( 95 % confidence interval ) of all cause mortality compared with the reference group of tinned fruit consumption less often than one serving per month were : 1.05 ( 0.99 , 1.12 ) for one to three servings per month , 1.10 ( 1.03 , 1.18 ) for one serving per week , and 1.13 ( 1.04 , 1.23 ) for two or more servings per week . Analysis of cause-specific mortality showed that tinned fruit consumption was associated with mortality from cardiovascular causes and from non-cardiovascular , non-cancer causes . In a pooled analysis of three prospect i ve cohorts from the United Kingdom self-reported tinned fruit consumption in the 1990s was weakly but positively associated with mortality during long-term follow-up . These findings raise questions about the evidence underlying dietary recommendations to promote tinned fruit consumption as part of a healthy diet OBJECTIVE Our purpose was to measure the agreement , reliability , construct validity , and feasibility of a measurement tool to assess systematic review s ( AMSTAR ) . STUDY DESIGN AND SETTING We r and omly selected 30 systematic review s from a data base . Each was assessed by two review ers using : ( 1 ) the enhanced quality assessment question naire ( Overview of Quality Assessment Question naire [ OQAQ ] ) ; ( 2 ) Sacks ' instrument ; and ( 3 ) our newly developed measurement tool ( AMST Output:	RESULTS The results showed that the degree of processing influences the health effects of fruit-based products . Fresh and dried fruits appeared to have a neutral or protective effect on health , 100 % fruit juices had intermediary effects , and high consumption of canned fruit and sweetened fruit juice was positively associated with the risk of all-cause mortality and type 2 diabetes , respectively .
MS213868	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: BACKGROUND Blockade of programmed death 1 ( PD-1 ) , an inhibitory receptor expressed by T cells , can overcome immune resistance . We assessed the antitumor activity and safety of BMS-936558 , an antibody that specifically blocks PD-1 . METHODS We enrolled patients with advanced melanoma , non-small-cell lung cancer , castration-resistant prostate cancer , or renal-cell or colorectal cancer to receive anti-PD-1 antibody at a dose of 0.1 to 10.0 mg per kilogram of body weight every 2 weeks . Response was assessed after each 8-week treatment cycle . Patients received up to 12 cycles until disease progression or a complete response occurred . RESULTS A total of 296 patients received treatment through February 24 , 2012 . Grade 3 or 4 drug-related adverse events occurred in 14 % of patients ; there were three deaths from pulmonary toxicity . No maximum tolerated dose was defined . Adverse events consistent with immune-related causes were observed . Among 236 patients in whom response could be evaluated , objective responses ( complete or partial responses ) were observed in those with non-small-cell lung cancer , melanoma , or renal-cell cancer . Cumulative response rates ( all doses ) were 18 % among patients with non-small-cell lung cancer ( 14 of 76 patients ) , 28 % among patients with melanoma ( 26 of 94 patients ) , and 27 % among patients with renal-cell cancer ( 9 of 33 patients ) . Responses were durable ; 20 of 31 responses lasted 1 year or more in patients with 1 year or more of follow-up . To assess the role of intratumoral PD-1 lig and ( PD-L1 ) expression in the modulation of the PD-1-PD-L1 pathway , immunohistochemical analysis was performed on pretreatment tumor specimens obtained from 42 patients . Of 17 patients with PD-L1-negative tumors , none had an objective response ; 9 of 25 patients ( 36 % ) with PD-L1-positive tumors had an objective response ( P=0.006 ) . CONCLUSIONS Anti-PD-1 antibody produced objective responses in approximately one in four to one in five patients with non-small-cell lung cancer , melanoma , or renal-cell cancer ; the adverse-event profile does not appear to preclude its use . Preliminary data suggest a relationship between PD-L1 expression on tumor cells and objective response . ( Funded by Bristol-Myers Squibb and others ; Clinical Trials.gov number , NCT00730639 . ) Treating advanced or recurrent melanoma remains a challenge . Cancer cells can evade the immune system by blocking T‐cell activation through overexpression of the inhibitory receptor programmed death 1 ( PD‐1 ) lig and s. The PD‐1 inhibitor nivolumab blocks the inhibitory signal in T cells , thus overcoming the immune resistance of cancer cells . Nivolumab has shown promising anticancer activity in various cancers . We carried out a single‐arm , open‐label , multicenter , phase II study to investigate the efficacy and safety of nivolumab in previously untreated Japanese patients with advanced melanoma . Twenty‐four patients with stage III/IV or recurrent melanoma were enrolled and received i.v . nivolumab 3 mg/kg every 2 weeks until disease progression or unacceptable toxicity . The primary endpoint was overall response rate evaluated by an independent radiology review committee . The independent radiology review committee‐assessed overall response rate was 34.8 % ( 90 % confidence interval , 20.8–51.9 ) , and the overall survival rate at 18 months was 56.5 % ( 90 % confidence interval , 38.0–71.4 ) . Treatment‐related adverse events ( AEs ) of grade 3 or 4 only occurred in three patients ( 12.5 % ) . Two patients discontinued nivolumab because of AEs , but all AEs were considered manageable by early diagnosis and appropriate treatment . Subgroup analyses showed that nivolumab was clinical ly beneficial and tolerable regardless of BRAF genotype , and that patients with treatment‐related select AEs and with vitiligo showed tendency for better survival . In conclusion , nivolumab showed favorable efficacy and safety profiles in Japanese patients with advanced or recurrent melanoma , with or without BRAF mutations . ( Trial registration no. JapicCTI‐142533 . Objectives To evaluate the prevalence and type of rheumatic immune-related adverse events ( irAEs ) in patients receiving immune checkpoint inhibitors ( ICIs ) , as well as the correlation with tumour response . Methods This was a single-centre prospect i ve observational study including all cancer patients receiving ICIs . The occurrence of irAEs and tumour response was assessed on a regular basis . Patients who experienced musculoskeletal symptoms were referred to the department of rheumatology for clinical evaluation and management . Results From September 2015 to May 2017 , 524 patients received ICIs and 35 were referred to the department of rheumatology ( 6.6 % ) . All but one of the rheumatic irAEs occurred with anti-programmed cell death protein 1(PD-1)/PD-1 lig and 1(PD-L1 ) antibodies , with a median exposure time of 70 days . There were two distinct clinical presentations : ( 1 ) inflammatory arthritis ( 3.8 % ) mimicking either rheumatoid arthritis ( n=7 ) , polymyalgia rheumatica ( n=11 ) or psoriatic arthritis ( n=2 ) and ( 2 ) non-inflammatory musculoskeletal conditions ( 2.8 % ; n=15 ) . One patient with rheumatoid arthritis was anti-cyclic citrullinated peptide ( anti-CCP ) positive . Nineteen patients required glucocorticoids , and methotrexate was started in two patients . Non-inflammatory disorders were managed with non-steroidal anti-inflammatory drugs , analgesics and /or physiotherapy . ICI treatment was pursued in all but one patient . Patients with rheumatic irAEs had a higher tumour response rate compared with patients without irAEs ( 85.7 % vs 35.3 % ; P<0.0001 ) . Conclusion Since ICIs are used with increasing frequency , knowledge of rheumatic irAEs and their management is of major interest . All patients were responsive either to low-to-moderate doses of prednisone or symptomatic therapies and did not require ICI discontinuation . Furthermore , tumour response was significantly higher in patients who experienced rheumatic irAEs Background Programmed cell death protein-1 ( PD-1 ) blockade therapies have demonstrated durable responses and prolonged survival in a variety of malignancies . Treatment is generally well tolerated although immune-related adverse events ( irAEs ) can occur . Autoimmune thyroid dysfunction is among the most common irAE , but an assessment of the clinical , mechanistic , and immunologic features has not been previously described . Patient and methods Patients with advanced non-small-cell lung cancer ( NSCLC ) treated with pembrolizumab at Memorial Sloan Kettering Cancer Center ( n = 51 ) as part of KEYNOTE-001 ( NCT01295827 ) were included . Thyroid function test and anti-thyroid antibodies were assessed prospect ively at each study visit , beginning before the first treatment . Frequency of development of thyroid dysfunction , association with anti-thyroid antibodies , clinical course , and relationship with progression-free survival and overall survival to treatment with pembrolizumab was evaluated . Results Of 51 patients treated , 3 were hypothyroid and 48 were not at baseline . Ten of 48 [ 21 % , 95 % confidence interval ( CI ) 10 % to 35 % ] patients developed thyroid dysfunction requiring thyroid replacement . Anti-thyroid antibodies were present in 8 of 10 patients who developed thyroid dysfunction , compared with 3 of 38 who did not ( 80 % versus 8 % , P < 0.0001 ) . Thyroid dysfunction occurred early ( median , 42 days ) in the pembrolizumab course , and a majority ( 6 of 10 patients ) experienced brief , transient hyperthyroidism preceding the onset of hypothyroidism ; no persistent hyperthyroidism occurred . Both hyperthyroidism and hypothyroidism were largely asymptomatic . Overall survival with pembrolizumab was significantly longer in subjects who developed thyroid dysfunction ( hazard ratio , 0.29 ; 95 % CI 0.09 - 0.94 ; P = 0.04 ) . Conclusions Thyroid dysfunction during pembrolizumab treatment of NSCLC is common and is characterized by early-onset , frequently preceded by transient hyperthyroidism , closely associated with anti-thyroid antibodies , and may be associated with improved outcomes . The presence of antibody-mediated toxicity in T-cell-directed therapy suggests an under-recognized impact of PD-1 biology in modulating humoral immunity BACKGROUND Atezolizumab is a humanised antiprogrammed death-lig and 1 ( PD-L1 ) monoclonal antibody that inhibits PD-L1 and programmed death-1 ( PD-1 ) and PD-L1 and B7 - 1 interactions , reinvigorating anticancer immunity . We assessed its efficacy and safety versus docetaxel in previously treated patients with non-small-cell lung cancer . METHODS We did a r and omised , open-label , phase 3 trial ( OAK ) in 194 academic or community oncology centres in 31 countries . We enrolled patients who had squamous or non-squamous non-small-cell lung cancer , were 18 years or older , had measurable disease per Response Evaluation Criteria in Solid Tumors , and had an Eastern Cooperative Oncology Group performance status of 0 or 1 . Patients had received one to two previous cytotoxic chemotherapy regimens ( one or more platinum based combination therapies ) for stage IIIB or IV non-small-cell lung cancer . Patients with a history of autoimmune disease and those who had received previous treatments with docetaxel , CD137 agonists , anti-CTLA4 , or therapies targeting the PD-L1 and PD-1 pathway were excluded . Patients were r and omly assigned ( 1:1 ) to intravenously receive either atezolizumab 1200 mg or docetaxel 75 mg/m2 every 3 weeks by permuted block r and omisation ( block size of eight ) via an interactive voice or web response system . Co primary endpoints were overall survival in the intention-to-treat ( ITT ) and PD-L1-expression population TC1/2/3 or IC1/2/3 ( ≥1 % PD-L1 on tumour cells or tumour-infiltrating immune cells ) . The primary efficacy analysis was done in the first 850 of 1225 enrolled patients . This study is registered with Clinical Trials.gov , number NCT02008227 . FINDINGS Between March 11 , 2014 , and April 29 , 2015 , 1225 patients were recruited . In the primary population , 425 patients were r and omly assigned to receive atezolizumab and 425 patients were assigned to receive docetaxel . Overall survival was significantly longer with atezolizumab in the ITT and PD-L1-expression population s. In the ITT population , overall survival was improved with atezolizumab compared with docetaxel ( median overall survival was 13·8 months [ 95 % CI 11·8 - 15·7 ] vs 9·6 months [ 8·6 - 11·2 ] ; hazard ratio [ HR ] 0·73 [ 95 % CI 0·62 - 0·87 ] , p=0·0003 ) . Overall survival in the TC1/2/3 or IC1/2/3 population was improved with atezolizumab ( n=241 ) compared with docetaxel ( n=222 ; median overall survival was 15·7 months [ 95 % CI 12·6 - 18·0 ] with atezolizumab vs 10·3 months [ 8·8 - 12·0 ] with docetaxel ; HR 0·74 [ 95 % CI 0·58 - 0·93 ] ; p=0·0102 ) . Patients in the PD-L1 low or undetectable subgroup ( TC0 and IC0 ) also had improved survival with atezolizumab ( median overall survival 12·6 months vs 8·9 months ; HR 0·75 [ 95 % CI 0·59 - 0·96 ] ) . Overall survival improvement was similar in patients with squamous ( HR 0·73 [ 95 % CI 0·54 - 0·98 ] ; n=112 in the atezolizumab group and n=110 in the docetaxel group ) or non-squamous ( 0·73 [ 0·60 - 0·89 ] ; n=313 and n=315 ) histology . Fewer patients had treatment-related grade 3 or 4 adverse events with atezolizumab ( 90 [ 15 % ] of 609 patients ) versus docetaxel ( 247 [ 43 % ] of Output:	In patients treated with ICIs , irAEs predict survival and response . Although this correlation can not be fully explained , it may be related to the strongest T-cell activation
MS213869	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: BACKGROUND Independent risk factors for surgical site infection ( SSI ) after cesarean section have not been well documented , despite the large number of cesarean sections performed and the relatively common occurrence of SSI . OBJECTIVE To determine independent risk factors for SSI after low transverse cesarean section . DESIGN Retrospective case-control study . SETTING Barnes-Jewish Hospital , a 1,250-bed tertiary care hospital . PATIENTS A total of 1,605 women who underwent low transverse cesarean section during the period from July 1999 to June 2001 . METHODS Using the International Classification of Diseases , Ninth Revision , Clinical Modification diagnosis codes for SSI or wound complication and /or data on antibiotic use during the surgical hospitalization or at readmission to the hospital or emergency department , we identified potential cases of SSI in a cohort of patients who underwent a low transverse cesarean section . Cases of SSI were verified by chart review using the definitions from the Centers for Disease Control and Prevention 's National Nosocomial Infections Surveillance System . Control patients without SSI or endomyometritis were r and omly selected from the population of patients who underwent cesarean section . Independent risk factors for SSI were determined by logistic regression . RESULTS SSIs were identified in 81 ( 5.0 % ) of 1,605 women who underwent low transverse cesarean section . Independent risk factors for SSI included development of subcutaneous hematoma after the procedure ( adjusted odds ratio [ aOR ] , 11.6 [ 95 % confidence interval [ CI ] , 4.1 - 33.2 ] ) , operation performed by the university teaching service ( aOR , 2.7 [ 95 % CI , 1.4 - 5.2 ] ) , and a higher body mass index at admission ( aOR , 1.1 [ 95 % CI , 1.0 - 1.1 ] ) . Cephalosporin therapy before or after the operation was associated with a significantly lower risk of SSI ( aOR , 0.2 [ 95 % CI , 0.1 - 0.5 ] ) . Use of staples for skin closure was associated with a marginally increased risk of SSI . CONCLUSIONS These independent risk factors should be incorporated into approaches for the prevention and surveillance of SSI after surgery OBJECTIVE The purpose of this prospect i ve study was to determine whether the timing of prophylactic antibiotics at cesarean delivery influences maternal/neonatal infectious morbidity . STUDY DESIGN In this double-blind placebo-controlled trial , cefazolin was given at skin incision ( group A ) or at cord clamping ( group B ) . Patients were eligible for the trial if they had labored and required a cesarean delivery . RESULTS Over a 30-month period 303 patients with singleton pregnancies entered the trial ; 153-group A , 149-group B. Demographics , indication for cesarean delivery ( P = .54 ) , and operative time ( P = .999 ) , as well as rates of endometritis ( RR 0.67 , 95 % CI 0.42 - 1.07 ) , wound infection ( RR 0.84 , 95 % CI 0.45 - 1.55 ) , neonatal sepis ( RR 1.28 , 95 % CI 0.91 - 1.79 ) , and NICU admissions ( RR 1.28 , 95 % CI 0.91 - 1.79 ) were similar between the 2 groups . CONCLUSION There was no difference in maternal infectious morbidity whether antibiotics were given before skin incision or at cord clamping In an ongoing prospect i ve study at 2 hospitals , 114 cesarean section patients were studied to determine whether giving ampicillin after umbilical cord clamping is as effective as perioperative ampicillin in reducing maternal postoperative morbidity . The same patients have also been studied to determine the effect of prophylactic cesarean section ampicillin on the newborn . Results have shown that prophylactic ampicillin initiated after cord clamping is as effective in reducing maternal morbidity as ampicillin initiated prior to the surgery . There is also no evidence from our study that the transplacental passage of prophylactic ampicillin increases immediate or delayed neonatal infections CONTEXT Perioperative antibiotic prophylaxis during elective cesarean delivery at term to reduce postoperative maternal infectious morbidity is generally used but may not be effective on the basis of the available data . Also , the optimal timing of prophylactic antibiotic administration is unclear . OBJECTIVE To compare the effectiveness of cefazolin administered before skin incision vs cefazolin administered after umbilical cord clamping vs placebo in a 3-arm r and omized trial . The primary objective of the study was to compare postoperative infectious morbidity , defined as wound infection , endometritis , or urinary tract infection ( primary end point ) , in women with cefazolin vs placebo . The comparison between the 2 arms administering cefazolin before skin incision vs after umbilical cord clamping was a secondary end point . DESIGN Double-blind , prospect i ve , r and omized , placebo-controlled trial . SETTING The Department of Obstetrics and Gynecology , Medical University of Vienna , Vienna , Austria . PATIENTS We recruited 1112 women undergoing elective cesarean delivery at term from March 1 , 2004 , through January 31 , 2010 . INTERVENTIONS In group 1 , cefazolin ( 2 g ) was administered 20 to 30 minutes before skin incision . In group 2 , cefazolin ( 2 g ) was administered immediately after clamping of the cord . In group 3 , placebo was administered before skin incision . RESULTS The primary outcome was observed in 18 of 370 women in group 1 ( 4.9 % ) and in 14 of 371 women in group 2 ( 3.8 % ) , whereas it was noted in 45 of 371 women in group 3 ( 12.1 % ) ( P < .001 for group 1 plus group 2 vs group 3 ) . The number needed to treat to avoid 1 primary outcome was 13 ( 95 % CI , 9 to 24 ) . Between groups 1 and 2 , there was no statistically significant difference regarding postoperative infectious morbidity ( P = .60 ) . CONCLUSION We were able to demonstrate the usefulness in elective cesarean delivery of prophylactic cefazolin vs placebo in reducing postoperative maternal infectious morbidity Objective The aim of this study was to determine whether the timing of prophylactic antibiotics at cesarean delivery influences maternal and neonatal infectious morbidity . Study design This was a prospect i ve , r and omized trial . Four hundred patients that underwent elective cesarean section between June and December 2007 formed the study population . Eleven patients were excluded from the study because they needed transfusion during the cesarean section . The population was divided into two groups : Group A , antibiotic prophylaxis was applied to 194 women before skin incision and Group B , antibiotic prophylaxis was applied to 195 women after umbilical cord clamping . The occurrence of endomyometritis/endometritis , wound infection , febrile morbidity , total infectious morbidity , and neonatal complications were compared . Results There were 389 patients enrolled . No demographic differences were observed between groups . No significant difference was found between the groups for total infectious morbidity [ relative risk ( RR ) 1.39 , 95 % confidence interval ( CI ) 0.71–2.69 ] and endometritis ( RR 1.40 , 95 % CI 0.43–4.51 ) . There was no increase in neonatal sepsis ( RR 1.47 , 95 % CI 0.61–3.53 ) , sepsis workup ( RR 1.35 , 95 % CI 0.75–2.42 ) , need for neonatal intensive care ( RR 1.77 , 95 % CI 0.51–6.16 ) , and intensive care stay period ( P = 0.16 ) . Conclusions Time of antibiotic prophylaxis application does not change maternal infectious morbidity in cesarean section deliveries . Preoperative prophylaxis application does not affect neonate morbidity rates as stated in literature OBJECTIVE To assess whether changing the entire surgical team 's gloves intraoperatively , after delivery of the placenta , would reduce the rate of postcesarean wound infection . STUDY DESIGN Women who underwent cesarean delivery were r and omized to a group where the surgical team changed the surgical gloves after delivery of the placenta or to a control group , where surgical gloves were not changed during the cesarean procedure . RESULTS Ninety-two patients were r and omized to 2 groups of 46 patients each . The group where the surgical team changed their gloves had significantly less serosanguineous drainage 24 hours after surgery ( 3 vs. 8 patients , 8.3 % vs. 22.2 % , P = .2 , RR 2.7 , CI 0.7 , 12.4 ) and fewer wound infections ( 2 vs. 9 women , 5.5 % vs. 25 % , P = .05 , RR 4.5 , CI 0.982 , 29.8 ) . CONCLUSION Obstetricians may decrease the number of postcesarean wound infections by having the entire team change surgical gloves after delivery of the placenta We compared maternal and neonatal outcomes in women who received prophylactic antibiotics prior to skin incision to those who received antibiotics at cord clamp . We performed a r and omized clinical trial at two sites . Eligible women included those undergoing nonemergency cesarean at 36 weeks ' gestation or greater . Subjects were r and omized ( permuted blocks ) into one of two treatments : " preoperative antibiotics " ( cefazolin 1 g given < 30 minutes prior to skin incision ) or " intraoperative antibiotics " ( cefazolin 1 g at cord clamping ) . Patients who reported an allergy to penicillin received clindamycin 900 mg . The trial primary outcome was a composite of maternal infectious morbidities , defined as having any one of the following : ( 1 ) postoperative fever ( defined as oral temperature > 38 ° C on two separate occasions more than 6 hours apart , after the initial 24-hour postoperative period ) ; ( 2 ) wound infection ( defined as purulent discharge from the incision ) ; ( 3 ) endomyometritis ( defined as fundal tenderness and fever malodorous lochia , fever ) ; ( 4 ) urinary tract infection ( defined as fever , positive urine culture ) . We enrolled a total of 434 subjects in this study , with 217 in each group . Overall , we found no difference in composite maternal infectious morbidity between those who received antibiotics preoperatively and those who received antibiotics at cord clamp ( relative risk = 1.2 , 95 % confidence interval 0.7 to 1.5 ) . Neonatal outcomes were also similar between the two intervention arms . The rate of suspected sepsis was similar between the two groups . There were no cases of antibiotic resistance in the neonates . Either preoperative antibiotic therapy or antibiotic administration after cord clamp is a reasonable clinical method for reducing the risk of postcesarean infectious morbidity The objective of this study was to test the hypothesis that 1 g of cefazolin administered preoperatively is no more effective than the same dose administered after cord clamping in preventing postcesarean infectious morbidity . Ninety consecutive laboring subjects undergoing cesarean delivery at > or = 37 weeks gestation were r and omized by computer to receive 1 g of cefazolin intravenously preoperatively or after cord clamping in a double-blinded , placebo-controlled study . The 2 groups were compared for differences in maternal and neonatal demographics , and intrapartum and operative characteristics associated with postcesarean infection . Primary maternal outcome variables were endometritis or wound infection . Secondary outcomes included intra-abdominal abscess formation , septic pelvic thrombophlebitis , pneumonia , or urinary tract infection . Neonatal outcomes included sepsis screens , sepsis , pneumonia , and meningitis . Subjects were followed 6 weeks postoperatively for late complications . Subjects receiving cefazolin preoperatively or after cord clamping had similar maternal and neonatal demographics , and intrapartum and operative characteristics . One patient in the former group experienced both endometritis and wound infection . In the latter group , 2 wound infections and 1 case of endometritis occurred ( P = 0.35 ) . There were no secondary maternal infections . Two infants treated for pneumonia and 2 other infants readmitted with febrile illnesses were born to mothers receiving cefazolin preoperatively . Overall , 8 neonates were evaluated for suspected sepsis and all had negative studies . Six of these infants ' mothers received cefazolin preoperatively ( P = 0.28 ) . In conclusion , 1 gram of cefazolin preoperatively is no more effective than the same dose administered after cord clamping in preventing postcesarean infectious morbidity , but is associated with a trend toward increased suspected sepsis in the newborn . However Output:	AUTHORS ' CONCLUSIONS Based on high quality evidence from studies whose overall risk of bias is low , intravenous prophylactic antibiotics for cesarean administered preoperatively significantly decreases the incidence of composite maternal postpartum infectious morbidity as compared with administration after cord clamp . There were no clear differences in adverse neonatal outcomes reported . Women undergoing cesarean delivery should receive antibiotic prophylaxis preoperatively to reduce maternal infectious morbidities .
MS213870	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: BACKGROUND Humeral shaft fractures account for 1 - 3 % of all fractures and 20 % of the fractures involving the humerus . The aim of the current study was to compare the outcome after operative and non-operative treatment of humeral shaft fractures , by comparing the time to radiological union and the rates of delayed union and complications . METHODS All patients aged 16 years or over treated for a humeral shaft fracture during a 5-year period were included in this retrospective analysis ; periprosthetic and pathological fractures were excluded . Radiographs and medical charts were retrieved and review ed in order to collect data on fracture classification , time to radiographic consolidation and the occurrence of adverse events . RESULTS A total of 186 patients were included ; 91 were treated non-operatively and 95 were treated operatively . Mean age was 58.7 ± 1.5 years and 57.0 % were female . In 83.3 % of the patients , only the humerus was affected . A fall from st and ing height was the most common cause of the fracture ( 72.0 % ) . Consolidation time varied from a median of 11 - 28 weeks . The rate of radial nerve palsy in both groups was similar : 8.8 % versus 9.5 % . In 5.3 % of the operatively treated patients , the palsy result ed from the operation . Likewise , delayed union rates were similar in both groups : 18.7 % following non-operative treatment versus 18.9 % following surgery . CONCLUSION The data indicated that consolidation time and complication rates were similar after operative and non-operative treatment . A prospect i ve r and omised clinical trial comparing non-operative with operative treatment is needed in order to examine other aspects of outcome , meaning shoulder and elbow function , postoperative infection rates , trauma-related quality of life and patient satisfaction Background : Nonoperative treatment has historically been considered the st and ard for fractures of the shaft of the humerus . Minimally invasive bridge-plate osteo synthesis for isolated humeral shaft fractures has been proven to be a safe technique , with good and reproducible results . This study was design ed to compare clinical and radiographic outcomes between patients who had been treated with bridge plate osteo synthesis and those who had been managed nonoperatively with a functional brace . Methods : A prospect i ve r and omized trial was design ed and included 110 patients allocated to 1 of 2 groups : surgery with a bridge plate or nonoperative treatment with a functional brace . The primary outcome was the Disabilities of the Arm , Shoulder and H and ( DASH ) score at 6 months . The score on the Short Form-36 ( SF-36 ) life- quality question naire , complications of treatment , Constant-Murley score for the shoulder , pain level , and radiographic results were assessed as secondary outcomes . Participants were assessed at 2 weeks ; 1 , 2 , and 6 months ; and 1 year after the interventions . Results : The mean DASH score of the bridge plate group was statistically superior to that of the functional brace group ( mean scores , 10.9 and 16.9 , respectively ; p = 0.046 ) only at 6 months . The bridge plate group also had a significantly more favorable nonunion rate ( 0 % versus 15 % ) and less mean residual angular displacement seen on the anteroposterior radiograph ( 2.0 ° versus 10.5 ° ) ( both p < 0.05 ) . No difference between the groups was detected with regard to the SF-36 score , pain level , Constant-Murley score , or angular displacement seen on the lateral radiograph . Conclusions : This trial demonstrates that , compared with functional bracing , surgical treatment with a bridge plate has a statistically significant advantage , of uncertain clinical benefit , with respect to self-reported outcome ( DASH score ) at 6 months , nonunion rate , and residual deformity in the coronal plane as seen on radiographs . Level of Evidence : Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence Background : Because of specific method ological difficulties in conducting r and omized trials , surgical research remains dependent predominantly on observational or non‐r and omized studies . Few vali date d instruments are available to determine the method ological quality of such studies either from the reader 's perspective or for the purpose of meta‐ analysis . The aim of the present study was to develop and vali date such an instrument BACKGROUND In the hierarchy of research design s , the results of r and omized , controlled trials are considered to be evidence of the highest grade , whereas observational studies are viewed as having less validity because they reportedly overestimate treatment effects . We used published meta-analyses to identify r and omized clinical trials and observational studies that examined the same clinical topics . We then compared the results of the original reports according to the type of research design . METHODS A search of the Medline data base for articles published in five major medical journals from 1991 to 1995 identified meta-analyses of r and omized , controlled trials and meta-analyses of either cohort or case-control studies that assessed the same intervention . For each of five topics , summary estimates and 95 percent confidence intervals were calculated on the basis of data from the individual r and omized , controlled trials and the individual observational studies . RESULTS For the five clinical topics and 99 reports evaluated , the average results of the observational studies were remarkably similar to those of the r and omized , controlled trials . For example , analysis of 13 r and omized , controlled trials of the effectiveness of bacille Calmette-Guérin vaccine in preventing active tuberculosis yielded a relative risk of 0.49 ( 95 percent confidence interval , 0.34 to 0.70 ) among vaccinated patients , as compared with an odds ratio of 0.50 ( 95 percent confidence interval , 0.39 to 0.65 ) from 10 case-control studies . In addition , the range of the point estimates for the effect of vaccination was wider for the r and omized , controlled trials ( 0.20 to 1.56 ) than for the observational studies ( 0.17 to 0.84 ) . CONCLUSIONS The results of well- design ed observational studies ( with either a cohort or a case-control design ) do not systematic ally overestimate the magnitude of the effects of treatment as compared with those in r and omized , controlled trials on the same topic PURPOSE The aim of this study is to examine the demographic factors , functional outcome and radiological data to predict the outcome of humeral diaphyseal fractures . METHODS We performed a prospect i ve study on a consecutive series of 110 patients of 16 years or over , who had sustained a humeral diaphyseal fracture . There were 42 males and 68 females , with an average age of 59 years ( range 16 - 93 years ) . A total of 72 % sustained low-energy injuries , and 89 patients ( 81 % ) were primarily treated non-operatively . Shoulder function was assessed using the Neer 's and Constant 's scores at 8 weeks , 3 months , 6 months and 1 year after injury . Muscle strength was determined isokinetically using a Biodex System 2 dynamometer . Non-union was defined as a failure to bridge at least three cortices and persistence of tenderness or mobility at the fracture site 16 weeks after fracture . RESULTS Sixteen patients ( 17 % ) had non-union at 16 weeks , while 80 had achieved union and a further 14 were lost to follow-up . After stepwise multiple linear regression was performed to isolate independent factors affecting outcome , only the presence of a proximal diaphyseal fracture was found to predict non-union along with a poor Neer 's score at 8 and 12 weeks . Poor Neer 's scores could be predicted at 26 weeks by age ( P<0.05 ) , previous stroke ( P<0.001 ) and non-union ( P<0.001 ) . At 52 weeks both age ( P<0.01 ) and previous stroke ( P<0.01 ) were independently predictive of poorer Neer 's scores . Malunion of any degree had no detectable effect on function . CONCLUSIONS Our results indicate that non-union of humeral diaphyseal fractures can be predicted in the presence of a proximal third fracture with a Neer 's score of less than 45 by 12 weeks after fracture . Early surgery improves early function , but this is not a lasting effect . Poor shoulder function is predicted by increasing age , proximal third fractures and non-union . We recommend that surgery to promote union be considered at 12 weeks after fracture in fit patients with fractures of the proximal third of the humerus , poor Neer 's scores and no radiographic progression to union Objective : The primary aim was to describe the epidemiology of the Holstein-Lewis humeral shaft fracture , its association with radial nerve palsy , and the outcome regarding recovery from the radial nerve palsy and fracture healing . The secondary aim was to analyze the long-term functional outcome . Setting : Six major hospitals in Stockholm County . Design : Descriptive study . Retrospective assessment of radial nerve recovery and fracture healing . Prospect i ve assessment of functional outcome . Patients : Twenty-seven patients with a 12A1.3 humeral shaft fracture according to the OTA classification satisfying the criteria of a Holstein-Lewis fracture in a population of 358 patients with 361 traumatic humeral shaft fractures . Intervention : Nonoperative or operative treatment according to the decision of the attending orthopaedic surgeon . Main Outcome Measurements : Recovery of the radial nerve , fracture healing , and functional outcome according to the Short Musculoskeletal Function Assessment ( SMFA ) . Results : The Holstein-Lewis humeral shaft fracture constitutes 7.5 % of all humeral shaft fractures and was associated with an increased risk of acute radial nerve palsy compared with other types of humeral shaft fractures , 22 % versus 8 % ( P < 0.05 ) . The fractures of 6 of the 7 operatively treated patients healed after the primary surgical procedure while 1 fracture healed after revision surgery . The fractures of all patients treated nonoperatively healed without any further intervention . All 6 radial nerve palsies ( 2 patients treated nonoperatively and 4 operatively ) recovered . The functional outcome according to the SMFA was good with no differences between the nonoperatively and operatively treated patients : SMFA dysfunction index 7.6 and 9.7 , respectively , and SMFA bother index 6.1 and 6.8 , respectively . Conclusions : The Holstein-Lewis humeral shaft fracture was associated with a significantly increased risk of acute radial nerve palsy . The overall outcome regarding fracture healing , radial nerve recovery , and function was very good regardless of the primary treatment modality , that is , operative or nonoperative treatment . The indication for primary operative intervention in this fracture type appears to be relative Summary . A comparison was made between 44 humeral fractures treated conservatively with functional bracing ( Group 1 ) and 45 treated by operation with a locking nail ( Group 2 ) . Thirty-eight of the 44 patients in Group 1 ( 86 % ) and 22 of the 45 patients in Group 2 ( 47 % ) regained full movement of the shoulder joint . The functional end results were somewhat better in Group 1 although over 90 % of patients in both groups were able to clasp their fingers behind their necks and to reach up their backs without restriction . Two patients developed a pseudarthrosis in Group 1 , and 2 patients in Group 2 required operative revision due to a haematoma in 1 case and as a result of an infection in the other . There were 6 cases of primary radial nerve damage in both groups , and 6 had to be decompressed operatively . Residual sensory and motor disturbance remained in 2 patients in Group 1 . Both methods are useful for the treatment of humeral shaft fractures . We advocate functional bracing as the method of choice if no contraindications exist . Résumé . 99 fractures de la diaphyse humérale ont été analysées , do nt 44 ont été traitées par brassard et 45 par clou intramédullaire . 86 % du groupe : traitement conservateur et 47 % du groupe : traitement opératoire présentaient un mouvement illimité de l’épaule , t and is que plus de 90 % des deux groupes arrivaient à toucher la nuque ( rotation externe en abduction ) et la sacrum ( rotation interne en adduction ) avec la main du bras blessé . Il y a eut deux pseudarthroses dans le groupe conservateur . Dans le groupe opératoire deux interventions chirurgicales ont été nécessaires en raison d’une infection et d’une hémorragie . Les deux groupes présentaient chacun 6 cas de paralysie primaire du nerf radial avec une décompression chirurgicale consécutive dans 6 cas . Des déficits moteurs et sensitifs persistaient chez deux malades du groupe conservateur . Les deux méthodes sont efficaces pour le traitement des fractures de la diaphyse de l’humérus . En cas d’absence des contre-indications nous recomm and ons le traitement par brassard comme traitement de premier choix BACKGROUND : For many years it has been cl aim ed that observational studies find stronger treatment effects than r and omized , controlled trials . We compared the results of observational studies with those of r and omized , controlled trials . METHODS : We search ed the Abridged Index Medicus and Cochrane data bases to identify observational studies reported between 1985 and 1998 that compared two or more treatments or interventions for the same condition . We then search ed the Medline and Cochrane data bases to identify all the r and omized , controlled trials and observational studies comparing the same treatments for these conditions . For Output:	There appeared to be no difference in mean time to union and mean Disabilities of the Arm , Shoulder and H and scores between the treatment groups . No difference was found between effect estimates form observational studies and RCTs . This systematic review shows that satisfactory results can be achieved with both conservative and operative management ; however , operative treatment reduces the risk of nonunion compared with conservative treatment , with comparable reintervention rates ( for indications other than nonunion ) . Furthermore , operative treatment results in a similar permanent radial nerve palsy rate , despite its inherent additional surgery-related risks .
MS213871	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: To assess quality of life and cost-effectiveness of additional acupuncture treatment for allergic rhinitis , patients were r and omly allocated to 2 groups ; both received usual care , but one group received an additional 10 acupuncture sessions . Quality of life ( according to the SF-36 Health Survey ) , and direct and indirect costs , were assessed at baseline and after 3 months , and the incremental cost-effectiveness ratio of acupuncture treatment was calculated . This German study ( December 2000-June 2004 ) involved 981 patients ( 64 % women , mean age 40.9 years ( st and ard deviation , 11.2 ) ; 36 % men , mean age 43.2 years ( st and ard deviation , 13.0 ) ) . At 3 months , quality of life was higher in the acupuncture group than in the control group ( mean Physical Component Score 51.99 ( st and ard error ( SE ) , 0.33 ) vs. 48.25 ( SE , 0.33 ) , P < 0.001 ; mean Mental Component Score 48.55 ( SE , 0.42 ) vs. 45.35 ( SE , 0.42 ) , respectively , P < 0.001 ) . Overall costs in the acupuncture group were significantly higher than those in the control group ( Euro ( euro ; 1 euro = US $ 1.27 ) 763 , 95 % confidence interval : 683 , 844 vs. 332 euro , 95 % confidence interval : 252 , 412 ; mean difference 432 euro , 95 % confidence interval : 318 , 545 ) . The incremental cost-effectiveness ratio was 17,377 euro per quality -adjusted life year ( women , 10,155 euro ; men , 44,871 euro ) and was robust in sensitivity analyses . Acupuncture , supplementary to routine care , was beneficial and , according to international benchmarks , cost-effective . However , because of the study design , it remains unclear whether the effects are acupuncture specific Asthma and rhinitis are common chronic conditions that affect adults of working age . Little is known about their relative impacts on work loss and decreased productivity . Using r and om digit telephone dialing , we carried out a population -survey of adults in Northern California aged 18 - 50 years . We interviewed 125 persons with asthma ( with or without concomitant rhinitis ) and 175 persons with rhinitis alone . Study eligibility was based on subject report of a physician 's diagnosis of asthma and /or a rhinitis-related condition . Any adult labor force participation since condition onset was lower among those with asthma ( 88 % ) than among those with rhinitis alone ( 97 % ) ( P = 0.002 ) . In contrast , among those still employed , decreased job effectiveness was more frequently reported in the rhinitis group ( 43 of 121 ; 36 % ) compared to those with asthma ( 14 of 72 ; 19 % ) ( P = 0.02 ) . Condition-attributed lost work was common in both groups , with more than 20 % reporting one or more complete or partial work days lost in the 4 weeks previous to interview . Taking into account age , gender , race , and smoking status , those with asthma were more likely to have no labor force participation after diagnosis ( OR = 3.0 ; 95 % CI 1.1 - 7.7 ) and less likely to report decreased job effectiveness among those remaining employed ( OR = 0.4 ; 95 % CI 0.2 - 0.9 ) . Excluding subjects from the rhinitis group most likely to have unreported asthma based on past medication use had little impact on these associations . Both asthma and rhinitis negatively affect work productivity . Those with asthma are less likely to be employed at all , while among those remaining on the job , rhinitis is a more potent cause of decreased work effectiveness . The economic impact of asthma and rhinitis and related conditions may be under-appreciated Background : Environmental control has been put forward as an integral part of the management of house dust mite ( HDM ) allergy in sensitized patients . To vali date this statement allergic disorders involved in HDM allergy – allergic asthma , rhinitis and atopic eczema/dermatitis syndrome ( AEDS ) – should be taken together and studied in terms of the efficacy of environmental control . Because a generic quality of life question naire exceeds the border of disease , this may be used as major outcome parameter Background Modification of allergens by glutaraldehyde in extracts used for immunotherapy reduces the risk for side effects , but therapeutic efficacy of such extracts requires further evaluation . The aim of this study was to evaluate the efficacy and safety of immunotherapy with PURETHAL Mites ( PM ) , a single-strength glutaraldehyde-modified aluminum hydroxide – adsorbed extract of house-dust mites ( HDM ) . Methods In a multicenter , r and omized , placebo-controlled double-blind setting , HDM-allergic subjects ( n = 140 ) were treated with modified allergen extract or placebo over a 1-year period . The primary outcome parameter was a combined symptom and medication score ( clinical index score [ CIS ] ) . Secondary efficacy parameters were the result of a titrated conjunctival provocation test ( CPT ) , rhinitis/rhinoconjunctivitis quality of life ( RQL ) score , and serum concentrations of IgE and IgG against specific HDM allergens and a documentation of adverse events ( AE ) . Results We evaluated 140 patients ( 66 treatment and 74 placebo ) for clinical efficacy . The allergoid treatment for 1 year result ed in significantly greater CIS improvement and higher RQL scores . The response threshold in the titrated CPT ( p = 0.009 ) and the serum concentrations of IgG4 ( p < 0.001 ) against Dermatophagoides pteronyssinus allergens after treatment were also significantly different between groups . In total , 88 patients ( 46 PM/42 placebo ) out of a safety population of 145 reported 278 ( 158 PM/120 placebo ) AE . Except for local reactions , no specific AE appeared to be associated with PURETHAL Mites ( HAL-Allergy , Leiden , The Netherl and s ) . Conclusion The findings of this study indicate that allergen injection therapy with modified HDM extract is superior to placebo in allergic rhinitis therapy . The treatment was well tolerated and no serious drug-related AE were observed The effect of cetirizine on quality of life ( QOL ) in subjects with perennial allergic rhinitis ( PAR ) has been previously evaluated using generic instruments . While generic QOL tools are used across various conditions , disease-specific instruments evaluate the impact of treatment on areas that are affected by that particular condition . This study evaluated the effect of cetirizine on symptom severity and health-related QOL , using a disease-specific instrument , in adults with PAR . This r and omized , double-blind , placebo-controlled study was conducted at 15 U.S. centers outside the pollen allergy season . After a 1-week placebo run-in period , qualified subjects aged 18 - 65 years with PAR were r and omized to once-daily cetirizine 10 mg ( n = 158 ) or placebo ( n = 163 ) for 4 weeks . Change from baseline in total symptom severity complex ( TSSC ) and overall Rhinitis Quality of Life Question naire ( RQLQ ) scores were primary efficacy end points . Cetirizine produced significantly greater improvements in mean TSSC for each treatment week ( p < 0.05 ) and for the entire 4-week treatment period ( p = 0.005 ) compared with placebo . After 4 weeks , cetirizine-treated subjects reported significantly greater overall improvement in RQLQ scores compared with placebo-treated subjects ( p = 0.004 ) . After 1 week , cetirizine produced significant improvements in the nasal symptoms , practical problems , and activities RQLQ domain scores compared with placebo ( p < 0.05 ) . After 4 weeks , cetirizine-treated subjects reported significant reductions in these RQLQ domain scores and in emotion domain scores compared with placebo-treated subjects ( p < 0.05 ) . Cetirizine 10 mg daily produced significant improvements in symptom severity and allergic rhinitis-related QOL compared with placebo in adults with PAR Objective To assess the efficacy of enzyme potentiated desensitisation in the treatment of severe summer hay fever poorly controlled by pharmacotherapy . Design Double blind r and omised placebo controlled parallel group study . Setting Hospital in Hampshire . Participants 183 participants aged between 18 and 64 with a history of severe summer hay fever for at least two years ; all were skin prick test positive to timothy grass pollen . 90 r and omised to active treatment ; 93 r and omised to placebo . Interventions Active treatment : two injections of enzyme potentiated desensitisation , given between eight and 11 weeks apart , each comprising 200 Fishman units of β glucuronidase , 50 pg 1,3-cyclohexanediol , 50 ng protamine sulphate , and a mixed inhaled allergen extract ( pollen mixes for trees , grasses , and weeds ; allergenic fungal spores ; cat and dog d and ers ; dust and storage mites ) in a total volume of 0.05 ml of buffered saline . Placebo : two injections of 0.05 ml buffered saline solution . Main outcome measures Proportion of problem-free days ; global rhinoconjunctivitis quality of life scores assessed weekly during pollen season . Results The active treatment group and the placebo group did not differ in the proportion of problem-free days , quality of life scores , symptom severity scores , change in quantitative skin prick provocation threshold , or change in conjunctival provocation threshold . No clinical ly significant adverse reactions occurred . Conclusions Enzyme potentiated desensitisation showed no treatment effect in this study Background Allergic Rhinitis is an inflammatory disease which is characterised by burdensome nasal and /or ocular symptoms . This study aim ed to assess the impact of symptoms ( number of symptom-free days ( SFD ) and Quality of Life ( QoL ) ) in patients with Seasonal Allergic Rhinitis ( SAR ) being treated with fluticasone furoate ( FF ) , mometasone furoate ( MF ) or fluticasone propionate ( FP ) . Methods In a cross-sectional , non-interventional , cohort analysis , primary care physicians and allergy specialists in France , Germany , and Spain were recruited via telephone interviews . Each physician prospect ively recruited 4 SAR patients - 2 receiving FF , 1 receiving MF and 1 receiving FP - during June 2009 . Patients answered questions on symptoms and completed question naires on QoL ( mini-rhinoconjunctivitis Quality of Life Question naire , RQLQ ) and burden of illness ( Pittsburgh Sleep Quality Index ) . Results A total of 540 patients were recruited during June 2009 . 88 patients were subsequently found to be ineligible and excluded from the analyses . In the 4 weeks prior to assessment , patients reported a mean of 14.58 ( ±8.42 ) SFD . Patients receiving FF had more SFD ( mean 15.45 ±8.29 ) than patients receiving MF ( adjusted mean difference -1.22 , 95 % Confidence Interval ( CI ) [ -3.16 to 0.72 ] , p=0.434 ) or FP ( adjusted mean difference -1.95 , 95 % CI [ -3.87 to -0.03 ] , p=0.092 ) , although statistical significance was not achieved . The mean RQLQ score was 1.54 ( ±1.06 ) . Patients receiving FF had a better quality of life in the previous week ( mini-RQLQ score : mean 1.42 , ±1.04 ) than patients receiving MF ( adjusted mean difference 0.28 , 95 % CI [ 0.03 to 0.52 ] , p=0.052 ) or FP ( adjusted mean difference 0.18 , 95 % CI [ -0.05 to 0.41 ] , p=0.244 ) . Again , none of these results achieved statistical significance . Conclusions At the height of the allergy season , patients with SAR suffer symptoms approximately 50 % of the time , and report an impact on their QoL. No significant differences were observed between FF , FP and MF related to SFD or QoL.Trial registration Clinical Trials.gov identifier : Background One fourth of the adult population in Europe suffer from respiratory allergy . Subcutaneous-allergen-specific-immunotherapy ( SCIT ) has long-term disease modifying effect on disease specific Health-Related Quality of Life ( HRQoL ) . The purpose of this study was to assess the effect of SCIT on alternative disease outcomes in patients with grass-pollen and /or house dust mite induced allergic rhino-conjunctivitis and /or an asthma diagnosis . Focus was on expressing outcomes in terms of generic quality of life ( Quality -Adjusted-Life-Years ( QALY ) ) and reductions in sick days . Methods The study was a multi-centre study with prospect i ve follow-up . 248 patients were initiated on SCIT . The disease specific Rhino-conjunctivitis Quality of Life Question naire ( RQLQ ) and two generic ( HRQoL ) instruments 15D and EQ-5D were used at baseline and at follow-up . The outcome measures included change in ; disease severity , RQLQ-scores , number of days with symptoms- Output:	Summary estimates obtained by meta- analysis showed that HRQL in patients with perennial HDM allergy was significantly worse than that of patients with seasonal pollen allergy , when measured by both disease-specific and generic HRQL instruments , and was reflected by an impact on both physical and mental health . A systematic review of cost data on AR and AA in selected European countries demonstrated that the majority of the economic burden was indirectly caused by high levels of absenteeism and presenteeism ; there was little or no evidence of increasing or decreasing cost trends .
MS213872	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: BACKGROUND Although early intubation to prevent the mortality that accompanies hypoxia is considered the st and ard of care for severe traumatic brain injury ( TBI ) , the efficacy of this approach remains unproven . METHODS Patients with moderate to severe TBI ( Head/Neck Abbreviated Injury Scale [ AIS ] score 3 + ) were identified from our county trauma registry . Logistic regression was used to explore the impact of prehospital intubation on outcome , controlling for age , gender , mechanism , Glasgow Coma Scale score , Head/Neck AIS score , Injury Severity Score , and hypotension . Neural network analysis was performed to identify patients predicted to benefit from prehospital intubation . RESULTS A total of 13,625 patients from five trauma centers were included ; overall mortality was 22.9 % , and 19.3 % underwent prehospital intubation . Logistic regression revealed an increase in mortality with prehospital intubation ( odds ratio , 0.36 ; 95 % confidence interval , 0.32 - 0.42 ; p < 0.001 ) . This was true for all patients , for those with severe TBI ( Head/Neck AIS score 4 + and /or Glasgow Coma Scale score of 3 - 8 ) , and with exclusion of patients transported by aeromedical crews . Patients intubated in the field versus the emergency department had worse outcomes . Neural network analysis identified a subgroup of patients with more significant injuries as potentially benefiting from prehospital intubation . CONCLUSION Prehospital intubation is associated with a decrease in survival among patients with moderate-to-severe TBI . More critically injured patients may benefit from prehospital intubation but may be difficult to identify prospect ively BACKGROUND Prehospital intubation and airway control is routinely performed by paramedics in critically injured patients . Despite the advantages provided by this procedure , numerous potential risks exist when this is performed in the field . We review ed the outcome of patients with severe head injury , to determine whether prehospital intubation is associated with an improved outcome . METHODS A retrospective review of registry data of patients admitted to an urban trauma center with severe head injury ( field Glasgow Coma Scale score of < or = 8 and head Abbreviated Injury Scale score of > or =3 ) was performed . Patients were stratified by methods of airway control performed by prehospital personnel : not intubated , intubated , or unsuccessful intubation . Mortality was determined for each group . To control for significant variables between these population s , matching and multivariate analysis were performed . RESULTS Patients requiring prehospital intubation or in whom intubation was attempted had an increased mortality ( 81 % and 77 % , respectively ) when compared with nonintubated patients ( 43 % ) . The mortality for patients who had prehospital intubation performed did not demonstrate an improved survival using matching . In fact , intubated patients had a significantly higher relative risk ( RR ) of mortality when compared with nonintubation ( RR = 1.74,p < 0.001 ) and unsuccessful intubation patients ( RR = 1.53 , p = 0.008 ) CONCLUSION For patients with severe head injury , prehospital intubation did not demonstrate an improvement in survival . Further prospect i ve r and omized trials are necessary to confirm these results The value of advanced prehospital life support for patients with severe trauma — for example , endotracheal intubation by ambulance staff — is unclear . Only one r and omised controlled trial was found among 2034 papers in a Cochrane review , concluding that advanced trauma life support by ambulance crews should be initiated only as part of rigorously conducted trials.1 A critical review also failed to show benefit and reported success rates for endotracheal intubation from 57 % to 92%.2 The review question ed whether prehospital staff could master the required skills . These review s focus on paramedic based systems . The helicopter emergency medical services in London is staffed by doctors ; the service studied 486 trauma patients OBJECTIVE To quantify the occurrence of arterial hypotension and arterial oxygen desaturation in a series of patients with head trauma rescued by helicopter . DESIGN Prospect i ve , observational study . MATERIAL S AND METHODS Arterial HbO2 was measured before tracheal intubation at the accident scene in 49 consecutive patients with head injuries . Arterial pressure was measured using a sphygmomanometer . MAIN RESULTS Mean arterial saturation was 81 % ( SD 24.24 ) ; mean arterial systolic pressure was 112 mm Hg ( SD 37.25 ) . Airway obstruction was detected in 22 cases . Twenty-seven patients showed an arterial saturation lower than 90 % on the scene , and 12 had a systolic arterial pressure of less than 100 mm Hg . The outcome was significantly worse in cases of hypotension , desaturation , or both . CONCLUSIONS Hypoxemia and shock are frequent findings on patients at the accident scene . Hypoxemia is more frequently detected and promptly corrected , white arterial hypotension is more difficult to control . Both insults may have a significant impact on outcome CONTEXT Endotracheal intubation ( ETI ) is widely used for airway management of children in the out-of-hospital setting , despite a lack of controlled trials demonstrating a positive effect on survival or neurological outcome . OBJECTIVE To compare the survival and neurological outcomes of pediatric patients treated with bag-valve-mask ventilation ( BVM ) with those of patients treated with BVM followed by ETI . DESIGN Controlled clinical trial , in which patients were assigned to interventions by calendar day from March 15 , 1994 , through January 1 , 1997 . SETTING Two large , urban , rapid-transport emergency medical services ( EMS ) systems . PARTICIPANTS A total of 830 consecutive patients aged 12 years or younger or estimated to weigh less than 40 kg who required airway management ; 820 were available for follow-up . INTERVENTIONS Patients were assigned to receive either BVM ( odd days ; n = 410 ) or BVM followed by ETI ( even days ; n = 420 ) . MAIN OUTCOME MEASURES Survival to hospital discharge and neurological status at discharge from an acute care hospital compared by treatment group . RESULTS There was no significant difference in survival between the BVM group ( 123/404 [ 30 % ] ) and the ETI group ( 110/416 [ 26 % ] ) ( odds ratio [ OR ] , 0.82 ; 95 % confidence interval [ CI ] , 0.61 - 1.11 ) or in the rate of achieving a good neurological outcome ( BVM , 92/404 [ 23 % ] vs ETI , 85/416 [ 20 % ] ) ( OR , 0.87 ; 95 % CI , 0.62 - 1.22 ) . CONCLUSION These results indicate that the addition of out-of-hospital ETI to a paramedic scope of practice that already includes BVM did not improve survival or neurological outcome of pediatric patients treated in an urban EMS system As triage and resuscitation protocol s evolve , it is critical to determine the major extracranial variables influencing outcome in the setting of severe head injury . We prospect ively studied the outcome from severe head injury ( GCS score < or = 8) in 717 cases in the Traumatic Coma Data Bank . We investigated the impact on outcome of hypotension ( SBP < 90 mm Hg ) and hypoxia ( Pao2 < or = 60 mm Hg or apnea or cyanosis in the field ) as secondary brain insults , occurring from injury through resuscitation . Hypoxia and hypotension were independently associated with significant increases in morbidity and mortality from severe head injury . Hypotension was profoundly detrimental , occurring in 34.6 % of these patients and associated with a 150 % increase in mortality . The increased morbidity and mortality related to severe trauma to an extracranial organ system appeared primarily attributable to associated hypotension . Improvements in trauma care delivery over the past decade have not markedly altered the adverse influence of hypotension . Hypoxia and hypotension are common and detrimental secondary brain insults . Hypotension , particularly , is a major determinant of outcome from severe head injury . Resuscitation protocol s for brain injured patients should assiduously avoid hypovolemic shock on an absolute basis OBJECTIVE Determine whether prehospital advanced life support ( ALS ) improves the survival of major trauma patients and whether it is associated with longer on-scene times . METHODS A 36-month retrospective study of all major trauma patients who received either prehospital bag-valve-mask ( BVM ) or endotracheal intubation ( ETI ) and were transported by paramedics to our Level I trauma center . Logistic regression analysis determined the association of prehospital ALS with patient survival . RESULTS Of 9,451 major trauma patients , 496 ( 5.3 % ) had either BVM or ETI . Eighty-one percent received BVM , with a mean Injury Severity Score of 29 and a mortality rate of 67 % ; 93 patients ( 19 % ) underwent successful ETI , with a mean Injury Severity Score of 35 and a mortality rate of 93 % . Adjusted survival for patients who had BVM was 5.3 times more likely than for patients who had ETI ( 95 % confidence interval , 2.3 - 14.2 , p = 0.00 ) . Survival among patients who received intravenous fluids was 3.9 times more likely than those who did not ( p = not significant ) . Average on-scene times for patients who had ETI or intravenous fluids were not significantly longer than those who had BVM or no intravenous fluids . CONCLUSION ALS procedures can be performed by paramedics on major trauma patients without prolonging on-scene time , but they do not seem to improve survival BACKGROUND Pre-hospital endotracheal intubation for the purpose of controlled ventilation may prevent secondary brain injury in patients with severe head injury . In view of the limited monitoring devices utilized in the pre-hospital setting , little is known about the ' quality ' of controlled ventilation initiated in the pre-hospital setting . METHODS Included in this prospect i ve study were 122 trauma patients with severe head injury ( abbreviated injury scale score > or = 3 ) . In all cases , the pre-hospital treatment included endotracheal intubation in the field . Upon hospital admission , and maintaining the same ventilation mode and setting initiated in the pre-hospital setting , arterial blood gas sample s were taken . RESULTS ' Optimal ' oxygenation ( PaO2 > 100 mm Hg ) was achieved in 85.2 % and ' adequate ' ventilation ( PaCO2 35 - 45 mm Hg ) in 42.6 % of the patients upon hospital admission . ' Optimal ' oxygenation as well as ' adequate ' ventilation was achieved in 37.7 % of the study population . Hypoxaemia ( PaO2 < 60 mm Hg ) was observed in 2.5 % , hypercapnia ( PaCO2 > 45 mm Hg ) in 16.4 % , and hypocapnia ( PaCO2 < 35 mm Hg ) in 40.9 % of the study patients . The incidence of hypocapnia was significantly more frequent in polytraumatized patients . Hypocapnia as well as hypercapnia was significantly more frequent in patients with associated pulmonary contusion . CONCLUSIONS Endotracheal intubation and controlled ventilation of the lungs initiated in the pre-hospital setting do not guarantee optimal oxygenaton and ventilation in patients with severe head injury STUDY OBJECTIVE We evaluate the ability of paramedic rapid sequence intubation ( RSI ) to facilitate intubation of patients with severe head injuries in an urban out-of-hospital system . METHODS Adult patients with head injuries were prospect ively enrolled over a 1-year period by using the following inclusion criteria : Glasgow Coma Scale score of 3 to 8 , transport time of greater than 10 minutes , and inability to intubate without RSI . Midazolam and succinylcholine were administered before laryngoscopy , and rocuronium was given after tube placement was confirmed by means of capnometry , syringe aspiration , and pulse oximetry . The Combitube was used as a salvage airway device . Outcome measures included intubation success rates , preintubation and postintubation oxygen saturation values , arrival arterial blood gas values , and total out-of-hospital times for patients intubated en route versus on scene . RESULTS Of 114 enrolled patients , 96 ( 84.2 % ) underwent successful endotracheal intubation , and 17 ( 14.9 % ) underwent Combitube intubation , with only 1 ( 0.9 % ) airway failure . There were no unrecognized esophageal intubations . On arrival at the trauma center , median oxygen saturation was 99 % , mean arrival PO2 was 307 mm Hg , and mean arrival PCO2 was 35.8 mm Hg . Total out-of-hospital times were higher when RSI was performed on scene ( 26 versus 13 minutes ) . CONCLUSION Paramedics can use RSI protocol s that include neuromuscular blocking and sedative agents to facilitate intubation of patients with head injuries OBJECTIVE To evaluate the effect of paramedic rapid sequence intubation ( RSI ) on outcome in patients with severe traumatic brain injury . METHODS Adult major trauma victims were prospect ively enrolled over two years using the following inclusion criteria : Glasgow Coma Scale ( GCS Output:	CONCLUSIONS Overall , the available evidence did not support any benefit from pre-hospital intubation and mechanical ventilation after TBI .
MS213873	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Despite many pharmacological and psychosocial treatment options , schizophrenia remains a debilitating disorder . Thus , new treatment strategies rooted in the pathophysiology of the disorder are needed . Recently , vagus nerve stimulation ( VNS ) has been proposed as a potential treatment option for various neuropsychiatric disorders including schizophrenia . The objective of this study was to investigate for the first time the feasibility , safety and efficacy of transcutaneous VNS in stable schizophrenia . A bicentric r and omized , sham-controlled , double-blind trial was conducted from 2010 to 2012 . Twenty schizophrenia patients were r and omly assigned to one of two treatment groups . The first group ( active tVNS ) received daily active stimulation of the left auricle for 26 weeks . The second group ( sham tVNS ) received daily sham stimulation for 12 weeks followed by 14 weeks of active stimulation . Primary outcome was defined as change in the Positive and Negative Symptom Scale total score between baseline and week 12 . Various other secondary measures were assessed to investigate safety and efficacy . The intervention was well tolerated with no relevant adverse effects . We could not observe a statistically significant difference in the improvement of schizophrenia psychopathology during the observation period . Neither psychopathological and neurocognitive measures nor safety measures showed significant differences between study groups . Application of tVNS was well tolerated , but did not improve schizophrenia symptoms in our 26-week trial . While unsatisfactory compliance questions the feasibility of patient-controlled neurostimulation in schizophrenia , the overall pattern of symptom change might warrant further investigations in this population BACKGROUND The need for effective , long-term treatment for recurrent or chronic , treatment-resistant depression is well established . METHODS This naturalistic follow-up describes out patients with nonpsychotic major depressive ( n = 185 ) or bipolar ( I or II ) disorder , depressed phase ( n = 20 ) who initially received 10 weeks of active ( n = 110 ) or sham vagus nerve stimulation ( VNS ) ( n = 95 ) . The initial active group received another 9 months , while the initial sham group received 12 months of VNS . Participants received antidepressant treatments and VNS , both of which could be adjusted . RESULTS The primary analysis ( repeated measures linear regression ) revealed a significant reduction in 24-item Hamilton Rating Scale for Depression ( HRSD(24 ) ) scores ( average improvement , .45 points [ SE = .05 ] per month ( p < .001 ) . At exit , HRSD(24 ) response rate was 27.2 % ( 55/202 ) ; remission rate ( HRSD(24 ) < or = 9 ) was 15.8 % ( 32/202 ) . Montgomery Asberg Depression Rating Scale ( 28.2 % [ 57/202 ] ) and Clinical Global Impression-Improvement ( 34.0 % [ 68/200 ] ) showed similar response rates . Voice alteration , dyspnea , and neck pain were the most frequently reported adverse events . CONCLUSIONS These 1-year open trial data found VNS to be well tolerated , suggesting a potential long-term , growing benefit in treatment-resistant depression , albeit in the context of changes in depression treatments . Comparative long-term data are needed to determine whether these benefits can be attributed to VNS OBJECTIVE To describe the outcomes of a consecutive series of depressed patients treated with vagus nerve stimulation ( VNS ) following US Food and Drug Administration ( FDA ) approval of this intervention . METHOD We implanted a VNS device in 15 consecutive out patients with treatment-resistant major depressive episodes , including 10 with major depressive disorder and 5 with bipolar disorder ( DSM-IV criteria ) , between November 2005 and August 2006 . Existing antidepressant treatment remained fixed as far as clinical ly possible . The primary outcome was change from baseline in the Beck Depression Inventory ( BDI ) score . Outcomes were assessed at 6 and 12 months postimplant and compared to those of the VNS pivotal efficacy trial that led to FDA approval of VNS . RESULTS The BDI score decreased significantly compared to baseline at 6 months ( P < .05 ) and 12 months ( P < .01 ) , from a mean of 37.8 ( SD = 7.8 ) before VNS activation to a mean of 24.6 ( SD = 11.4 ) at 12 months . By 1 year , 28.6 % ( n = 4 ) of the sample responded to VNS and 7.1 % ( n = 1 ) remitted according to the BDI . Secondary outcomes on the Hamilton Depression Rating Scale 24-Item showed similar improvement at 1 year , with a 43 % response rate ( n = 6 ) and 14.3 % remission rate ( n = 2 ) . No obvious predictors of response were detected . Side effects of VNS included hoarseness ( 73 % ) , dyspnea ( 47 % ) , nausea ( 40 % ) , pain ( 33 % ) , and anxiety ( 20 % ) ; no patient terminated treatment due to intolerable side effects . CONCLUSIONS We found that a substantial minority of patients with extremely difficult-to-treat depressive disorders benefited from VNS in an ambulatory clinical practice , with outcomes comparable to those observed in previous VNS efficacy studies and with a similar side effect profile BACKGROUND Major depressive disorder is a prevalent , disabling , and often chronic or recurrent psychiatric condition . About 35 % of patients fail to respond to conventional treatment approaches and are considered to have treatment-resistant depression ( TRD ) . OBJECTIVE We compared the safety and effectiveness of different stimulation levels of adjunctive vagus nerve stimulation ( VNS ) therapy for the treatment of TRD . METHODS In a multicenter , double blind study , 331 patients with TRD were r and omized to one of three dose groups : LOW ( 0.25 mA current , 130 μs pulse width ) , MEDIUM ( 0.5 - 1.0 mA , 250 μs ) , or HIGH ( 1.25 - 1.5 mA , 250 μs ) . A highly treatment-resistant population ( > 97 % had failed to respond to ≥6 previous treatments ) was enrolled . Response and adverse effects were assessed for 22 weeks ( end of acute phase ) , after which output current could be increased , if clinical ly warranted . Assessment s then continued until Week 50 ( end of long-term phase ) . RESULTS VNS therapy was well tolerated . During the acute phase , all groups showed statistically significant improvement on the primary efficacy endpoint ( change in Inventory of Depressive Symptomatology-Clinician Administered Version [ IDS-C ] ) , but not for any between-treatment group comparisons . In the long-term phase , mean change in IDS-C scores showed continued improvement . Post-hoc analyses demonstrated a statistically significant correlation between total charge delivered per day and decreasing depressive symptoms ; and analysis of acute phase responders demonstrated significantly greater durability of response at MEDIUM and HIGH doses than at the LOW dose . CONCLUSIONS TRD patients who received adjunctive VNS showed significant improvement at study endpoint compared with baseline , and the effect was durable over 1 year . Higher electrical dose parameters were associated with response durability BACKGROUND Chronic vagus nerve stimulation ( VNS ) is effective in the management of treatment-resistant epilepsy . Open-trial evidence suggests that VNS has clinical ly significant antidepressant effects in some individuals who experience treatment-resistant major depressive episodes . However , limited information regarding the effects of VNS on neurocognitive performance exists . OBJECTIVE The primary aim of this study was to determine whether VNS leads to neurocognitive deterioration . METHOD A neuropsychological battery was administered to 27 patients with treatment-resistant depression before and after 10 weeks of VNS . Thirteen neurocognitive tests sample d the domains of motor speed , psychomotor function , language , attention , memory , and executive function . RESULTS No evidence of deterioration in any neurocognitive measure was detected . Relative to baseline , improvement in motor speed ( finger tapping ) , psychomotor function ( digit-symbol test ) , language ( verbal fluency ) , and executive functions ( logical reasoning , working memory , response inhibition , or impulsiveness ) was found . For some measures , improved neurocognitive performance correlated with the extent of reduction in depressive symptoms , but VNS output current was not related to changes in cognitive performance . CONCLUSIONS Vagus nerve stimulation in treatment-resistant depression may result in enhanced neurocognitive function , primarily among patients who show clinical improvement . Controlled investigation is needed to rule out the contribution of practice effects This open pilot study of vagus nerve stimulation ( VNS ™ ) in 60 patients with treatment-resistant major depressive episodes ( MDEs ) aim ed to : 1 ) define the response rate ; 2 ) determine the profile of side effects ; and , most importantly ; 3 ) establish predictors of clinical outcome . Participants were out patients with nonatypical , nonpsychotic , major depressive or bipolar disorder who had not responded to at least two medication trials from different antidepressant classes in the current MDE . While on stable medication regimens , the patients completed a baseline period followed by device implantation . A 2-week , single blind , recovery period ( no stimulation ) was followed by 10 weeks of VNS . Of 59 completers ( one patient improved during the recovery period ) , the response rate was 30.5 % for the primary HRSD28 measure , 34.0 % for the Montgomery-Äsberg Depression Rating Scale ( MADRAS ) , and 37.3 % for the Clinical Global Impression-Improvement Score ( CGI-I of 1 or 2 ) . The most common side effect was voice alteration or hoarseness , 55.0 % ( 33/60 ) , which was generally mild and related to output current intensity . History of treatment resistance was predictive of VNS outcome . Patients who had never received ECT ( lifetime ) were 3.9 times more likely to respond . Of the 13 patients who had not responded to more than seven adequate antidepressant trials in the current MDE , none responded , compared to 39.1 % of the remaining 46 patients ( p = .0057 ) . Thus , VNS appears to be most effective in patients with low to moderate , but not extreme , antidepressant resistance . Evidence concerning VNS ' long-term therapeutic benefits and tolerability will be critical in determining its role in treatment-resistant depression AIM The purpose of this study was to evaluate the efficacy of vagus nerve stimulation ( VNS ) as a therapeutic option for treatment-resistant depression ( TRD ) , with follow-up periods of 1 , 3 and 5 years after VNS surgery . METHODS We examined 27 consecutive patients with unipolar TRD . Depressive symptoms were evaluated both at baseline and at follow-up after the surgery by means of the 21-item Hamilton Rating Scale for Depression ( HAM-D 21 ) . RESULTS The mean HAM-D preoperative score was 25.6 . Twenty-two patients were evaluated after 1 year of treatment , and the mean improvement of the HAM-D score was of 10.3 . Five patients ( 20 % ) went into complete remission ( HAM-D < 7 ) after 1 year , six patients ( 22.3 % ) were considered responders ( 50 % reduction of HAM-D scoring ) and eight patients had score reduction of less then 20 % . Nineteen patients were evaluated after 24–36 months : the average improvement on the HAM-D score was of 12.1 points ( 47.2 % ) . One patient went into complete remission and eight patients ( 42.1 % ) were responders . Up to the present date , seven patients have undergone re-evaluation at 48–60 months from surgery showing an average score reduction of 14.2 . Two more patients obtained complete remission , while four of them did not have any improvement since their last follow-up control visit . CONCLUSION VNS antidepressant was successful in 20 % of TRD patients , although some patients required several months to obtain clinical improvement or remission of symptomatology . Nonetheless this procedure can be considered as a useful option in treating TRD BACKGROUND Vagus nerve stimulation ( VNS ) alters both concentrations of neurotransmitters or their metabolites and functional activity of central nervous system regions dysregulated in mood disorders . An open trial has suggested efficacy . METHODS This 10-week , acute , r and omized , controlled , masked trial compared adjunctive VNS with sham treatment in 235 out patients with nonpsychotic major depressive disorder ( n = 210 ) or nonpsychotic , depressed phase , bipolar disorder ( n = 25 ) . In the current episode , participants had not responded adequately to between two and six research -qualified medication trials . A two-week , single-blind recovery period ( no stimulation ) and then 10 weeks of masked active or sham VNS followed implantation . Medications were kept stable . Primary efficacy outcome among 222 evaluable participants was based on response rates ( > /=50 % reduction from baseline on the 24-item Hamilton Rating Scale for Depression [ HRSD(24 ) ] ) . RESULTS At 10-weeks , HRSD(24 ) response rates were 15.2 % for the active ( n = 112 ) and 10.0 % for the sham ( n = 110 ) groups Output:	At this point , no final conclusion can be made regarding the efficacy of VNS to improve symptoms in psychiatric disorders other than in affective disorders
MS213874	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: OBJECTIVE To study the pharmacodynamic properties of the subcutaneously injected long-acting insulin analog HOE901 ( 30 microg/ml zinc ) in comparison with those of NPH insulin and placebo . RESEARCH DESIGN AND METHODS In this single-center double-blind euglycemic glucose clamp study , 15 healthy male volunteers ( aged 27 + /- 4 years , BMI 22.2 + /- 1.8 kg/m2 ) received single subcutaneous injections of 0.4 U/kg body wt of HOE901 , NPH insulin , or placebo on 3 study days in a r and omized order . The necessary glucose infusion rates ( GIRs ) to keep blood glucose concentrations constant at 5.0 mmol/l were determined over a 30-h period after administration . RESULTS The injection of HOE901 did not induce the pronounced peak in metabolic activity observed with NPH insulin ( GIRmax 5.3 + /- 1.1 vs. 7.7 + /- 1.3 mg x kg(-1 ) x min(-1 ) ) ( P < 0.05 ) ; after an initial rise , metabolic activity was rather constant over the study period . This lack of peak was confirmed by a lower glucose consumption in the first 4 h after injection ( area under the curve from 0 to 4 h [ AUC(0 - 4 h ) ] 1.02 + /- 0.34 vs. 1.48 + /- 0.34 g/kg ) ( P < 0.001 ) with HOE901 , as compared with NPH insulin . In this single-dose study , the metabolic effect measured over a period of 30 h was lower with HOE901 than with NPH insulin ( AUC(0 - 30 h ) 7.93 + /- 1.82 vs. 9.24 + /- 1.29 g/kg ) ( P < 0.05 ) . CONCLUSIONS This study shows that the soluble long-acting insulin analog HOE901 induces a smoother metabolic effect than NPH insulin , from which a better substitution of basal insulin requirements may follow Insulin glulisine is appealing in principle , but the advantages of this drug over the other rapid-acting insulin analogs are still relatively unknown . The frequency of hypoglycemia , convenience in the timing of administration , and improvements in terms of HbA1c seem similar among the rapid-acting insulin analogs , including insulin glulisine . Only properly r and omized long-term clinical studies with insulin glulisine will reveal the true value of this novel insulin analog AIMS The IMPROVE observational study evaluated the safety profile and effectiveness of biphasic insulin aspart 30/70 ( BIAsp 30 ) in patients with type 2 diabetes in routine practice in 11 countries . METHODS Patients who initiated insulin therapy with , or switched existing insulin therapy to , BIAsp 30 in routine care were eligible for this 26-week , non-interventional observational study . Data on adverse events , hypoglycaemia and glycaemic parameters were obtained from patients ' diaries and medical notes . Question naire-based patient treatment satisfaction was also measured . We report global results and , uniquely for a diabetes observational study , country-specific data . RESULTS A total of 52,419 patients were enrolled from three pre study treatment groups : no pharmaceutical therapy ( n = 8966 , diabetes duration 2.0 years , baseline HbA1c 9.9 % ) , oral antidiabetic drugs ( OADs ) only ( n = 33,797 , diabetes duration 7.4 years , baseline HbA1c 9.2 % ) and insulin + /- OADs ( n = 9568 , diabetes duration 10.4 years , baseline HbA1c 9.3 % ) . At final visit , HbA1c , fasting and postpr and ial blood glucose were significantly reduced from baseline in all subgroups ( no pharmaceutical therapy : -3.1 % , -5.9 and -9.0 mmol/l , respectively ; OADs-only : -2.1 % , -4.1 and -6.1 mmol/l ; insulin + /- OADs : -2.0 % , -3.3 and -5.1 mmol/l ) . Major hypoglycaemia rates decreased in all subgroups ; minor hypoglycaemia increased in the insulin-naïve groups . There was no mean weight gain across subgroups . Across all countries , glycaemic parameters and major hypoglycaemia were reduced ; weight increases were seen in some countries . Treatment satisfaction increased in all subgroups and countries following BIAsp 30 therapy . CONCLUSIONS Initiating insulin with , or switching insulin therapy to , BIAsp 30 in routine care result ed in improved glycaemic control , reduced major hypoglycaemia and greater treatment satisfaction OBJECTIVE Insulin degludec ( IDeg ) is a basal insulin that forms soluble multihexamers after subcutaneous injection , result ing in an ultra-long action profile . We assessed the efficacy and safety of IDeg formulations administered once daily in combination with mealtime insulin aspart in people with type 1 diabetes . RESEARCH DESIGN AND METHODS In this 16-week , r and omized , open-label trial , participants ( mean : 45.8 years old , A1C 8.4 % , fasting plasma glucose [ FPG ] 9.9 mmol/L , BMI 26.9 kg/m2 ) received subcutaneous injections of IDeg(A ) ( 600 μmol/L ; n = 59 ) , IDeg(B ) ( 900 μmol/L ; n = 60 ) , or insulin glargine ( IGlar ; n = 59 ) , all given once daily in the evening . Insulin aspart was administered at mealtimes . RESULTS At 16 weeks , mean A1C was comparable for IDeg(A ) ( 7.8 ± 0.8 % ) , IDeg(B ) ( 8.0 ± 1.0 % ) , and IGlar ( 7.6 ± 0.8 % ) , as was FPG ( 8.3 ± 4.0 , 8.3 ± 2.8 , and 8.9 ± 3.5 mmol/L , respectively ) . Estimated mean rates of confirmed hypoglycemia were 28 % lower for IDeg(A ) compared with IGlar ( rate ratio [ RR ] : 0.72 [ 95 % CI 0.52–1.00 ] ) and 10 % lower for IDeg(B ) compared with IGlar ( RR : 0.90 [ 0.65–1.24 ] ) ; rates of nocturnal hypoglycemia were 58 % lower for IDeg(A ) ( RR : 0.42 [ 0.25–0.69 ] ) and 29 % lower for IDeg(B ) ( RR : 0.71 [ 0.44–1.16 ] ) . Mean total daily insulin dose was similar to baseline . The frequency and pattern of adverse events was similar between insulin treatments . CONCLUSIONS In this clinical exploratory phase 2 trial in people with type 1 diabetes , IDeg is safe and well tolerated and provides comparable glycemic control to IGlar at similar doses , with reduced rates of hypoglycemia Aims /hypothesisThe aim of the trial was to compare the efficacy and tolerability of two types of basal-bolus therapy , using either the soluble long-acting basal insulin analogue , insulin detemir , in combination with the rapid-acting analogue , insulin aspart , or NPH insulin in combination with mealtime regular human insulin . Methods In this 18-week , 1:1 r and omised , open-labelled , parallel trial , 595 patients with Type 1 diabetes mellitus received insulin detemir or NPH insulin in the morning and at bedtime in combination with mealtime insulin aspart or regular human insulin respectively . Results Glycaemic control with insulin detemir/insulin aspart was improved in comparison with NPH insulin/regular human insulin ( HbA1c : 7.88 % vs 8.11 % ; mean difference : −0.22 % point [ 95 % CI : −0.34 to −0.10 ] ; p<0.001 ) . Self-measured 8-point plasma glucose profiles differed between the groups ( p<0.001 ) , with lower postpr and ial plasma glucose levels in the insulin detemir/insulin aspart group . Within-person day-to-day variation in plasma glucose was lower with insulin detemir/insulin aspart than with NPH insulin/regular human insulin ( SD : 2.88 vs 3.12 mmol/l ; p<0.001 ) . Risk of overall and nocturnal hypoglycaemia ( 23.00–06.00 hours ) was , respectively , 21 % ( p=0.036 ) and 55 % ( p<0.001 ) lower in the insulin detemir/insulin aspart group than in the NPH insulin/regular human insulin group . Body weight ( adjusted for baseline and change in HbA1c ) was 1 kg lower with insulin detemir/insulin aspart than with NPH insulin/regular human insulin ( p<0.001 ) . Conclusions /interpretationBasal-bolus therapy using insulin detemir/insulin aspart offers a better balance of control and tolerability than with NPH insulin/regular human insulin . The low variability and more physiological action profiles generated with these insulin analogues result ed in improved glycaemic control with lower risk of hypoglycaemia and no concomitant body weight increase BACKGROUND The positive association between obesity and postmenopausal breast cancer has been attributed , in part , to the fact that estrogen , a risk factor for breast cancer , is synthesized in adipose tissue . Obesity is also associated with high levels of insulin , a known mitogen . However , no prospect i ve studies have directly assessed associations between circulating levels of insulin and /or insulin-like growth factor (IGF)-I , a related hormone , and the risk of breast cancer independent of estrogen level . METHODS We conducted a case-cohort study of incident breast cancer among nondiabetic women who were enrolled in the Women 's Health Initiative Observational Study ( WHI-OS ) , a prospect i ve cohort of 93,676 postmenopausal women . Fasting serum sample s obtained at study entry from 835 incident breast cancer case subjects and from a subcohort of 816 r and omly chosen WHI-OS subjects were tested for levels of insulin , glucose , total IGF-I , free IGF-I , insulin-like growth factor binding protein-3 , and estradiol . Multivariable Cox proportional hazards models were used to estimate associations between levels of the serologic factors and baseline characteristics ( including body mass index [ BMI ] ) and the risk of breast cancer . All statistical tests were two-sided . Results Insulin levels were positively associated with the risk of breast cancer ( hazard ratio [ HR ] for highest vs lowest quartile of insulin level = 1.46 , 95 % confidence interval [ CI ] = 1.00 to 2.13 , P(trend ) = .02 ) ; however , the association with insulin level varied by hormone therapy ( HT ) use ( P(interaction ) = .01 ) . In a model that controlled for multiple breast cancer risk factors including estradiol , insulin level was associated with breast cancer only among nonusers of HT ( HR for highest vs lowest quartile of insulin level = 2.40 , 95 % CI = 1.30 to 4.41 , P(trend ) < .001 ) . Obesity ( BMI > or=30 kg/m(2 ) ) was also associated with the risk of breast cancer among nonusers of HT ( HR for BMI > or=30 kg/m(2 ) vs 18.5 to < 25 kg/m(2 ) = 2.12 , 95 % CI = 1.26 to 3.58 , P(trend ) = .003 ) ; however , this association was attenuated by adjustment for insulin ( P(trend ) = .40 ) . CONCLUSION These data suggest that hyperinsulinemia is an independent risk factor for breast cancer and may have a substantial role in explaining the obesity-breast cancer relationship Insulin detemir is an analog of human insulin design ed to provide a long duration of basal insulin action . This is achieved by protracted absorption from the injection depot , which results in part from increased self-association of insulin detemir molecules and in part from reversible albumin binding . Subsequent albumin binding in the circulation is thought to buffer changes in the effects at target tissues that could otherwise arise from variability in absorption rate . In consequence , insulin detemir has shown a less variable pharmacodynamic profile than alternative basal insulins ; this manifests as more consistent temporal glucose reduction profiles in repeat-clamp studies . In clinical trials , insulin detemir has been characterized by consistent risk reductions in hypoglycemia , as well as reduced weight gain in comparison with other basal insulins . Given some recent associations that have been made in Output:	Results While the discovery of animal insulin significantly decreased mortality rates from diabetes , issues with availability and large variability between batches led to difficulty in determining proper doses and , subsequently , challenges in achieving glycemic control and avoiding hypoglycemia . The development of synthetic insulin created a more readily available supply , but hypoglycemia still persisted . Recombinant DNA technology solved insulin production problems and allowed for the development of better retarding agents , but pharmacokinetic/pharmacodynamic profiles still did not mimic natural insulin . Insulin premixes offered improved glycemic control , decreased intrapatient variability versus self-mixing , and required fewer injections per day ; however , patient adherence remained a problem due to the need to inject 30–60 minutes before a meal for optimal control . This prompted the development of rapid-acting insulin analogs that could be injected right before a meal and long-acting insulin analogs with flatter time-action profiles . Newer insulin analogs and more convenient routes of insulin delivery have shown promising safety and efficacy results .
MS213875	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: BACKGROUND In a multicenter , r and omized , open-label phase III study , patients ≥ 65 years with newly diagnosed AML received decitabine 20 mg/m(2 ) once daily for 5 days every 4 weeks ( n = 242 ) or treatment choice ( supportive care or cytarabine 20 mg/m(2 ) once daily for 10 days every 4 weeks ; n = 243 ) . Decitabine use demonstrated greater response rates ( P = .001 ) and OS data favored decitabine . PATIENTS AND METHODS In a post hoc sensitivity analysis of mature data of patients in the intent-to-treat population ( N = 485 ) , OS at 3 , 6 , 12 , 18 , and 24 months after r and omization was estimated for each arm using Kaplan-Meier methods . Age , cytogenetic risk , and Eastern Cooperative Oncology Group performance status were used as stratification factors in the Cox regression model to estimate the hazard ratio . RESULTS A survival advantage was seen with decitabine at each cutoff time point ; hazard ratios for OS for decitabine vs. treatment choice were 0.83 , 0.71 , 0.83 , 0.80 , and 0.79 at 3 , 6 , 12 , 18 , and 24 months , respectively . A trend toward improved OS with decitabine was observed at fixed time points over 2 years . CONCLUSION Decitabine should be considered as a treatment option for older patients with AML and poor prognostic risk factors Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more Introduction . The incidence of Acute Myeloid Leukemia ( AML ) increases progressively with age and its treatment is challenging . This prospect i ve case control study was undertaken to compare the safety , efficacy , and cost-effectiveness of decitabine with those of cytarabine in older patients with newly diagnosed AML who are not fit for intensive chemotherapy . Material s and Methods . 30 eligible patients above 60 years old with newly diagnosed AML were assigned to receive decitabine or cytarabine . The primary end point was overall survival ( OS ) . The secondary objective was to compare adverse events and cost-effectiveness of therapy in the two study groups . Results . In this study , 15 patients received decitabine and 15 patients received cytarabine . The median OS was 5.5 months for each of the treatment groups . The hazard ratio between the treatment groups was 0.811 with 95 % CI of 0.390 to 1.687 . Toxicity profile was similar in both groups . Cost per cycle of chemotherapy in INR was 24,200 for decitabine and 1,600 for low-dose cytarabine group . Median of simplified cost-effectiveness ratio was 0.00022 for decitabine group and 0.0034 for low-dose cytarabine group . Conclusions . For elderly patients with AML , decitabine and low-dose cytarabine should be chosen based on the patient 's choice and affordability . Our study has shown that both of these agents have similar OS and toxicity . Low-dose cytarabine scores over decitabine in developing countries as it is more cost-effective We conducted an open-label phase 1 study exploring the feasibility , safety , and biologic activity of epigenetic priming with decitabine before st and ard induction chemotherapy in patients with less-than-favorable risk of acute myelogenous leukemia ( AML ) . We directly compared the clinical and DNA-hypomethylating activity of decitabine delivered at 20 mg/m² by either a 1-hour infusion ( Arm A ) or a continuous infusion ( Arm B ) for 3 , 5 , or 7 days before a single , st and ard induction with infusional cytarabine ( 100 mg/m² for 7 days ) and daunorubicin ( 60 mg/m² × 3 doses ) . Toxicity was similar to that of st and ard induction chemotherapy alone . Although we did not identify a maximum tolerated dose , there was more gastro-intestinal toxicity with 7 days of decitabine priming . Decitabine induced DNA hypomethylation at all dose levels and there was a trend toward greater hypomethylation in CD34(+ ) bone marrow cells when decitabine was delivered by a short pulse ( Arm A ) . Twenty-seven subjects ( 90 % ) responded to therapy : 17 with complete remission ( 57 % ) and 10 with partial remission ( 33 % ) . Of the patients with partial remission to protocol treatment , 8 achieved remission to their next therapy , bringing the overall complete remission rate to 83 % . We conclude that epigenetic priming of intensive chemotherapy can be safely delivered in an attempt to improve response rates . This trial was registered at www . clinical trials.gov as NCT00538876 Background The treatment of acute myeloid leukemia of older , medically non-fit patients still poses a highly unmet clinical need , and only few large , prospect i ve studies have been performed in this setting . Given the established activity of hypomethylating agents such as 5-aza-2'-deoxycytidine ( decitabine ) in myelodysplastic syndromes and acute myeloid leukemia with 20–30 % bone marrow blasts , we investigated whether this drug is also active in patients with more than 30 % blasts . Design and Methods To evaluate the efficacy and toxicity of decitabine in patients over 60 years old with untreated acute myeloid leukemia ineligible for induction chemotherapy , 227 patients ( median age , 72 years ) , many with comorbidities , adverse cytogenetics and /or preceding myelodysplastic syndrome were treated with this hypomethylating agent . During the initial decitabine treatment ( 135 mg/m2 total dose infused intravenously over 72 hours every 6 weeks ) , a median of two cycles was administered ( range , 1–4 ) . All-trans retinoic acid was administered to 100 patients during course 2 . Fifty-two patients who completed four cycles of treatment subsequently received a median of five maintenance courses ( range , 1–19 ) with a lower dose of decitabine ( 20 mg/m2 ) infused over 1 hour on 3 consecutive days every 4–6 weeks . Results The complete and partial remission rate was 26 % , 95 % CI ( 20 % , 32 % ) , and an antileukemic effect was noted in 26 % of patients . Response rates did not differ between patients with or without adverse cytogenetics ; patients with monosomal karyotypes also responded . The median overall survival from the start of decitabine treatment was 5.5 months ( range , 0–57.5 + ) and the 1-year survival rate was 28 % , 95%CI ( 22%,34 % ) . Toxicities were predominantly hematologic . Conclusions Decitabine is well tolerated by older , medically non-fit patients with acute myeloid leukemia ; myelosuppression is the major toxicity . The response rate and overall survival were not adversely influenced by poor-risk cytogenetics or myelodysplastic syndrome . Because of these encouraging results , r and omized studies evaluating single-agent decitabine versus conventional treatment are warranted . The study is registered with the German Clinical Trials Registry , number DRKS00000069 Decitabine may open the chromatin structure of leukemia cells making them accessible to the calicheamicin epitope of gemtuzumab ozogamicin ( GO ) . A total of 110 patients ( median age 70 years ; range 27–89 years ) were treated with decitabine and GO in a trial design ed on model-based futility to accommo date subject heterogeneity : group 1 : relapsed/refractory acute myeloid leukemia ( AML ) with complete remission duration ( CRD ) < 1 year ( N=28 , 25 % ) ; group 2 : relapsed/refractory AML with CRD ⩾1 year ( N=5 , 5 % ) ; group 3 : untreated AML unfit for intensive chemotherapy or untreated myelodysplastic syndrome ( MDS ) or untreated myelofibrosis ( MF ; N=57 , 52 % ) ; and group 4 : AML evolving from MDS or relapsed/refractory MDS or MF ( N=20 , 18 % ) . Treatment consisted of decitabine 20 mg/m2 daily for 5 days and GO 3 mg/m2 on day 5 . Post-induction therapy included five cycles of decitabine+GO followed by decitabine alone . Complete remission (CR)/CR with incomplete count recovery was achieved in 39 ( 35 % ) patients ; group 1= 5/28 ( 17 % ) , group 2=3/5 ( 60 % ) , group 3=24/57 ( 42 % ) and group 4=7/20 ( 35 % ) . The 8-week mortality in groups 3 and 4 was 16 % and 10 % , respectively . Common drug-related adverse events included nausea , mucositis and hemorrhage . Decitabine and GO improved the response rate but not overall survival compared with historical outcomes in untreated AML ⩾60 years BACKGROUND The molecular determinants of clinical responses to decitabine therapy in patients with acute myeloid leukemia ( AML ) or myelodysplastic syndromes ( MDS ) are unclear . METHODS We enrolled 84 adult patients with AML or MDS in a single-institution trial of decitabine to identify somatic mutations and their relationships to clinical responses . Decitabine was administered at a dose of 20 mg per square meter of body-surface area per day for 10 consecutive days in monthly cycles . We performed enhanced exome or gene-panel sequencing in 67 of these patients and serial sequencing at multiple time points to evaluate patterns of mutation clearance in 54 patients . An extension cohort included 32 additional patients who received decitabine in different protocol s. RESULTS Of the 116 patients , 53 ( 46 % ) had bone marrow blast clearance ( < 5 % blasts ) . Response rates were higher among patients with an unfavorable-risk cytogenetic profile than among patients with an intermediate-risk or favorable-risk cytogenetic profile ( 29 of 43 patients [ 67 % ] vs. 24 of 71 patients [ 34 % ] , P<0.001 ) and among patients with TP53 mutations than among patients with wild-type TP53 ( 21 of 21 [ 100 % ] vs. 32 of 78 [ 41 % ] , P<0.001 ) . Previous studies have consistently shown that patients with an unfavorable-risk cytogenetic profile and TP53 mutations who receive conventional chemotherapy have poor outcomes . However , in this study of 10-day courses of decitabine , neither of these risk factors was associated with a lower rate of overall survival than the rate of survival among study patients with intermediate-risk cytogenetic profiles . CONCLUSIONS Patients with AML and MDS who had cytogenetic abnormalities associated with unfavorable risk , TP53 mutations , or both had favorable clinical responses and robust ( but incomplete ) mutation clearance after receiving serial 10-day courses of decitabine . Although these responses were not durable , they result ed in rates of overall survival that were similar to those among patients with AML who had an intermediate-risk cytogenetic profile and who also received serial 10-day courses of decitabine . ( Funded by the National Cancer Institute and others ; Clinical Trials.gov number , NCT01687400 . ) Novel , non-intensive treatment options in older MDS/AML patients planned for allografting , with the goal of down-staging the underlying disease and bridging time to transplantation , are presently being developed . 5-azacytidine and decitabine ( DAC ) are of particular interest , as they can be given repetitively , with very limited non-hematologic toxicity and result in responses both in MDS and AML even at low doses . We describe 15 consecutive patients ( median age 69 years , range 60–75 years ) with MDS ( n=10 ) or AML ( n=5 ) who all received first-line treatment with DAC and subsequent allografting ( from sibling donor in four patients , unrelated donor in 11 ) after reduced-intensity conditioning with the FBM regimen . Successful engraftment was attained in 14/15 patients , all of whom achieved a CR , with a median duration of 5 months ( range 1 + to 51 + ) . Six of these 14 patients are alive ( 4 with complete donor chimerism ) , 8 have died either from relapse ( n=4 ) or treatment-related complications while in CR ( n=4 ) . We conclude that allografting after low-dose DAC and subsequent conditioning with FBM is feasible , with no unexpected toxicities and appears as a valid alternative to st and ard chemotherapy ( ‘ InDACtion instead of induction ’ ) in elderly patients with MDS/AML PURPOSE Older patients with acute myeloid leukemia ( AML ) have limited treatment options because of the Output:	Subgroup analyses of age , cytogenetics risk , AML type and bone marrow blast percentage showed no significant differences of treatment response to decitabine . In conclusion , decitabine is an effective and well-tolerated therapeutic alternative with acceptable side effects in elderly AML patients
MS213876	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: To evaluate the effects of a rehabilitation brace locked in extension for the first week on the recovery of full extension after ACL reconstruction we compared two groups of subjects who underwent ACL bone-patellar tendon-bone reconstruction . The brace was unlocked twice a day for assisted physiotherapy . In Group A , 18 male subjects wore a post-operative brace locked from 0 ° to 90 ° . In Group B , 18 male subjects wore the same post-op brace locked in full extension for the first week . In both groups the brace was unlocked ( 0 ° -120 ° ) at the beginning of the second postoperative week , and then removed at the beginning of the third week . All the subjects followed the same rigorous , accelerated rehabilitation protocol . Each subject was evaluated pre and post-operatively ( at second , fourth and eighth week ) with bubble-level heel height difference ( HHD ) measurements and KT 1000 arthrometric assessment at the fourth postoperative month . Preoperative bubble-level HHD measurements of the two groups were statistically similar ( Group A 0.6 cm , Group B 1 cm ; not significant , n.s . ) . At the fourth week ( Group A 2.2 cm , Group B 0.6 cm ) and eighth week ( Group A 1.6 cm , Group B 0.1 cm ) follow-ups , bubble-level HHD measurements showed that the extension of the operated knees of Group B was significantly greater than in Group A. KT 1000 arthrometric scores showed no difference between the two groups ( Group A 1.8 mm , Group B 1.5 ; n.s . ) PURPOSE To evaluate the effects an anterior cruciate ligament ( ACL ) brace has on various measures of knee proprioception and postural control . METHODS Thirty subjects ( mean age 27 + /- 11 yr ) having undergone unilateral ACL reconstruction were tested with and without wearing their own custom-fit brace on their involved limb . Proprioception was assessed using joint angle replication tests completed on an isokinetic dynamometer . Postural control was assessed using a series of single-limb st and ing balance tests completed on a force platform . The balance tests included : 1 ) st and ing on the stable platform with eyes open , 2 ) st and ing on a foam mat placed over the platform with eyes open , 3 ) st and ing on the platform with eyes closed , and 4 ) st and ing on the platform after l and ing from a maximal single-limb forward hop . RESULTS The brace provided a small but statistically significant improvement in proprioception ( mean reduction in error scores between target and reproduced angles = 0.64 + /- 1.4 degrees , P = 0.02 ) . For the postural control tests , there was a significant brace condition by test situation interaction ( P = 0.02 ) , with the brace providing a small but statistically significant improvement during the test completed on the stable platform with eyes open ( mean reduction in center of pressure path length = 4.2 + /- 8.4 cm , P = 0.02 ) but not during the other more challenging test situations . Additional post hoc analyses indicated that the relationship between knee proprioception and postural control measures were low and not significant ( r = 0.003 to 0.19 , P > 0.32 ) , consistent with the suggestion that changes in knee proprioception can occur in the absence of substantial changes in postural control . Also , st and ing balance tests that challenged the somatosensory contribution to postural control ( i.e. , those completed on foam , or with eyes closed ) were significantly related to single-limb forward hop distances ( r = -0.4 , P < 0.05 ) , whereas performance during the proprioception test was not ( r = 0.1 , P > 0.50 ) . CONCLUSIONS In general , bracing appears to improve performance during tasks characterized by relatively limited somatosensory input but not during tasks characterized by increased somatosenory input . The small magnitude of the improvements , coupled with their apparent lack of carry over to more difficult and functionally relevant tasks , questions the clinical benefit of the present effects of bracing Abstract Despite changes in rehabilitation protocol s , an extension deficit remains an important potential cause of significant morbidity following anterior cruciate ligament ( ACL ) reconstruction . An extension-assisting brace was design ed using a limited motion brace and an elastic strap across a fulcrum on the anterior aspect of the knee joint . The effects of the brace were investigated in 40 patients undergoing primary ACL reconstruction using an autogenous central third patellar tendon graft . The patients were r and omized either to use the brace in the first 6 weeks postoperatively or to undertake the same accelerated rehabilitation programme but without any brace , and they were review ed at 4 months postoperatively . The following data were recorded : passive and active extension and flexion deficits compared with the non-operated limb , KT-1000 assessment of anterior laxity and isometric quadriceps and hamstring strength . There was no difference between the two groups for any of the recorded variables . This was largely attributed to satisfactory tunnel placement and emphasis on the restoration of extension and quadriceps function during the early postoperative rehabilitation The prospect i ve study examined two different postoperative treatments on 46 patients with acute and isolated disruption of the anterior cruciate ligament ( acl ) , who were treated with reconstruction and augmentation using the semitendinosus-tendon . The patients were r and omised and divided into two groups either to use a postoperative brace ( Donjoy Ind. ) set at full extension ( group A ) or to use the same brace set at a flexion of 20 degrees ( group B ) on the first 3 days after surgery . All patients undertook a st and ard " accelerated " rehabilitation protocol and were evaluated after 3 , 6 and 12 months after surgery . The results were as follow : the patients of group A reached the full extension faster than group B without any loss of knee stability . Postoperative extension even led to an earlier return to work and sport activities . The muscle strength side-to-side difference ( Cybex-measurement ) was lower in group A. The severity and intensity of postoperative pain , swelling and giving-way was reduced in group A as was the risk of arthrofibrosis . Evaluated with the scoring scales of the " Orthopädische Arbeitsgruppe Knie " ( OAK ) , the " International Knee Documentation Committee " ( IKDC ) , the Tegner activity score and the Lysholm score , the clinical outcome and activity-level were higher in group A than in group B. This prospect i ve study shows , that immediate postoperative extension , compared to the postoperative flexion of 20 degrees , reduces the term of rehabilitation and optimizes the operative results after acl-reconstruction Abstract Forty patients were prospect ively investigated to evaluate the effects of b and aging after reconstructive surgery of the anterior cruciate ligament ( ACL ) . For the 6 weeks of the postoperative course , the operated knee was b and aged in 20 patients ( group A ) and braced in the other 20 patients ( group B ) . The isokinetic torque for extension and flexion ( Cybex ) and the range of motion ( ROM ) were investigated after 6 , 12 , 24 and 52 weeks postoperatively . At 24 weeks and 1 year postoperatively the stability of the knee joint ( KT-1000 ) as well as the clinical outcome ( ‘ Orthopädische Arbeitsgemeinschaft Knie ’ ) were evaluated . No statistically significant differences between the two groups were found for the extension and flexion strengths . Free ROM was achieved significantly earlier in group A than in group B. No statistically significant differences regarding the stability of the operated knee joint nor the early outcome were found between the two groups . This study demonstrated that the renunciation of using a brace had no adverse effect on the early outcome with respect to stability and function . On the contrary , bracing seems not to be m and atory after ACL reconstruction when the central third of the patellar tendon is used It has been our observation that post-operative anterior cruciate ligament ( ACL ) braces together with the post-operative b and ages do not always allow the knee to reach full extension . In ten uninjured knees with known hyperextension , the knees were b and aged in the same way as after an ACL-reconstruction . The knees were then studied radiologically in a Hypex brace set at 0 ° , −5 ° and −10 ° of knee extension . Not a single knee was found to be straight in the brace set at 0 ° . At −5 ° most of the knees were straight or in slight hyperextension . It took −10 ° to get all knees straight or in hyperextension . In a prospect i ve r and omised study 44 patients who underwent an arthroscopic ACL-reconstruction with a bone patellar tendon bone graft were r and omised to use either a brace set at −5 ° or a straight brace ( 0 ° ) for at least the first three postoperative weeks . Before and three months after surgery range of motion was determined , using a goniometer with long arms , and sagittal knee laxity was measured with a KT-2000 arthrometer at manual max . Pre- and post-operative pain was evaluated with the Visual Analogue Scale ( VAS ) . The same examiner ( blindfolded to what type of brace was used ) performed all the measurements . At three months , two of the 22 patients with the brace set at −5 ° and twelve of the 22 patients with the straight brace had a loss of full extension of 2 ° or more ( p<0.001 ) . No significant differences were found between the groups in terms of knee flexion , sagittal knee laxity or post-operative pain . Although extension deficit after ACL-reconstruction can be prevented also in other ways , a Hypex brace set at −5 ° seems to be an easy way of ensuring full knee extension Sixty patients were prospect ively r and omized to brace and no-brace groups after bone-tendon-bone patellar tendon anterior cruciate ligament ( ACL ) reconstruction . The brace group wore a rehabilitation knee brace for 12 weeks post-operatively , while the no-brace group was mobilized immediately , and crutches were discarded 2 weeks post-operatively . The groups were comparable with respect to age , gender , time from injury to surgery and concomitant injuries . There were no differences either pre-operatively or 5 years post-operatively ( 80 % of patients review ed ) between the groups in terms of the knee score ( Lysholm ) , activity level ( Tegner ) , degree of laxity or isokinetic peak muscle torque . Thus it appears that knee braces are not needed in the post-operative rehabilitation after ACL reconstruction with the patellar tendon graft The purpose of this study was to compare the clinical outcomes of rehabilitation after ACL reconstruction using a water-filled soft brace to those using a hard brace . The method used in this study was a prospect i ve r and omised clinical trial including 36 patients wearing a hard brace and 37 patients wearing a water-filled soft brace for 6 weeks after surgery . Preoperative and postoperative ( seven examinations ) clinical evaluation within a follow-up period of 1 year including effusion status , swelling and range of motion ( ROM ) , IKDC 2000 , KT1000 Arthrometer , Lysholm knee scoring scale and Tegner activity score . Mean values are presented with st and ard deviations . Data was analysed using descriptive statistics and Student 's t-test for unpaired sample s. Significantly less effusion was found in the soft brace group from 5 days ( p=0.002 ) to 12 weeks ( p<0.024 ) postoperative . Hard brace patients presented with significantly more extension deficit from 5 days ( p=0.036 ) to 12 months ( p=0.014 ) postoperative but no significant difference was detected in complete ROM , laxity or thigh atrophy at any follow-up examination . Patients treated with a soft brace had significantly higher IKDC subjective ratings at 6 weeks ( p=0.02 ) up to 12 months after operation ( p=0.002 ) and rated significantly higher in Tegner activity score ( p=0.004 ) and Lysholm knee scoring scale ( p=0.006 ) 6 and 12 months ( p<0.001 for both scores ) postoperatively . The water-filled soft brace was superior regarding effusion , swelling , extension deficit and patient-measured midterm outcome . The soft brace presents a safe , easy-to-use and effective alternative to the hard brace STUDY DESIGN R and omized clinical trial . OBJECTIVES To investigate the effects of functional knee braces on postural control in patients with anterior cruciate ligament ( ACL ) rupture . BACKGROUND ACL rupture leads to both mechanical knee instability and deficits in proprioception . Although elastic knee braces do not increase mechanical stability , patients report improved stability when wearing a brace . Elastic braces were found to reduce the loss of proprioception . It is , however , still unclear whether they also improve postural control , which involves the processing of proprioceptive input at a higher level . METHODS We studied 58 patients with isolated unilateral ACL rupture using computerized dynamic posturography and compared overall stability index ( OSI ) scores for injured and uninjured legs with and without a knee brace . In addition , patients were classified as copers and non-copers depending on knee function . RESULTS Within subjects , OSI scores were 3.0 ± 1.1 ° for uninjured legs when unbraced , 2.8±1.3 ° for uninjured legs when braced ( p=0.17 ) , 3.7 ± 1.5 ° for unbraced injured legs , and 2.9 ± 1.3 ° for braced injured legs ( p<0.001 ) . For the injured legs of copers and non-copers , Output:	Although some articles in the literature are in favor of the use of a postoperative brace after anterior cruciate ligament ( ACL ) reconstruction , this review found that several systematic review s and other reports on the topic do not support the use of a postoperative brace after ACL reconstruction . There is no scientific evidence so far to support the routine use of a functional knee brace following a successful ACL reconstruction in the postoperative course . Most authors believe that bracing is not necessary . Postoperative bracing after ACL reconstruction does not seem to help with pain , function , rehabilitation , and stability .
MS213877	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: OBJECTIVE The objective of this study was to test whether heart-rate feedback prompts increased physical activity ( PA ) in primary school students . METHODS A controlled trial with 210 9 - 11 year olds from subsidized Hong Kong Government primary schools was completed in December 2006 . Schools were r and omly assigned to one of three groups : Control ( CG ) ; Educational program ( EG ) ; No-educational program ( NEG ) . INTERVENTION In a short-term school-based intervention , heart-rate feedback was given either in combination with an educational program ( EG ) or in isolation ( NEG ) . Long-term retention was assessed in comparison to the control group after 6 months follow-up . MAIN OUTCOME MEASURES Physical activity and changes in attraction to PA . RESULTS In the short-term , heart-rate monitor feedback increased total daily PA by an average of 24 % ( p<0.001 ) and vigorous PA by 0.6 % ( p<0.05 ) . No change was found for moderate PA . Increases occurred regardless of involvement in the educational program , and in the absence of any change in attitudes towards PA . No long-term retention was apparent . CONCLUSIONS The findings from the study suggest that feedback from heart-rate monitors encourages low intensity PA , but when removed increases do not persist Developing an evidence base for making public health decisions will require using data from evaluation studies with r and omized and nonr and omized design s. Assessing individual studies and using studies in quantitative research syntheses require transparent reporting of the study , with sufficient detail and clarity to readily see differences and similarities among studies in the same area . The Consoli date d St and ards of Reporting Trials ( CONSORT ) statement provides guidelines for transparent reporting of r and omized clinical trials . We present the initial version of the Transparent Reporting of Evaluations with Nonr and omized Design s ( TREND ) statement . These guidelines emphasize the reporting of theories used and descriptions of intervention and comparison conditions , research design , and methods of adjusting for possible biases in evaluation studies that use nonr and omized design The purpose of this study was to investigate the associations between obesity and motor coordination ability in Taiwanese children with and without developmental coordination disorder ( DCD ) . 2029 children ( 1078 boys , 951 girls ) aged nine to ten years were chosen r and omly from 14 elementary schools across Taiwan . We used bioelectrical impedance analysis to measure percentage of body fat ( PBF ) and the Movement Assessment Battery for Children test ( MABC test ) to evaluate the motor coordination ability . Using cut-off points based on PBF from past studies , boys and girls were divided into obese , overweight and normal-weight groups , respectively . In boys , total impairment scores and scores on balance subtest in the MABC were significantly higher in the obese and overweight groups when compared against the normal-weight group . Girls in the obese and the overweight groups had higher balance impairment scores than those of the normal-weight group . Among boys , the prevalence of obesity was highest in the DCD group , when compared to the borderline DCD and TD boys . A higher percentage of DCD girls were overweight and obese than TD girls . Obesity may be associated with poor motor coordination ability among boys and girls , and particularly in relation to balance ability . Children with DCD may have a higher risk to be overweight or obese in Taiwan OBJECTIVE To assess differences through grade 8 in diet , physical activity , and related health indicators of students who participated in the Child and Adolescent Trial for Cardiovascular Health ( CATCH ) school and family intervention from grade s 3 through 5 . DESIGN Follow-up of the 4-center , r and omized , controlled field trial with 56 intervention and 40 control elementary schools . PARTICIPANTS We studied 3714 ( 73 % ) of the initial CATCH cohort of 5106 students from ethnically diverse background s in California , Louisiana , Minnesota , and Texas at grade s 6 , 7 , and 8 . RESULTS Self-reported daily energy intake from fat at baseline was virtually identical in the control ( 32.7 % ) and intervention ( 32.6 % ) groups . At grade 5 , the intake for controls remained at 32.2 % , while the intake for the intervention group declined to 30.3 % ( P<.001 ) . At grade 8 , the between-group differential was maintained ( 31.6 % vs 30.6 % , P = .01 ) . Intervention students maintained significantly higher self-reported daily vigorous activity than control students ( P = .001 ) , although the difference declined from 13.6 minutes in grade 5 to 11.2 , 10.8 , and 8.8 minutes in grade s 6 , 7 , and 8 , respectively . Significant differences in favor of the intervention students also persisted at grade 8 for dietary knowledge and dietary intentions , but not for social support for physical activity . No impact on smoking behavior or stages of contemplating smoking was detected at grade 8 . No significant differences were noted among physiologic indicators of body mass index , blood pressure , or serum lipid and cholesterol levels . CONCLUSION The original CATCH results demonstrated that school-level interventions could modify school lunch and school physical education programs as well as influence student behaviors . This 3-year follow-up without further intervention suggests that the behavioral changes initiated during the elementary school years persisted to early adolescence for self-reported dietary and physical activity behaviors Background Physical inactivity is recognised as a public health concern within children and interventions to increase physical activity are needed . GreatFun2Run was a school-based healthy lifestyles intervention that showed positive changes in physical activity levels and body composition immediately post-intervention . The purpose of this paper was to examine whether these changes in physical activity and body composition were maintained 18 - 20 months after the intervention ended . Method Participants ( n = 589 , aged 7 - 11 yrs ) from 4 intervention and 4 control schools took part in the 10-month intervention , of which 421 ( 71 % ) were present for follow-up . The intervention comprised a CD-rom learning and teaching re source for teachers ; an interactive website for pupils , teachers and parents ; two highlight physical activity events ( 1 mile school runs/walks ) ; a local media campaign ; and a summer activity wall planner and record . R and omisation was not possible because of local media content . Outcome measures were objective ly measured physical activity ( pedometers and accelerometers ) and body composition variables ( body mass index , waist circumference , estimated percent body fat , and sum of skinfolds ) . Teacher interviews and participant focus groups were conducted . Multi-level modelling was employed for the data analysis . Results Both control and intervention participants had increased their physical activity at follow-up but there was no group by time interaction ( control : 2726 steps per day increase ; intervention 3404 steps per day increase , p > .05 ) . There were significant increases in estimated percent body fat , sum of skinfolds , waist circumference and body mass index ( BMI ) with increasing age . In the control group , there was evidence for a plateauing in the rate of change in all body composition variables with increasing age , except BMI . In contrast , significant interaction terms suggest that the rate of change in waist circumference , BMI and BMI SDS continued to increase with age in the intervention group . Teacher interviews suggested that because of time pressures , competing re sources , curriculum dem and s and staff changes the majority of teachers had not continued to use the re sources . Conclusions While the intervention initially produced positive changes in physical activity levels and body composition , these changes were not sustained once the intervention ended . Facilitating long-term health behaviour change in children remains a challenge Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more Background Physical activity ( PA ) rates decline precipitously during the high school years and are consistently lower among adolescent girls than adolescent boys . Due to cultural barriers , this problem might be exacerbated in female Iranian adolescents . However , little intervention research has been conducted to try to increase PA participation rates with this population . Because PA interventions in schools have the potential to reach many children and adolescents , this study reports on PA intervention research conducted in all-female Iranian high schools . Methods A r and omized controlled trial was conducted to examine the effects of two six-month tailored interventions on potential determinants of PA and PA behavior . Students ( N = 161 ) were r and omly allocated to one of three conditions : an intervention based on Pender 's Health Promotion model ( HP ) , an intervention based on an integration of the health promotion model and selected constructs from the Transtheoretical model ( THP ) , and a control group ( CON ) . Measures were administered prior to the intervention , at post-intervention and at a six-month follow-up . Results Repeated measure ANOVAs showed a significant interaction between group and time for perceived benefits , self efficacy , interpersonal norms , social support , behavioral processes , and PA behavior , indicating that both intervention groups significantly improved across the 24-week intervention , whereas the control group did not . Participants in the THP group showed greater use of counter conditioning and stimulus control at post-intervention and at follow-up . While there were no significant differences in PA between the HP and CON groups at follow-up , a significant difference was still found between the THP and the CON group . Conclusion This study provides the first evidence of the effectiveness of a PA intervention based on Pender 's HP model combined with selected aspects of the TTM on potential determinants to increase PA among Iranian high school girls Aims : In this paper we evaluate the sustainability of changes of involvement in physical activity . The paper examines the effectiveness of a model aim ing at influencing the frequency of leisuretime physical activity , physical fitness and body constituency in youth . Methods : The baseline of this study was a r and omly selected sample of 13 year olds who participated in an intervention programme carried out in three schools in Poznan in 2005—08 . From a total of 199 adolescent boys a sub sample of 38 individuals from the experimental group and 34 from the control group were followed for 15 months after the interventional programme finished . From 170 girls , a sub sample of 33 from the experimental group and 32 girls from the control group were also r and omly selected for the follow-up study . Among the variables monitored were : physical fitness , body constituency , and frequency of leisuretime physical activity . All the variables were monitored in pre-test , post-test and follow-up examinations . Results : It was established that 15 months after the end of the interventional programme boys and girls from the intervention groups maintained a higher level of leisuretime physical activity than their control group peers , and similarly in the case of selected health-related components of physical fitness . No distinctive differences were found in the case of body constituency , though , apart from muscle mass and the sum of skinfolds in girls . Conclusions : The study exposed an increase in leisuretime physical activity in time and a positive influence on selected components of health-related variables . The findings confirm the effectiveness of a multi-level intervention programme involving self-determined out-of-school physical activity planning for school-age youths , indicating the importance of personal and social context Objectives : To evaluate the effectiveness of an intervention to prevent excess weight gain , reduce time spent in screen behaviours , promote participation in and enjoyment of physical activity ( PA ) , and improve fundamental movement skills among children . Participants : In 2002 , 311 children ( 78 % response ; 49 % boys ) , average age 10 years 8 months , were recruited from three government schools in low socioeconomic areas of Melbourne , Australia . Design : Group-r and omized controlled trial . Children were r and omized by class to one of the four conditions : a behavioural modification group ( BM ; n=66 ) ; a fundamental movement skills group ( FMS ; n=74 ) ; a combined BM/FMS group ( BM/FMS ; n=93 ) ; and a control ( usual curriculum ) group ( n=62 ) . Data were collected at baseline , post intervention , 6- and 12-month follow-up periods . Results : BMI data were available for 295 children at baseline and 268 at 12-month follow-up . After adjusting for food intake and PA , there was a significant intervention effect from baseline to post intervention on age- and sex-adjusted BMI in the BM/FMS group compared with controls ( −1.88 kg m−2 , P<0.01 ) , which was maintained at 6- and 12-month follow-up periods ( −1.53 kg m−2 , P<0.05 ) . Children in the BM/FMS group were less likely than controls to be overweight/obese between baseline and post intervention ( adjusted odds ratio (AOR)=0.36 , P<0.05 ) ; also maintained at 12-month follow-up ( AOR=0.38 , P<0.05 ) . Compared with controls , FMS group children recorded higher levels and greater enjoyment of PA ; and BM children recorded higher levels of PA and TV viewing across all four time points . Gender moderated the intervention effects for participation in and enjoyment of PA , and fundamental movement skills . Conclusion : This programme represents a promising approach to preventing excess weight gain and promoting participation in and enjoyment of PA . Examination of the mediators of this intervention and further tailoring of the programme to suit both genders is required UNLABELLED The aim of this study was to examine the relationship between motor proficiency and pedometer-determined physical activity in 5 - 6 year-old children . Participants ( n = 232 ) were r and omly recruited and assessed from 30 kindergartens in Northern Greece . Two trained research ers administered the measurements for the assessment of children 's motor proficiency by using the BOTMP-SF . Physical activity was assessed by OMRON pedometers . Significant relationships between BOTMP-SF st and ard score and steps ( S ) , aerobic walking time ( AWT ) and aerob Output:	Conclusion It is likely that PA is a sustainable outcome from interventions in children and adolescents , and there is reasonable evidence that interventions of longer than 1 year and interventions that utilize a theoretical model or framework are effective in producing this sustained impact .
MS213878	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Postoperative acute urinary retention was evaluated in the patients who underwent Pereyra procedure . Comparison of suprapubic and urethral catheterization . Between January 1994 and July 1995 , fifty two patients with urinary stress incontinence underwent Pereyra procedure , 31 female patient with suprapubic drainage ( cistofix Ch 15 ) and 17 urethral catherization with a latex foley catheter . Sponatneous micturition and urinary retention was evaluated until the catheter was removed . Mean age was 43.8 years ( 32 a 66 ) , the duration of suprapubic vesical drainage with suprapubic catheter were 3 days in 58.6 % of the patients , and more than 3 days in 41.29 % . Recatheterizacion in the patients with urethral drainage was more frequent . Urinary retention after 7 days was present in 23.99 % with suprapubic vesical drainage and 28.5 % with urethral catheter . Recatheterization is more frequent in patients with urethral catheter In a prospect i ve study the results of postoperative urinary discharge by suprapubic catheterisation ( SC ) are compared with those of transurethral catheterisation ( TC ) in a r and omised collective of gynaecological patients after vaginal hysterectomy with front ( resp . front and back ) plastic . During November 1979 and September 1980 157 patients were examined , 88 patients by suprapubic catheterisation and 69 by transurethral catheterisation , with r and om distribution . Additionally , 430 other patients with suprapubic aspiration after vaginal hysterectomy with front and /or back plastic performed between September 1980 and October 1982 were examined retrospectively especially under the aspect of possible complications . The advantages of suprapubic urinary discharge are shown in the significantly reduced rate of primary infections . 20.5 per cent of infections are opposed to 67.1 per cent in the comparative group with TC . Spontaneous miction was possible in the SC group two days earlier than in the group of TC ( 5.2 days opposed to 7.35 days ) . Additional drug treatment for restitution of the bladder function was more often necessary for patients with TC , although the results with 43.5 per cent against 29.5 per cent in the SC collective are not significant . The number of renewed catheterisations after removal of the catheter was higher by 27 per cent in the group of patients with SC . Subjective complaints were stated by patients with TC in 66.7 per cent against 18.2 per cent of women with SC . This result is significant . In the TC collective there were significantly more patients with leucocyturia ( 88.5 per cent against 48.7 per cent ) . Antibiotic treatment of an urinary tract infection with typical symptoms was necessary in 35.8 per cent for patients with TC and in 14.1 per cent for women with SC . ( ABSTRACT TRUNCATED AT 250 WORDS The objective of this study is to assess the impact of bladder catheterization on the incidence of postoperative urinary tract infection ( UTI ) and urinary retention ( PUR ) following laparoscopic-assisted vaginal hysterectomy ( LAVH ) . One hundred fifty patients undergoing LAVH were r and omly assigned to no catheter use , 1-day , and 2-day catheter groups . The relationship between preoperative , intraoperative , and postoperative factors and the rates of UTI and PUR were determined . The incidences of UTI and PUR were 9.3 % and 18.7 % , respectively . The highest rate of UTI occurred in the 2-day catheter group ; the highest rate of PUR occurred in no-catheter-use group . Multivariable logistical regression showed the duration of catheterization was the single predictor of UTI ; duration of catheterization and diabetes mellitus were predictors for PUR . While short-term indwelling catheterization result ed in decreased rate of PUR , UTI rate increased among patients undergoing LAVH . Nonetheless , most patients resumed normal urination shortly after surgery Abstract . Ninety‐two patients with preoperative sterile urine undergoing colposuspension or vaginal repair operation for stress urinary incontinence and /or genital descensus were r and omized to either suprapubic or transurethral postoperative catheter drainage . The prevalence of significant bac‐teriuria on the fifth postoperative day was statistically significantly lower when using suprapubic catheter ( 20.8 % ) than with transurethral catheter drainage ( 45.5 % ) . This applied especially to colposuspension . The rate of postoperatively impaired bladder emptying also tended to be reduced when using suprapubic catheter . At follow‐up after one year , postoperative bacteriuria was closely correlated to increased rates of both clinical cystitis and asymptomatic significant bacteriuria . Thus it is recommended to use suprapubic bladder drainage not only after colposuspension but also after vaginal repair in an effort to avoid an increased risk of urinary infections Introduction and hypothesisDifferent forms of urinary drainage are applied after anterior colporrhaphy . Suprapubic urinary catheter ( SUC ) and indwelling urinary catheter ( IUC ) for 2 to 96 h are preferred . If there is no difference in symptomatic urinary tract infection ( SUTI ) or complications between IUCs for 96 and 24 h , the latter will be considered sufficient . If IUCs have no higher rate of infections or complications compared to SUC for 96 h , the former could be considered sufficient . Methods It was a three-arm prospect i ve , r and omized study including 257 patients . The three arms were : IUCs for 24 h , IUCs for 96 h , and SUCs for 96 h. Results We found no significant difference in SUTIs between all three groups . Although the SUC arm showed no SUTIs , a significant higher rate of complications was seen . Conclusion The optimal bladder catheter after anterior colporrhaphy was , in our trial , the IUC for 24 A controversy exists concerning the most appropriate method of bladder drainage after vaginal hysterectomy and anterior-posterior repair . The present study compares the use of the Foley catheter and the suprapubic tube following these operations . One hundred and fifty suitable c and i date s were selected , with 75 using each system . The results showed that the suprapubic group had one-third the rate { 12 % vs 38 % ) of significant bacteriuria when compared to the Foley group at the time the instruments were removed on the fourth postoperative day . In addition the Foley group also had a significant increase in the number of positive urine cultures 6 weeks after the operation ( 10 % vs 2 % ) , a higher incidence of prolonged hospitalization ( greater than 6 days ) , and a more frequent use of bladder analgesics ( 69 % vs 41 % ) . Other advantages in the use of suprapubic tubes after vaginal surgery appeared to be ease of care by ward personnel , greater patient comfort , and a reduced incidence of severe complications . An additional finding of this study was related to the increase of significant bacteriuria in patients receiving cold knife conization prior to hysterectomy . This factor appeared to be constant regardless of the drainage system used although a greater number of cases were found in the Foley group OBJECTIVE To determine the potential benefits of ISC ( intermittent self-catheterisation ) over SPC ( supra-pubic catheterisation ) in the post-operative bladder care of women following radical hysterectomy . METHODS A prospect i ve r and omised controlled trial of women treated by radical hysterectomy for early stage cervical cancer . RESULTS . : 40 women were recruited to the study , 21 to ISC and 19 to SPC . All patients r and omised to ISC were able to learn the technique of ISC satisfactorily following a period of pre-operative training . The day 3 and day 5 positive CSU ( catheter specimen of urine ) rate was significantly higher in the ISC group ( 42 % and 63 % ) compared to the SPC group ( 6 % and 18 % ) , P = 0.05 and P = 0.004 , respectively ) . Eight of 17 patients r and omised to SPC ( 47 % ) documented having symptoms/problems arising from the SPC site of which 4 ( 23 % ) were shown to have a positive wound swab . There was no significant difference in length of period for bladder care between the two groups , P = 0.83 . However , there were significant differences in patient acceptability ( P = 0.009 ) , freedom to lead a normal life ( P = 0.000 ) , disturbance at night ( P = 0.006 ) and patient anxiety/embarrassment ( P = 0.005 ) between the two groups . CONCLUSIONS Patients are able to learn the technique of ISC without difficulty . Despite a greater urinary tract infection rate , the high incidence of SPC site problems can be avoided by use of ISC . The technique of ISC was seen to be more acceptable to patients allowing fewer disturbances at night , greater freedom to lead a normal life during the day and less anxiety/embarrassment compared to SPC In a prospect i ve r and omized study comprising 90 women undergoing vaginal plastic surgery , suprapubic and transurethral catheter drainage of the bladder were compared regarding urinary tract infection and asymptomatic bacteriuria . No statistically significant differences were found . The mean duration of catheterization was 4.9 days for suprapubic vs 3.3 days for transurethral catheter patients . Postoperative urinary tract infection was diagnosed in 23.7 % of patients with suprapubic and in 27.5 % of patients with transurethral catheters . Asymptomatic bacteriuria at catheter removal was found in 21.0 % of suprapubic and in 12.5 % of transurethral catheter patients . More mechanical complications were seen with SPCsthan with TUCs . It is concluded that the two methods involve similar risks of infectious complications but that SPCs have a higher rate of mechanical complications OBJECTIVE To compare the use of intermittent urethral catheterization with indwelling suprapubic catheterization in women undergoing surgery for urodynamic stress incontinence or uterovaginal prolapse . DESIGN R and omized controlled trial . SETTING Tertiary referral urogynaecology unit . POPULATION Women undergoing surgery for pelvic organ prolapse and /or stress urinary incontinence . METHODS Women were r and omized into one of two groups . Group 1 had bladder drainage using a suprapubic catheter inserted in theatre . The catheter was left on free drainage for 48 hours post-operatively before clamping . Group 2 was catheterized intermittently post-operatively . MAIN OUTCOME MEASURES Length of post-operative hospital stay : time to resume normal voiding ( defined as voided volumes greater than 200 mls and residual urine volumes less than 100 mls on three occasions ) ; number of urinary tract infections ( UTIs ) ; catheterization costs ; patient experience ( determined from question naire ) ; and a pain score . RESULTS 75 women were r and omized ; 38 to suprapubic catheterization ; 37 to intermittent catheterization . Three were withdrawn from study , leaving 36 women in each group . Groups were closely matched for age and type of surgery undertaken . Length of hospital stay and total duration of catheterization were both significantly shorter for the intermittent catheterization group ; although there was no difference in the rate of UTI between the two groups . There was no clear patient preference for a specific catheterization method . CONCLUSIONS The use of intermittent catheterization following urogynaecological surgery is associated with a more rapid return to normal micturition and a shorter hospital stay , although the clinical significance of the difference is perhaps limited Fifty-one patients with clinical and urodynamic diagnoses of stress urinary incontinence were r and omly allocated to either suprapubic ( N = 24 ) or transurethral ( N = 27 ) bladder drainage after vaginal surgery for stress incontinence ( revised Pereyra procedure ) . Postoperative use of suprapubic bladder drainage significantly reduced febrile morbidity ( calculated as fever index ; P < .01 ) and length of hospitalization ( P < .05 ) . Postoperative normal bladder functions resumed more quickly when suprapubic drainage was used ( P < .05 ) , so that most patients did not need bladder catheterization upon discharge , as opposed to more than half of those with Foley catheters , who left the hospital with a catheter in place ( P < .05 ) . We conclude that it is both beneficial and cost-effective to use suprapubic bladder drainage after a Pereyra operation for stress urinary incontinence STUDY OBJECTIVE We sought to evaluate the incidence of postoperative voiding dysfunction in patients undergoing vaginal hysterectomy ( VH ) or total laparoscopic hysterectomy ( TLH ) and to identify risk factors for the development of postoperative urinary retention after uncomplicated total hysterectomy . DESIGN Prospect i ve cohort study ( Canadian Task Force classification II-2 ) . SETTING Gynecology department of a university hospital . PATIENTS Two hundred thirty-three consecutive women undergoing TLH or VH Output:	Complications were mostly related to catheter tube malfunction with no visceral injuries reported . No differences in the rate of recatheterization or hospital stay were demonstrated . : Based on the best available evidence , no route for bladder drainage in gynecologic patients is clearly superior . The reduced rate of infective morbidity with suprapubic catheterization is offset by a higher rate of catheter-related complications and crucially does not translate into reduced hospital stay . Minimally invasive surgery may alter the requirement for prolonged postoperative catheterization
MS213879	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: BACKGROUND We conducted a r and omized , placebo-controlled , double-blind trial to determine whether the epidermal growth factor receptor inhibitor erlotinib prolongs survival in non-small-cell lung cancer after the failure of first-line or second-line chemotherapy . METHODS Patients with stage IIIB or IV non-small-cell lung cancer , with performance status from 0 to 3 , were eligible if they had received one or two prior chemotherapy regimens . The patients were stratified according to center , performance status , response to prior chemotherapy , number of prior regimens , and prior platinum-based therapy and were r and omly assigned in a 2:1 ratio to receive oral erlotinib , at a dose of 150 mg daily , or placebo . RESULTS The median age of the 731 patients who underwent r and omization was 61.4 years ; 49 percent had received two prior chemotherapy regimens , and 93 percent had received platinum-based chemotherapy . The response rate was 8.9 percent in the erlotinib group and less than 1 percent in the placebo group ( P<0.001 ) ; the median duration of the response was 7.9 months and 3.7 months , respectively . Progression-free survival was 2.2 months and 1.8 months , respectively ( hazard ratio , 0.61 , adjusted for stratification categories ; P<0.001 ) . Overall survival was 6.7 months and 4.7 months , respectively ( hazard ratio , 0.70 ; P<0.001 ) , in favor of erlotinib . Five percent of patients discontinued erlotinib because of toxic effects . CONCLUSIONS Erlotinib can prolong survival in patients with non-small-cell lung cancer after first-line or second-line chemotherapy PURPOSE In non-small-cell lung cancer ( NSCLC ) , clinical and biologic predictors for epidermal growth factor receptor ( EGFR ) tyrosine kinase inhibitor sensitivity have been identified in retrospective studies , and there is urgent need to vali date these results in prospect i ve trials . The ONCOBELL trial is a prospect i ve phase II study evaluating gefitinib sensitivity in NSCLC patients who never smoked or have increased EGFR gene copy number or activation of the antiapoptotic protein Akt . PATIENTS AND METHODS EGFR gene copy number was evaluated using fluorescence in situ hybridization ( FISH ) , and presence of phospho-Akt was evaluated using immunohistochemistry . Additional tests included immunohistochemistry analysis of EGFR , FISH analysis of HER2 , and mutation analysis of EGFR , HER2 , and K-ras . RESULTS From November 2004 to February 2006 , 183 patients were screened , and 42 patients were enrolled onto the trial . We observed one complete and 19 partial responses , for an overall response rate ( RR ) of 47.6 % ( 95 % CI , 32.5 % to 62.7 % ) . Median duration of response was 6.1 months , median time to progression ( TTP ) was 6.4 months , 1-year survival rate was 64.3 % , and median survival time was not reached . EGFR FISH-positive patients , compared with negative patients , had higher RR ( 68.0 % v 9.1 % , respectively ; P < .001 ) , longer TTP ( 7.6 v 2.7 months , respectively ; P = .02 ) , and a trend for longer survival ( median survival not reached v 7.4 months , respectively ; P = .3 ) . Therapy was well tolerated , and there were no drug-related deaths . Median follow-up time was too short for significance tests of differences in survival outcomes . CONCLUSION Gefitinib is active and well tolerated in patients with trial characteristics , and EGFR FISH analysis is an accurate predictor for such therapy Purpose : In patients with non – small cell lung cancer ( NSCLC ) , mutations in the epidermal growth factor receptor ( EGFR ) tyrosine kinase domain have been associated with sensitivity to erlotinib and gefitinib . We undertook this study to explore the relationship between EGFR mutation type and clinical variables , including treatment with gefitinib and erlotinib . Experimental Design : In patients with NSCLC , EGFR exon 19 deletion mutations and EGFR L858R point mutations were analyzed by nonsequencing PCR-based methods from paraffin blocks of tissue obtained before treatment . The results were correlated with clinical information ( sex , pathologic subtype , race/ethnicity , treatment , and overall survival ) . Results : The two most common EGFR mutations were identified in 24 % ( 70 of 291 ; 95 % confidence interval , 26%-38 % ) of tumors from patients with NSCLC . EGFR mutation was associated with Asian ethnicity ( P = 0.0023 ) and being a “ never smoker ” ( P = 0.0001 ) . Among patients with EGFR mutations , 39 % ( 27 of 70 ) had EGFR L858R , whereas 61 % ( 43 of 70 ) had an EGFR exon 19 deletion . After treatment with erlotinib ( n = 12 ) or gefitinib ( n = 22 ) , patients with EGFR mutations had a median overall survival of 20 months . After treatment with erlotinib or gefitinib , patients with EGFR exon 19 deletions had significantly longer median survival than patients with EGFR L858R ( 34 versus 8 months ; log-rank P = 0.01 ) . Conclusions : EGFR mutations in exons 19 or 21 are correlated with clinical factors predictive of response to gefitinib and erlotinib . Those with EGFR exon 19 deletion mutations had a longer median survival than patients with EGFR L858R point mutation . These observations warrant confirmation in a prospect i ve study and exploration of the biological mechanisms of the differences between the two major EGFR mutations PURPOSE Epidermal growth factor receptor ( EGFR ) mutations have been associated with tumor response to treatment with single-agent EGFR inhibitors in patients with relapsed non-small-cell lung cancer ( NSCLC ) . The implication s of EGFR mutations in patients treated with EGFR inhibitors plus first-line chemotherapy are unknown . KRAS is frequently activated in NSCLC . The relationship of KRAS mutations to outcome after EGFR inhibitor treatment has not been described . PATIENTS AND METHODS Previously untreated patients with advanced NSCLC in the phase III TRIBUTE study who were r and omly assigned to carboplatin and paclitaxel with erlotinib or placebo were assessed for survival , response , and time to progression ( TTP ) . EGFR exons 18 through 21 and KRAS exon 2 were sequenced in tumors from 274 patients . Outcomes were correlated with EGFR and KRAS mutations in retrospective subset analyses . RESULTS EGFR mutations were detected in 13 % of tumors and were associated with longer survival , irrespective of treatment ( P < .001 ) . Among erlotinib-treated patients , EGFR mutations were associated with improved response rate ( P < .05 ) and there was a trend toward an erlotinib benefit on TTP ( P = .092 ) , but not improved survival ( P = .96 ) . KRAS mutations ( 21 % of tumors ) were associated with significantly decreased TTP and survival in erlotinib plus chemotherapy-treated patients . CONCLUSION EGFR mutations may be a positive prognostic factor for survival in advanced NSCLC patients treated with chemotherapy with or without erlotinib , and may predict greater likelihood of response . Patients with KRAS-mutant NSCLC showed poorer clinical outcomes when treated with erlotinib and chemotherapy . Further studies are needed to confirm the findings of this retrospective subset analysis PURPOSE To evaluate the relationship between mutations of the epidermal growth factor receptor ( EGFR ) gene and the effectiveness of gefitinib treatment in patients with recurrent lung cancer after pulmonary resection . PATIENTS AND METHODS We sequenced exons 18 - 21 of the EGFR gene using total RNA extracted from 59 patients with lung cancer who were treated with gefitinib for recurrent lung cancer . Gefitinib effectiveness was evaluated by both imaging studies and change in serum carcinoembryonic antigen ( CEA ) levels . RESULTS EGFR mutations were found in 33 patients ( 56 % ) . Of these mutations , 17 were deletions around codons 746 - 750 and 15 were point mutations ( 12 at codon 858 , three at other codons ) , and one was an insertion . EGFR mutations were significantly more prevalent in females , adenocarcinoma , and never-smokers . Gefitinib treatment result ed in tumor shrinkage and /or CEA decrease to less than half of the baseline level in 26 patients , tumor growth and /or CEA elevation in 24 patients , and gefitinib effect was not assessable in nine patients . Female , never-smoking patients with adenocarcinoma tended to respond better to gefitinib treatment . Gefitinib was effective in 24 of 29 patients with EGFR mutations , compared with two of 21 patients without mutations ( P < .0001 ) . Of note , del746 - 750 might be superior to L858R mutations for prediction of gefitinib response . Patients with EGFR mutations survived for a longer period than those without the mutations after initiation of gefitinib treatment ( P = .0053 ) . CONCLUSION EGFR mutations were a good predictor of clinical benefit of gefitinib in this setting Purpose : Erlotinib has proven activity in pretreated patients with advanced non – small cell lung cancer ( NSCLC ) . We evaluated erlotinib in the frontline treatment of advanced NSCLC and assessed biological predictors of outcome . Experimental Design : In this phase II study , chemotherapy-naive patients with stage IIIB/IV NSCLC received oral erlotinib ( 150 mg/d ) until disease progression or unacceptable toxicity occurred . Tumor response was assessed every 6 weeks , and sample s were analyzed for potential molecular markers of treatment response and survival . The primary end point was the proportion of patients without disease progression after 6 weeks of treatment . Results : Fifty-three patients were eligible . The overall rate of nonprogression at 6 weeks was 52.8 % ( 28 of 53 patients ) . Tumor response rate was 22.7 % , with 1 complete response , 11 partial responses , and 16 cases of stable disease . Responses were seen across most patient clinical characteristics . The median duration of tumor response was 333 days ; median overall survival was 391 days ; and median time to disease progression was 84 days . Erlotinib was well tolerated , the main treatment-related adverse events being mild-to-moderate rash and diarrhea . Histologic material for biological studies was available in 29 cases . Four of five responders and one patient with stable disease had a classic epidermal growth factor receptor tyrosine kinase mutation . Two progressing patients exhibited epidermal growth factor receptor point mutations ( one with T790 M mutation ) , and K-ras mutations were detected in 10 nonresponders . Conclusions : Erlotinib shows significant antitumor activity in the first-line treatment of advanced NSCLC and may be a viable alternative to chemotherapy . Patient selection can not easily be based on clinical or biological variables PURPOSE The phase III Iressa Survival Evaluation in Lung Cancer ( ISEL ) trial compared gefitinib with placebo in 1,692 patients with refractory advanced non-small-cell lung cancer . We analyzed ISEL tumor biopsy sample s to examine relationships between biomarkers and clinical outcome after gefitinib treatment in a placebo-controlled setting . METHODS Biomarkers included epidermal growth factor receptor ( EGFR ) gene copy number by fluorescence in situ hybridization ( n = 370 ) ; EGFR ( n = 379 ) and phosphorylated Akt ( p-Akt ) protein expression ( n = 382 ) by immunohistochemistry ; and mutations in EGFR ( n = 215 ) , KRAS ( n = 152 ) , and BRAF ( n = 118 ) . RESULTS High EGFR gene copy number was a predictor of a gefitinib-related effect on survival ( hazard ratio [ HR ] , 0.61 for high copy number and HR , 1.16 for low copy number ; comparison of high v low copy number HR , P = .045 ) . EGFR protein expression was also related to clinical outcome ( HR for positive , 0.77 ; HR for negative , 1.57 ; comparison of high v low protein expression HR , P = .049 ) . Patients with EGFR mutations had higher response rates than patients without EGFR mutations ( 37.5 % v 2.6 % ) ; there were insufficient data for survival analysis . No relationship was observed between p-Akt protein expression and survival outcome , and the limited amount of data collected for KRAS and BRAF mutations prevented any meaningful evaluation of clinical outcomes in relation to these mutations . CONCLUSION EGFR gene copy number was a predictor of clinical benefit from gefitinib in ISEL . Additional studies are warranted to assess these biomarkers fully for the identification of patients most likely to benefit from gefitinib treatment Output:	Conclusion In conclusion , EGFR mutation and protein expression status may provide useful clinical information in terms of the likelihood of tumor response and disease prognosis .
MS213880	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Background As a result of inappropriate feeding , poor health and hygiene , and poor caring practice s , the nutritional status of many young infants deteriorates with advancing age . Objective To explore the effectiveness of a nutrition education package to prevent malnutrition among young children . Methods A community-based , r and omized , controlled trial was conducted among 605 normal and mildly malnourished children aged 6 to 9 months in 121 Community Nutrition Centers ( CNCs ) of the Bangladesh Integrated Nutrition Project ( BINP ) in four regions of Bangladesh from 2000 to 2002 . The intervention group received weekly nutrition education based on the nutrition triangle concept of UNICEF for 6 months , whereas the control group received regular BINP services . Both groups were observed for a further 6 months to assess the sustainability of the effects . Information on socio-economic status , feeding patterns , morbidity , and anthropometric features was collected . Results A significant increase in the frequency of complementary feeding was observed in the intervention group as compared with the control group , and the increase was sustained throughout the observation period . The intervention group had a higher weight gain than the control group after the end of the intervention ( 0.86 vs. 0.77 kg , p = 0.053 ) and after the end of the observation period ( 1.81 vs. 1.39 kg , p < .001 ) . The proportion of normal and mildly malnourished children was greater in the intervention group than in the control group after the end of the observations ( 88.9 % vs. 61.5 % , p < .001 ) . Nutrition education successfully prevented malnutrition in all the areas . Variation in the outcome of nutrition education among the regions was observed . Conclusions This culturally appropriate nutrition education package based on the nutrition triangle model effectively prevented growth faltering and malnutrition among young children ABSTRACT OBJECTIVE To assess the effect of educational dietary intervention offered in the child ’s first year of life , as well as teenage mothers and gr and mothers in carrying out the dietary recommendations at four to seven years . METHODS R and omized clinical trial initiated in 2006 , in Porto Alegre , RS , involving 323 teenage mothers and gr and mothers who cohabited . The intervention consisted of six counseling sessions on breastfeeding and healthy complementary feeding . The first session occurred in the maternity ward and the other ones in the households of mothers at seven , 15 , 30 , 60 , and 120 days of the child ’s life . The information about the child ’s diet were obtained on a monthly basis in the first six months , every two months in the second half-year , and at four to seven years , using a food frequency question naire . To assess the adequacy of food consumption to the recommendations from the Ministry of Health , we elaborated a score system that would reflect the compliance with the Ten Steps for Healthy Toddlers from 2 to 10 Years . The average scores of intervention and control groups were compared using the t-test . RESULTS Low adherence to recommendations on child nutrition was found in the study population , with no difference in implementation the steps between the groups . The score on the compliance with the steps was similar in both groups ( 9.6 [ SD = 1.63 ] and 9.3 [ SD = 1.60 ] in the intervention and control groups , respectively ) and no influence of the cohabitation with the gr and mother was found . CONCLUSIONS Educational dietary intervention in the first four months of the child ’s life for teenage mothers and gr and mothers had no effect on the compliance with the recommendations at four to seven years of the child ’s life Summary Background Many countries now offer support to teenage mothers to help them to achieve long-term socioeconomic stability and to give a successful start to their children . The Family Nurse Partnership ( FNP ) is a licensed intensive home-visiting intervention developed in the USA and introduced into practice in Engl and that involves up to 64 structured home visits from early pregnancy until the child 's second birthday by specially recruited and trained family nurses . We aim ed to assess the effectiveness of giving the programme to teenage first-time mothers on infant and maternal outcomes up to 24 months after birth . Methods We did a pragmatic , non-blinded , r and omised controlled , parallel-group trial in community midwifery setting s at 18 partnerships between local authorities and primary and secondary care organisations in Engl and . Eligible participants were nulliparous and aged 19 years or younger , and were recruited at less than 25 weeks ' gestation . Field-based research ers r and omly allocated mothers ( 1:1 ) via remote r and omisation ( telephone and web ) to FNP plus usual care ( publicly funded health and social care ) or to usual care alone . Allocation was stratified by site and minimised by gestation ( < 16 weeks vs ≥16 weeks ) , smoking status ( yes vs no ) , and preferred language of data collection ( English vs non-English ) . Mothers and assessors ( local research ers at baseline and 24 months ' follow-up ) were not masked to group allocation , but telephone interviewers were blinded . Primary endpoints were biomarker-calibrated self-reported tobacco use by the mother at late pregnancy , birthweight of the baby , the proportion of women with a second pregnancy within 24 months post-partum , and emergency attendances and hospital admissions for the child within 24 months post-partum . Analyses were by intention to treat . This trial is registered with IS RCT N , number IS RCT N23019866 . Findings Between June 16 , 2009 , and July 28 , 2010 , we screened 3251 women . After enrolment , 823 women were r and omly assigned to receive FNP and 822 to usual care . All follow-up data were retrieved by April 25 , 2014 . 304 ( 56 % ) of 547 women assigned to FNP and 306 ( 56 % ) of 545 assigned to usual care smoked at late pregnancy ( adjusted odds ratio [ AOR ] 0·90 , 97·5 % CI 0·64–1·28 ) . Mean birthweight of 742 babies with mothers assigned to FNP was 3217·4 g ( SD 618·0 ) , whereas birthweight of 768 babies assigned to usual care was 3197·5 g ( SD 581·5 ; adjusted mean difference 20·75 g , 97·5 % CI −47·73 to 89·23 . 587 ( 81 % ) of 725 assessed children with mothers assigned to FNP and 577 ( 77 % ) of 753 assessed children assigned to usual care attended an emergency department or were admitted to hospital at least once before their second birthday ( AOR 1·32 , 97·5 % CI 0·99–1·76 ) . 426 ( 66 % ) of 643 assessed women assigned to FNP and 427 ( 66 % ) 646 assigned to usual care had a second pregnancy within 2 years ( AOR 1·01 , 0·77–1·33 ) . At least one serious adverse event ( mainly clinical events associated with pregnancy and infancy period ) was reported for 310 ( 38 % ) of 808 participants ( mother – child ) in the usual care group and 357 ( 44 % ) of 810 in the FNP group , none of which were considered related to the intervention . Interpretation Adding FNP to the usually provided health and social care provided no additional short-term benefit to our primary outcomes . Programme continuation is not justified on the basis of available evidence , but could be reconsidered should supportive longer-term evidence emerge . Funding Department of Health Policy Research Programme OBJECTIVE To assess the impact of a child feeding training program for primary care health professionals about breastfeeding and complementary feeding practice s. METHODS Cluster-r and omized field trial conducted in the city of Porto Alegre , ( RS ) , Brazil . Twenty primary health care centers ( HCC ) were r and omized into intervention ( n = 9 ) and control ( n = 11 ) groups . The health professionals ( n = 200 ) at the intervention group centers received training about healthy feeding practice s. Pregnant women were enrolled at the study . Up to six months of child 's age , home visits were made to obtain variables related to breastfeeding and introduction of foods . RESULTS 619 children were evaluated : 318 from the intervention group and 301 from the control group . Exclusive breastfeeding prevalence in the first ( 72.3 versus 59.4 % ; RR = 1.21 ; 95%CI 1.08 - 1.38 ) , second ( 62.6 versus 48.2 % ; RR = 1.29 ; 95%CI 1.10 - 1.53 ) , and third months of life ( 44.0 % versus 34.6 % ; RR = 1.27 ; 95%CI 1.04 - 1.56 ) was higher in the intervention group compared to the control group . The prevalence of children who consumed meat four or five times per week was higher in the intervention group than in the control group ( 36.8 versus 22.6 % ; RR = 1.62 ; 95%CI 1.32 - 2.03 ) . The prevalence of children who had consumed soft drinks ( 34.9 versus 52.5 % ; RR = 0.66 ; 95%CI 0.54 - 0.80 ) , chocolate ( 24.5 versus 36.7 % RR = 0.66 95%CI 0.53 - 0.83 ) , petit suisse ( 68.9 versus 79.7 ; 95%CI 0.75 - 0.98 ) and coffee ( 10.4 versus 20.1 % ; RR = 0.51 ; 95%CI 0.31 - 0.85 ) in their six first months of life was lower in the intervention group . CONCLUSION The training of health professionals had a positive impact on infant feeding practice s , contributing to the promotion of child health The WHO ( 2001 ) recommends exclusive breast-feeding and delaying the introduction of solid foods to an infant 's diet until 6 months postpartum . However , in many countries , this recommendation is followed by few mothers , and earlier weaning onto solids is a commonly reported global practice . Therefore , this prospect i ve , observational study aim ed to assess compliance with the WHO recommendation and examine weaning practice s , including the timing of weaning of infants , and to investigate the factors that predict weaning at ≤ 12 weeks . From an initial sample of 539 pregnant women recruited from the Coombe Women and Infants University Hospital , Dublin , 401 eligible mothers were followed up at 6 weeks and 6 months postpartum . Quantitative data were obtained on mothers ' weaning practice s using semi-structured question naires and a short dietary history of the infant 's usual diet at 6 months . Only one mother ( 0.2 % ) complied with the WHO recommendation to exclusively breastfeed up to 6 months . Ninety-one ( 22.6 % ) infants were prematurely weaned onto solids at ≤ 12 weeks with predictive factors after adjustment , including mothers ' antenatal reporting that infants should be weaned onto solids at ≤ 12 weeks , formula feeding at 12 weeks and mothers ' reporting of the maternal gr and mother as the principal source of advice on infant feeding . Mothers who weaned their infants at ≤ 12 weeks were more likely to engage in other sub-optimal weaning practice s , including the addition of non-recommended condiments to their infants ' foods . Provision of professional advice and exploring antenatal maternal misperceptions are potential areas for targeted interventions to improve compliance with the recommended weaning practice The effectiveness of in-hospital self-care patient education , delivered to patients following heart surgery , is question able , as evidence indicates individuals are not able to absorb and /or retain information at this time . In the absence of adequate instruction , individuals will not have the relevant information to engage in specific self-care behaviors , result ing in the onset of complications and /or hospital readmissions . The purpose of this pilot study was to collect preliminary evidence to demonstrate the impact of an individualized education intervention given above and beyond usual care , delivered , at two points in time , following hospital discharge . A r and omized controlled trial was used in which 34 patients were r and omly assigned to one of two groups . Chi-square analyses to examine differences between groups on complications and hospital readmission rates were conducted . Findings point to the impact of the intervention in reducing the number of hospital readmissions and complications at 3 months following hospital discharge Background Many HIV/AIDS patients experience pain often due to advanced HIV/AIDS infection and side effects of treatment . In sub-Saharan Africa , pain management for people with HIV/AIDS is suboptimal . With survival extended as a direct consequence of improved access to antiretroviral therapy , the prevalence of HIV/AIDS related pain is increasing . As most care is provided at home , the management of pain requires patient and family involvement . Pain education is an important aspect in the management of pain in HIV/AIDS patients . Studies of the effectiveness of pain education interventions for people with HIV/AIDS have been conducted almost exclusively in western countries . Methods / design A r and omised controlled trial is being conducted at the HIV and palliative care clinics of two public hospitals in Malawi . To be elig Output:	There was limited ( low to very low- quality ) evidence of an effect for all growth outcomes . Quality of evidence There is moderate to very low- quality evidence that educational interventions can improve complementary feeding practice s but insufficient evidence to conclude that it impacts growth outcomes . AUTHORS ' CONCLUSIONS Overall , we found evidence that education improves complementary feeding practice
MS213881	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: BACKGROUND Structural and functional alterations of the vasculature may contribute to complications of hypertension . Because angiotensin II may be pivotal in some of these vascular abnormalities , we tested the hypothesis that the angiotensin type 1 ( AT(1 ) ) receptor antagonist losartan , in contrast to the beta-blocker atenolol , would correct resistance artery abnormalities in patients with essential hypertension . METHODS AND RESULTS Nineteen untreated patients with mild essential hypertension ( 47+/-2 years , range 30 to 65 years ; 57 % male ) were r and omly assigned in double-blind fashion to losartan or atenolol treatment for 1 year . Nine age/sex-matched normotensive subjects were also studied . Both treatments reduced blood pressure to a comparable degree ( losartan , from 149+/-4.1/101+/-1.6 to 128+/-3.6/86+/-2.2 mm Hg , P<0.01 ; atenolol , from 150+/-4.0/99+/-1.2 to 130+/-3.2/84+/-1.4 mm Hg , P<0.01 ) . Resistance arteries ( luminal diameter 150 to 350 microm ) dissected from gluteal subcutaneous biopsies were studied on a pressurized myograph . After 1 year of treatment , the ratio of the media width to lumen diameter of arteries from losartan-treated patients was significantly reduced ( from 8.4+/-0.4 % to 6.7+/-0.3 % , P<0.01 ) . Arteries from atenolol-treated patients exhibited no significant change ( from 8 . 3+/-0.3 % to 8.8+/-0.5 % after treatment ) . Endothelium-dependent relaxation ( acetylcholine-induced ) was normalized by losartan ( from 82.1+/-4.9 % to 94.7+/-1.1 % , P<0.01 ) but not by atenolol ( from 80 . 4+/-2.7 % to 81.7+/-4.6 % ) . Endothelium-independent relaxation ( by sodium nitroprusside ) was unchanged after treatment . CONCLUSIONS The AT(1 ) antagonist losartan corrected the altered structure and endothelial dysfunction of resistance arteries from patients with essential hypertension , whereas the beta-blocker atenolol had no effect To investigate the time course of cardiovascular structural changes in patients with essential hypertension after angiotensin-converting enzyme ( ACE ) inhibition , we determined left ventricular structure , minimal vascular resistance in the forearm as an index of resistance vessel structure and stiffness beta of carotid artery in 15 essential hypertensive subjects during a placebo period and after 2 , 6 , and 12 months of temocapril treatment . Blood pressure decreased within 2 weeks , and the antihypertensive effects were noted throughout the 12-month administration period . Left ventricular mass index decreased significantly after 2 months ( 120+/-12 to 106+/-9 g/m2 ; p < 0.01 ) and was normalized after 12 months ( 88+/-6 g/m2 ) . Postischemic minimal vascular resistance in the forearm decreased gradually from 2.1+/-0.5 to 1.6+/-0.4 PRU at month 12 of temocapril treatment . In contrast , increased stiffness index beta of carotid artery was not altered during a 1-year treatment period ( 11.4+/-4.9 to 11.6+/-3.8 at month 12 of treatment ) . These data indicated that the regression of structural changes of left ventricle and arterioles occurred gradually and progressively for 1-year treatment with ACE inhibition , but large arteries were not affected Seventeen male untreated mild essential hypertensive patients aged 41 + /- 2 years agreed to participate in a double-blind r and omized trial to test the effects of antihypertensive treatment on the structure and function of subcutaneous resistance arteries . Patients were treated with either 50 to 100 mg/d atenolol or 2.5 to 5 mg/d cilazapril . Blood pressure before treatment was 148 + /- 6/99 + /- 1 and 147 + /- 2/99 + /- 1 mm Hg , respectively . At 1 year of treatment blood pressure was 131 + /- 4/85 + /- 2 and 132 + /- 2/87 + /- 1 mm Hg , respectively . Resistance arteries ( 200 to 400 microns lumen diameter ) dissected from subcutaneous gluteal biopsies obtained before treatment and at 1 year showed that the media-lumen ratio of arteries from patients treated with cilazapril was reduced to 6.31 + /- 0.21 % from 7.54 + /- 0.31 % before treatment ( P < .05 ) , still slightly but significantly larger ( P < .05 ) than the media-lumen ratio of resistance arteries of normotensive control subjects ( 5.15 + /- 0.30 % ) . In contrast , in arteries from patients treated with atenolol there was no significant change with treatment ( 7.97 + /- 0.60 % before and 8.07 + /- 0.45 % after 1 year of treatment ) . Active wall tension responses to endothelin-1 were blunted in hypertensive patients and normalized in the cilazapril-treated patients . Depressed active media stress responses to norepinephrine , arginine vasopressin , and endothelin-1 were accordingly normalized in the patients receiving cilazapril as the media width became thinner but were unchanged in those taking atenolol . ( ABSTRACT TRUNCATED AT 250 WORDS Our study attempted to evaluate the importance of changes in the circulating renin-angiotensin-aldosterone system ( RAAS ) and in hemodynamics in relation to observed changes in cardiovascular structure . We studied previously untreated men ( n = 28 ) with essential nonmalignant hypertension and a supine casual diastolic blood pressure > 95 mm Hg on three to four separate ( > 1-week interval ) occasions measured in triplicate . We used intraarterial blood pressure , dye-dilution technique , plethysmography ( h and s ) , eye-ground photos , M-mode echocardiography , radio immunoassays , and multiple regression analysis . Patients were r and omized to 6 months of double-blind treatment with either enalapril or hydrochlorothiazide , following 4 to 6 weeks on placebo . We found that enalapril blocked the plasma angiotensin converting enzyme ( ACE ) with a secondary increment in plasma renin activity ( PRA ) and reductions in angiotensin II ( AII ) and aldosterone . Blood pressure was lowered through a reduction in total peripheral resistance ( TPR ) . Hydrochlorothiazide increased PRA , AII , and aldosterone , and lowered blood pressure mainly through a reduction in cardiac output . Enalapril was significantly more effective than hydrochlorothiazide in reversing structural changes in the retinal and h and vasculature as well as in the heart . A reduction in cardiac hypertrophy was seen even in the occasional enalapril-treated patient , in whom little or no reduction in blood pressure occurred . In the stepwise regression analyses , the changes in retinal and h and vascular structure were most strongly related to various changes in the RAAS , explaining 15 to 34 % of the variance . For the changes in cardiac structure , the type of therapy ( enalapril or hydrochlorothiazide ) appeared to be the most important factor , explaining between 29 and 50 % of the variance . The changes in cardiac structure were even more strongly related to changes in the RAAS for the enalapril treated patients and explained up to 55 % of the variance in cardiac structure . It can be concluded that the reversal of structural vascular changes during antihypertensive therapy was more dependent on the blockade of the RAAS than on lowering of the blood pressure In a double-blind r and omized trial , the effects of treatment with an angiotensin-converting enzyme ( ACE ) inhibitor ( perindopril ) and a beta-blocker ( atenolol ) on small artery structure were compared in previously untreated essential hypertensive patients . Subjects ( diastolic blood pressure > or = 100 and < or = 120 mm Hg ) were r and omly assigned to treatment for 12 months with either perindopril ( n = 13 , 4 to 8 mg/d ) or atenolol ( n = 12 , 50 to 100 mg/d ) ; the dosage was adjusted upward and in some cases combined ( n = 5 , perindopril ; n = 2 , atenolol ) with thiazide diuretic to achieve target blood pressure ( diastolic blood pressure below 90 mm Hg ) . Before and at the end of treatment , gluteal biopsies were taken under local anesthetic ; from these biopsies , two small arteries were dissected and mounted on a myograph for morphometry . The reduction in blood pressure with atenolol ( drop in mean blood pressure 28.4 + /- 1.8 mm Hg ) was greater than with perindopril ( 20.6 + /- 1.8 mm Hg , P < .05 ) . Perindopril treatment caused an increase in small artery diameter ( 231 + /- 14 to 274 + /- 13 microns , P < .05 ) and a reduction in the ratio of media thickness to lumen diameter ( 7.94 + /- 0.65 % to 5.96 + /- 0.42 % , P < .05 ) , whereas atenolol had no effect ( 246 + /- 14 to 231 + /- 13 microns and 7.14 + /- 0.47 % to 6.79 + /- 0.45 % , respectively ) . The change in small artery morphology caused by perindopril was not accompanied by any change in media cross-sectional area , suggesting that the change was due to " remodeling . " ( ABSTRACT TRUNCATED AT 250 WORDS In order to investigate whether hypertension-related structural vascular changes may be influenced by antihypertensive treatment , 10 patients were studied suffering from essential arterial hypertension , five males and five females , aged between 34 and 61 years ( mean age : 46.9 + /- 8.13 years ) . All patients received a placebo for 1 week and then captopril , 75 mg b.i.d . for 3 months . After placebo and captopril treatments , the following parameters were evaluated : SBP , DBP , mean blood pressure ( MBP ) , by the formula 1/3 ( SBP + 2 x DBP ) and basal and minimal vascular resistances , respectively obtained by the ratios MBP/rest flow and MBP/peak flow . Blood flows have been obtained by strain gauge plethysmography . A significant decrease in systolic ( P less than 0.025 ) , diastolic ( P less than 0.01 ) and mean blood pressure ( P less than 0.01 ) , basal vascular resistances ( 52 + /- 19 vs 28 + /- 12 A.U. , P less than 0.01 ) and minimal vascular resistances ( 6.3 + /- 2.2 vs 3.9 + /- 2.8 A.U. , P less than 0.025 ) has been observed after captopril treatment in comparison to placebo , whereas rest ( 2.9 + /- 0.7 vs 4.1 + /- 0.9 ml.min-1.100 g-1 , P less than 0.01 ) and peak blood flows ( 21.3 + /- 5.8 vs 29.7 + /- 9.4 ml.min-1.100 g-1 ) significantly increased . These data seem to indicate that antihypertensive treatment with the angiotensin-converting enzyme inhibitor , captopril , is not only efficacious in inducing a significant blood pressure decrease , consequent to the reduction of basal vascular resistance ( due to the vasodilating effects of the drug ) , but is also able to reduce minimal vascular resistance . ( ABSTRACT TRUNCATED AT 250 WORDS We studied the structural and functional characteristics of the vascular bed at calf level in 46 middle aged hypertensive patients ( 20 males and 26 females ) treated with different beta-blockers . After one week of placebo , the patients were divided into three groups : group 1 was treated with labetalol , an alpha-beta-blocker ( 200 mg t.t.d . ) ; group 2 was treated with acebutolol , a cardioselective beta-blocker with intrinsic sympathomimetic activity ( ISA ) ( 200 mg t.t.d . ) ; group 2 was treated with acebutolol , a cardioselective beta-blocker with intrinsic sympathomimetic activity ( ISA ) ( 200 mg t.t.d . ) ; group 3 was treated with metoprolol , a cardioselective beta-blocker without ISA ( 100 mg t.t.d . ) . Before and after placebo , and after three months of active drug treatment , we measured blood pressure , and rest and peak flow at the calf level by strain gauge plethysmography . Basal and minimal vascular resistances were calculated as the ratio between mean blood pressure and rest or peak flow , respectively . A Output:	The survey shows that change in blood pressure in indeed a poor indicator of change in resistance vessel structure . However , it is a remarkably consistent finding that normalization of resistance vessel structure is obtained with therapeutic regimens which reduce blood pressure by vasodilation rather than by lowering cardiac output Thus , to the extent that normalization of resistance vessel structure is deemed a goal of antihypertensive treatment , the survey points towards the importance of considering not only the treatment effect on blood pressure , but also the haemodynamic effects within patients with essential hypertension
MS213882	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: BACKGROUND In the ESSENCE trial , subcutaneous low-molecular-weight heparin ( enoxaparin ) reduced the 30-day incidence of death , myocardial infa rct ion , and recurrent angina relative to intravenous unfractionated heparin in 3171 patients with acute coronary syndrome ( unstable angina or non-Q-wave myocardial infa rct ion ) . No increase in major bleeding was seen . METHODS AND RESULTS Of the 936 ESSENCE patients r and omized in the United States , 655 had hospital billing data collected . For the remainder , hospital costs were imputed with a multivariable linear regression model ( R2=.86 ) . Physician fees were estimated from the Medicare Fee Schedule . During the initial hospitalization , major re source use was reduced for enoxaparin patients , with the largest effect seen with coronary angioplasty ( 15 % versus 20 % for heparin , P=.04 ) . At 30 days , these effects persisted , with the largest reductions seen in diagnostic catheterization ( 57 % versus 63 % for heparin , P=.04 ) and coronary angioplasty ( 18 % versus 22 % , P=.08 ) . All re source use trends seen in the US cohort were also evident in the overall ESSENCE study population . In the United States , the mean cost of a course of enoxaparin therapy was $ 155 , whereas that for heparin was $ 80 . The total medical costs ( hospital , physician , drug ) for the initial hospitalization were $ 11 857 for enoxaparin and $ 12620 for heparin , a cost advantage for the enoxaparin arm of $ 763 ( P=.18 ) . At the end of 30 days , the cumulative cost savings associated with enoxaparin was $ 1172 ( P=.04 ) . In 200 bootstrap sample s of the 30-day data , 94 % of the sample s showed a cost advantage for enoxaparin . CONCLUSIONS In patients with acute coronary syndrome , low-molecular-weight heparin ( enoxaparin ) both improves important clinical outcomes and saves money relative to therapy with st and ard unfractionated heparin BACKGROUND Despite the use of aspirin , there is still a risk of ischaemic events after percutaneous coronary intervention ( PCI ) . We aim ed to find out whether , in addition to aspirin , pretreatment with clopidogrel followed by long-term therapy after PCI is superior to a strategy of no pretreatment and short-term therapy for only 4 weeks after PCI . METHODS 2658 patients with non-ST-elevation acute coronary syndrome undergoing PCI in the CURE study had been r and omly assigned double-blind treatment with clopidogrel ( n=1313 ) or placebo ( n=1345 ) . Patients were pretreated with aspirin and study drug for a median of 6 days before PCI during the initial hospital admission , and for a median of 10 days overall . After PCI , most patients ( > 80 % ) in both groups received open-label thienopyridine for about 4 weeks , after which study drug was restarted for a mean of 8 months . The primary endpoint was a composite of cardiovascular death , myocardial infa rct ion , or urgent target-vessel revascularisation within 30 days of PCI . The main analysis was by intention to treat . FINDINGS There were no drop-outs . 59 ( 4.5 % ) patients in the clopidogrel group had the primary endpoint , compared with 86 ( 6.4 % ) in the placebo group ( relative risk 0.70 [ 95 % CI 0.50 - 0.97 ] , p=0.03 ) . Long-term administration of clopidogrel after PCI was associated with a lower rate of cardiovascular death , myocardial infa rct ion , or any revascularisation ( p=0.03 ) , and of cardiovascular death or myocardial infa rct ion ( p=0.047 ) . Overall ( including events before and after PCI ) there was a 31 % reduction cardiovascular death or myocardial infa rct ion ( p=0.002 ) . There was less use of glycoprotein IIb/IIIa inhibitor in the clopidogrel group ( p=0.001 ) . At follow-up , there was no significant difference in major bleeding between the groups ( p=0.64 ) . INTERPRETATION In patients with acute coronary syndrome receiving aspirin , a strategy of clopidogrel pretreatment followed by long-term therapy is beneficial in reducing major cardiovascular events , compared with placebo OBJECTIVES The aim of this study was to determine the economic impact of several anticoagulation strategies for moderate- and high-risk non-ST-segment elevation acute coronary syndrome ( NSTE-ACS ) patients managed invasively . BACKGROUND The ACUITY ( Acute Catheterization and Urgent Intervention Triage Strategy ) trial demonstrated that bivalirudin monotherapy yields similar rates of ischemic complications and less bleeding than regimens incorporating glycoprotein IIb/IIIa receptor inhibitors ( GPI ) for moderate- and high-risk NSTE-ACS . METHODS In ACUITY , 7,851 U.S. patients were r and omized to : 1 ) heparin ( unfractionated or enoxaparin ) + GPI ; 2 ) bivalirudin + GPI ; or 3 ) bivalirudin monotherapy . Patients assigned to GPI were also r and omized to upstream GPI before catheterization or selective GPI only with percutaneous coronary intervention . Re source use data were collected prospect ively through 30-day follow-up . Costs were estimated with st and ard methods including re source -based accounting , hospital billing data , and the Medicare fee schedule . RESULTS At 30 days , ischemic events were similar for all groups . Major bleeding was reduced with bivalirudin monotherapy compared with heparin + GPI or bivalirudin + GPI ( p < 0.001 ) . Length of stay was lowest with bivalirudin monotherapy or bivalirudin + catheterization laboratory GPI ( p = 0.02 ) . Despite higher drug costs , aggregate hospital stay costs were lowest with bivalirudin monotherapy ( mean difference range : $ 184 to $ 1,081 , p < 0.001 for overall comparison ) and at 30 days ( mean difference range : $ 123 to $ 938 , p = 0.005 ) . Regression modeling demonstrated that hospital savings were primarily due to less major and minor bleeding with bivalirudin ( $ 8,658/event and $ 2,282/event , respectively ) . CONCLUSIONS Among U.S. patients in the ACUITY trial , bivalirudin monotherapy compared with heparin + GPI result ed in similar protection from ischemic events , reduced bleeding , and shorter length of stay . Despite higher drug costs , aggregate hospital and 30-day costs were lowest with bivalirudin monotherapy . Thus bivalirudin monotherapy seems to be an economically attractive alternative to heparin + GPI for patients with moderate- and high-risk NSTE-ACS . ( Comparison of Angiomax Versus Heparin in Acute Coronary Syndromes [ ACS ] ; NCT00093158 ) Background The CURE study demonstrated that clopidogrel prevents a range of ischaemic cardiovascular events in patients with Acute Coronary Syndromes ( unstable angina or non-ST-segment elevation MI ) . Design We undertook an economic analysis of the use of clopidogrel in the UK , USA , Sweden , France and Canada based on the CURE study . Methods The costs of hospitalization , study drug and other medications were calculated , based on re source utilization for all patients in CURE . Unit costs were obtained for all re source items for each country , and are reported in local currencies in 2001 prices . Results While hospitalization costs were lower in the clopidogrel group , when the acquisition cost of clopidogrel for 9 months is included , the average cost per patient is higher in the clopidogrel group than the placebo group in all countries [ difference in costs ( with 95 % CI ) UK £ 208 ( 119 , 297 ) , US$ 451 ( 58 , 845 ) , SKr 2571 ( 728 , 4412 ) , Fr ∊325 ( 85 , 565 ) , C$ 161 ( −185 , 506 ) ] . The absolute reduction in the number of total primary events was 2.0 % , result ing in an incremental cost-effectiveness ratio ( ICER ) of £ 10,366 in the UK , $ 22,484 in the USA , SKr 127,951 in Sweden , ∊16,186 in France , and C$ 7973 in Canada per primary event avoided with clopidogrel . Conclusions Clopidogrel in CURE reduced hospitalization costs but the acquisition cost of clopidogrel creates an overall increase in direct health care costs over 9 months . Nevertheless , the cost-effectiveness is in a range comparable to other therapies currently utilized for acute coronary syndromes BACKGROUND In the PURSUIT trial , eptifibatide significantly reduced the 30-day incidence of death and myocardial infa rct ion relative to placebo in 9461 patients with an acute coronary syndrome ( unstable angina or non-Q-wave myocardial infa rct ion ) . METHODS AND RESULTS We conducted a 2-part prospect i ve economic sub study of the 3522 US patients enrolled in PURSUIT : ( 1 ) an empirical intention-to-treat comparison of medical costs ( hospital plus physician ) up to 6 months after hospitalization and ( 2 ) a lifetime cost-effectiveness analysis . The base-case cost-effectiveness ratio was expressed as the 1996 US dollars required to add 1 life-year with eptifibatide therapy . The 2 treatment arms had equivalent re source consumption and medical costs ( exclusive of the cost of the eptifibatide regimen ) during the index ( enrollment ) hospitalization ( P=0.78 ) and up to 6 months afterward ( P=0.60 ) . The average wholesale price of the eptifibatide regimen was $ 1217 , but a typical hospital discounted price was $ 1014 . The estimated life expectancy from r and omization in the US patients was 15.96 years for eptifibatide and 15.85 years for placebo , an incremental difference of 0.111 . The incremental cost-effectiveness ratio for eptifibatide therapy in US PURSUIT patients was $ 16 491 per year of life saved . This result was robust through a wide range of sensitivity analyses . The cost-utility ratio for eptifibatide ( using time trade-off defined utilities ) was $ 19 693 per added quality -adjusted life-year . CONCLUSIONS Based on the results observed in the US PURSUIT patients , the routine addition of eptifibatide to st and ard care for non-ST-elevation acute coronary syndrome patients is economically attractive by conventional st and ards AIMS To assess the direct medical costs and cost effectiveness of routine eptifibatide use amongst patients with unstable angina and myocardial infa rct ion without persistent ST-segment elevation in the Western European subgroup of the PURSUIT trial . METHODS AND RESULTS Health care re sources were collected for the Western European PURSUIT trial patients ( n=3697 ) . Unit costs for major re sources were developed within six countries using a consistent bottom-up methodology . Re source consumption from the Western European population was used to calculate the average direct medical costs per patient in the eptifibatide and placebo arms of the trial . Eptifibatide was estimated to cost 524 Euros per treatment . Long-term survival estimated from the 6-month trial survival data and combined with the cost data was used to calculate cost-effectiveness ratios . Additionally , cost per death and non-fatal myocardial infa rct ion at 30 days was calculated . Sensitivity analyses were conducted on the discount rate and re source consumption . Cost-effectiveness ratios ranged from 9603 Euros to 18 115 Euros per year of life saved with 3 % discount . Using re source consumption based on countries with low coronary arteriography rates , the cost per year of life saved was between 3329 Euros and 10 079 Euros . Using re source consumption based on high coronary arteriography rate countries , the cost per year of life saved was between 17 089 Euros and 24 099 Euros . Assuming no difference in treatment costs except for the addition of eptifibatide , the incremental cost per year of life saved was 23 818 Euros . CONCLUSIONS Routine eptifibatide use was associated with a reduction in the combined end-point of death and myocardial infa rct ion at 30 days , which was sustained at 6 months . Long-term projections indicate a modest increase in survival in eptifibatide patients . These data translate into cost-effectiveness ratios that compare favourably with other new technologies that are currently in use BACKGROUND Dual-antiplatelet therapy with aspirin and a thienopyridine is a cornerstone of treatment to prevent thrombotic complications of acute coronary syndromes and percutaneous coronary intervention . METHODS To compare prasugrel , a new th Output:	Conclusions Evidence from the present systematic review suggests that the majority of the available treatments represent either cost-saving or cost-effective options for NSTE-ACS patients .
MS213883	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Aims Atrial fibrillation ( AF ) is associated with adverse outcome . Whether recently discovered genetic risk markers improve AF risk prediction is unknown . Methods and results We derived and vali date d a novel AF risk prediction model from 32 possible predictors in the Women 's Health Study ( WHS ) , a cohort of 20 822 women without cardiovascular disease ( CVD ) at baseline followed prospect ively for incident AF ( median : 14.5 years ) . We then created a genetic risk score ( GRS ) comprised of 12 risk alleles in nine loci and assessed model performance in the validation cohort with and without the GRS . The newly derived WHS AF risk algorithm included terms for age , weight , height , systolic blood pressure , alcohol use , and smoking ( current and past ) . In the validation cohort , this model was well calibrated with good discrimination [ C-index ( 95 % CI ) = 0.718 ( 0.684–0.753 ) ] and improved all reclassification indices when compared with age alone . The addition of the genetic score to the WHS AF risk algorithm model improved the C-index [ 0.741 ( 0.709–0.774 ) ; P = 0.001 ] , the category-less net reclassification [ 0.490 ( 0.301–0.670 ) ; P < 0.0001 ] , and the integrated discrimination improvement [ 0.00526 ( 0.0033–0.0076 ) ; P < 0.0001 ] . However , there was no improvement in net reclassification into 10-year risk categories of < 1 , 1–5 , and 5+% [ 0.041 ( −0.044–0.12 ) ; P = 0.33 ] . Conclusion Among women without CVD , a simple risk prediction model utilizing readily available risk markers identified women at higher risk for AF . The addition of genetic information result ed in modest improvements in predictive accuracy that did not translate into improved reclassification into discrete AF risk categories BACKGROUND Cigarette smoking increases the risk of coronary heart disease , but whether smoking increases atrial fibrillation ( AF ) is uncertain . OBJECTIVE The purpose of this study was to determine the association of cigarette smoking with incident AF in a population -based cohort of blacks and whites . METHODS We determined the risk of incident AF through December 2002 in relation to baseline ( 1987 - 1989 ) smoking status and cigarette-years of smoking in over 15,000 participants of the prospect i ve Atherosclerosis Risk in Communities ( ARIC ) study . RESULTS Over a mean follow-up of 13.1 years , 876 incident AF events were identified . Compared to never smokers , the multivariable-adjusted hazard ratios ( HRs ) for AF were 1.32 ( 95 % confidence interval [ CI ] 1.10 - 1.57 ) in former smokers , 2.05 ( 95 % CI 1.71 - 2.47 ) in current smokers , and 1.58 ( 95 % CI 1.35 - 1.85 ) in ever smokers . In the highest tertile of accumulated smoking amount ( > 675 cigarette-years ) , the incidence of AF was 2.10 times greater ( 95 % CI 1.74 - 2.53 ) than in those who never smoked . Associations were similar by gender , race , type of event ( AF and atrial flutter ) , and when only AF events identified by study exam ECGs were included . Finally , individuals who quit smoking exhibited a trend indicating a slightly lower risk of developing AF ( HR 0.88 , 95 % CI 0.65 - 1.17 ) compared to those who continued to smoke . CONCLUSION Smoking was associated with the incidence of AF , with more than a two-fold increased risk of AF attributed to current smoking . In addition , a trend toward a lower incidence of AF appeared among smokers who quit compared to continued smokers BACKGROUND Cigarette smoking is a known risk factor for cardiovascular disease ( CVD ) , but its relationship to the development of hypertension is unclear . Previous epidemiological studies have shown inconsistent results , having demonstrated inverse and positive associations between cigarette smoking and the development of hypertension . METHODS We analyzed 13,529 male participants from the Physicians ' Health Study free of baseline hypertension and CVD who provided information about smoking status . Smoking status was categorized as never , past , or current < 20 cigarettes/day , or current > or = 20 cigarettes/day . Incident hypertension was defined as either the initiation of antihypertensive treatment , self-reported systolic blood pressure ( BP ) > or = 140 mm Hg , or diastolic BP > or = 90 mm Hg . RESULTS Over a median follow-up of 14.5 years , 4,904 men developed hypertension . We modeled the risk of developing hypertension by baseline smoking status adjusting for known risk factors for hypertension or CVD . In a fully adjusted Cox proportional hazards model , we found that compared with never smokers , past smokers and current smokers had corresponding relative risks ( RRs ) of 1.08 and 1.15 of developing hypertension . The risk for smokers did not appear to differ based on number of cigarettes smoked daily . Further , the RR of hypertension was higher for men with normal vs. prehypertensive levels of systolic ( SBP ) or diastolic BP ( DBP ) . CONCLUSIONS This prospect i ve cohort data suggests that cigarette smoking may be a modest but important risk factor for the development of hypertension The validity of atrial fibrillation ( AF ) diagnoses in national registers for use as endpoints in prospect i ve studies has not been evaluated . We studied the validity of AF diagnoses in Swedish national hospital discharge and cause of death registers and the occurrence of and risk factors for AF in a middle-aged Swedish population using these registers . Our study included the 30,447 individuals ( age 44–73 ) who attended baseline visits in 1991–1996 of the Malmö Diet and Cancer study . Individuals with a first AF diagnosis were identified by record linkage with national registers . A subset of cases was r and omly selected for validation by examination of electrocardiograms and patient records . Electrocardiograms were available in 98 % of the validation sample ( 95 % definitive AF , 3 % no AF ) . The 2 % with ECGs unavailable had probable AF . Baseline AF prevalence was 1.3 % , higher in men and increased with age . During 11.2 years of follow-up 1430 first AF diagnoses occurred . Risk factors were age , hypertension , BMI , diabetes , history of heart failure , history of myocardial infa rct ion and , in men but not women , current smoking . The strongest risk factors were history of heart failure ( hazard ratio men 4.5 , women 8.7 ) and myocardial infa rct ion ( hazard ratio men 2.0 , women 1.8 ) . The largest population attributable risks were observed for hypertension ( men 38 % , women 34 % ) and obesity ( men 11 % , women 10 % ) . In conclusion , case misclassification of AF in national registers is small , indicating feasibility of use in prospect i ve studies . Hypertension and obesity account for large portions of population risk in middle-aged individuals with low prevalence of manifest cardiac disease Atrial fibrillation ( AF ) is the most frequently encountered cardiac arrhythmia . It is a risk factor for stroke and premature death . We studied the temporal changes in the prevalence of AF from 1976 to 1994 in a r and om population aged 50 to 89 years . The prevalence of AF , diagnosed from electrocardiograms ( ECGs ) , was determined in 8,606 patients examined in 1976 to 1978 , in 8,943 patients examined in 1981 to 1983 , and in 6,733 subjects examined in 1991 to 1994 . Changes in prevalence of AF were estimated by logistic regression analysis . In men , the age-st and ardized prevalence of AF increased from 1.4 % in 1976 to 1978 ( odds ratio [ OR ] 1.0 , reference ) to 1.9 % in 1981 to 1983 ( OR 1.6 , 95 % confidence interval [ CI ] 1.1 to 2.1 ) , and to 3.3 % in 1991 to 1994 ( OR 2.3 , 95 % CI 1.6 to 3.4 , p<0.001 , adjusted for age ) . In women , the prevalence of AF decreased from 1.5 % in 1976 to 1978 ( OR 1.0 , reference ) to 1.0 % in 1981 to 1983 ( OR 0.7 , 95 % CI 0.5 to 1.0 ) , and to 1.1 % in 1991 to 1994 ( OR 0.7 , 95 % CI 0.5 to 1.0 ) , although the overall decrease was not significant ( p=0.11 , adjusted for age ) . After adjusting for changes in comorbidity , body weight , and height , the increase in the prevalence of AF in men from 1976 to 1978 and from 1991 to 1994 remained significant ( OR 1.9 , 95 % CI 1.3 to 2.8 , p=0.002 ) . Although unchanged in women , the prevalence of AF in men more than doubled from the 1970s to the 1990s . The factors responsible for this gender-specific increase in the prevalence of this common arrhythmia have yet to be identified BACKGROUND An atrial fibrillation ( AF ) risk score for a non-Western general population has not been established . Methods and Results : A total of 6,898 participants ( 30 - 79 years old ) initially free of AF have been prospect ively followed for incident AF since 1989 . AF was diagnosed when AF or atrial flutter was present on ECG at a biannual health examination ; was indicated as a current illness ; or was in the medical records during follow-up . Cox proportional hazard ratios were analyzed after adjusting for cardiovascular risk factors at baseline . During the 95,180 person-years of follow-up , 311 incident AF events occurred . We developed a scoring system for each risk factor as follows : 0/-5 , 3/0 , 7/5 , and 9/9 points for men/women in their 30 s-40 s , 50 s , 60 s , and 70 s , respectively ; 2 points for systolic hypertension , overweight , excessive drinking , or coronary artery disease ; 1 point for current smoking ; -1 point for moderate non-high-density lipoprotein-cholesterol ; 4 points for arrhythmia ; and 8 , 6 , and 2 points for subjects with cardiac murmur in their 30 s-40 s , 50 s , and 60 s , respectively ( C-statistic 0.749 ; 95 % confidence interval , 0.724 - 0.774 ) . Individuals with score ≤2 , 10 - 11 , or ≥16 points had , respectively , ≤1 % , 9 % , and 27 % observed probability of developing AF in 10 years . CONCLUSIONS We developed a 10-year risk score for incident AF using traditional risk factors that are easily obtained in routine outpatient clinics/health examinations without ECG Background Identification of individuals at risk for developing atrial fibrillation ( AF ) will help to target screening and preventive interventions . We aim ed to vali date the CHARGE-AF model ( including variables age , race , height , weight , blood pressure , smoking , antihypertensive medication , diabetes , myocardial infa rct ion and heart failure ) for prediction of five-year incident AF in a representative European population with a wide age range . Methods and results The CHARGE-AF model was calculated in 24,020 participants of the population -based EPIC Norfolk study with 236 cases of hospitalization with diagnosis of AF within five years . The model showed good discrimination ( c-statistic 0.81 , 95 % confidence interval ( CI ) 0.75–0.85 ) , but weak calibration ( Chi2-statistic 142 ) with an almost two-fold overestimation of AF incidence . A recalibration to characteristics of the European Prospect i ve Investigation into Cancer and Nutrition ( EPIC ) Norfolk cohort improved calibration considerably ( Chi2-statistic 13.3 ) , with acceptable discrimination in participants both > 65 and ≤65 years of age ( c-statistics 0.70 , 95 % CI 0.61–0.77 and 0.83 , 95 % CI 0.74–0.88 ) . The recalibrated model also showed good discrimination in participants free of cardiovascular disease ( c-statistics 0.80 , 95 % CI 0.75–0.84 ) . Categories of predicted risk ( < 2.5 % , 2.5–5 % or > 5 % ) showed good concordance with observed five-year AF incidence of 0.62 % , 3.49 % and 8.74 % ( log rank test p < 0.001 ) , respectively . Conclusion A recalibration of the CHARGE-AF model is Output:	Conclusions The current meta- analysis suggests that smoking is associated with an increased risk of atrial fibrillation in a dose-dependent matter , but the association is weaker among former smokers compared to current smokers
MS213884	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Background Web-based and mobile health interventions ( also called “ Internet interventions ” or " eHealth/mHealth interventions ") are tools or treatments , typically behaviorally based , that are operationalized and transformed for delivery via the Internet or mobile platforms . These include electronic tools for patients , informal caregivers , healthy consumers , and health care providers . The Consoli date d St and ards of Reporting Trials ( CONSORT ) statement was developed to improve the suboptimal reporting of r and omized controlled trials ( RCTs ) . While the CONSORT statement can be applied to provide broad guidance on how eHealth and mHealth trials should be reported , RCTs of web-based interventions pose very specific issues and challenges , in particular related to reporting sufficient details of the intervention to allow replication and theory-building . Objective To develop a checklist , dubbed CONSORT-EHEALTH ( Consoli date d St and ards of Reporting Trials of Electronic and Mobile HEalth Applications and onLine TeleHealth ) , as an extension of the CONSORT statement that provides guidance for authors of eHealth and mHealth interventions . Methods A literature review was conducted , followed by a survey among eHealth experts and a workshop . Results A checklist instrument was constructed as an extension of the CONSORT statement . The instrument has been adopted by the Journal of Medical Internet Research ( JMIR ) and authors of eHealth RCTs are required to su bmi t an electronic checklist explaining how they addressed each subitem . Conclusions CONSORT-EHEALTH has the potential to improve reporting and provides a basis for evaluating the validity and applicability of eHealth trials . Subitems describing how the intervention should be reported can also be used for non- RCT evaluation reports . As part of the development process , an evaluation component is essential ; therefore , feedback from authors will be solicited , and a before-after study will evaluate whether reporting has been improved Developing an evidence base for making public health decisions will require using data from evaluation studies with r and omized and nonr and omized design s. Assessing individual studies and using studies in quantitative research syntheses require transparent reporting of the study , with sufficient detail and clarity to readily see differences and similarities among studies in the same area . The Consoli date d St and ards of Reporting Trials ( CONSORT ) statement provides guidelines for transparent reporting of r and omized clinical trials . We present the initial version of the Transparent Reporting of Evaluations with Nonr and omized Design s ( TREND ) statement . These guidelines emphasize the reporting of theories used and descriptions of intervention and comparison conditions , research design , and methods of adjusting for possible biases in evaluation studies that use nonr and omized design Background Women ’s physical activity levels decline during their transition to parenthood . Facebook is widely used by Australian mothers and provides the opportunity to target social networks in order to maintain and increase physical activity . Method This mixed method study aim ed to pilot and assess the usability of the Mums Step It Up Facebook app , a new team-based physical activity intervention for mothers with young children . A purposive sample of five “ Captain ” women with young children , were recruited through personal contacts . These women used the app to recruit 3–7 Facebook friends ( with children under 5 ) to join their respective teams ( total n = 25 ) . The app encourages women to take 10,000 steps a day measured by a pedometer . Women used the app for 28 days to log steps , interact with team mates and monitor progress . Physical activity was assessed at two time points ( baseline and final week ) using the Active Australia Survey . Usability testing with the five “ Captain ” women took place over two one hour face-to-face sessions . A question naire seeking feedback on the app was completed at time point two . Results Participants ’ total physical activity increased by an average of 177 minutes per week ( p = 0.01 ) . The complexity of the team forming process and issues using the Facebook environment , where a variety of devices and software platforms are used , was highlighted . Discussion A team-based Facebook app shows considerable promise for the recruitment and retention of participants to a social network-based physical activity intervention . A r and omised controlled trial to further evaluate the effectiveness of the intervention is warranted BACKGROUND Despite the increasing popularity of activity trackers , little evidence exists that they can improve health outcomes . We aim ed to investigate whether use of activity trackers , alone or in combination with cash incentives or charitable donations , lead to increases in physical activity and improvements in health outcomes . METHODS In this r and omised controlled trial , employees from 13 organisations in Singapore were r and omly assigned ( 1:1:1:1 ) with a computer generated assignment schedule to control ( no tracker or incentives ) , Fitbit Zip activity tracker , tracker plus charity incentives , or tracker plus cash incentives . Participants had to be English speaking , full-time employees , aged 21 - 65 years , able to walk at least ten steps continuously , and non-pregnant . Incentives were tied to weekly steps , and the primary outcome , moderate-to-vigorous physical activity ( MVPA ) bout min per week , was measured via a sealed accelerometer and assessed on an intention-to-treat basis at 6 months ( end of intervention ) and 12 months ( after a 6 month post-intervention follow-up period ) . Other outcome measures included steps , participants meeting 70 000 steps per week target , and health-related outcomes including weight , blood pressure , and quality -of-life measures . This trial is registered at Clinical Trials.gov , number NCT01855776 . FINDINGS Between June 13 , 2013 , and Aug 15 , 2014 , 800 participants were recruited and r and omly assigned to the control ( n=201 ) , Fitbit ( n=203 ) , charity ( n=199 ) , and cash ( n=197 ) groups . At 6 months , compared with control , the cash group logged an additional 29 MVPA bout min per week ( 95 % CI 10 - 47 ; p=0·0024 ) and the charity group an additional 21 MVPA bout min per week ( 2 - 39 ; p=0·0310 ) ; the difference between Fitbit only and control was not significant ( 16 MVPA bout min per week [ -2 to 35 ; p=0·0854 ] ) . Increases in MVPA bout min per week in the cash and charity groups were not significantly greater than that of the Fitbit group . At 12 months , the Fitbit group logged an additional 37 MVPA bout min per week ( 19 - 56 ; p=0·0001 ) and the charity group an additional 32 MVPA bout min per week ( 12 - 51 ; p=0·0013 ) compared with control ; the difference between cash and control was not significant ( 15 MVPA bout min per week [ -5 to 34 ; p=0·1363 ] ) . A decrease in physical activity of -23 MVPA bout min per week ( 95 % CI -42 to -4 ; p=0·0184 ) was seen when comparing the cash group with the Fitbit group . There were no improvements in any health outcomes ( weight , blood pressure , etc ) at either assessment . INTERPRETATION The cash incentive was most effective at increasing MVPA bout min per week at 6 months , but this effect was not sustained 6 months after the incentives were discontinued . At 12 months , the activity tracker with or without charity incentives were effective at stemming the reduction in MVPA bout min per week seen in the control group , but we identified no evidence of improvements in health outcomes , either with or without incentives , calling into question the value of these devices for health promotion . Although other incentive strategies might generate greater increases in step activity and improvements in health outcomes , incentives would probably need to be in place long term to avoid any potential decrease in physical activity result ing from discontinuation . FUNDING Ministry of Health , Singapore Background While there has been an explosion of mobile device applications ( apps ) promoting healthful behaviors , including physical activity and sedentary patterns , surprisingly few have been based explicitly on strategies drawn from behavioral theory and evidence . Objective This study provided an initial 8-week evaluation of three different customized physical activity-sedentary behavior apps drawn from conceptually distinct motivational frames in comparison with a commercially available control app . Study Design and Methods Ninety-five underactive adults ages 45 years and older with no prior smartphone experience were r and omized to use an analytically framed app , a socially framed app , an affectively framed app , or a diet-tracker control app . Daily physical activity and sedentary behavior were measured using the smartphone ’s built-in accelerometer and daily self-report measures . Results Mixed-effects models indicated that , over the 8-week period , the social app users showed significantly greater overall increases in weekly accelerometry-derived moderate to vigorous physical activity relative to the other three arms ( P values for between-arm differences = .04-.005 ; Social vs. Control app : d = 1.05 , CI = 0.44,1.67 ; Social vs. Affect app : d = 0.89 , CI = 0.27,1.51 ; Social vs. Analytic app : d = 0.89 , CI = 0.27,1.51 ) , while more variable responses were observed among users of the other two motivationally framed apps . Social app users also had significantly lower overall amounts of accelerometry-derived sedentary behavior relative to the other three arms ( P values for between-arm differences = .02-.001 ; Social vs. Control app : d = 1.10,CI = 0.48,1.72 ; Social vs. Affect app : d = 0.94 , CI = 0.32,1.56 ; Social vs. Analytic app : d = 1.24 , CI = 0.59,1.89 ) . Additionally , Social and Affect app users reported lower overall sitting time compared to the other two arms ( P values for between-arm differences < .001 ; Social vs. Control app : d = 1.59,CI = 0.92 , 2.25 ; Social vs. Analytic app : d = 1.89,CI = 1.17 , 2.61 ; Affect vs. Control app : d = 1.19,CI = 0.56 , 1.81 ; Affect vs. Analytic app : d = 1.41,CI = 0.74 , 2.07 ) . Conclusion The results provide initial support for the use of a smartphone-delivered social frame in the early induction of both physical activity and sedentary behavior changes . The information obtained also sets the stage for further investigation of subgroups that might particularly benefit from different motivationally framed apps in these two key health promotion areas . Trial Registration Clinical Trials.gov Background In young men , unhealthy lifestyle behaviours can be detrimental to their physical and /or mental health and set them on a negative health trajectory into adulthood . Despite this , there is a lack of evidence to guide development of effective health behaviour change interventions for young men . This study assessed the feasibility and preliminary efficacy of the ‘ HEYMAN ’ ( Harnessing Ehealth to enhance Young men ’s Mental health , Activity and Nutrition ) healthy lifestyle program for young men . Methods A pilot RCT with 50 young men aged 18–25 years r and omised to the HEYMAN intervention ( n = 26 ) or waitlist control ( n = 24 ) . HEYMAN was a 3-month intervention , targeted for young men to improve eating habits , activity levels and well-being . Intervention development was informed by a participatory research model ( PRECEDE-PROCEED ) . Intervention components included eHealth support ( website , wearable device , Facebook support group ) , face-to-face sessions ( group and individual ) , a personalised food and nutrient report , home-based resistance training equipment and a portion control tool . Outcomes included : feasibility of research procedures ( recruitment , r and omisation , data collection and retention ) and of intervention components . Generalized linear mixed models estimated the treatment effect at 3-months for the primary outcomes : pedometer steps/day , diet quality , well-being and several secondary outcomes . Results A 7-week recruitment period was required to enrol 50 young men . A retention rate of 94 % was achieved at 3-months post-intervention . Retained intervention participants ( n = 24 ) demonstrated reasonable usage levels for most program components and also reported reasonable levels of program component acceptability for attractiveness , comprehension , usability , support , satisfaction and ability to persuade , with scores ranging from 3.0 to 4.6 ( maximum 5 ) . No significant intervention effects were observed for the primary outcomes of steps/day ( 1012.7 , 95 % CI = −506.2 , 2531.6 , p = 0.191 , d = 0.36 ) , diet quality score ( 3.6 , 95 % CI = −0.4 , 7.6 , p = 0.081 , d = 0.48 ) or total well-being score ( 0.4 , 95 % CI = −1.6 , 2.5 , p = 0.683 , d = 0.11 ) . Significant intervention effects were found for daily vegetable servings , energy-dense , nutrient-poor foods , MVPA , weight , BMI , fat mass , waist circumference and cholesterol ( all p < 0.05 ) . Conclusions The HEYMAN program demonstrated feasibility in assisting young men to make some positive lifestyle changes . This provides support for the conduct of a larger , fully-powered RCT , but with minor amendments to research procedures and intervention components required . Trial registration Australian New Zeal and Clinical Trials Registry ACTRN12616000350426 BACKGROUND This pilot study evaluated the feasibility and preliminary effectiveness of a 10-week WhatsApp-based intervention aim ed at enhancing health-related physical fitness components and cardiovascular disease ( CVD ) risk factors compared with a face-to- Output:	Users ’ preferences of social features were mixed : some felt more motivated by social support and competition , while others expressed concerns about comparison , indicating that a one-size-fits-all approach is insufficient . In summary , this is an emerging area of research , with limited evidence suggesting that social features may increase user engagement .
MS213885	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: The aim of the study was to evaluate the safety and efficacy of viscosupplementation with hylan G-F 20 in patients with mild to moderate osteoarthritis ( OA ) presenting with persistent knee pain 4–12 weeks after arthroscopic meniscectomy . A prospect i ve , multi-centre , open study was carried out in patients with pain due to OA of the knee , not resolved by simple analgesics , 4–12 weeks after undergoing arthroscopic meniscectomy . To be eligible , patients had to score ≥50 mm and ≤90 mm on both walking pain and patient global assessment visual analogue scales ( VAS ; 0–100 mm ) at baseline and be radiologically diagnosed pre-operatively with OA grade I or II on the Kellgren-Lawrence scale , with < 50 % joint space narrowing . Patients received three intra-articular , 2 ml injections of hylan G-F 20 in the target knee with an interval of 1 week between injections , and were followed for 52 weeks . The primary efficacy endpoint was the change from baseline in the walking pain VAS score at 26 weeks . Secondary outcome measures were the walking pain VAS scores at all other time points , the WOMAC Index at all time points , and patient and physician global assessment at all time points . The safety of the treatment was assessed using adverse event ( AE ) reports . A total of 62 patients ( mean age 55.4 years , 52 % male ) were enrolled . The mean walking pain VAS score decreased by 36.8 mm from baseline at 26 weeks ( P < 0.0001 ) , and also showed statistically significant decreases ( P < 0.0001 ) at all other time points . The change in WOMAC total and subscale scores from baseline were statistically significant ( P < 0.0001 ) at all time points , as were the decreases in the physician and patient global assessment VAS scores . There were 18 target knee AEs ( mostly pain and /or swelling and /or effusion ) in 12 patients ( 19 % ) considered to be at least possibly related to treatment . The majority of these ( 78 % ) were mild or moderate in intensity . One patient ( 1.6 % ) experienced a serious adverse event ( synovitis ) in the target knee that was considered possibly related to study treatment . Hylan G-F 20 provides effective pain relief and improves stiffness and physical function in patients with mild to moderate OA presenting with persistent osteoarthritic pain 4–12 weeks after arthroscopic meniscectomy . Symptomatic efficacy was maximised at 12 weeks and maintained at 26 and 52 weeks . The type ( pain and /or swelling and /or effusion ) and the intensity ( mostly mild/moderate ) of AEs reported in this study are similar to those reported in other trials in different patient population s , but the incidence was higher ( 19 % ) . The risk/benefit of hylan G-F 20 in this particular population of patients is favourable Background Osteoarthritis is the most prevalent joint disease and a frequent cause of joint pain , functional loss , and disability . Osteoarthritis often becomes chronic , and conventional treatments have demonstrated only modest clinical benefits without lesion reversal . Cell-based therapies have shown encouraging results in both animal studies and a few human case reports . We design ed a pilot study to assess the feasibility and safety of osteoarthritis treatment with mesenchymal stromal cells ( MSCs ) in humans and to obtain early efficacy information for this treatment . Methods Twelve patients with chronic knee pain unresponsive to conservative treatments and radiologic evidence of osteoarthritis were treated with autologous exp and ed bone marrow MSCs by intra-articular injection ( 40 × 106 cells ) . Clinical outcomes were followed for 1 year and included evaluations of pain , disability , and quality of life . Articular cartilage quality was assessed by quantitative magnetic resonance imaging T2 mapping . Results Feasibility and safety were confirmed , and strong indications of clinical efficacy were identified . Patients exhibited rapid and progressive improvement of algofunctional indices that approached 65 % to 78 % by 1 year . This outcome compares favorably with the results of conventional treatments . Additionally , quantification of cartilage quality by T2 relaxation measurements demonstrated a highly significant decrease of poor cartilage areas ( on average , 27 % ) , with improvement of cartilage quality in 11 of the 12 patients . Conclusions MSC therapy may be a valid alternative treatment for chronic knee osteoarthritis . The intervention is simple , does not require hospitalization or surgery , provides pain relief , and significantly improves cartilage quality Systematic review s ( SRs ) are an increasingly popular evidence -based tool and are often used to answer complex research questions across many different research domains . Early SR methodology was advanced by social scientists , and the term meta- analysis was coined by a social scientist who also conducted research in psychology . SRs have recently become popular in healthcare and are likely to be beneficial in any field . The aim of this report is to highlight issues in SR conduct with a focus on the field of nutrition and to make recommendations on improving SR conduct in this area . Development of the research question is probably the most important step in conducting an SR . The 4 main components of an answerable question are 1 ) the patient , population , or problem ; 2 ) the intervention , independent variable , or exposure ; 3 ) the comparators ; and 4 ) the dependent variables or outcomes of interest . The question will be used to determine the optimal methods for conducting the SR . SRs often include study design s beyond r and omized trials and do not always include a meta- analysis of the results . Other topics explored include underst and ing and interpreting discordant review s and the importance of reporting tools [ eg , QUality Of Reporting Of Meta-analyses ( QUOROM Statement ) or CONsoli date d St and ards Of Reporting of Trials ( CONSORT Statement ) ] . Recommendations are then provided , such as developing a capacity-building program , search ing the primary literature for research gaps , and extending reporting tools such as the QUOROM Statement to the field of nutrition Objective To examine the long-term efficacy and safety of five intra-articular injections with hyaluronan in knee osteoarthritis . Methods A multicentre , r and omised , placebo-controlled double-blind study of 337 patients fulfilling the American College of Rheumatology ( ACR ) criteria for knee osteoarthritis ( clinical and laboratory ) and with a Lequesne algofunctional index score ( LFI ) of 10 or greater . Patients received a hyaluronan product ( sodium hyaluronate ; Hyalgan ) ( n=167 ) or saline ( n=170 ) intra-articularly weekly for 5 weeks and were followed up to 1 year . Time to recurrence was the primary efficacy parameter . LFI , pain on walking 50 m based on visual analogue scale ( VAS pain 50 m ) , paracetamol consumption , patients ' global assessment , Nottingham health profile , joint effusion and number of responders were secondary efficacy parameters . The efficacy parameters were analysed by intention to treat ( ITT ) and per protocol ( PP ) . All adverse events ( AE ) were recorded as safety parameters . Results Time to recurrence showed no significant treatment effect ( ITT analysis , p=0.26 ) . Change from baseline in LFI and VAS pain 50 m for the ITT population showed no treatment effect . Paracetamol consumption , patients ' global assessment , responder rates and AE displayed no significant difference between treatment groups , analysed by both ITT and PP . Treatment compliance was 95 % in the hyaluronan group and 99 % in the placebo group . No safety problems were registered . Conclusion In patients fulfilling the ACR criteria for osteoarthritis of the knee with moderate to severe disease activity ( LFI ≥10 ) , five intra-articular injections of hyaluronan did not improve pain , function , paracetamol consumption or other efficacy parameters 3 , 6 , 9 and 12 months after the treatment OBJECTIVE The Arthritis , Diet , and Activity Promotion Trial ( ADAPT ) was a r and omized , single-blind clinical trial lasting 18 months that was design ed to determine whether long-term exercise and dietary weight loss are more effective , either separately or in combination , than usual care in improving physical function , pain , and mobility in older overweight and obese adults with knee osteoarthritis ( OA ) . METHODS Three hundred sixteen community-dwelling overweight and obese adults ages 60 years and older , with a body mass index of > or = 28 kg/m(2 ) , knee pain , radiographic evidence of knee OA , and self-reported physical disability , were r and omized into healthy lifestyle ( control ) , diet only , exercise only , and diet plus exercise groups . The primary outcome was self-reported physical function as measured with the Western Ontario and McMaster Universities Osteoarthritis Index ( WOMAC ) . Secondary outcomes included weight loss , 6-minute walk distance , stair-climb time , WOMAC pain and stiffness scores , and joint space width . RESULTS Of the 316 r and omized participants , 252 ( 80 % ) completed the study . Adherence was as follows : for healthy lifestyle , 73 % ; for diet only , 72 % ; for exercise only , 60 % ; and for diet plus exercise , 64 % . In the diet plus exercise group , significant improvements in self-reported physical function ( P < 0.05 ) , 6-minute walk distance ( P < 0.05 ) , stair-climb time ( P < 0.05 ) , and knee pain ( P < 0.05 ) relative to the healthy lifestyle group were observed . In the exercise group , a significant improvement in the 6-minute walk distance ( P < 0.05 ) was observed . The diet-only group was not significantly different from the healthy lifestyle group for any of the functional or mobility measures . The weight-loss groups lost significantly ( P < 0.05 ) more body weight ( for diet , 4.9 % ; for diet plus exercise , 5.7 % ) than did the healthy lifestyle group ( 1.2 % ) . Finally , changes in joint space width were not different between the groups . CONCLUSION The combination of modest weight loss plus moderate exercise provides better overall improvements in self-reported measures of function and pain and in performance measures of mobility in older overweight and obese adults with knee OA compared with either intervention alone Background Osteoarthritis is the most prevalent joint disease and a common cause of joint pain , functional loss , and disability . Conventional treatments demonstrate only modest clinical benefits without lesion reversal . Autologous mesenchymal stromal cell ( MSC ) treatments have shown feasibility , safety , and strong indications for clinical efficacy . We performed a r and omized , active control trial to assess the feasibility and safety of treating osteoarthritis with allogeneic MSCs , and we obtain information regarding the efficacy of this treatment . Methods We r and omized 30 patients with chronic knee pain unresponsive to conservative treatments and showing radiological evidence of osteoarthritis into 2 groups of 15 patients . The test group was treated with allogeneic bone marrow MSCs by intra-articular injection of 40 × 106 cells . The control group received intra-articular hyaluronic acid ( 60 mg , single dose ) . Clinical outcomes were followed for 1 year and included evaluations of pain , disability , and quality of life . Articular cartilage quality was assessed by quantitative magnetic resonance imaging T2 mapping . Results Feasibility and safety were confirmed and indications of clinical efficacy were identified . The MSC-treated patients displayed significant improvement in algofunctional indices versus the active controls treated with hyaluronic acid . Quantification of cartilage quality by T2 relaxation measurements showed a significant decrease in poor cartilage areas , with cartilage quality improvements in MSC-treated patients . Conclusions Allogeneic MSC therapy may be a valid alternative for the treatment of chronic knee osteoarthritis that is more logistically convenient than autologous MSC treatment . The intervention is simple , does not require surgery , provides pain relief , and significantly improves cartilage quality BACKGROUND Treatment of osteoarthritis is usually limited to short-term symptom control . We assessed the effects of the specific drug glucosamine sulphate on the long-term progression of osteoarthritis joint structure changes and symptoms . METHODS We did a r and omised , double-blind placebo controlled trial , in which 212 patients with knee osteoarthritis were r and omly assigned 1500 mg sulphate oral glucosamine or placebo once daily for 3 years . Weightbearing , anteroposterior radiographs of each knee in full extension were taken at enrolment and after 1 and 3 years . Mean joint-space width of the medial compartment of the tibiofemoral joint was assessed by digital image analysis , whereas minimum joint-space width -- ie , at the narrowest point -- was measured by visual inspection with a magnifying lens . Symptoms were scored by the Western Ontario and McMaster Universities ( WOMAC ) osteoarthritis index . FINDINGS The 106 patients on placebo had a progressive joint-space narrowing , with a mean joint-space loss after 3 years of -0.31 mm ( 95 % CI -0.48 to -0.13 ) . There was no significant joint-space loss in the 106 patients on glucosamine sulphate : -0.06 mm ( -0.22 to 0.09 ) . Similar results were reported with minimum joint-space narrowing . As assessed by WOMAC scores , symptoms worsened slightly in patients on placebo compared with Output:	Lifestyle modifications ( moderate exercise and weight loss ) , paracetamol , glucosamine , Intraarticular Hyaluronic Acid ( IAHA ) and platelet-rich-plasma ( PRP ) injections have a low risk of harm and beneficial ≥12 month outcomes . Although Nonsteroidal Anti-inflammatory Drugs ( NSAIDs ) provide pain relief , they are associated with increased risk of medical complications . Cortisone injections are associated with radiological cartilage degeneration at > 12 months . Arthroscopy for degenerative meniscal tears in KOA leads to a 3-fold increase in total knee arthroplasty ( TKA ) . TKA improves primary outcomes of KOA but has a low rate of significant medical complications . Treatment with opioids has a lack of evidence for use and a high risk of long-term harm . The use of IAHA and PRP may provide additional symptomatic benefit without the risk of harm . TKA is associated with significant medical complications but is justified by the efficacy of joint replacement in late-stage disease .
MS213886	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Objective Pregnancies complicated by intrauterine growth retardation ( IUGR ) beyond 36 weeks of gestation are at increased risk of neonatal morbidity and mortality . Optimal treatment in IUGR at term is highly debated . Results from the multicenter DIGITAT ( Disproportionate Intrauterine Growth Intervention Trial At Term ) trial show that induction of labor and expectant monitoring result in equal neonatal and maternal outcomes for comparable cesarean section rates . We report the maternal health-related quality of life ( HR-QoL ) that was measured alongside the trial at several points in time . Methods Both r and omized and non-r and omized women were asked to participate in the HR-QoL study . Women were asked to fill out written vali date d question naires , covering background characteristics , condition-specific issues and the Short Form ( SF-36 ) , European Quality of Life ( EuroQoL 6D3L ) , Hospital Anxiety and Depression scale ( HADS ) , and Symptom Check List ( SCL-90 ) at baseline , 6 weeks postpartum and 6 months postpartum . We compared the difference scores of all summary measures between the two management strategies by ANOVA . A repeated measures multivariate mixed model was defined to assess the effect of the management strategies on the physical ( PCS ) and mental ( MCS ) components of the SF-36 . Analysis was by intention to treat . Results We analyzed data of 361 r and omized and 198 non-r and omized patients . There were no clinical ly relevant differences between the treatments at 6 weeks or 6 months postpartum on any summary measures ; e.g. , on the SF-36 ( PCS : P = .09 ; MCS : P = .48 ) . The PCS and the MCS were below norm values at inclusion . The PCS improved over time but stayed below norm values at 6 months , while the MCS did not improve . Conclusion In pregnancies complicated by IUGR beyond 36 weeks , induction of labor does not affect the long-term maternal quality of life Background Around 80 % of intrauterine growth restricted ( IUGR ) infants are born at term . They have an increase in perinatal mortality and morbidity including behavioral problems , minor developmental delay and spastic cerebral palsy . Management is controversial , in particular the decision whether to induce labour or await spontaneous delivery with strict fetal and maternal surveillance . We propose a r and omised trial to compare effectiveness , costs and maternal quality of life for induction of labour versus expectant management in women with a suspected IUGR fetus at term . Methods / design The proposed trial is a multi-centre r and omised study in pregnant women who are suspected on clinical grounds of having an IUGR child at a gestational age between 36 + 0 and 41 + 0 weeks . After informed consent women will be r and omly allocated to either induction of labour or expectant management with maternal and fetal monitoring . R and omisation will be web-based . The primary outcome measure will be a composite neonatal morbidity and mortality . Secondary outcomes will be severe maternal morbidity , maternal quality of life and costs . Moreover , we aim to assess neurodevelopmental and neurobehavioral outcome at two years as assessed by a postal enquiry ( Child Behavioral Check List-CBCL and Ages and Stages Question naire-ASQ ) . Analysis will be by intention to treat . Quality of life analysis and a preference study will also be performed in the same study population . Health technology assessment with an economic analysis is part of this so called Digitat trial ( Disproportionate Intrauterine Growth Intervention Trial At Term ) . The study aims to include 325 patients per arm . Discussion This trial will provide evidence for which strategy is superior in terms of neonatal and maternal morbidity and mortality , costs and maternal quality of life aspects . This will be the first r and omised trial for IUGR at term . Trial registration Dutch Trial Register and IS RCT N-Register : IS RCT N10363217 OBJECTIVE To test whether steroids reduce respiratory distress in babies born by elective caesarean section at term . DESIGN Multicentre pragmatic r and omised trial . SETTING 10 maternity units . PARTICIPANTS 998 consenting women r and omised at decision to deliver by elective caesarean section ; 503 r and omised to treatment group . INTERVENTIONS The treatment group received two intramuscular doses of 12 mg betamethasone in the 48 hours before delivery . The control group received treatment as usual . OUTCOME MEASURES The primary outcome was admission to special care baby unit with respiratory distress . Secondary outcomes were severity of respiratory distress and level of care in response . RESULTS Sex , birth weight , and gestation were not different between the two groups . Of the 35 babies admitted to special baby units with respiratory distress , 24 were in the control group and 11 in the intervention group ( P = 0.02 ) . The incidence of admission with respiratory distress was 0.051 in the control group and 0.024 in the treatment group ( relative risk 0.46 , 95 % confidence interval 0.23 to 0.93 ) . The incidence of transient tachypnoea of the newborn was 0.040 in the control group and 0.021 in the treatment group ( 0.54 , 0.26 to 1.12 ) . The incidence of respiratory distress syndrome was 0.011 in the control group and 0.002 in the treatment group ( 0.21 , 0.03 to 1.32 ) . CONCLUSIONS Antenatal betamethasone and delaying delivery until 39 weeks both reduce admissions to special care baby units with respiratory distress after elective caesarean section at term OBJECTIVE The Disproportionate Intrauterine Growth Intervention Trial at Term ( DIGITAT trial ) showed that in women with suspected intrauterine growth restriction ( IUGR ) at term , there were no substantial outcome differences between induction of labour and expectant monitoring . The objective of the present analysis is to evaluate whether maternal or fetal markers could identify IUGR fetuses who would benefit from early labour induction . STUDY DESIGN The DIGITAT trial was a multicenter , parallel and open-label r and omised controlled trial in women who had a singleton pregnancy beyond 36 + 0 weeks ' gestation with suspected IUGR ( n=650 ) . Women had been r and omly allocated to either labour induction or expectant monitoring . The primary outcome was a composite measure of adverse neonatal outcome , defined as neonatal death before hospital discharge , Apgar score < 7 , umbilical artery pH < 7.05 , or admission to neonatal intensive care . Using logistic regression modelling , we investigated associations between outcome and 17 markers , maternal characteristics and fetal sonographic and Doppler velocimetry measurements , all collected at study entry . RESULTS 17 ( 5.3 % ) infants in the induction group had an adverse neonatal outcome compared to 20 ( 6.1 % ) in the expectant monitoring group . The only potentially informative marker for inducing labour was maternal pre-pregnancy body mass index ( BMI ) . Otherwise , we observed at best weak associations between a benefit from labour induction and maternal age , ethnicity , smoking , parity , pregnancy-induced hypertension or preeclampsia , Bishop score and gestational age , or fetal sonographic markers ( gender , estimated fetal weight , body measurements , oligohydramnios , or umbilical artery pulsatility index and end diastolic flow ) . CONCLUSION In late preterm and term pregnancies complicated by suspected intrauterine growth restriction , most of the known prognostic markers seem unlikely to be helpful in identifying women who could benefit from labour induction , except for maternal pre-pregnancy BMI Objective To compare the effect of induction of labour with a policy of expectant monitoring for intrauterine growth restriction near term . Design Multicentre r and omised equivalence trial ( the Disproportionate Intrauterine Growth Intervention Trial At Term ( DIGITAT ) ) . Setting Eight academic and 44 non-academic hospitals in the Netherl and s between November 2004 and November 2008 . Participants Pregnant women who had a singleton pregnancy beyond 36 + 0 weeks ’ gestation with suspected intrauterine growth restriction . Interventions Induction of labour or expectant monitoring . Main outcome measures The primary outcome was a composite measure of adverse neonatal outcome , defined as death before hospital discharge , five minute Apgar score of less than 7 , umbilical artery pH of less than 7.05 , or admission to the intensive care unit . Operative delivery ( vaginal instrumental delivery or caesarean section ) was a secondary outcome . Analysis was by intention to treat , with confidence intervals calculated for the differences in percentages or means . Results 321 pregnant women were r and omly allocated to induction and 329 to expectant monitoring . Induction group infants were delivered 10 days earlier ( mean difference −9.9 days , 95 % CI −11.3 to −8.6 ) and weighed 130 g less ( mean difference −130 g , 95 % CI −188 g to −71 g ) than babies in the expectant monitoring group . A total of 17 ( 5.3 % ) infants in the induction group experienced the composite adverse neonatal outcome , compared with 20 ( 6.1 % ) in the expectant monitoring group ( difference −0.8 % , 95 % CI −4.3 % to 3.2 % ) . Caesarean sections were performed on 45 ( 14.0 % ) mothers in the induction group and 45 ( 13.7 % ) in the expectant monitoring group ( difference 0.3 % , 95 % CI −5.0 % to 5.6 % ) . Conclusions In women with suspected intrauterine growth restriction at term , we found no important differences in adverse outcomes between induction of labour and expectant monitoring . Patients who are keen on non-intervention can safely choose expectant management with intensive maternal and fetal monitoring ; however , it is rational to choose induction to prevent possible neonatal morbidity and stillbirth . Trial registration International St and ard R and omised Controlled Trial number IS RCT N10363217 Objectives : In low-risk pregnancies , the management of oligohydramnios is not clear . The aim of this study was to compare maternal and neonatal outcomes in cases of isolated oligohydramnios r and omised to either induction of labour or expectant management . Methods : 87 women pregnant beyond 40 completed weeks were asked to participate in the study . Fifty-four accepted and were r and omised at 288 days of pregnancy . Twenty-six were r and omised to expectant management and 28 to induction of labour . The primary maternal outcome was the mode of delivery and the primary neonatal outcomes were cord blood pH and Apgar score at delivery . Results : No significant differences were found for any important maternal or neonatal outcome . Conclusion : Based on these results , the decisions about management could be individualised . Even though the number of patients included was small , these results are well in concordance with others The association between a reduction in fetal movements ( RFM ) and stillbirth has been noted for at least 450 years . This was formalised from the 1970s onwards in a series of studies that noted the increased incidence of stillbirth and FGR in women presenting with RFM , which in some cases preceded intrauterine fetal death by several days . Interpretation of the literature relating RFM to stillbirth and FGR is complicated by differences in studies ’ definitions of RFM and FGR [ 1 ] . Nevertheless , the association between RFM and stillbirth remains , irrespective of the definitions used . Recently , the Auckl and Stillbirth Study confirmed that women who had a RFM were 2.4 times ( 95 % CI 1.29 - 4.35 ) more likely to have a late stillbirth [ 2 ] , which is strikingly similar to a UK-based study which found a 3-fold increase in stillbirth after one presentation with RFM [ 3 ] . RFM , FGR and stillbirth are thought to be related by placental insufficiency , with RFM representing fetal compensation to restriction of nutrients and oxygen in utero [ 4,5 ] . This hypothesis is supported by evidence of abnormal placental structure and amino acid transport in women with RFM , even in the absence of a small-for-gestational age fetus [ 6 ] . Despite the association between RFM and stillbirth , RFM is frequently suboptimally managed clinical ly . Of 422 stillbirths review ed in a confidential enquiry , 16.4 % of cases had suboptimal care related to RFM , including : not communicating the importance of RFM to mothers and a failure to act on RFM [ 7 ] . Reasons for clinicians ’ behaviour have been explored by two related question naire studies , one in the UK and one in Australia and New Zeal and . Both of these studies found significant variations in the definitions of RFM applied to clinical practice and varied knowledge of the association between RFM , FGR and stillbirth . As a consequence clinical management of women with RFM varied significantly , with cardiotocography being used in 80 - 90 % of cases and ultrasound assessment of fetal growth , liquor volume and umbilical artery Doppler in approximately 20 % of cases [ 8,9 ] . Due to the association between RFM , FGR and stillbirth , ultrasound assessment of fetal growth , liquor volume and umbilical artery Doppler may be useful screening tests to identify placental insufficiency [ 10 ] . Norwegian studies have suggested that asking women to be more aware of fetal movements did not increase the number of attendances with RFM . Importantly , the implementation of an associated quality -improvement programme was associated with increased use of ultrasound , but a reduction of stillbirth from 4.2 % to 2.4 % [ 11 ] , strongly suggesting that appropriate identification of , and intervention following , R Output:	AUTHORS ' CONCLUSIONS A policy for planned early delivery versus expectant management for a suspected compromised fetus at term does not demonstrate any differences in major outcomes of perinatal mortality , significant neonatal or maternal morbidity or neurodevelopmental disability . There was also a significant difference in the proportion of babies with a birthweight centile < 2.3rd , however this did not translate into a reduction in morbidity .
MS213887	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Objective To evaluate the efficacy , safety , and quality of life of 5 mg mifepristone per day compared with a placebo in treating uterine fibroids . Design R and omized , double-blind clinical study . Location Eusebio Hernández Gynecology and Obstetrics Teaching Hospital , Havana , Cuba . Subjects One hundred twenty-four subjects with symptomatic uterine fibroids . Treatment One daily capsule of 5 mg mifepristone or a mifepristone placebo over 3 months . Variables in evaluating safety Changes in fibroid and uterine volumes , changes in symptom prevalence and intensity , and changes in quality of life . Results Three months into treatment , fibroid volume was reduced by 28.5 % in the mifepristone group with an increase of 1.8 % in the placebo group ( P = 0.031 ) . There were significant differences between the groups with respect to pelvic pain prevalence ( P = 0.006 ) , pelvic pressure ( P = 0.027 ) , rectal pain ( P = 0.013 ) , hypermenorrhea ( P < 0.001 ) , and metrorrhagia ( P = 0.002 ) at the end of treatment . Amenorrhea was 93.1 % and 4.3 % in the mifepristone and placebo groups , respectively ( P < 0.001 ) . Treatment side effects were significantly greater in the mifepristone group . Estradiol levels did not differ significantly between the placebo and mifepristone groups at the end of treatment . Improvement in quality of life was significantly greater in the categories of “ symptoms ” ( P = 0.004 ) and “ activity ” ( P = 0.045 ) in the mifepristone group . Conclusion The 5 mg dosage of mifepristone presented significantly superior efficacy compared to the placebo BACKGROUND The efficacy and side-effect profile of ulipristal acetate as compared with those of leuprolide acetate for the treatment of symptomatic uterine fibroids before surgery are unclear . METHODS In this double-blind noninferiority trial , we r and omly assigned 307 patients with symptomatic fibroids and excessive uterine bleeding to receive 3 months of daily therapy with oral ulipristal acetate ( at a dose of either 5 mg or 10 mg ) or once-monthly intramuscular injections of leuprolide acetate ( at a dose of 3.75 mg ) . The primary outcome was the proportion of patients with controlled bleeding at week 13 , with a prespecified noninferiority margin of -20 % . RESULTS Uterine bleeding was controlled in 90 % of patients receiving 5 mg of ulipristal acetate , in 98 % of those receiving 10 mg of ulipristal acetate , and in 89 % of those receiving leuprolide acetate , for differences ( as compared with leuprolide acetate ) of 1.2 percentage points ( 95 % confidence interval [ CI ] , -9.3 to 11.8 ) for 5 mg of ulipristal acetate and 8.8 percentage points ( 95 % CI , 0.4 to 18.3 ) for 10 mg of ulipristal acetate . Median times to amenorrhea were 7 days for patients receiving 5 mg of ulipristal acetate , 5 days for those receiving 10 mg of ulipristal acetate , and 21 days for those receiving leuprolide acetate . Moderate-to-severe hot flashes were reported for 11 % of patients receiving 5 mg of ulipristal acetate , for 10 % of those receiving 10 mg of ulipristal acetate , and for 40 % of those receiving leuprolide acetate ( P<0.001 for each dose of ulipristal acetate vs. leuprolide acetate ) . CONCLUSIONS Both the 5-mg and 10-mg daily doses of ulipristal acetate were noninferior to once-monthly leuprolide acetate in controlling uterine bleeding and were significantly less likely to cause hot flashes . ( Funded by PregLem ; Clinical Trials.gov number , NCT00740831 . ) Clinical trials , systematic review s , and guidelines compare beneficial and non-beneficial outcomes following interventions . Often , however , various studies on a particular topic do not address the same outcomes , making it difficult to draw clinical ly useful conclusions when a group of studies is looked at as a whole.1 This problem was recently thrown into sharp focus by a systematic review of interventions for preterm birth prevention , which found that among 103 r and omized trials , no fewer than 72 different outcomes were reported.2 There is a growing recognition among clinical research ers that this variability undermines consistent synthesis of the evidence , and that what is needed is an agreed st and ardized collection of outcomes —a “ core outcomes set”—for all trials in a specific clinical area.1 Recognizing that the current inconsistency is a serious hindrance to progress in our specialty , the editors of over 50 journals related to women ’s health have come together to support The CROWN ( CoRe Outcomes in WomeN ’s health ) Initiative ( ► Table 1 ) . Development of consensus is required around a set of welldefined , relevant , and feasible outcomes for all trials concerning particular obstetric and gynaecologic health conditions , such as preterm birth , incontinence , infertility , and menstrual problems . With somany subspecialties involved , this is no easy task . Duplication of effort can be avoided by working with the Core Outcome Measures in Effectiveness Trials ( COMET ) Initiative , which is working toward core data sets for all medical specialties.3 Production of trustworthy core outcome sets will require engagement with patients , healthcare professionals , research ers , industry , and regulators , and the employment of scientifically robust consensus methods .1 The data for these core outcome sets , once agreed upon , should be collected in trials and reported in publications as st and ard practice in the future . Journal editors now invite research ers to take the lead in beginning this work . What will we do as editors to support them and their colleagues ? First , we are drawing wide attention toThe CROWN Initiative by publishing this editorial in the journals listed below . We shall ensure that the global research community , which includes our many review ers , is aware of the need for core outcome sets . Su bmi ssions which describe development of core outcome sets , if deemed acceptable after peer review , will be effectively disseminated . Our collaboration is not for enforcing harmony at the expense of innovation . To quote from the COMET home page ( www.comet-initiative.org ) : “ The existence or use of a core outcome set does not imply that outcomes in a particular trial should be restricted to those in the relevant core outcome set . Rather , there is an expectation that the core outcomes will be collected and reported , making it easier for the results of trials to be compared , contrasted and combined as appropriate ; while research ers continue to explore other outcomes as well . ” We also expect that as new or superior ways of capturing outcomes emerge , core outcome sets will themselves need updating . Table 1 Aims of The CROWN Objectives The aim of this study was to evaluate the safety and improvement in quality of life using 10 mg and 5 mg daily doses of mifepristone for the treatment of uterine fibroids . Design The research was a r and omized double-blind clinical study undertaken at the Eusebio Hernández Hospital in Havana , Cuba . Subjects and methods Seventy subjects with symptomatic uterine fibroids took one daily capsule of 10 mg or 5 mg mifepristone orally for 9 months . One to three endometrial biopsies were performed . In evaluating safety , the variables studied were endometrial changes associated with mifepristone , elevation of hepatic transaminases , side effects of mifepristone , and instances and duration of irregular bleeding . Results There were 30/49 ( 61.2 % ) and 13/24 ( 54.2 % ) diagnoses of endometrial changes associated with mifepristone in the 10 mg and 5 mg groups , respectively ( P = 0.282 ) . At every evaluation visit the average endometrial thickness was significantly greater in the 10 mg group than in the 5 mg group ( P = 0.013 , P = 0.002 , and P = 0.013 , respectively ) . Only five subjects had slight elevations in their hepatic transaminases after 9 months ’ treatment . Sixteen of 35 ( 45.7 % ) and eight of 33 ( 24.2 % ) subjects had the occasional hot flush in the 10 mg and 5 mg groups , respectively ( P = 0.032 ) . In total , there were 12.9 ± 4.6 ( n = 21 ) and 9.1 ± 3.9 ( n = 18 ) days of irregular bleeding in the 10 mg and 5 mg groups , respectively ( P = 0.009 ) . Conclusion According to the study findings , a 5 mg daily dose over 9 months has a relatively better safety profile than the 10 mg dose OBJECTIVE : To estimate the efficacy of daily administration of 5 mg compared with 10 mg of mifepristone for the treatment of uterine myomas . METHODS : One hundred women were r and omly assigned to receive oral mifepristone 5 mg or 10 mg daily for 3 months ( 50 per group ) . Abdominal ultrasonography was performed before treatment , at 45 days , and at 3 months to evaluate leiomyoma and uterine volumes . Endometrial biopsy specimens were taken before and after treatment . Efficacy was estimated by the reduction percentages of the leiomyoma and uterine volumes . RESULTS : After 90 days treatment there was a 45 % ( 95 % confidence interval [ CI ] 37–54 , P<.001 ) and a 57 % ( 95 % CI 48–67 , P<.001 ) reduction in the leiomyoma volume in the 10-mg and 5-mg groups , respectively , and one of 40 % ( 95 % CI 34–46 , P=.002 ) , and 36 % ( 95 % CI 31–40 , P<.001 ) , respectively , in the uterine volume . Symptomatic improvement was noted , and the prevalence of symptoms diminished significantly . There were no significant differences in reduction of volume and symptoms in the treatment groups , P>.05 in all cases . After treatment , 44 of 49 ( 89.8 % ) women from the mifepristone 10 mg group and 45 of 50 ( 90.0 % ) from the 5-mg group , respectively , were amenorrheic ( P=.487 ) . Endometrial biopsy after treatment showed simple hyperplasia in 1 of 50 ( 2.0 % ) in the mifepristone 10 mg group . CONCLUSION : Five-milligram doses of mifepristone produce reductions in leiomyoma and uterine volumes and symptomatic improvement similar to 10-mg doses . LEVEL OF EVIDENCE : OBJECTIVE Our purpose was to examine the effects of RU 486 and leuprolide acetate on uterine artery blood flow and uterine volume . STUDY DESIGN Patients were r and omly assigned to group A ( eight patients ) receiving 25 mg of RU 486 daily for 3 months or group B ( six patients ) receiving 3.75 mg of leuprolide acetate monthly for 3 months . Uterine artery blood flow change was determined by resistive index by means of vaginal color Doppler ultrasonography . Uterine volume was measured before and during the study with abdominal ultrasonography . RESULTS Both groups showed an increase in resistive index . Patients receiving RU 486 had uterine artery blood flow decreased by 40 % , and those receiving leuprolide acetate had a 21 % decrease . We noted a significant decrease in uterine volume compared with pretreatment in both groups at 3 months . There was no significant decrease between groups . CONCLUSION Both RU 486 ( 25 mg daily ) and leuprolide acetate ( 3.75 mg monthly ) are effective in decreasing blood flow to the uterus ( increasing resistive index ) and decreasing uterine volume at 3 months . A significant decrease in uterine artery blood flow may provide a mechanism for the decrease in uterine size and the decrease in uterine blood loss at the time of surgery Background & objectives : Uterine myoma is a common indication for hysterectomy in India . An effective medical treatment option may reduce hysterectomy associated morbidity . This study was undertaken to evaluate efficacy and safety of low dose mifepristone in medical management of myoma and to compare two doses - 10 vs. 25 mg/day . Methods : In this r and omized clinical trial , women with symptomatic myoma or myoma>5 cm were included . Uterine size > 20 wk , fibroids > 15 cm were excluded . Pictorial blood loss assessment chart ( PBAC ) score was used to assess menstrual-blood-loss and visual analog scale ( VAS ) for other symptoms . Haemogram , liver function test , ultrasound with doppler and endometrial histology was performed . Patients were r and omized and were given oral mifepristone as 25 mg/day in group 1 and 10 mg/day in group 2 for 3 months . Patients were followed at 1 , 3 and 6 months Output:	Short-term use of SPRMs result ed in improved quality of life , reduced menstrual bleeding and higher rates of amenorrhoea than were seen with placebo . Thus , SPRMs may provide effective treatment for women with symptomatic fibroids . Evidence derived from one RCT showed no difference between leuprolide acetate and SPRM with respect to improved quality of life and bleeding symptoms . Evidence was insufficient to show whether effectiveness was different between SPRMs and leuprolide . Investigators more frequently observed SPRM-associated endometrial changes in women treated with SPRMs than in those treated with placebo or leuprolide acetate . As noted above , SPRM-associated endometrial changes are benign , are not related to cancer and are not precancerous .
MS213888	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Abstract Objective To explore the efficacy and safety of fluticasone propionate , cream and ointment , applied twice weekly in addition to maintenance treatment with emollients , in reducing the risk of relapse of chronic recurrent atopic dermatitis . Design R and omised , double blind , parallel group study of 20 weeks ' duration . Setting Dermatology outpatient clinics ( 6 countries , 39 centres ) . Participants Adult ( aged 12 - 65 ) patients with moderate to severe atopic dermatitis who were experiencing a flare . Methods Participants applied fluticasone propionate ( 0.05 % cream or 0.005 % ointment ; once or twice daily ) regularly for four weeks to stabilise their condition . The patients whose disease was brought under control then continued into a 16 week maintenance phase , applying emollient on a daily basis with a bath oil as needed and either the same formulation of fluticasone propionate or its placebo base ( emollient alone ) twice weekly to the areas that were usually affected . Main outcome measure Time to relapse of atopic dermatitis during maintenance phase . Results 376 patients entered the stabilisation phase , and 295 continued into the maintenance phase . After 16 weeks in the maintenance phase , the disease remained under control in 133 patients ( 87 using fluticasone propionate twice weekly , 46 using emollient alone ) , 135 ( 40 fluticasone propionate , 95 emollient ) had experienced a relapse , and 27 had discontinued . Median time to relapse was six weeks for emollient alone compared with more than 16 weeks for additional fluticasone propionate . Patients who applied fluticasone propionate cream twice weekly were 5.8 times less likely ( 95 % confidence interval 3.1 to 10.8 , P < 0.001 ) and patients using fluticasone propionate ointment 1.9 times less likely ( 1.2 to 3.2 , P=0.010 ) to have a relapse than patients applying emollient alone . The groups showed no differences in adverse events . Conclusion After atopic dermatitis had been stabilised the addition of fluticasone propionate twice weekly to maintenance treatment with emollients significantly reduced the risk of relapse BACKGROUND Intermittent dosing of a topical calcineurin inhibitor for preventing atopic dermatitis ( AD ) disease relapse in patients with stabilized AD has not been evaluated . OBJECTIVE We sought to evaluate the long-term efficacy and safety of 3-times-weekly use of tacrolimus ointment in preventing AD disease relapse . METHODS Adult and pediatric patients with moderate to severe AD who were clear of disease after up to 16 weeks of treatment with tacrolimus ointment were r and omized in a double-blind fashion to 3-times-weekly treatment with either tacrolimus ointment ( 0.03 % or 0.1 % ) or vehicle for 40 weeks . The primary end point was the number of flare-free treatment days . RESULTS A total of 125 patients were r and omized to tacrolimus and 72 patients to vehicle . The mean number of flare-free treatment days was 177 for tacrolimus and 134 for vehicle ( P = .003 ) . Median time to first relapse was 169 days for tacrolimus and 43 for vehicle ( P = .037 ) . LIMITATIONS Generalizability to all patients seen in clinic may be limited because only patients who responded to tacrolimus ointment in the stabilization phase were r and omized into the maintenance phase of the trial . CONCLUSIONS Maintenance therapy with tacrolimus ointment was associated with significantly more flare-free days compared with vehicle , and a significantly longer time until first disease relapse Background Rational health care decision‐making based on outcomes and economic evidence is essential to provide the best possible care for individual patients with atopic dermatitis ( AD ) Abstract Objective : To determine whether a three day burst of a potent corticosteroid is more effective than a mild preparation used for seven days in children with mild or moderate atopic eczema . Design : R and omised , double blind , parallel group study of 18 weeks ' duration . Setting : 13 general practice s and a teaching hospital in the Nottingham area . Participants : 174 children with mild or moderate atopic eczema recruited from general practice s and 33 from a hospital outpatient clinic . Interventions : 0.1 % betamethasone valerate applied for three days followed by the base ointment for four days versus 1 % hydrocortisone applied for seven days . Main outcome measures : Primary outcomes were total number of scratch-free days and number of relapses . Secondary outcomes were median duration of relapses , number of undisturbed nights , disease severity ( six area , six sign atopic dermatitis severity scale ) , scores on two quality of life measures ( children 's life quality index and dermatitis family impact question naire ) , and number of patients in whom treatment failed in each arm . Results : No differences were found between the two groups . This was consistent for all outcomes . The median number of scratch-free days was 118.0 for the mild group and 117.5 for the potent group ( difference 0.5 , 95 % confidence interval −2.0 to 4.0 , P=0.53 ) . The median number of relapses for both groups was 1.0 . Both groups showed clinical ly important improvements in disease severity and quality of life compared with baseline . Conclusion : A short burst of a potent topical corticosteroid is just as effective as prolonged use of a milder preparation for controlling mild or moderate atopic eczema in children . What is already known on this topic Topical corticosteroids have been used to control atopic eczema for 40 years No studies have compared short bursts of a potent preparation with prolonged use of a weak preparation for controlling mild or moderate disease What this study adds A short burst of a potent topical steroid is as effective and safe as prolonged use of a weak preparation for mild or moderate atopic eczema The type of preparation is i m material provided that the dosage is In this study several schedules of discontinuous application ( DA ) were tested , using various weak and strong topical corticosteroids ( CS ) . The purpose of this study was to measure the influence of corticosteroids on skin thickness by means of a mechanical method . In a first experiment , betamethasone 17,21-dipropionate ( Bet ) and fluprednidene 21-acetate ( Flu ) were applied to the skin of the volar side of the forearm at a rhythm of 1:1 ( 1 day CS , 1-day interval ) and 1:2 under occlusive dressing . The investigation period was 8 weeks . For comparison , Bet and Flu were applied continuously ( CA ) for 3 weeks . Flu thinned the skin to a lesser extent than Bet . With DA the skin was thinned to the same extent as with CA . In a second experiment , hydrocortisone 17-butyrate , betamethasone 17-valerate , desoxymethasone and hydrocortisone were tested . Here the treatment regimen was 5:9 . The CS preparations were tested for 3 months on the volar side of the forearms under occlusive dressing . Skin thinning occurred during the 5 days of CS action and , in the beginning , receded again in the CS-free interval . However , this regressive process became weaker each time . At the end of the experiment the skin thinning persisted . With the exception of hydrocortisone , all CS tested produced statistically significant skin thinning after DA . The results of the investigation presented here show that thinning of the skin must also be expected with discontinuous application of topical CS Different scoring systems have been developed to determine the severity of atopic dermatitis . The SCORAD ( SCORing Atopic Dermatitis ) , one of the best vali date d systems , is suited for clinical trials , but is too complicated and time consuming for routine clinical use . The TIS score ( Three Item Severity score ) , a simplified system , is based on the evaluation of erythema , oedema/papulation and excoriation on a scale from 0 to 3 . In order to determine the value of the TIS score we conducted a prospect i ve study in 126 children with mild to severe atopic dermatitis . Both the TIS score and the SCORAD were assessed by trained investigators . Interobserver agreement was investigated in 20 children by comparing the independently performed scores of three investigators . A positive correlation was found between the TIS score and the SCORAD ( Rank Spearman r(s)=0.86 ; p<0.0005 ) . The item which correlated best with the SCORAD was excoriation ( r(s)=0.72 ; p<0.0005 ) followed by oedema/papulations ( r(s)=0.66 ; p<0.0005 ) . Interobserver agreement which was calculated by Cohen 's kappa ( kappa ) was " excellent " for SCORAD ( kappa=0.82 ; p<0.001 ) and " fair " for TIS score ( kappa=0.58 ; p<0.01 ) . We conclude that the TIS score is a rough , though reliable and simple system for scoring atopic dermatitis . It is particularly suitable in general practice , for routine clinical use and for screening purpose s in clinical trials . For research purpose s , the objective SCORAD offers a more detailed and comprehensive assessment This study was design ed to investigate a long‐term therapeutic strategy for the management of recurring atopic dermatitis ( AD ) in adults using fluticasone propionate ( FP ) ointment ( CutivateTM ) whereby FP could help to prevent a relapse of AD once symptoms were under control . Adult patients with chronic , moderate to severe AD entered this multicentre study . All patients were initially treated with FP 0.005 % ( g/g ) ointment in two different regimens . Patients whose AD had been completely healed by these treatments then entered a long‐term treatment phase applying FP or placebo ointment once daily , two times per week for 16 weeks to ‘ known ’ healed lesions . By the end of the initial treatment period , mean SCORAD values had significantly ( P < 0.0005 ) improved from baseline . Patients who entered the maintenance phase and were treated with intermittent FP for up to 16 weeks , demonstrated its superior efficacy ( P = 0.018 ) over placebo , maintaining the improvements achieved after the initial treatment phase , reducing risk of relapse and delaying time to relapse ( P = 0.013 ) . No significant changes were detected in either treatment group in serum cortisol levels or in skin thickness measurements . Intermittent FP applied two times per week maintained a significant level of control , and delayed relapse of AD by comparison with placebo Background : Long‐term treatment for atopic dermatitis ( AD ) using low dose , intermittent , topical anti‐inflammatory agents may control acute disease and prevent relapses . This 12‐month , European , multicentre , r and omized study investigated whether the proactive use of 0.1 % tacrolimus ointment applied twice weekly can keep AD in remission and reduce the incidence of disease exacerbations ( DE ) Question : How effective and safe is the addition of twiceweekly fluticasone propionate cream or ointment to regular emollient therapy for reducing relapses in people with chronic relapsing atopic dermatitis ( AD ) ? Design : R and omized , double-blind , parallel-group study . Setting : Thirty-nine dermatology outpatient clinics in 6 European countries . Participants : PeoplewithAD , asdefinedbytheUKWorkingParty ’s refinementofHanifin and Rajka’sdiagnostic criteria , aged 12 to 65 years with moderate to severe disease who were experiencing a flare at study recruitment . Interventions : For the first 4-week phase of the study , all participants weregiven0.05%fluticasonepropionatecream or 0.005 % fluticasone propionate ointment to apply once or twice daily to stabilize their disease . Patients whose disease was brought under control were then entered into a 16-weekmaintenancephaseduringwhich timeemollients and bathoilswereusedasneeded . During themaintenance phase , patients werer and omizedto1of4groups : (1)0.05 % fluticasone propionate cream , ( 2 ) vehicle control for the cream , ( 3 ) 0.005 % fluticasone propionate ointment , or ( 4 ) vehicle control ointment . Each group was instructed toapplythecream/ointmenton2consecutivedayseachweek to areas usually affected by AD plus any new affected areas . Main Outcome Measures : Median time to relapse of AD during the 16-week maintenance phase . Severity was measured using a 3-item severity ( TIS ) score that sums the score on a scale of 0 ( absent ) to 3 ( severe ) for the 3 signs of erythema , edema/papulation , and excoriation at any site displaying a flare during the maintenance phase . A relapse was defined as a score of 4 or more and a remission as a score of 1 or less . Results : A total of 376 patients entered the initial 4-week stabilization phase during which time no significant differences in efficacy were shown between twice and once-daily application of topical fluticasone in cream or ointment form . There were 295 patients who continued into the maintenance phase ( 33 patients discontinued during the stabilization phase and 48 did not meet eligibility criteria for the maintenance phase ) . Median time to relapse was 6 weeks for emollients alone compared with more than 16 weeks for additional twiceweekly fluticasone ( P .001 for cream and P=.010 for ointment ) . After 16 weeks in the maintenance Output:	Meta-regression indicated robustness of these findings . Proactive anti-inflammatory therapy was generally well tolerated . Vehicle-controlled trials indicate efficacy of proactive treatment with tacrolimus , fluticasone propionate and methylprednisolone aceponate to prevent AE flares . Indirect evidence from vehicle-controlled trials suggests that twice weekly application of the potent topical corticosteroid fluticasone propionate may be more efficacious to prevent AE flares than tacrolimus ointment .
MS213889	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: BACKGROUND AND STUDY AIMS Histological examination of core tissue sample s may have advantages over cytology in endoscopic ultrasound (EUS)-guided sampling . We aim ed to evaluate the feasibility and efficiency of a new 22 G core biopsy needle . PATIENTS AND METHODS Consecutive patients with a pancreatic mass lesion or peri-intestinal lymphadenopathy sequentially underwent fine needle biopsy with both a newly developed 22 G core needle ( the FNB needle ) and a st and ard 22 G fine needle aspiration ( FNA ) needle , in r and omized order . RESULTS In 144 patients , mean age 48 years ( ± st and ard deviation [ SD ] 14 ; range 18 - 82 ) , with 145 lesions ( mean lesion size 39 ± 15 mm , range 15 - 99 ) , EUS-guided sampling was technically feasible with both needles in all patients . Mean number of passes to obtain sufficient tissue was 1.2 ± 0.5 with the core needle vs. 2.5 ± 0.9 with the st and ard needle ( P < 0.001 ) . FNB specimens were adequate for evaluation in 125 ( 86.2 % ) vs. 127 ( 87.6 % ) with FNA ( P = 0.72 ) . Among 139 patients available for follow-up , FNB provided a correct diagnosis in 110 ( 79.1 % ) and FNA in 112 ( 80.6 % ) ( P = 0.73 ) . Sensitivity , specificity , positive and negative predictive values , and accuracy for diagnosis of malignancy were 90 % , 100 % , 100 % , 93 % , 96 % for FNB and 77 % , 100 % , 100 % , 85 % , 92 % for FNA , respectively ( P > 0.05 ) . CONCLUSION FNB with the new 22 G core needle was technically feasible , efficient and comparable to FNA with a st and ard needle . The core needle required fewer passes to provide an adequate sample , offering potentially shorter procedure time BACKGROUND A trucut needle biopsy device that can be used to obtain specimens from the pancreas and other perigastric organs under EUS guidance has been developed and successfully tested in animals . Moreover , EUS-guided trucut needle biopsy has been used safely in humans and appears to provide more accurate results than EUS-guided FNA . This study prospect ively assessed the clinical utility of this new device in patients with solid pancreatic masses . METHODS Twenty-three consecutive patients with radiologically detected solid pancreatic masses underwent EUS-guided trucut needle biopsy . Pancreatic malignancy detected by EUS-guided trucut needle biopsy was considered a definitive diagnosis . Further diagnostic procedures and clinical course were used to establish or exclude the presence of malignancy in all other patients . RESULTS Pancreatic tissue was obtained in 17 of the 23 patients ( 74 % ) , including all patients in whom the transgastric approach was used . No acute or long-term complication was observed . Histopathologic evaluation revealed pancreatic cancer in 12 patients . CT-guided biopsy specimens were obtained in 4 of the 5 patients with a negative EUS-guided trucut needle biopsy result ; two were positive for adenocarcinoma . Overall diagnostic accuracy was 61 % . Subgroup analysis of the 16 patients in whom EUS-guided trucut needle biopsy was successful and who were available for follow-up revealed a diagnostic accuracy of 87.5 % . CONCLUSIONS This prospect i ve study demonstrates that EUS-guided trucut needle biopsy , when performed transgastrically , is safe and accurate in the evaluation of patients with solid pancreatic masses The specific needle sizes/types used in performing endoscopic ultrasound-guided fine needle aspirations ( EUS-FNA ) vary . The HD ProCore ( ™ ) is a 22-gauge beveled needle allowing for core biopsy along with aspiration material . In this study we compare this needle with a st and ard 22-gauge needle . Between April 1 , 2011 and November 15 , 2011 , 18 patients undergoing EUS-FNA using the HD ProCore ( ™ ) needle were compared to a control group of 18 cases using the st and ard 22-gauge needle . Smears were assessed for : three-dimensional clusters , thick obscuring clusters , monolayer sheets , cellularity , crowded obscuring single cells , blood , and nuclear staining . Cell blocks were assessed for cellularity and presence of diagnostic material . Records were review ed for the overall adequacy , number of FNA passes , and patient follow-up . Overall , the two needle groups demonstrated similar results for the cytology parameters , amount of diagnostic cell block material , adequacy , and accuracy . The mean number of passes to achieve adequacy varied between the groups [ 2.94 for the st and ard 22-gauge needle group versus 2.11 for the beveled needle group ( P=0.03 ) ] with no meaningful difference in case duration between needle groups . No complications were reported . The beveled EUS needle affords similar cytologic interpretability , adequacy , diagnostic accuracy , and amount of cell block material as a st and ard needle . There was a statistically significant trend toward fewer passes to achieve adequacy with the beveled EUS-FNA needle . Therefore , the EUS-FNA needle with a lateral bevel is a diagnostically similar alternative to st and ard endoscopy needles , the possibility that this beveled needle may improve per pass adequacy requires further verification Background and aims : Endoscopic ultrasound‐guided fine needle aspiration ( EUS‐FNA ) has a diagnostic accuracy of 70–90 % , depending on the site under evaluation . In order to improve EUS‐guided tissue sampling a novel 19‐gauge trucut‐type needle has been design ed to obtain core biopsies during EUS . We prospect ively evaluated the safety and accuracy of EUS‐FNA alone versus combined EUS‐FNA and trucut needle biopsy ( TNB ) in patients referred to our Unit over a 3‐year period Abstract Objective . Endoscopic ultrasonography (EUS)-guided fine-needle aspiration ( EUS-FNA ) may facilitate tissue sampling for histopathological diagnosis of subepithelial tumors ( SETs ) in the gastrointestinal ( GI ) tract . However , immunohistochemistry is not always feasible using EUS-FNA sample s due to the low quality of specimens often obtained by aspiration . This study aim ed to compare the use of 22-gauge ( G ) EUS-guided fine-needle biopsy ( EUS-FNB ) with 22 G EUS-FNA for core sampling used for histopathological examination , including immunohistochemistry , in patients with GI SETs . Methods . Twenty-eight patients with GI SETs ≥2 cm in size were prospect ively enrolled at five university hospitals in Korea between January and June 2013 . They were r and omized to undergo either EUS-FNB or EUS-FNA . Results . A total of 22 patients was finally analyzed in this study : 10 and 12 patients underwent EUS-FNA and EUS-FNB , respectively . Compared to the EUS-FNA group , the EUS-FNB group had a significantly lower median number of needle passes to obtain macroscopically optimal core sample s ( 4 vs. 2 , p = 0.025 ) ; higher yield rates of macroscopically and histologically optimal core sample s with three needle passes ( 30 % vs. 92 % , p = 0.006 ; 20 % vs. 75 % , p = 0.010 , respectively ) ; and a higher diagnostic sufficiency rate ( 20 % vs. 75 % , p = 0.010 ) . No technical difficulties were encountered in either group . Conclusions . This study shows that EUS-FNB has a better ability to obtain histological core sample s and a higher diagnostic sufficiency rate than EUS-FNA and that EUS-FNB is a feasible , safe , and preferable modality for adequate core sampling for histopathological diagnosis of GI SETs BACKGROUND AND STUDY AIMS The fanning technique for endoscopic ultrasound-guided fine-needle aspiration ( EUS - FNA ) involves sampling multiple areas within a lesion with each pass . The aim of this study was to compare the fanning and st and ard techniques for EUS - FNA of solid pancreatic masses . PATIENTS AND METHODS Consecutive patients with solid pancreatic mass lesions were r and omized to undergo EUS - FNA using either the st and ard or the fanning technique . The main outcome measure was the median number of passes required to establish diagnosis . The secondary outcome measures were the diagnostic accuracy , technical failure , and complication rate of the two techniques . RESULTS Of 54 patients , 26 were r and omized to the st and ard technique and 28 to the fanning technique . There was no difference in diagnostic accuracy ( 76.9 % vs. 96.4 % ; P = 0.05 ) , technical failure or complication rates ( none in either cohort ) . There was a significant difference in both the number of passes required to establish diagnosis ( median 1 [ interquartile range 1 - 3 ] vs. 1 [ 1 - 1 ] ; P = 0.02 ) and the percentage of patients in whom a diagnosis was achieved on pass one ( 57.7 % vs. 85.7 % ; P = 0.02 ) between the st and ard and fanning groups , respectively . CONCLUSIONS The fanning technique of FNA was superior to the st and ard approach because fewer passes were required to establish the diagnosis . If these promising data are confirmed by other investigators , consideration should be given to incorporating the fanning technique into routine practice of EUS - FNA . Registered at Clinical Trials.gov ( NCT 01501903 ) BACKGROUND AND STUDY AIMS The aim of this prospect i ve study was to compare fine-needle aspiration guided by endoscopic ultrasonography ( EUS-FNA ) using 25-gauge and 22-gauge needles with the EUS-guided 19-gauge Trucut needle biopsy ( EUS-TNB ) in patients with solid pancreatic mass . PATIENTS AND METHODS Twenty-four consecutive patients with pancreatic mass underwent biopsies by both EUS-FNA and EUS-TNB . Three needles were compared with respect to technical success rate , tissue size obtained , overall diagnostic accuracy and accuracy for histological and cytological diagnosis . RESULTS The 25-gauge EUS-FNA was technically easier and obtained superior overall diagnostic accuracy than the 22-gauge and Trucut needles , especially in lesions of the pancreas head and uncinate process . Overall accuracy for the 25-gauge , 22-gauge and Trucut needle was 91.7 % , 79.7 % and 54.1 % , respectively . Accuracy for cytological diagnosis irrespective the site of lesions with 25-gauge , 22-gauge and Trucut needles was 91.7 % , 75.0 % , and 45.8 % , respectively . For uncinate masses , it was 100 % , 33.3 % , and 0.0 % , respectively . These differences were significant . Among technically successful patients , the accuracy for histological diagnosis using the 25-gauge was significantly inferior ( P < 0.05 ) to 22-gauge and Trucut needles and the rates were 45.8 % , 78.9 % and 83.3 % . CONCLUSIONS The 25-gauge FNA needle was significantly superior in terms of technical success rate and overall diagnostic accuracy , especially for the head and uncinate lesions , compared to the 22-gauge and Trucut needles and could be considered ' the best choice needle for cytological diagnosis ' of solid pancreatic lesions . If histological diagnosis is required , the 22-gauge FNA needle and Trucut needle may be advantageous for use in head/uncinate and body/tail lesions , respectively Endoscopic ultrasound-guided fine-needle aspiration ( EUS-FNA ) is widely used for diagnosis of pancreatic lesions . The Echotip Procore Needle ( Wilson-Cook Medical ) is a new 22 G fine biopsy needle ( FNB ) for obtaining core biopsy material at time of EUS . This study aim ed to compare the technical and diagnostic performance of conventional FNA and FNB . Thirty-two patients met the design criteria for this prospect i ve paired cohort study . All lesions sample d were solid ( non-cystic ) pancreatic masses by EUS appearance . Patients were r and omized to receive FNA or FNB by first attempt . A cytopathologist performed on-site evaluations . Sample s were assessed for accuracy of diagnosis , cellularity , contamination , and sufficiency for ancillary studies . Technical and diagnostic performances were compared . Compared to FNA , there was a statistically significant decreased ability of FNB to achieve a diagnosis ( FNA 93.8 % , FNB 28.1 % , P < 0.001 ) . FNB was diagnostically superior to FNA in 1 of 32 cases . Technical failures were observed in five cases due to resistance to advancement of the FNB needle . Regarding operator perceived ease-of-use , FNA outperformed F Output:	Current data do not demonstrate a significant difference between the ProCore and st and ard FNA needles for sample adequacy , diagnostic accuracy or acquisition of a core specimen . However , the ProCore needle establishes the diagnosis with fewer passes
MS213890	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: OBJECTIVES To study the feasibility and effectiveness of a discharge planning intervention . DESIGN Quasi-experimental pre-post study design . SETTING General medicine wards at three hospitals : an academic medical center , a community teaching hospital , and a community-based nonteaching hospital . PARTICIPANTS All patients aged 65 and older admitted to the hospitalist services . INTERVENTION The intervention toolkit had five core elements : admission form with geriatric cues , facsimile to the primary care provider , interdisciplinary worksheet to identify barriers to discharge , pharmacist-physician collaborative medication reconciliation , and predischarge planning appointments . MEASUREMENTS Thirty-day readmission and return to emergency department rates and patient satisfaction with discharge . Odds ratios were determined , and site effects were examined accordig to interaction terms and Breslow Day statistics . RESULTS Two hundred thirty-seven patients were followed during the preintervention period , and 185 were exposed to the intervention . Patients characteristics were similar across the two time periods . The proportion of patients with high- quality transitions home , measured according to Coleman 's Care Transition Measures , increased from 68 % to 89 % ( odds ratio (OR)=3.49 , 95 % confidence interval (CI)=2.06 - 5.92 ) . Return to the emergency department within 3 days of discharge was lower in the intervention period ( 10 % vs 3 % , OR=0.25 , 95 % CI=0.10 - 0.62 ) . At 30 days , there was a lower rate of readmission ( 22 % vs 14 % , OR=0.59 , 95 % CI=0.34 - 0.97 ) and fewer visits to the emergency department ( 21 % vs 14 % , OR=0.61 , 95 % CI=0.36 - 1.03 ) ( P=.06 ) . CONCLUSION When hospitalized elderly patients are treated with consideration of their specific needs , healthcare outcomes can be improved BACKGROUND Falls are the leading cause of both fatal and nonfatal injuries among older adults in the United States . Medications that affect the central nervous system are known to increase the risk of falling . OBJECTIVE The purpose of this study was to assess the effects of a community pharmacy-based falls-prevention program targeting high-risk older adults on the rates of recurrent falls , injurious falls , and filling prescriptions for medications that have been associated with an increased risk of falling . METHODS This was a r and omized controlled trial of participants recruited through a community pharmacy chain in North Carolina . The 2-year study consisted of a 1-year " look-back " period before r and omization and a 1-year follow-up period after r and omization . Patients were eligible to participate if they were ≥65 years of age , had fallen at least once during the 1-year period preceding enrollment , and were taking medications associated with an increased risk of falling . Medications classified as high risk included benzodiazepines , antidepressants , anticonvulsants , sedative hypnotics , opioid analgesics , antipsychotics , and skeletal muscle relaxants . Participants were assigned to either the intervention arm or the control arm ; participants in the intervention arm were invited to attend a face-to-face medication consultation conducted by a community pharmacy resident , whereas those in the control arm received no medication consultation . The primary end point was the rate of recurrent falls during the 1-year followup period . Secondary end points were the total number of prescriptions for high-risk medications filled during the follow-up period and either discontinued use or a reduction in the dosage of a high-risk medication during the follow-up period . RESULTS One hundred eighty-six patients ( 132 women , 54 men ; 88.7 % white ) were enrolled . Intention-to-treat ( ITT ) analyses revealed no significant differences in the rates of recurrent falls , injurious falls , or filling prescriptions for high-risk medications . However , 13 patients in the intervention group either discontinued use of a high-risk medication or had the dosage reduced during the follow-up period , compared with 5 patients in the control group ( χ(2 ) = 3.94 ; P < 0.05 ) . As-treated analyses revealed numeric reductions in the rates of falls ( rate ratio [ RR ] = 0.76 ; 95 % CI , 0.53 - 1.09 ) , injurious falls ( RR= 0.67 ; 95 % CI , 0.43 - 1.05 ) , and filling prescriptions for high-risk medications ( RR= 0.85 ; 95 % CI , 0.72 - 1.03 ) after receipt of the intervention , but the differences were not statistically significant . CONCLUSIONS Results of this study support the feasibility of using community pharmacies to deliver a falls-prevention program targeting high-risk older adults . Although the ITT analyses revealed no significant reduction in the rate of recurrent falls , injurious falls , or overall use of high-risk medications , individuals in the intervention group were more likely than those in the control group to discontinue use of a high-risk medication or have the dosage reduced during the 1-year follow-up period . More work is needed to evaluate the intervention using a larger sample size that provides greater power to detect clinical ly meaningful effects of reduction in the use of high-risk medications on preventing or reducing falls in the high-risk population The effects of a fall-focused pharmaceutical intervention program ( FFPIP ) on the clinical and economic outcomes of elderly patients who fall while residing in a rehabilitation center are described . The objectives of this retrospective observational study were to identify the differences in the number of patient falls among elderly patients before and after pharmaceutical interventions , identify the cost savings related to decreasing the number of falls , and determine whether a relationship exists between falls among the elderly and specific medication classes . A data collection tool was developed by the investigators to record demographics and medication use . Two hundred patients were r and omly selected from the preintervention ( October 1 , 1999-September 30 , 2000 ) and postintervention ( October 1 , 2000-September 30 , 2001 ) periods . Two data collectors collected data from patient medical records to test the data collection tool and ensure accuracy . The number of patient falls was reduced in the postintervention group by 47 % , result ing in a future savings of $ 7.74 per patient per day . The use of several classes of medication also decreased in the postintervention period : cardiovascular agents , 10.7 % ; analgesics , 6.3 % ; psychoactive drugs , 18.2 % ; and sedatives and hypnotics , 13.9 % . Patients most likely to fall were male , greater than 76 years of age , had a cardiovascular- or orthopedic-related diagnosis , and were taking analgesics , cardiovascular agents , and central nervous system agents , yet the intervention had a more significant effect on female patients . Implementation of an FFPIP decreased falls by 47 % and decreased the use of cardiovascular drugs , analgesics , psychoactive medications , and sedatives and hypnotics CONTEXT Poor medication adherence diminishes the health benefits of pharmacotherapies . Elderly patients with coronary risk factors frequently require treatment with multiple medications , placing them at increased risk for nonadherence . OBJECTIVE To test the efficacy of a comprehensive pharmacy care program to improve medication adherence and its associated effects on blood pressure ( BP ) and low-density lipoprotein cholesterol ( LDL-C ) . DESIGN , SETTING , AND PATIENTS A multiphase , prospect i ve study with an observational phase and a r and omized controlled trial conducted at the Walter Reed Army Medical Center of 200 community-based patients aged 65 years or older taking at least 4 chronic medications . The study was conducted from June 2004 to August 2006 . INTERVENTION After a 2-month run-in phase ( measurement of baseline adherence , BP , and LDL-C ) , patients entered a 6-month intervention phase ( st and ardized medication education , regular follow-up by pharmacists , and medications dispensed in time-specific packs ) . Following the intervention phase , patients were r and omized to continued pharmacy care vs usual care for an additional 6 months . MAIN OUTCOME MEASURES Primary end point of the observation phase was change in the proportion of pills taken vs baseline ; secondary end points were the associated changes in BP and LDL-C. Primary end point of the r and omization phase was the between-group comparison of medication persistence . RESULTS A total of 200 elderly patients ( 77.1 % men ; mean [ SD ] age , 78 [ 8.3 ] years ) , taking a mean ( SD ) of 9 ( 3 ) chronic medications were enrolled . Coronary risk factors included drug-treated hypertension in 184 patients ( 91.5 % ) and drug-treated hyperlipidemia in 162 ( 80.6 % ) . Mean ( SD ) baseline medication adherence was 61.2 % ( 13.5 % ) . After 6 months of intervention , medication adherence increased to 96.9 % ( 5.2 % ; P<.001 ) and was associated with significant improvements in systolic BP ( 133.2 [ 14.9 ] to 129.9 [ 16.0 ] mm Hg ; P = .02 ) and LDL-C ( 91.7 [ 26.1 ] to 86.8 [ 23.4 ] mg/dL ; P = .001 ) . Six months after r and omization , the persistence of medication adherence decreased to 69.1 % ( 16.4 % ) among those patients assigned to usual care , whereas it was sustained at 95.5 % ( 7.7 % ) in pharmacy care ( P<.001 ) . This was associated with significant reductions in systolic BP in the pharmacy care group ( -6.9 mm Hg ; 95 % CI , -10.7 to -3.1 mm Hg ) vs the usual care group ( -1.0 mm Hg ; 95 % CI , -5.9 to 3.9 mm Hg ; P = .04 ) , but no significant between-group differences in LDL-C levels or reductions . CONCLUSIONS A pharmacy care program led to increases in medication adherence , medication persistence , and clinical ly meaningful reductions in BP , whereas discontinuation of the program was associated with decreased medication adherence and persistence . TRIAL REGISTRATION clinical trials.gov Identifier : Clinical pharmacists , under the supervision of a family practitioner physician , assumed responsibility for drug management of geriatric patients in a Los Angeles skilled nursing facility . In a quasi-experimental , pretest-post-test control group design , outcome criteria were measured . Compared with the control group which received traditional patient care , the prescribing clinical pharmacists ' group had a significantly lower number of deaths ( P = 0.05 ) , a significantly higher number of patients being discharged to lower levels of care ( P = 0.03 ) , and a significantly lower average number of drugs per patient ( P = 0.04 ) . The lower number of patients hospitalized approached significance ( P = 0.06 ) in the prescribing clinical pharmacists ' group . The practice of having clinical pharmacists prescribe drug therapy and render general care , under the supervision of a physician , has the potential for saving the health care system approximately $ 70,000 per year per 100 skilled nursing facility beds The outcome of a department of pharmacy-initiated " streamlining " study design ed to promote cost-conscious modifications of empirically selected antibiotic therapy is described . Two hundred forty-one evaluable adult patients started on restricted-use antibiotics at this university-affiliated community private teaching hospital were enrolled in a 9-week prospect i ve streamlining study . Patients were alternately assigned to a Control ( i.e. , no pharmacist-initiated streamlining recommendations offered based on culture and susceptibility reports ) or a Pharmacist Intervention group ( i.e. , pharmacist offers recommendations to streamline therapy ) . A statistically significant greater number of patients had their empiric antibiotic treatment courses modified to more appropriate antibiotic choices after receipt of culture and susceptibility reports among private prescribers in the Pharmacist Intervention group ( 83 % ) than in the Control group ( 38 % ) ( p = .006 ) . Additionally , pharmacists were overall successful in gaining prescriber acceptance for 64 % of recommended changes of empiric antibiotic treatment courses before the receipt of culture and susceptibility reports ( e.g. , dose and /or frequency changes ) . There was no program effect observed with respect to improved physician response to microbiologic data that would allow streamlining empirical antibiotic choices in the Housestaff ( i.e. , medical or surgical residents ) , or infectious disease consultant prescriber groups . Projected overall annual cost savings that would be achieved as a result of continued efforts by pharmacists directed at streamlining empirical " restricted " antibiotic regimens is approximately + 40,000 RATIONALE Care coordination has shown inconsistent results as a mechanism to reduce hospital readmission and postdischarge emergency department ( ED ) visit rates . OBJECTIVE To assess the impact of a supplemental care bundle targeting high-risk elderly in patients implemented by hospital-based staff compared to usual care on a composite outcome of hospital readmission and /or ED visitation at 30 and 60 days following discharge . PATIENTS / METHODS R and omized controlled pilot study in 41 medical in patients predisposed to unpl Output:	Favorable results were found in all outcome categories , and meta-analyses conducted for therapeutic , safety , hospitalization , and adherence were significant ( P < .001 ) , favoring pharmacist care over comparison . Pharmacist intervention has favorable effects on therapeutic , safety , hospitalization , and adherence outcomes in older adults .
MS213891	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: This study examined the reinforcing effects of hydromorphone ( HYD ) ( 0 , 4 , 8 , and 16 mg/70 kg i.m . ) in heroin-dependent outpatient volunteers maintained on buprenorphine ( BUP ) at doses of 2 , 4 , and 8 mg , each for 2 weeks . Following a week of maintenance at each dose , volunteers received injections of one of the four HYD doses under double-blind conditions . Eight volunteers ( abstainers ) were heroin-free during HYD test weeks , whereas six volunteers remained heroin-positive ( nonabstainers ) . Among abstainers , HYD had minimal reinforcing value , whereas in nonabstainers there were marked dose-related increases in HYD reinforcing value , which were not attenuated by increasing doses of BUP . A similar pattern was found for HYD subjective agonist effects . Heroin craving among nonabstainers was significantly higher compared with abstainers , and was reduced in a dose-related manner by HYD . Although BUP and HYD produced dose-related miosis , abstinence status had no differential effect . In summary , BUP effects on opioid reinforcement were consistent from outpatient setting ( heroin abstinence ) to laboratory setting ( decreased HYD reinforcement ) , supporting the validity of this laboratory model It is estimated that more than 500 000 people in the United States are dependent on opioids [ 1 , 2 ] . Methadone , a synthetic opioid first reported as a treatment agent for opioid dependence by Dole and Nysw and er in 1965 [ 3 ] , is the most widely used pharmacologic treatment for opioid dependence . The National Drug and Alcoholism Treatment Unit Survey ( NDATUS ) determined a point prevalence of 92 715 opioid abusers treated in 758 methadone treatment programs on 30 September 1989 [ 4 ] . When used in conjunction with counseling services , methadone treatment has been associated with reduced rates of criminal activity , illicit drug use , and needle sharing and with improved rates of employment [ 5 - 9 ] . With the recognition of intravenous drug use as a primary risk factor for infection with human immunodeficiency virus ( HIV ) , improved access to methadone treatment has been identified as an important means for reducing the risk of HIV infection [ 10 , 11 ] . Although methadone treatment is effective in decreasing opioid use , recent studies have reported considerable variability across clinics in rates of continued intravenous drug use during treatment [ 12 ] . One aspect of this problem is that intravenous use of cocaine has become a serious problem among methadone treatment patients [ 13 - 16 ] . Few systematic studies have addressed the efficacy of methadone treatment since the onset of the cocaine epidemic [ 17 ] . Such research could re-evaluate in a contemporary population sample methadone 's specific pharmacologic efficacy in decreasing opioid use [ 18 - 20 ] while providing new information about any potential effect of methadone treatment on concurrent cocaine use . The issue of appropriate methadone dosing levels is highly pertinent because low-dose treatment has been strongly associated with poor drug use outcomes in descriptive clinical studies [ 12 , 21 ] and because a substantial number of clinics continue to use low doses of methadone [ 22 ] . For example , a report prepared by the General Accounting Office ( GAO ) that summarized the dosing practice s of 24 methadone programs in eight states found that doses ranged widely ( from 21 to 68 mg ) and 29 % had a mean dose of less than 40 mg [ 23 ] . Thus , despite more than 25 years of clinical experience , optimal dosing levels of methadone remain controversial [ 24 , 25 ] . Previous studies of methadone dosing have either surveyed clinics for their dosing practice and related doses to clinic-wide outcomes or have r and omly assigned patients to a specific predetermined dose of methadone using clinical trial methods . Naturalistic survey studies [ 5 , 6 , 12 , 21 , 26 ] , although valuable for identifying associations between dose and outcome , are method ologically compromised by confounding factors that differ across the clinics surveyed . Previous early clinical trials of methadone dosing [ 27 - 29 ] are also method ologically compromised ( for example , being single-blinded ) or only tested higher doses of methadone [ 30 ] . Thus there is a need for well-controlled research on methadone dosing reflecting doses in common use and incorporating the changing patient population . In this controlled clinical trial we compared moderate and low methadone dosing to methadone-free treatment , providing data in a contemporary population sample of opioid addicts and examining the effect of methadone dose on cocaine as well as opioid use . Methods Participants were 247 persons who had consecutive admissions to a methadone research clinic from September 1988 through July 1990 . The mean age was 34 years , 70 % were male , and 50 % were black . Most were unmarried ( 84 % ) and unemployed ( 62 % ) . They had an average of 11 years of education , were generally legally free ( 72 % ) , and had a mean of two previous admissions for drug abuse treatment . Their primary drug of choice was intravenous heroin , and 47 % reported using cocaine in the 30 days before their application to treatment . Eligibility criteria for study participation were age between 18 and 50 years , history of intravenous opioid dependence ( including documentation of previous treatment for opioid dependence or legal involvement secondary to opioid use , a urine sample positive for opioids , and physical examination consistent with acute and chronic needle use ) , no chronic medical illnesses , absence of a major mental illness , a negative pregnancy test for women , and at least 3 months since the patient 's last treatment at the clinic . Applicants who failed to fulfill the study 's eligibility criteria were assisted in seeking an alternate treatment program . The study was approved by the institutional review board , and informed consent was obtained from each patient at the time of admission to the study . Study Procedures Applicants who fulfilled the eligibility criteria were admitted to a 6-month short-term methadone treatment program . Participants were stratified as to race and sex and were assigned to one of three fixed-dose methadone schedules ( Figure 1 ) . Treatment group assignment , stabilization doses , and dosing schedules were double-blind for all patients and the clinic staff who had patient contact . All patients received a minimum of 35 days of active methadone during the first 5 weeks of treatment ; this was followed by a 15-week stabilization period at either 50 , 20 , or 0 mg of methadone . Thus , patients assigned to the 0-mg treatment group received 35-day methadone detoxification . During weeks 21 through 26 , the methadone dose was gradually tapered for those patients still receiving active medication because this was a short-term ( 182-day ) treatment episode . A sub sample of patients ( n = 44 ) assigned to the 0-mg treatment group received a more prolonged ( 8-week ) induction period , reaching 0 mg at the start of week 9 to compare the effects of a faster to a slower detoxification protocol . In this report data for patients in the alternate 0-mg treatment groups are collapsed . Figure 1 . Dosing schedule . Treatment Procedures Patients were assigned an individual counselor who set treatment goals and developed an individualized treatment plan . Patients were given weekly group therapy focusing on relapse prevention . On-site medical services were provided by a full-time internist and a part-time nurse practitioner . Take-home medication was provided only on legal holidays and for documented extenuating circumstances ( for example , funeral out of town for a death in the family ) . Patients who failed to attend the clinic for 3 consecutive days were discharged from treatment . Outcome Measures Treatment Retention and Compliance Treatment retention was calculated as the total number of days between the day of admission and the day of discharge , or the last day of the stable dosing period ( day 140 ) if the patient remained in treatment beyond the stable dosing period . Compliance with treatment was assessed through treatment attendance , the number of days medicated divided by days in treatment , and counseling contacts , which were based on the length ( minutes ) and number of contacts the patient had with either individual or group treatments . Urine Testing Patients provided a supervised urine sample for toxicology screening three times per week . Sample s were tested on-site using EMIT ( Syva Corporation , Palo Alto , California ) for the presence of opioids , cocaine , and benzodiazepines ; and cut-off calibration concentrations were set at 300 g/mL for each test ( morphine , benzoylecgonine , oxazepam ) . The specificity of the EMIT system ranges from 96 % to 100 % . One sample each week was r and omly selected to be sent to an outside laboratory for thin-layer chromatography analysis , which detects these same compounds and a wide variety of other less commonly abused substances . Data Analysis Retention to week 20 , days in treatment , percentage of days attended , and amount of counseling contact time were analyzed with a one-way analysis of variance with methadone dose as the grouping factor and the Tukey Honestly Significant Difference ( HSD ) test was used for post hoc analyses . Comparisons for which the critical difference value corresponding to P < 0.05 are reported as significant for this and all subsequently described analyses . Treatment survival curves were compared using the Lee-Desu statistic , with pairwise comparisons between each of the three treatment groups . The percentages of urine positive for opioids , cocaine , benzodiazepines , and any other drugs were calculated for each patient through the end of the stable dosing period . A one-factor analysis of variance with methadone dose as the grouping factor was used for each of these analyses . Results Table 1 shows the demographic features of the 247 patients enrolled in the study . The only difference across the three treatment groups on any variable was marital status ; 8 % of the patients in the 50-mg treatment group were married compared to 17 % in the 20-mg and 25 % in the 0-mg groups . Table 1 . Demographic Characteristics for Patients ( n = 247 ) Assigned to Different Methadone Doses * Treatment Retention and Compliance Orderly dose effects were seen for survival in treatment ( Figure 2 ) . Although the three treatment groups had similar rates of retention during the first 4 weeks of treatment , when all participants were receiving active methadone , retention rates diverged between weeks 4 and 8 and dose effects were seen from weeks 8 through 20 . In the survival analysis , there was an overall difference between the three curves ( P < 0.01 ) , and pairwise comparison between the 50-mg and 0-mg treatment groups differed significantly ( P < 0.01 ) ; the differences between the 50-mg and 20-mg , and 20-mg and 0-mg treatment groups approached significance ( P = 0.1 and P = 0.08 , respectively ) . At week 20 , the end of the stable dosing period , retention was 52.4 % for the 50-mg , 41.5 % for the 20-mg , and 21.0 % for the 0-mg groups ( 50 versus 0 and 20 versus 0 , P < 0.05 ; 50 versus 20 , P > 0.05 ) . Figure 2 . Retention in treatment . n The number of days retained in treatment was also dose related ( P < 0.01 ) ; Buprenorphine at 2 mg and 6 mg daily was compared with methadone at 35 mg and 65 mg during 24 weeks of maintenance among 125 opioid-dependent patients . As hypothesized , 6 mg of buprenorphine were superior to 2 mg of buprenorphine in reducing illicit opioid use , but higher dosage did not improve treatment retention . Self-reported illicit opioid use declined substantially in all groups , but by the third month , significantly more heroin abuse was reported at 2 mg than at 6 mg of buprenorphine or of methadone . From an initial average of $ 1860/month , month 3 usage dropped to $ 41 ( methadone 65 mg ) , $ 73 ( methadone 35 mg ) , $ 118 ( buprenorphine 6 mg ) , and $ 35I/month ( buprenorphine 2 mg ) . Days of use also dropped from 29 days to 1.7 ( methadone 65 mg ) , 2.8 ( methadone 35 mg ) , 4.0 ( buprenorphine 6 mg ) , and 6.6 days/month ( buprenorphine 2 mg ) . This relatively low efficacy for 2 mg of buprenorphine persisted through month 6 of the trial , with 7.2 days/month and $ 235/month of use for buprenorphine at 2 mg versus 1.9 days/month and $ 65/month for the other three groups . Increased opioid abuse also was associated with significantly greater and persistent opioid withdrawal symptoms . Our secondary hypothesis , that buprenorphine would be equivalent to methadone in efficacy , was not supported . Treatment retention was significantly better on methadone ( 20 us . 16 weeks ) , and methadone patients had significantly more opioid-free urines ( 51 % Output:	The evidence indicated that higher doses of methadone and buprenorphine are associated with better treatment outcomes . Low-dose methadone ( 20 mg per day ) is less effective than buprenorphine ( 2 - 8 mg per day ) . Higher doses of methadone ( > 50 - 65 mg per day ) are slightly more effective than buprenorphine ( 2 - 8 mg per day ) . There was some evidence that primary care could be an effective setting to provide this treatment , but such evidence was sparse . The literature supports the effectiveness of substitute prescribing with methadone or buprenorphine in treating opiate dependence . Evidence is also emerging that the provision of methadone or buprenorphine by primary care physicians is feasible and may be effective
MS213892	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Most patients with chronic myeloid leukemia ( CML ) treated with imatinib will relapse if treatment is withdrawn . We conducted a prospect i ve clinical trial of imatinib withdrawal in 40 chronic-phase CML patients who had sustained undetectable minimal residual disease ( UMRD ) by conventional quantitative polymerase chain reaction ( PCR ) on imatinib for at least 2 years . Patients stopped imatinib and were monitored frequently for molecular relapse . At 24 months , the actuarial estimate of stable treatment-free remission was 47.1 % . Most relapses occurred within 4 months of stopping imatinib , and no relapses beyond 27 months were seen . In the 21 patients treated with interferon before imatinib , a shorter duration of interferon treatment before imatinib was significantly associated with relapse risk , as was slower achievement of UMRD after switching to imatinib . Highly sensitive patient-specific BCR-ABL DNA PCR showed persistence of the original CML clone in all patients with stable UMRD , even several years after imatinib withdrawal . No patients with molecular relapse after discontinuation have progressed or developed BCR-ABL mutations ( median follow-up , 42 months ) . All patients who relapsed remained sensitive to imatinib re-treatment . These results confirm the safety and efficacy of a trial of imatinib withdrawal in stable UMRD with frequent , sensitive molecular monitoring and early rescue of molecular relapse We present long-term follow-up of a dasatinib phase 3 study of patients with imatinib-resistant/-intolerant chronic myeloid leukemia ( CML ) . In the CA180 - 034 study , 670 patients with imatinib-resistant/-intolerant CML in chronic phase ( CML-CP ) received dasatinib 100 mg once daily , 50 mg twice daily , 140 mg once daily , or 70 mg twice daily . At 6 years , 188 ( 28 % ) of 670 patients remained on study treatment . Estimated 6-year protocol -defined progression-free survival ( PFS ) rates were 49 % , 51 % , 40 % , and 47 % , respectively , and estimated 6-year overall survival ( OS ) rates were 71 % , 74 % , 77 % , and 70 % , respectively ( intent-to-treat population , including protocol -defined progression or death after discontinuation ) . Estimated 6-year rates of survival without transformation on study treatment were 76 % , 80 % , 83 % , and 74 % , respectively . Major molecular response was achieved in 43 % ( 100 mg once daily ) and 40 % ( all other arms ) of patients by 6 years . Molecular and cytogenetic responses at 3 and 6 months were highly predictive of PFS and OS . Notably , estimated 6-year PFS rates based on ≤1 % , > 1 % to 10 % , and > 10 % BCR-ABL transcripts at 3 months were 68 % , 58 % , and 26 % , respectively . Most adverse events occurred by 2 years . Imatinib-resistant/-intolerant patients with CML-CP can experience long-term benefit with dasatinib therapy , particularly if achieving BCR-ABL ≤10 % at 3 months . This study was registered at Clinical Trials.gov : NCT00123474 Imatinib mesylate ( imatinib ) has been shown to be highly efficacious in the treatment of chronic myeloid leukemia ( CML ) . Continuous and adequate dosing is essential for optimal outcomes and with imatinib treatment possibly being lifelong , patient adherence is critical . The ADAGIO ( Adherence Assessment with Glivec : Indicators and Outcomes ) study aim ed to assess prospect ively over a 90-day period the prevalence of imatinib nonadherence in patients with CML ; to develop a multivariate canonical correlation model of how various determinants may be associated with various measures of nonadherence ; and to examine whether treatment response is associated with adherence levels . A total of 202 patients were recruited from 34 centers in Belgium , of whom 169 were evaluable . One-third of patients were considered to be nonadherent . Only 14.2 % of patients were perfectly adherent with 100 % of prescribed imatinib taken . On average , patients with suboptimal response had significantly higher mean percentages of imatinib not taken ( 23.2 % , st and ard deviation [ SD ] = 23.8 ) than did those with optimal response ( 7.3 % , SD = 19.3 , P = .005 ; percentages calculated as proportions x 100 ) . Nonadherence is more prevalent than patients , physicians , and family members believe it is , and therefore should be assessed routinely . It is associated with poorer response to imatinib . Several determinants may serve as alert signals , many of which are clinical ly modifiable We developed a module of the MD And erson Symptom Inventory ( MDASI ) for patients with chronic myeloid leukemia ( CML ) . To develop the MDASI-CML , we identified CML-specific symptoms from qualitative interviews with 35 patients . A list of c and i date symptoms was reduced by a panel of patients , caregivers , and clinicians to the 13 core MDASI symptom items and 6 CML-specific items ; these items were subsequently administered to 30 patients . Cognitive debriefing confirmed that the items were clear , relevant , and easy to use . One additional CML-specific symptom item was added , for a total of 7 . The refined MDASI-CML was administered to 152 patients once every 2 weeks for 1 year . The content , concurrent , known-group , and construct validity of the MDASI-CML were evaluated . The internal consistency and test-retest reliabilities of the module were adequate . Longitudinal analysis showed relatively stable symptom severity scores over time . The most severe symptoms were fatigue , drowsiness , disturbed sleep , muscle soreness and cramping , and trouble remembering things . Approximately one-third of the patients who completed the MDASI-CML reported persistent moderate-to-severe symptoms . The MDASI-CML is a valid and reliable symptom assessment instrument that can be used in clinical studies of symptom status in patients with CML This analysis explores the impact of early cytogenetic and molecular responses on the outcomes of patients with chronic myeloid leukemia in chronic phase ( CML-CP ) in the phase 3 DASatinib versus Imatinib Study In treatment-Naive CML patients trial with a minimum follow-up of 3 years . Patients with newly diagnosed CML-CP were r and omized to receive 100 mg dasatinib ( n = 259 ) or 400 mg imatinib ( n = 260 ) once daily . The retrospective l and mark analysis included patients evaluable at the relevant time point ( 3 , 6 , or 12 months ) . Median time to complete cytogenetic response was 3 vs 6 months with dasatinib vs imatinib . At 3 and 6 months , the proportion of patients with BCR-ABL transcript levels ≤10 % was higher in the dasatinib arm . Deeper responses at 3 , 6 , and 12 months were observed in a higher proportion of patients on dasatinib therapy and were associated with better 3-year progression-free survival and overall survival in both arms . First-line dasatinib result ed in faster and deeper responses compared with imatinib . The achievement of an early molecular response was predictive of improved progression-free survival and overall survival , supporting new milestones for optimal response in patients with early CML-CP treated with tyrosine kinase inhibitors . This study was registered at www . clinical trials.gov as NCT00481247 BACKGROUND Imatinib , a selective inhibitor of the BCR-ABL tyrosine kinase , produces high response rates in patients with chronic-phase chronic myeloid leukemia ( CML ) who have had no response to interferon alfa . We compared the efficacy of imatinib with that of interferon alfa combined with low-dose cytarabine in newly diagnosed chronic-phase CML . METHODS We r and omly assigned 1106 patients to receive imatinib ( 553 patients ) or interferon alfa plus low-dose cytarabine ( 553 patients ) . Crossover to the alternative group was allowed if stringent criteria defining treatment failure or intolerance were met . Patients were evaluated for hematologic and cytogenetic responses , toxic effects , and rates of progression . RESULTS After a median follow-up of 19 months , the estimated rate of a major cytogenetic response ( 0 to 35 percent of cells in metaphase positive for the Philadelphia chromosome ) at 18 months was 87.1 percent ( 95 percent confidence interval , 84.1 to 90.0 ) in the imatinib group and 34.7 percent ( 95 percent confidence interval , 29.3 to 40.0 ) in the group given interferon alfa plus cytarabine ( P<0.001 ) . The estimated rates of complete cytogenetic response were 76.2 percent ( 95 percent confidence interval , 72.5 to 79.9 ) and 14.5 percent ( 95 percent confidence interval , 10.5 to 18.5 ) , respectively ( P<0.001 ) . At 18 months , the estimated rate of freedom from progression to accelerated-phase or blast-crisis CML was 96.7 percent in the imatinib group and 91.5 percent in the combination-therapy group ( P<0.001 ) . Imatinib was better tolerated than combination therapy . CONCLUSIONS In terms of hematologic and cytogenetic responses , tolerability , and the likelihood of progression to accelerated-phase or blast-crisis CML , imatinib was superior to interferon alfa plus low-dose cytarabine as first-line therapy in newly diagnosed chronic-phase CML BACKGROUND In a r and omized trial , 1106 patients with chronic myeloid leukemia ( CML ) in chronic phase were assigned to imatinib or interferon alfa plus cytarabine as initial therapy . We measured levels of BCR-ABL transcripts in the blood of all patients in this trial who had a complete cytogenetic remission . METHODS Levels of BCR-ABL transcripts were measured by a quantitative real-time polymerase-chain-reaction assay . Results were expressed relative to the median level of BCR-ABL transcripts in the blood of 30 patients with untreated CML in chronic phase . RESULTS In patients who had a complete cytogenetic remission , levels of BCR-ABL transcripts after 12 months of treatment had fallen by at least 3 log in 57 percent of those in the imatinib group and 24 percent of those in the group given interferon plus cytarabine ( P=0.003 ) . On the basis of the rates of complete cytogenetic remission of 68 percent in the imatinib group and 7 percent in the group given interferon plus cytarabine at 12 months , an estimated 39 percent of all patients treated with imatinib but only 2 percent of all those given interferon plus cytarabine had a reduction in BCR-ABL transcript levels of at least 3 log ( P<0.001 ) . For patients who had a complete cytogenetic remission and a reduction in transcript levels of at least 3 log at 12 months , the probability of remaining progression-free was 100 percent at 24 months , as compared with 95 percent for such patients with a reduction of less than 3 log and 85 percent for patients who were not in complete cytogenetic remission at 12 months ( P<0.001 ) . CONCLUSIONS The proportion of patients with CML who had a reduction in BCR-ABL transcript levels of at least 3 log by 12 months of therapy was far greater with imatinib treatment than with treatment with interferon plus cytarabine . Patients in the imatinib group with this degree of molecular response had a negligible risk of disease progression during the subsequent 12 months BACKGROUND Nilotinib has been shown to be a more potent inhibitor of BCR-ABL than imatinib . We evaluated the efficacy and safety of nilotinib , as compared with imatinib , in patients with newly diagnosed Philadelphia chromosome-positive chronic myeloid leukemia ( CML ) in the chronic phase . METHODS In this phase 3 , r and omized , open-label , multicenter study , we assigned 846 patients with chronic-phase Philadelphia chromosome-positive CML in a 1:1:1 ratio to receive nilotinib ( at a dose of either 300 mg or 400 mg twice daily ) or imatinib ( at a dose of 400 mg once daily ) . The primary end point was the rate of major molecular response at 12 months . RESULTS At 12 months , the rates of major molecular response for nilotinib ( 44 % for the 300-mg dose and 43 % for the 400-mg dose ) were nearly twice that for imatinib ( 22 % ) ( P<0.001 for both comparisons ) . The rates of complete cytogenetic response by 12 months were significantly higher for nilotinib ( 80 % for the 300-mg dose and 78 % for the 400-mg dose ) than for imatinib ( 65 % ) ( P<0.001 for both comparisons ) . Patients receiving either the 300-mg dose or the 400-mg dose of nilotinib twice daily had a significant improvement in the time to progression to the accelerated phase Output:	The results were robust to multiple sensitivity analyses . When imatinib loses patent protection and its price declines , its use will be the cost-effective initial treatment strategy for CML-CP
MS213893	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: BACKGROUND Data collected on more than 12,000 women in 15 r and omized controlled trials provide robust evidence of the beneficial effects of doula support on medical outcomes to childbirth . The objective of this paper was to examine the association between doula support and maternal perceptions of the infant , self , and support from others at 6 to 8 weeks postpartum . The doula was a minimally trained close female relative or friend . METHODS Six hundred low-risk , nulliparous women were enrolled in the original clinical trial and r and omized to doula support ( n = 300 ) or st and ard care ( n = 300 ) . The mother-to-be and her doula attended two 2-hour classes about providing nonmedical , continuous support to laboring women . For the secondary study , presented here , research participants ( N = 494 ) were interviewed by telephone using a 42-item question naire . RESULTS Overall , when doula-supported mothers ( n = 229 ) were compared with mothers who received st and ard care ( n = 265 ) , they were more likely to report positive prenatal expectations about childbirth and positive perceptions of their infants , support from others , and self-worth . Doula-supported mothers were also most likely to have breastfed and to have been very satisfied with the care they received at the hospital . CONCLUSIONS Labor support by a minimally trained female friend or relative , selected by the mother-to-be , enhances the postpartum well-being of nulliparous mothers and their infants , and is a low-cost alternative to professional doulas Background To evaluate the effectiveness and safety of the support given to women by a companion of their choice during labor and delivery . Methods A total of 212 primiparous women were enrolled in a r and omized controlled clinical trial carried out between February 2004 and March 2005 . One hundred and five women were allocated to the group in which support was permitted and 107 to the group in which there was no support . Variables regarding patient satisfaction and events related to obstetrical care , neonatal results and breastfeeding were evaluated . Student 's t-test or Wilcoxon 's test , chi-square or Fisher 's exact test , risk ratios , and their respective 95 % confidence intervals were used in the statistical analysis . Results Overall , the women in the support group were more satisfied with labor ( median 88.0 versus 76.0 , p < 0.0001 ) and delivery ( median 91.4 versus 77.1 , p < 0.0001 ) . During labor , patient satisfaction was associated with the presence of a companion ( RR 8.06 ; 95%CI : 4.84 – 13.43 ) , with care received ( RR 1.11 ; 95%CI : 1.01 – 1.22 ) and with medical guidance ( RR 1.14 95%CI : 1.01 – 1.28 ) . During delivery , satisfaction was associated with having a companion ( RR 5.57 , 95%CI : 3.70 – 8.38 ) , with care received ( RR 1.11 95%CI : 1.01 – 1.22 ) and with vaginal delivery ( RR 1.33 95%CI:1.02 – 1.74 ) . The only factor that was significantly lower in the support group was the occurrence of meconium-stained amniotic fluid ( RR 0.51 ; 95%CI : 0.28 – 0.94 ) . There was no statistically significant difference between the two groups with respect to any of the other variables . Conclusion The presence of a companion of the woman 's choice had a positive influence on her satisfaction with the birth process and did not interfere with other events and interventions , with neonatal outcome or breastfeeding Abstract Background Most women delivering in South African State Maternity Hospitals do not have a childbirth companion ; in addition , the quality of care could be better , and at times women are treated inhumanely . We piloted a multi-faceted intervention to encourage uptake of childbirth companions in state hospitals , and hypothesised that lay carers would improve the behaviour of health professionals . Methods We conducted a pilot r and omised controlled trial of an intervention to promote childbirth companions in hospital deliveries . We promoted evidence -based information for maternity staff at 10 hospitals through access to the World Health Organization Reproductive Health Library ( RHL ) , computer hardware and training to all ten hospitals . We surveyed 200 women at each site , measuring companionship , and indicators of good obstetric practice and humanity of care . Five hospitals were then r and omly allocated to receive an educational intervention to promote childbirth companions , and we surveyed all hospitals again at eight months through a repeat survey of postnatal women . Changes in median values between intervention and control hospitals were examined . Results At baseline , the majority of hospitals did not allow a companion , or access to food or fluids . A third of women were given an episiotomy . Some women were shouted at ( 17.7 % , N = 2085 ) , and a few reported being slapped or struck ( 4.3 % , N = 2080 ) . Despite an initial positive response from staff to the childbirth companion intervention , we detected no difference between intervention and control hospitals in relation to whether a companion was allowed by nursing staff , good obstetric practice or humanity of care . Conclusion The quality and humanity of care in these state hospitals needs to improve . Introducing childbirth companions was more difficult than we anticipated , particularly in under-re source d health care systems with frequent staff changes . We were unable to determine whether the presence of a lay carer impacted on the humanity of care provided by health professionals . Trial registration : Current Controlled Trials IS RCT The purpose of this stratified r and omized trial was to determine the physical and psychological effects of continuous , one-to-one professional support on childbirth outcomes . Data were gathered during prenatal and postpartum interviews with , and from the medical records of , 103 low-risk women . All subjects had attended one of two types of prenatal education programs , were accompanied by husb and s or partners during labor , and had vaginal deliveries . Subjects in the experimental group were less likely to have medication for pain relief and less likely to have episiotomies . Three variables were found to predict perceived control during childbirth -- expectations of control , the presence of a continuous professional caregiver , and pain medication usage . The results demonstrate the importance of the traditional nursing support role during childbirth OBJECTIVES : Despite recent efforts to increase breastfeeding , young African American mothers continue to breastfeed at low rates , and commonly introduce complementary foods earlier than recommended . This study examines the effects of a community doula home visiting intervention on infant feeding practice s among young mothers . METHODS : Low-income , African American mothers ( n = 248 ) under age 22 years participated in a r and omized trial of a community doula intervention . Intervention-group mothers received services from paraprofessional doulas : specialized home visitors trained as childbirth educators and lactation counselors . Doulas provided home visits from pregnancy through 3 months postpartum , and support during childbirth . Control-group mothers received usual prenatal care . Data were obtained from medical records and maternal interviews at birth and 4 months postpartum . RESULTS : Intent-to-treat analyses showed that doula-group mothers attempted breastfeeding at a higher rate than control-group mothers ( 64 % vs 50 % ; P = .02 ) and were more likely to breastfeed longer than 6 weeks ( 29 % vs 17 % ; P = .04 ) , although few mothers still breastfed at 4 months . The intervention also impacted mothers ’ cereal/solid food introduction ( P = .008 ) : fewer doula-group mothers introduced complementary foods before 6 weeks of age ( 6 % vs 18 % ) , while more waited until at least 4 months ( 21 % vs 13 % ) compared with control-group mothers . CONCLUSIONS : Community doulas may be effective in helping young mothers meet breastfeeding and healthy feeding guidelines . The intervention ’s success may lie in the relationship that develops between doula and mother based on shared cultural background and months of prenatal home visiting , and the doula ’s presence at the birth , where she supports early breastfeeding experiences Background Initiation of breastfeeding can be difficult in a busy maternity centre with inadequate manpower and social support . This study aims to explore the role of psychosocial support offered by companions on breastfeeding initiation among first-time mothers . Methods This is a secondary data analysis of a r and omised controlled trial conducted among women attending the antenatal clinic of the University College Hospital , Ibadan , Nigeria in 2007 . Those in the experimental group were asked to bring someone of their choice to the labour room to act as a companion ; the comparison group received st and ard care . The results of 209 HIV negative women who had vaginal births were analysed . The main outcome measure was time to initiation of breastfeeding after childbirth . Results Of the total , 94 had companions during labour while 115 did not have a companion . The median time to breastfeeding initiation was significantly shorter in those with companions compared to controls ( 16 vs. 54 minutes ; p < 0.01 ) . The cumulative survival analysis indicated that all in the treatment group had initiated breastfeeding by 26 minutes , while among the control group none had commenced at 30 minutes post-delivery with some as late as 12 hours . After Cox regression analysis was used to adjust for possible confounders , the outcome still showed a significant hazard ratio of 207.8 ( 95%CI 49.2 , 878.0 ; p < 0.01 ) among women who were supported by a companion . Conclusion Use of companions during labour is associated with earlier time to breastfeeding initiation among first-time mothers in Nigeria . Trial Registration Australian New Zeal and Clinical Trials Registry : ACTRN12609000994280 To establish the spontaneous miscarriage rate and compare it with the procedure related miscarriage rate for amniocentesis and chorionic villus sampling ( CVS ) by experienced operators OBJECTIVE To study the availability of humanized service and healthy birth and it 's effect on maternal and neonatal outcomes . METHODS A multicenteral prospect i ve r and omized control study was carried out in 9 maternity hospitals from Nov. 2000 to June 2001 . 6,758 laboring women were r and omly divided into study group and control group . In study group ( n = 3,437 ) , midwives accompany laboring women in whole course of birth until two hours after delivery . According WHO " Monitoring rules for normal birth " medical staff support the mothers in physiological , psychological and physical aspects . In control group ( n = 3,321 ) mothers receive traditional management . Midwives visit and check the mothers discoutinually . In two groups husb and s can company laboring women according women 's requirement . A question naire will be filled on the second day after birth . RESULTS In study group the spontaneous delivery rate was significant higher than that of control group ( 85.5 % vs 66.0 % , P < 0.01 ) . The cesarean section rate , postpartum hemorrhage rate , neonatal asphyxia rate and neonatal morbidity were marked lower in study group than those of control group ( P < 0.01 and P < 0.05 ) . CONCLUSIONS Appropriate mode of intrapartum care can decrease the cesarean section rate and promote the vaginal delivery , also it can improve the maternal and neonatal outcomes OBJECTIVE To compare labor outcomes in women accompanied by an additional support person ( doula group ) with outcomes in women who did not have this additional support person ( control group ) . DESIGN R and omized controlled trial . SETTING A women 's ambulatory care center at a tertiary perinatal care hospital in New Jersey . PATIENTS / PARTICIPANTS Six hundred nulliparous women carrying a singleton pregnancy who had a low-risk pregnancy at the time of enrollment and were able to identify a female friend or family member willing to act as their lay doula . INTERVENTIONS The doula group was taught traditional doula supportive techniques in two 2-hour sessions . MAIN OUTCOME MEASURES Length of labor , type of delivery , type and timing of analgesia/anesthesia , and Apgar scores . RESULTS Significantly shorter length of labor in the doula group , greater cervical dilation at the time of epidural anesthesia , and higher Apgar scores at both 1 and 5 minutes . Differences did not reach statistical significance in type of analgesia/anesthesia or cesarean delivery despite a trend toward lower cesarean delivery rates in the doula group . CONCLUSION Providing low-income pregnant women with the option to choose a female friend who has received lay doula training and will act as doula during labor , along with other family members , shortens the labor process We wanted to study the effect of extra emotional support in the form of a non-professional woman ( doula ) before and during delivery . About 200 primiparae were invited to participate in a prospect i ve study which intended to assess differences in delivery outcome between women with and without a doula . Fifty-four declined to participate , 55 had a delivery with doula and 46 were controls . Lower rate of emergency caesarean sections in the doula-group was noted . The parents as well as the staff , became to regard the doula as a valuable support during delivery Objective : Vasoconstriction during anxiety reduces fetal oxygenation and leads to hypoxia . Hypoxia in turn results in increase of the number of nucleated red blood cells ( NRBCs ) in the cord blood . The present study aim ed to assess the effect of decreasing maternal anxiety on fetal oxygenation and NRBCs count in the cord blood . Output:	There was no apparent impact on other intrapartum interventions , maternal or neonatal complications , such as admission to special care nursery ( average RR 0.97 , 95 % CI 0.76 to 1.25 ; 7 trials , 8897 women ; low- quality evidence ) , and exclusive or any breastfeeding at any time point ( average RR 1.05 , 95 % CI 0.96 to 1.16 ; 4 trials , 5584 women ; low- quality evidence ) .Subgroup analyses suggested that continuous support was most effective at reducing caesarean birth , when the provider was present in a doula role , and in setting s in which epidural analgesia was not routinely available . Continuous labour support in setting s where women were not permitted to have companions of their choosing with them in labour , was associated with greater likelihood of spontaneous vaginal birth and lower likelihood of a caesarean birth . Subgroup analysis of trials conducted in high-income compared with trials in middle-income countries suggests that continuous labour support offers similar benefits to women and babies for most outcomes , with the exception of caesarean birth , where studies from middle-income countries showed a larger reduction in caesarean birth . No conclusions could be drawn about low-income setting s , electronic fetal monitoring , the timing of onset of continuous support or model of support . Continuous support during labour may improve outcomes for women and infants , including increased spontaneous vaginal birth , shorter duration of labour , and decreased caesarean birth , instrumental vaginal birth , use of any analgesia , use of regional analgesia , low five-minute Apgar score and negative feelings about childbirth experiences . We found no evidence of harms of continuous labour support . Subgroup analyses should be interpreted with caution , and considered as exploratory and hypothesis-generating , but evidence suggests continuous support with certain provider characteristics , in setting s where epidural analgesia was not routinely available , in setting s where women were not permitted to have companions of their choosing in labour , and in middle-income country setting s , may have a favourable impact on outcomes such as caesarean birth .
MS213894	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: BACKGROUND The recent recognition that coronary-artery stenting has improved the short- and long-term outcomes of patients treated with angioplasty has made it necessary to reevaluate the relative benefits of bypass surgery and percutaneous interventions in patients with multivessel disease . METHODS A total of 1205 patients were r and omly assigned to undergo stent implantation or bypass surgery when a cardiac surgeon and an interventional cardiologist agreed that the same extent of revascularization could be achieved by either technique . The primary clinical end point was freedom from major adverse cardiac and cerebrovascular events at one year . The costs of hospital re sources used were also determined . RESULTS At one year , there was no significant difference between the two groups in terms of the rates of death , stroke , or myocardial infa rct ion . Among patients who survived without a stroke or a myocardial infa rct ion , 16.8 percent of those in the stenting group underwent a second revascularization , as compared with 3.5 percent of those in the surgery group . The rate of event-free survival at one year was 73.8 percent among the patients who received stents and 87.8 percent among those who underwent bypass surgery ( P<0.001 by the log-rank test ) . The costs for the initial procedure were $ 4,212 less for patients assigned to stenting than for those assigned to bypass surgery , but this difference was reduced during follow-up because of the increased need for repeated revascularization ; after one year , the net difference in favor of stenting was estimated to be $ 2,973 per patient . CONCLUSION As measured one year after the procedure , coronary stenting for multivessel disease is less expensive than bypass surgery and offers the same degree of protection against death , stroke , and myocardial infa rct ion . However , stenting is associated with a greater need for repeated revascularization CONTEXT Percutaneous coronary intervention ( PCI ) is associated with excellent short-term improvements in ischemic symptoms , yet only three fifths of PCI patients at 5 years and one third of patients at 10 years remain free of major adverse cardiac events ( MACE ) . OBJECTIVE To determine whether treatment with fluvastatin reduces MACE in patients who have undergone PCI . DESIGN AND SETTING R and omized , double-blind , placebo-controlled trial conducted at 77 referral centers in Europe , Canada , and Brazil . PATIENTS A total of 1677 patients ( aged 18 - 80 years ) recruited between April 1996 and October 1998 with stable or unstable angina or silent ischemia following successful completion of their first PCI who had baseline total cholesterol levels between 135 and 270 mg/dL ( 3.5 - 7.0 mmol/L ) , with fasting triglyceride levels of less than 400 mg/dL ( 4.5 mmol/L ) . INTERVENTIONS Patients were r and omly assigned to receive treatment with fluvastatin , 80 mg/d ( n = 844 ) , or matching placebo ( n = 833 ) at hospital discharge for 3 to 4 years . MAIN OUTCOME MEASURE Survival time free of MACE , defined as cardiac death , nonfatal myocardial infa rct ion , or reintervention procedure , compared between the treatment and placebo groups . RESULTS Median time between PCI and first dose of study medication was 2.0 days , and median follow-up was 3.9 years . MACE-free survival time was significantly longer in the fluvastatin group ( P = .01 ) . One hundred eighty-one ( 21.4 % ) of 844 patients in the fluvastatin group and 222 ( 26.7 % ) of 833 patients in the placebo group had at least 1 MACE ( relative risk [ RR ] , 0.78 ; 95 % confidence interval [ CI ] , 0.64 - 0.95 ; P = .01 ) . This result was independent of baseline total cholesterol levels ( above [ RR , 0.76 ; 95 % CI , 0.56 - 1.04 ] vs below [ RR , 0.77 ; 95 % CI , 0.57 - 1.02 ] the median ) . In subgroup analysis , the risk of MACE was reduced in patients with diabetes ( n = 202 ; RR , 0.53 ; 95 % CI , 0.29 - 0.97 ; P = .04 ) and in those with multivessel disease ( n = 614 ; RR , 0.66 ; 95 % CI , 0.48 - 0.91 ; P = .01 ) who received fluvastatin compared with those who received placebo . There were no instances of creatine phosphokinase elevations 10 or more times the upper limit of normal or rhabdomyolysis in the fluvastatin group . CONCLUSION Fluvastatin treatment in patients with average cholesterol levels undergoing their first successful PCI significantly reduces the risk of major adverse cardiac events BACKGROUND The objective of this study was to assess the cost-effectiveness of pravastatin therapy in survivors of myocardial infa rct ion with average cholesterol levels . METHODS We performed a cost-effectiveness analysis based on actual clinical , cost , and health-related quality -of-life data from the Cholesterol and Recurrent Events ( CARE ) trial . Survival and recurrent coronary heart disease events were modeled from trial data in Markov models , with the use of different assumptions regarding the long-term benefit of therapy . RESULTS Pravastatin therapy increased quality -adjusted life expectancy at an incremental cost of $ 16,000 to $ 32,000 per quality -adjusted life-year gained . In subgroup analyses , the cost-effectiveness of pravastatin therapy was more favorable for patients > 60 years of age and for patients with pretreatment low-density lipoprotein cholesterol levels > 125 mg/dL. Results were sensitive to the cost of pravastatin and to assumptions about long-term survival benefits from pravastatin therapy . CONCLUSIONS The cost-effectiveness of pravastatin therapy in survivors of myocardial infa rct ion with average cholesterol levels compares favorably with other interventions OBJECTIVE To evaluate the incremental cost-effectiveness ratio ( ICER ) of switching to ezetimibe/simvastatin ( Eze/Simva ) compared with doubling the submaximal statin doses , in patients with acute coronary syndrome ( ACS ) events in the INFORCE study . METHODS Lifetime treatment costs and benefits were computed using a Markov model . Model inputs included each patient 's cardiovascular risk factor profile and actual lipid values at baseline and 12 weeks ( endpoint ) . Cardiovascular event and drug costs were discounted at 3.5 % . Age-specific utilities were based on UK literature values and non-coronary heart disease mortality rates on the Office of National Statistics data . In the INFORCE study , 384 patients taking statins at stable doses for ≥6 weeks before hospital admission were stratified by statin dose/potency ( low , medium , and high ) and then r and omized to doubling the statin dose or switching to Eze/Simva 10/40 mg for 12 weeks . RESULTS The Eze/Simva group ( n=195 ) had a higher mean baseline total cholesterol than the double-statin group ( n=189 ) . Analyses were adjusted for baseline characteristics . In the INFORCE study , Eze/Simva reduced low-density lipoprotein cholesterol ( LDL-C ) by ∼30 % ( vs. 4 % with doubling statin doses ) and significantly enhanced LDL-C goal attainment . In the cost-effectiveness analysis , Eze/Simva conferred 0.218 incremental discounted quality -adjusted life year ( QALY ) at a discounted incremental cost of £ 2524 , for an ICER of £ 11,571/QALY ( 95 % confidence interval=£8181-£18,600/QALY ) . The ICER was £ 13,552/QALY , £ 11,930/QALY , and £ 10,148/QALY in the low- , medium- , and high-potency strata , respectively . CONCLUSIONS Switching to Eze/Simva 10/40 mg is projected to be a cost-effective treatment ( vs. double-statin ) in UK patients with ACS The Beaver Dam Health Outcomes Study ( BDHOS ) is an ongoing longitudinal cohort study of health status and health-related quality of life for a r and om sample of adults ( age range at interview was 45 to 89 years ; mean = 64.1 , SD = 10.8 ) in a community population . In a face-to-face interview lasting approximately an hour , each participant responds to several batteries of questions . Included are a history of chronic medical conditions , current medi cations , and past surgeries ; the SF-36 ( a general health-status question naire ) ; the Quality of Well-being index ; self-rated health status on a five-point scale from " excellent " to " poor " ; and evaluation of current health using the method of time tradeoffs . The authors present results from 1,356 interviews on these four principal measures , reporting mean scores by sex , by age , and for persons reporting being affected by various medical conditions . They believe data from the BDHOS will provide research ers and policy makers a reference col lection of vital statistics for health-related quality of life . Additionally , the data provide a way to compare results from studies that utilize different indices from among the four principal measures of the BDHOS . Key words : health status ; quality of life ( health-related ) ; population study ; cohort study . ( Med Decis Making 1993;13:89 - 102 Drug therapy for hypercholesterolaemia has remained controversial mainly because of insufficient clinical trial evidence for improved survival . The present trial was design ed to evaluate the effect of cholesterol lowering with simvastatin on mortality and morbidity in patients with coronary heart disease ( CHD ) . 4444 patients with angina pectoris or previous myocardial infa rct ion and serum cholesterol 5.5 - 8.0 mmol/L on a lipid-lowering diet were r and omised to double-blind treatment with simvastatin or placebo . Over the 5.4 years median follow-up period , simvastatin produced mean changes in total cholesterol , low-density-lipoprotein cholesterol , and high-density-lipoprotein cholesterol of -25 % , -35 % , and + 8 % , respectively , with few adverse effects . 256 patients ( 12 % ) in the placebo group died , compared with 182 ( 8 % ) in the simvastatin group . The relative risk of death in the simvastatin group was 0.70 ( 95 % CI 0.58 - 0.85 , p = 0.0003 ) . The 6-year probabilities of survival in the placebo and simvastatin groups were 87.6 % and 91.3 % , respectively . There were 189 coronary deaths in the placebo group and 111 in the simvastatin group ( relative risk 0.58 , 95 % CI 0.46 - 0.73 ) , while noncardiovascular causes accounted for 49 and 46 deaths , respectively . 622 patients ( 28 % ) in the placebo group and 431 ( 19 % ) in the simvastatin group had one or more major coronary events . The relative risk was 0.66 ( 95 % CI 0.59 - 0.75 , p < 0.00001 ) , and the respective probabilities of escaping such events were 70.5 % and 79.6 % . This risk was also significantly reduced in subgroups consisting of women and patients of both sexes aged 60 or more . Other benefits of treatment included a 37 % reduction ( p < 0.00001 ) in the risk of undergoing myocardial revascularisation procedures . This study shows that long-term treatment with simvastatin is safe and improves survival in CHD patients Objective : To identify sociodemographic differences in the incidence of the subtypes of first ever stroke in a multiethnic population . Methods : A prospect i ve community stroke register ( 1995–8 ) was developed using multiple notification sources and pathological and clinical classifications of stroke . St and ardisation of rates was to European and World population s and adjusted for age , sex and socioeconomic status in multivariate analyses . A multiethnic population of 234 533 in south London , of whom 21 % are black was studied . Results : A total of 1254 cases were registered . The average age of stroke was 71.7 years with black patients being 11.3 years younger than white patients ( p<0.0001 ) . The incidence rate/1000 population was 1.33 ( crude ) ( 95 % CI 1.26 to 1.41 ) , 1.28 ( European adjusted ) ( 95 % CI 1.2 to 1.35 ) with a 2.18 ( 95 % CI 1.86 to 2.56 ) ( p<0.0001 ) age and sex adjusted incidence rate ratio in the black population . Radiological diagnosis was confirmatory in 1107 ( 88.3 % ) with 862 ( 68.7 % ) infa rct ion , 168 ( 13.4 % ) primary intracerebral haemorrhage , and 77 ( Output:	Conclusions This review reveals method ological changes over time , but reporting weaknesses remain , particularly with respect to transparency of model reporting
MS213895	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: OBJECTIVES To compare the efficacy and safety of nifedipine and ritodrine in preventing preterm labor , and to evaluate maternal side effects and neonatal outcome . STUDY DESIGN Non-blind , r and omized controlled trial RESULTS A r and omized trial of 102 pregnant women with gestational ages under 34 weeks , including 24 with twin pregnancies and 45 on betasympathicomimetic drugs , who had regular uterine contractions with either observed cervical changes or preterm rupture of membranes . After stratification women were r and omly assigned to receive either ritodrine intravenously or nifedipine orally . Fifty-five women were r and omized to the nifedipine group and 47 to the ritodrine group . As expected , both groups were comparable in terms of several entry variables , including mean gestational age , ruptured membranes , treatment with tocolytic drugs , cervical examination , contraction frequency , age , and twin gestation . Delivery of women in the nifedipine group was delayed for 48 h , 7 days , and until 34 weeks gestation in 33 ( 60 % ) , 26 ( 47 % ) and 21(38 % ) cases , respectively , compared with 31 ( 66 % ) , 21(45 % ) and 11(23 % ) women in the ritodrine group ( no significant difference ) . Maternal side effects were significantly less common in the nifedipine group than in the ritodrine group , however after 7 days of therapy there was no difference between the two groups . Neonatal outcome was similar in the two groups , with four neonatal deaths in the nifedipine and five in the ritodrine group . CONCLUSIONS Nifedipine seems to be as effective as ritodrine in the treatment of preterm labor and is associated with less frequent side effects Ninety-six patients with preterm labor at 28 weeks to 35 weeks gestation were r and omized to terbutaline or magnesium sulfate untill 36 weeks gestation , 25 patients were excluded from the study . Of the remaining 71 patients , 35 patients received terbutaline and 36 patients received magnesium sulfate . The result of the study showed that , there were no significant differences ( P > 0.05 ) regarding time to stop , mean gestational age at delivery , time gained , failure rate , time to recurrent labor and readmission for recurrent labor , birth weight , apgar score and fetal survival . Serious maternal side effects were not observed with terbutaline or magnesium sulfate , although the majority of women also received dexamethasone . Neither drug caused serious adverse neonatal effects PURPOSE to compare the effectiveness of transdermal nitroglycerin with oral nifedipine in the inhibition of preterm delivery . METHODS a clinical essay has been performed with 50 women in preterm delivery , r and omly divided into two groups , 24 receiving oral nifedipine ( 20 mg ) , and 26 , transdermal nitroglycerin ( 10 mg patch ) . Patients with a single gestation , between the 24th and the 34th weeks and diagnosis of preterm delivery were selected . Women with fetal malformation and clinical or obstetric diseases were excluded . The variables analyzed were : effective tocolysis , time needed for tocolysis , recurrence frequency , progression to preterm delivery , and side effects . RESULTS tocolysis efficacy in the first 12 hours was similar between the groups ( nitroglycerin : 84.6 % versus nifedipine : 87.5 % ; p=0.50 ) . The time average time needed for tocolysis was also similar ( 6.6 versus 5.8 hours ; p=0.30 ) . There was no difference between the groups , concerning the recurrence of preterm delivery ( 26.9 versus 16.7 % ; p=0.30 ) , and neither in the rate of preterm delivery within 48 hours ( 15.4 versus 12.5 % ; p=0.50 ) . Nevertheless , the cephalea rate was significantly higher in the Nitroglycerin Group ( 30.8 versus 8.3 % ; p=0.04 ) . CONCLUSIONS transdermal nitroglycerin has presented similar effectiveness to oral nifedipine to inhibit preterm delivery in the first 48 hours , however with higher cephalea frequency OBJECTIVE To compare the effectiveness and adverse effects of nifedipine versus indomethacin in the treatment of preterm labor . METHODS In a r and omized clinical trial , 79 women with labor pain at 26 - 33 weeks of gestation were treated with either oral nifedipine ( n=40 ) or rectal indomethacin ( n=39 ) . RESULTS Twenty-three ( 59 % ) women in the indomethacin group , and 10 ( 25 % ) in the nifedipine group did not respond to treatment ( P=0.002 ) . None of the 16 and 30 women remaining in the indomethacin and nifedipine groups , respectively , delivered during the subsequent 48 hours . Of these remaining women , 1 ( 6.25 % ) in the indomethacin group and 4 ( 13.3 % ) in the nifedipine group delivered between 48 hours and 7 days ( P=0.162 ) . For the women who responded to treatment , the mean gestational age at time of delivery was 238.5±19.4 days and 246.4±15.4 days in the nifedipine and indomethacin groups , respectively ( P=0.182 ) . Seventeen ( 42.5 % ) women in the nifedipine group , and 11 ( 28.2 % ) in the indomethacin group showed adverse effects ( P=0.184 ) . CONCLUSION Indomethacin was less effective than nifedipine for the fast treatment of preterm labor . For women who responded to treatment within 2 hours , however , the delaying of delivery by indomethacin was similar to that by nifedipine Mixed treatment comparison ( MTC ) meta- analysis is a generalization of st and ard pairwise meta- analysis for A vs B trials , to data structures that include , for example , A vs B , B vs C , and A vs C trials . There are two roles for MTC : one is to strengthen inference concerning the relative efficacy of two treatments , by including both ' direct ' and ' indirect ' comparisons . The other is to facilitate simultaneous inference regarding all treatments , in order for example to select the best treatment . In this paper , we present a range of Bayesian hierarchical models using the Markov chain Monte Carlo software WinBUGS . These are multivariate r and om effects models that allow for variation in true treatment effects across trials . We consider models where the between-trials variance is homogeneous across treatment comparisons as well as heterogeneous variance models . We also compare models with fixed ( unconstrained ) baseline study effects with models with r and om baselines drawn from a common distribution . These models are applied to an illustrative data set and posterior parameter distributions are compared . We discuss model critique and model selection , illustrating the role of Bayesian deviance analysis , and node-based model criticism . The assumptions underlying the MTC models and their parameterization are also discussed OBJECTIVE to establish the efficacy and safety of nifedipine and magnesium sulfate in arresting preterm labor . METHOD seventy-four patients with singleton pregnancies at 23 - 36 weeks in preterm labor , were selected r and omly to receive either oral nifedipine or intravenous magnesium sulfate . RESULTS both drugs had similar tocolytic efficacy and side effects while nifedipine was faster than magnesium sulfate in arresting uterine contractions ( 4.8 + /- 4.23 vs. 2.98 + /- 3.03 h ) P = 0.04 . CONCLUSION this data suggests that oral nifedipine with the same efficacy , side effects and faster action could be a suitable and more convenient alternative to intravenous magnesium sulfate in arresting preterm labor In a multicenter series of r and omized prospect i ve doubleblind controlled studies , ritodrine hydrochloride was compared with either ethanol or placebo in treatment of idiopathic preterm labor . When compared with controls , there was , among offspring of ritodrine-treated mothers , a significantly reduced incidence of neonatal death and respiratory distress syndrome ( P<.05 in both comparisons ) and a significantly higher proportion of infants achieving 36 weeks ' gestation ( P<.05 ) or birth weight greater than 2500 g ( P<.05 ) . There was also a significant improvement in gestational age at delivery ( P<.05 ) and in the number of days gained in utero ( P<.001 ) among ritodrine-treated patients as compared with controls . These results , coupled with a finding of generally acceptable side effects , have contributed to ritodrine 's becoming the first drug approved for the treatment of preterm labor in the United OBJECTIVE This study was undertaken to assess the effectiveness of glyceryl trinitrate ( GTN ) patches in comparison with beta2 sympathomimetics ( beta2 ) for the treatment of preterm labor . STUDY DESIGN A multicenter , multinational , r and omized controlled trial was conducted in tertiary referral teaching hospitals . Women in threatened preterm labor with positive fetal fibronectin or ruptured membranes between 24 and 35 weeks ' gestation were recruited and r and omly assigned to either beta2 or GTN with rescue beta2 tocolysis if moderate-to-strong contractions persisted at 2 hours . Obstetric and neonatal outcomes were assessed . RESULTS Two hundred thirty-eight women were recruited and r and omly assigned , 117 to beta2 and 121 to GTN . On a strict intention-to-treat basis , there was no significant difference in the time to delivery using Kaplan-Meier curves ( P = .451 ) . At 2 hours , 27 % of women receiving beta2 had moderate or stronger contractions compared with 53 % in the GTN group ( P < .001 ) . This led to 35 % of women in the GTN group receiving rescue treatment . If delivery or requirement for beta2 rescue are regarded as treatment failure , then a significant difference was observed between the 2 arms ( P = .0032 ) . There were no significant differences in neonatal outcomes . CONCLUSION GTN is a less efficacious tocolytic compared with ss2 sympathomimetics Objective To compare a new loading dose regimen for intravenous ritodrine administration in preterm labour with the conventional dose regimen The authors compare the efficiency of two drugs in the treatment of threatened premature labour , the one being the calcium inhibitor ( nifedipine ) and the other a beta-mimetic drug ( ritodrine ) . 62 patients after r and om selection were divided into two groups : 32 treated with ritodrine and 30 treated with nifedipine . The treatment was carried out over 7 days . The success rate was similar in both groups -72 % for the ritodrine group and 63.33 % for the nifedipine group . Women receiving nifedipine had slightly greater gain in weeks , six as against five for ritodrine . The side effects which were often found with nifedipine were ; hot flushes ( in 10 cases ) and headaches ( 4 cases ) . These symptoms appeared 15 - 30 minutes after the first dose and were transitory . No neonatal complications were found . The ease with which a calcium inhibitor can be given suggests that it should be used more frequently in the treatment of threatened premature labour and particularly when there are contra-indications to the use of beta-mimetic drugs One hundred six patients in preterm labor with intact amniotic membranes and gestational age less than or equal to 32 weeks were r and omized to receive either ritodrine hydrochloride or a 48-hour course of indomethacin for tocolysis . The relative efficacy , maternal and neonatal safety , and costs were evaluated to determine which may be the more appropriate first-line pharmacologic agent used to manage preterm labor . Fifty-four patients and 52 patients were r and omized to receive ritodrine hydrochloride or indomethacin , respectively . Ritodrine hydrochloride and indomethacin were equally effective in inhibiting uterine contractions and delaying delivery . Delivery was delayed for at least 48 hours in 83 and 94 % , and for at least 7 days in 70 and 75 % of patients receiving ritodrine or indomethacin , respectively . Tocolysis with indomethacin was associated with no maternal side effects , whereas tocolysis with ritodrine hydrochloride was associated with a 24 % incidence of serious cardiovascular and metabolic adverse effects prompting discontinuation of the drug . There were no differences in outcome between the infants exposed to indomethacin versus ritodrine hydrochloride when delivered either remote from therapy or during therapy , except for a statistically higher serum glucose in the infants exposed to ritodrine hydrochloride when delivered during tocolytic therapy . There were no cases of premature closure of the ductus arteriosus or pulmonary hypertension . Tocolysis with indomethacin was 17 times less costly than tocolysis with ritodrine hydrochloride . For gestations less than or equal to 32 weeks complicated by preterm labor , indomethacin may be an appropriate alternative as a first-line tocolytic agent One hundred women in preterm labor were r and omly treated with ritodrine or terbutaline in a double-blind fashion . The drugs were comparably effective during intravenous therapy but , in women with intact membranes , an oral dose of terbutaline Output:	No class of tocolytic was significantly superior to placebo in reducing neonatal respiratory distress syndrome . Prostagl and in inhibitors and calcium channel blockers were the tocolytics with the best probability of being ranked in the top three medication classes for the outcomes of 48 hour delay in delivery , respiratory distress syndrome , neonatal mortality , and maternal side effects ( all cause ) . Conclusions Prostagl and in inhibitors and calcium channel blockers had the highest probability of delaying delivery and improving neonatal and maternal outcomes
MS213896	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: OBJECTIVE To evaluate the efficacy and safety of alpha-lipoic acid given intravenously , followed by oral treatment in type 2 diabetic patients with symptomatic polyneuropathy . RESEARCH DESIGN AND METHODS In a multicenter r and omized double-blind placebo-controlled trial ( Alpha-Lipoic Acid in Diabetic Neuropathy [ ALADIN ] III Study ) , 509 out patients were r and omly assigned to sequential treatment with 600 mg alpha-lipoic acid once daily intravenously for 3 weeks , followed by 600 mg alpha-lipoic acid three times a day orally for 6 months ( A-A ; n = 167 ) ; 600 mg alpha-lipoic acid once daily intravenously for 3 weeks , followed by placebo three times a day orally for 6 months ( A-P ; n = 174 ) ; and placebo once daily intravenously for 3 weeks , followed by placebo three times a day orally for 6 months ( P-P ; n = 168 ) . Outcome measures included the Total Symptom Score ( TSS ) for neuropathic symptoms ( pain , burning , paresthesias , and numbness ) in the feet , and the Neuropathy Impairment Score ( NIS ) . Data analysis was based on the intention to treat . RESULTS No significant differences between the groups were noted for the demographic variables and the nerve function parameters at baseline . The TSS in the feet decreased from baseline to day 19 ( median [ range ] ) by -3.7 ( -12.6 to 5.0 ) points in the group given alpha-lipoic acid intravenously and by -3.0 ( -12.3 to 8.0 ) points in the placebo group ( P = 0.447 ) , but the area under curve on a daily basis was significantly smaller in the active as compared with the placebo group ( 85.6 [ 0 - 219 ] vs. 95.9 [ 5.5 - 220 ] ) ; P = 0.033 ) . After 7 months , the changes in the TSS from baseline were not significantly different between the three groups studied , which could be due to increasing intercenter variability in the TSS during the trial . The NIS decreased after 19 days by -4.34+/-0.35 points ( mean + /- SEM ) in A-A and A-P and -3.49+/-0.58 points in P-P ( P = 0.02 for alpha-lipoic acid versus placebo ) and after 7 months by -5.82+/-0.73 points in A-A , -5.76+/-0.69 points in A-P , and -4.37+/-0.83 points in P-P ( P = 0.09 for A-A vs. P-P ) . The rates of adverse events were not different between the groups throughout the study . CONCLUSIONS These findings indicate that a 3-week intravenous treatment with alpha-lipoic acid , followed by a 6-month oral treatment , had no effect on neuropathic symptoms distinguishable from placebo to a clinical ly meaningful degree , possibly due to increasing intercenter variability in symptom scoring during the study . However , this treatment was associated with a favorable effect on neuropathic deficits without causing significant adverse reactions . Long-term trials that focus on neuropathic deficits rather than symptoms as the primary criterion of efficacy are needed to see whether oral treatment with alpha-lipoic acid over several years may slow or reverse the progression of diabetic neuropathy BACKGROUND Amelioration of insulin resistance could improve both glycaemic control and cardiovascular risk factors in patients with type 2 diabetes mellitus . Alpha-lipoic acid has been shown to improve insulin action after parenteral administration . OBJECTIVE the aim of the study was to assess the effect of oral administration of alpha-lipoic acid on insulin sensitivity in patients with type 2 diabetes . DESIGN twelve patients ( mean+/-sD ; age 52.9+/-9.9 yrs ; body mass index 33.9+/-7.4 kg/m(2 ) ) were treated with oral alpha-lipoic acid , 600 mg twice daily over a period of 4 weeks . twelve subjects with normal glucose tolerance served as a control group in terms of insulin sensitivity ( Is ) . Is was measured by a 2h manual hyperinsulinaemic ( insulin infusion rate-40 mU/m(2 ) body surface area/min ) euglycaemic ( blood glucose kept at 5 mmol/l ) clamp technique and expressed as a glucose disposal rate ( M ) and insulin sensitivity index ( IsI ) . RESULTS At the end of the treatment period , Is of diabetic patients was significantly increased : M from 3.202+/-1.898 to 5.951+/-2.705 mg/kg/min ( mean+/-sD ) , p<0.01 ; and IsI from 4.706+/-2.666 to 7.673+/-3.559 mg/kg/min per mIU/l x 100 ( mean+/-sD ) , p<0.05 . the difference was not statistically significant between the Is of diabetic patients after alpha-lipoic acid therapy and control subjects . CONCLUSION short-term oral alpha-lipoic acid treatment increases peripheral insulin sensitivity in patients with type 2 diabetes mellitus BACKGROUND The diabetic state , in both humans and experimental animals , is associated with oxidative stress . Lipid peroxidation of nerve membranes has been suggested as a mechanism by which peripheral nerve ischemia and hypoxia could cause neuropathy . Lipoic acid ( LA ) is a powerful inhibitor of iron-dependent lipid peroxidation and reactive oxygen species . The treatment of diabetic peripheral and cardiac autonomic neuropathy with LA is based on good clinical and experimental evidence . MATERIAL S AND METHODS To investigate the magnitude of the oxidative stress , serum ceruloplasmin ( Cp ) and lipid peroxide ( Lp ) levels were measured in 10 patients with diabetic neuropathy , before and 70 days after treatment with single dose of 600 mg LA/day . For other 12 healthy age- and sex-matched control subjects the serum Cp and Lp levels were evaluated . RESULTS Our results show that hyperglycemia is a factor for an increase in serum ceruloplasmin in patients with diabetic neuropathy compared to healthy subjects ( p < 0.0001 ) . High serum ceruloplasmin ( Cp ) level in patients with diabetes may be related to antioxidant defense . The treatment of diabetic neuropathy with LA does not affect significantly the serum Cp activity . The serum Lp levels after LA administration were significantly lower ( p < 0.005 ) than those before treatment . CONCLUSIONS The antioxidant therapy with LA improves and may prevent diabetic neuropathy . This improvement is associated with a reduction in the indexes of lipid peroxidation . Oxidative stress appears to be primarily due to the processes of nerve ischemia and hyperglycemia autooxidation Diabetic polyneuropathy is a serious complication in patients with diabetes mellitus . In addition to the maintenance of a sufficient metabolic control , alpha-lipoic acid ( ALA ) ( Thioctacid , Asta Medica ) is known to have beneficial effects on diabetic polyneuropathy although the exact mechanism by which ALA exerts its effect is unknown . In order to study the effect of ALA on microcirculation in patients with diabetes mellitus and peripheral neuropathy one group of patients ( 4 female , 4 male , age 60+/-3 years , diabetes duration 19+/-4 years , BMI 24.8+/-1.3 kg/m2 ) received 1200 mg ALA orally per day over 6 weeks ( trial 1 ) . A second group of patients ( 5 female , 4 male , age 65+/-3 years , diabetes duration 14+/-4 years , BMI 23.6+/-0.7 kg/m2 ) was studied before and after they had received 600 mg ALA or placebo intravenously over 15 minutes in order to investigate whether ALA has an acute effect on microcirculation ( trial 2 ) . Patients were investigated by nailfold video-capillaroscopy . Capillary blood cell velocity was examined at rest and during postreactive hyperemia ( occlusion of the wrist for 2 minutes , 200 mmHg ) which is a parameter of the perfusion reserve on dem and . The oral therapy with ALA result ed in a significant decrease in the time to peak capillary blood cell velocity ( tpCBV ) during postocclusive hyperemia ( trial 1 : 12.6+/-3.1 vs 35.4+/-10.9 s , p<0.05 ) . The infusion of ALA also decreased the tpCBV in patients with diabetic neuropathy ( trial 2 : before : 20.8+/-4,5 , ALA : 11.74+/-4.4 , placebo : 21.9 - 5.0 s , p<0.05 ALA vs both placebo and before infusions ) indicating that ALA has an acute effect on microcirculation . Capillary blood cell velocity at rest ( rCBV ) , hemodynamic parameters , hemoglobinA1c and local skin temperature remained unchanged in both studies . These results demonstrate that in patients with diabetic polyneuropathy ALA improves microcirculation as indicated by an increased perfusion reserve on dem and . The observed effects are apparently acute effects . With the restriction of the pilot character of this investigation the findings support the assumption that ALA might exert its beneficial effects at least partially by improving microcirculation which is likely to occur also at the level of the vasa nervorum OBJECTIVE —The aim of this trial was to evaluate the effects of α-lipoic acid ( ALA ) on positive sensory symptoms and neuropathic deficits in diabetic patients with distal symmetric polyneuropathy ( DSP ) . RESEARCH DESIGN AND METHODS —In this multicenter , r and omized , double-blind , placebo-controlled trial , 181 diabetic patients in Russia and Israel received once-daily oral doses of 600 mg ( n = 45 ) ( ALA600 ) , 1,200 mg ( n = 47 ) ( ALA1200 ) , and 1,800 mg ( ALA1800 ) of ALA ( n = 46 ) or placebo ( n = 43 ) for 5 weeks after a 1-week placebo run-in period . The primary outcome measure was the change from baseline of the Total Symptom Score ( TSS ) , including stabbing pain , burning pain , paresthesia , and asleep numbness of the feet . Secondary end points included individual symptoms of TSS , Neuropathy Symptoms and Change ( NSC ) score , Neuropathy Impairment Score ( NIS ) , and patients ’ global assessment of efficacy . RESULTS —Mean TSS did not differ significantly at baseline among the treatment groups and on average decreased by 4.9 points ( 51 % ) in ALA600 , 4.5 ( 48 % ) in ALA1200 , and 4.7 ( 52 % ) in ALA1800 compared with 2.9 points ( 32 % ) in the placebo group ( all P < 0.05 vs. placebo ) . The corresponding response rates ( ≥50 % reduction in TSS ) were 62 , 50 , 56 , and 26 % , respectively . Significant improvements favoring all three ALA groups were also noted for stabbing and burning pain , the NSC score , and the patients ’ global assessment of efficacy . The NIS was numerically reduced . Safety analysis showed a dose-dependent increase in nausea , vomiting , and vertigo . CONCLUSIONS —Oral treatment with ALA for 5 weeks improved neuropathic symptoms and deficits in patients with DSP . An oral dose of 600 mg once daily appears to provide the optimum risk-to-benefit ratio Aims To evaluate the efficacy and safety of short‐term oral treatment with the antioxidant thioctic acid ( TA ) on neuropathic symptoms and deficits in patients with Type 2 diabetes mellitus with symptomatic polyneuropathy Anti-oxidant treatment has been shown to prevent nerve dysfunction in experimental diabetes mellitus , thus providing a rationale of potential therapeutic value for diabetic patients . The effects of the anti-oxidant alpha-lipoic acid ( thioctic acid ) were studied in a 3-week multicentre , r and omized , double-blind placebo-controlled trial ( Alpha-Lipoic Acid in Diabetic Neuropathy ; ALADIN ) in 328 non-insulin-dependent diabetic patients with symptomatic peripheral neuropathy who were r and omly assigned to treatment with intravenous infusion of alpha-lipoic acid using three doses ( 1200 , 600 , or 100 mg ALA ) or placebo ( PLAC ) . Neuropathic symptoms ( pain , burning , paraesthesiae , and numbness ) were scored at baseline and at each visit ( days 2 - 5 , 8 - 12 , and 15 - 19 ) prior to infusion . In addition , the Hamburg Pain Adjective List , a multidimensional specific pain question naire , and the Neuropathy Symptom and Disability Scores were assessed at baseline and day 19 . According to the protocol 260 ( 65/63/66/66 ) patients Output:	The results of this meta- analysis provide evidence that treatment with ALA ( 300 - 600 mg/day i.v . for 2 - 4 weeks ) is safe and that the treatment can significantly improve both nerve conduction velocity and positive neuropathic symptoms .
MS213897	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: OBJECTIVES This study sought to evaluate whether remote ischemic post-conditioning ( RIPC ) could reduce enzymatic infa rct size in patients with anterior ST-segment elevation myocardial infa rct ion undergoing primary percutaneous coronary intervention ( pPCI ) . BACKGROUND Myocardial reperfusion injury may attenuate the benefit of pPCI . In animal models , RIPC mitigates myocardial reperfusion injury . METHODS One hundred patients with anterior ST-segment elevation myocardial infa rct ion and occluded left anterior descending artery were r and omized to pPCI + RIPC ( n = 50 ) or conventional pPCI ( n = 50 ) . RIPC consisted of 3 cycles of 5 min/5 min ischemia/reperfusion by cuff inflation/deflation of the lower limb . The primary endpoint was infa rct size assessed by the area under the curve of creatinine kinase-myocardial b and release ( CK-MB ) . Secondary endpoints included the following : infa rct size assessed by cardiac magnetic resonance delayed enhancement volume ; T2-weighted edema volume ; ST-segment resolution > 50 % ; TIMI ( Thrombolysis In Myocardial Infa rct ion ) frame count ; and myocardial blush grading . RESULTS Four patients ( 2 RIPC , 2 controls ) were excluded due to missing sample s of CK-MB . A total of 96 patients were analyzed ; median area under the curve CK-MB was 8,814 ( interquartile range [ IQR ] : 5,567 to 11,325 ) arbitrary units in the RIPC group and 10,065 ( IQR : 7,465 to 14,004 ) arbitrary units in control subjects ( relative reduction : 20 % , 95 % confidence interval : 0.2 % to 28.7 % ; p = 0.043 ) . Seventy-seven patients underwent a cardiac magnetic resonance scan 3 to 5 days after r and omization , and 66 patients repeated a second scan after 4 months . T2-weighted edema volume was 37 ± 16 cc in RIPC patients and 47 ± 22 cc in control subjects ( p = 0.049 ) . ST-segment resolution > 50 % was 66 % in RIPC and 37 % in control subjects ( p = 0.015 ) . We observed no significant differences in TIMI frame count , myocardial blush grading , and delayed enhancement volume . CONCLUSIONS In patients with anterior ST-segment elevation myocardial infa rct ion , RIPC at the time of pPCI reduced enzymatic infa rct size and was also associated with an improvement of T2-weighted edema volume and ST-segment resolution > 50 % . ( Remote Postconditioning in Patients With Acute Myocardial Infa rct ion Treated by Primary Percutaneous Coronary Intervention [ PCI ] [ RemPostCon ] ; NCT00865722 ) BACKGROUND Whether remote ischemic preconditioning ( transient ischemia and reperfusion of the arm ) can improve clinical outcomes in patients undergoing coronary-artery bypass graft ( CABG ) surgery is not known . We investigated this question in a r and omized trial . METHODS We conducted a multicenter , sham-controlled trial involving adults at increased surgical risk who were undergoing on-pump CABG ( with or without valve surgery ) with blood cardioplegia . After anesthesia induction and before surgical incision , patients were r and omly assigned to remote ischemic preconditioning ( four 5-minute inflations and deflations of a st and ard blood-pressure cuff on the upper arm ) or sham conditioning ( control group ) . Anesthetic management and perioperative care were not st and ardized . The combined primary end point was death from cardiovascular causes , nonfatal myocardial infa rct ion , coronary revascularization , or stroke , assessed 12 months after r and omization . RESULTS We enrolled a total of 1612 patients ( 811 in the control group and 801 in the ischemic-preconditioning group ) at 30 cardiac surgery centers in the United Kingdom . There was no significant difference in the cumulative incidence of the primary end point at 12 months between the patients in the remote ischemic preconditioning group and those in the control group ( 212 patients [ 26.5 % ] and 225 patients [ 27.7 % ] , respectively ; hazard ratio with ischemic preconditioning , 0.95 ; 95 % confidence interval , 0.79 to 1.15 ; P=0.58 ) . Furthermore , there were no significant between-group differences in either adverse events or the secondary end points of perioperative myocardial injury ( assessed on the basis of the area under the curve for the high-sensitivity assay of serum troponin T at 72 hours ) , inotrope score ( calculated from the maximum dose of the individual inotropic agents administered in the first 3 days after surgery ) , acute kidney injury , duration of stay in the intensive care unit and hospital , distance on the 6-minute walk test , and quality of life . CONCLUSIONS Remote ischemic preconditioning did not improve clinical outcomes in patients undergoing elective on-pump CABG with or without valve surgery . ( Funded by the Efficacy and Mechanism Evaluation Program [ a Medical Research Council and National Institute of Health Research partnership ] and the British Heart Foundation ; ERICCA Clinical Trials.gov number , NCT01247545 . ) Background : Two preconditioning stimuli should induce a more consistent overall cell protection . We hypothesized that remote ischemic preconditioning ( RIPC , second preconditioning stimulus ) applied during isoflurane inhalation ( first preconditioning stimulus ) would provide more protection to the myocardium of patients undergoing on-pump coronary artery bypass grafting . Methods : In this placebo-controlled r and omized controlled study , patients in the RIPC group received four 5-min cycles of 300 mmHg cuff inflation/deflation of the leg before aortic cross-clamping . Anesthesia consisted of opioids and propofol for induction and isoflurane for maintenance . The primary outcome was high-sensitivity cardiac troponin T release . Secondary endpoints were plasma levels of N-terminal pro-brain natriuretic peptide , high-sensitivity C-reactive protein , S100 protein , and short- and long-term clinical outcomes . Gene expression profiles were obtained from atrial tissue using microarrays . Results : RIPC ( n = 27 ) did not reduce high-sensitivity cardiac troponin T release when compared with placebo ( n = 28 ) . Likewise , N-terminal pro-brain natriuretic peptide , a marker of myocardial dysfunction ; high-sensitivity C-reactive protein , a marker of perioperative inflammatory response ; and S100 , a marker of cerebral injury , were not different between the groups . The incidence for the perioperative composite endpoint combining new arrhythmias and myocardial infa rct ions was higher in the RIPC group than the placebo group ( 14/27 vs. 6/28 , P = 0.036 ) . However , there was no difference in the 6-month cardiovascular outcome . N-terminal pro-brain natriuretic peptide release correlated with isoflurane-induced transcriptional changes in fatty-acid metabolism ( P = 0.001 ) and DNA-damage signaling ( P < 0.001 ) , but not with RIPC-induced changes in gene expression . Conclusions : RIPC applied during isoflurane inhalation provides no benefit to the myocardium of patients undergoing on-pump coronary artery bypass grafting BACKGROUND Remote ischemic preconditioning ( RIPC ) is reported to reduce biomarkers of ischemic and reperfusion injury in patients undergoing cardiac surgery , but uncertainty about clinical outcomes remains . METHODS We conducted a prospect i ve , double-blind , multicenter , r and omized , controlled trial involving adults who were scheduled for elective cardiac surgery requiring cardiopulmonary bypass under total anesthesia with intravenous propofol . The trial compared upper-limb RIPC with a sham intervention . The primary end point was a composite of death , myocardial infa rct ion , stroke , or acute renal failure up to the time of hospital discharge . Secondary end points included the occurrence of any individual component of the primary end point by day 90 . RESULTS A total of 1403 patients underwent r and omization . The full analysis set comprised 1385 patients ( 692 in the RIPC group and 693 in the sham-RIPC group ) . There was no significant between-group difference in the rate of the composite primary end point ( 99 patients [ 14.3 % ] in the RIPC group and 101 [ 14.6 % ] in the sham-RIPC group , P=0.89 ) or of any of the individual components : death ( 9 patients [ 1.3 % ] and 4 [ 0.6 % ] , respectively ; P=0.21 ) , myocardial infa rct ion ( 47 [ 6.8 % ] and 63 [ 9.1 % ] , P=0.12 ) , stroke ( 14 [ 2.0 % ] and 15 [ 2.2 % ] , P=0.79 ) , and acute renal failure ( 42 [ 6.1 % ] and 35 [ 5.1 % ] , P=0.45 ) . The results were similar in the per- protocol analysis . No treatment effect was found in any subgroup analysis . No significant differences between the RIPC group and the sham-RIPC group were seen in the level of troponin release , the duration of mechanical ventilation , the length of stay in the intensive care unit or the hospital , new onset of atrial fibrillation , and the incidence of postoperative delirium . No RIPC-related adverse events were observed . CONCLUSIONS Upper-limb RIPC performed while patients were under propofol-induced anesthesia did not show a relevant benefit among patients undergoing elective cardiac surgery . ( Funded by the German Research Foundation ; RIPHeart Clinical Trials.gov number , NCT01067703 . ) Background Remote ischemic preconditioning ( RIPC ) harnesses an innate defensive mechanism that protects against inflammatory activation and ischemia‐reperfusion injury , known sequelae of cardiac surgery with cardiopulmonary bypass . We sought to determine the impact of RIPC on clinical outcomes and physiological markers related to ischemia‐reperfusion injury and inflammatory activation after cardiac surgery in children . Methods and Results Overall , 299 children ( aged neonate to 17 years ) were r and omized to receive an RIPC stimulus ( inflation of a blood pressure cuff on the left thigh to 15 mm Hg above systolic for four 5‐minute intervals ) versus a blinded sham stimulus during induction with a st and ardized anesthesia protocol . Primary outcome was duration of postoperative hospital stay , with serial clinical and laboratory measurements for the first 48 postoperative hours and clinical follow‐up to discharge . There were no significant baseline differences between RIPC ( n=148 ) and sham ( n=151 ) . There were no in‐hospital deaths . No significant difference in length of postoperative hospital stay was noted ( sham 5.4 versus RIPC 5.6 days ; difference + 0.2 ; adjusted P=0.91 ) , with the 95 % confidence interval ( −0.7 to + 0.9 ) excluding a prespecified minimal clinical ly significant differences of 1 or 1.5 days . There were few significant differences in other clinical outcomes or values at time points or trends in physiological markers . Benefit was not observed in specific subgroups when explored through interactions with categories of age , sex , surgery type , Aristotle score , or first versus second half of recruitment . Adverse events were similar ( sham 5 % , RIPC 6 % ; P=0.68 ) . Conclusions RIPC is not associated with important improvements in clinical outcomes and physiological markers after cardiac surgery in children . Clinical Trial Registration URL : clinical trials.gov . Unique identifier : NCT00650507 BACKGROUND Although remote ischemic preconditioning ( RIPC ) has emerged as an attractive strategy to reduce cardiac injury in patients undergoing diverse cardiac surgical procedures , it is unclear whether RIPC has protective effects in patients undergoing aortic valve replacement surgery without coronary artery bypass grafting ( CABG ) . METHODS Hence , 100 adult patients undergoing elective aortic valve replacement for aortic valve stenosis , without combined surgery with CABG , were prospect ively r and omly assigned in a 1:1 ratio to either the RIPC group or the control group . The RIPC group underwent three cycles of 5-min inflation to 200mmHg and 5-min deflation of an automated upper-arm cuff inflator after induction of anesthesia . The control group had a deflated cuff placed on upper arm for 30min . The primary endpoint was 72-h area under curve ( AUC ) for troponin I ( cTnI ) . Secondary endpoints were 72-h AUC for creatine kinase-MB isoenzyme ( CK-MB ) release , incidence of acute kidney injury , extubation time , length of stay in intensive care unit , and simplified acute physi Output:	There was no difference for changes in the incidence of renal replacement therapy , estimated glomerular filtration rate or serum creatinine . CONCLUSIONS RIC might be beneficial for the prevention of investigator-defined AKI ; however , the effect is likely small . Moreover , due to lack of an effect on use of renal replacement therapy , estimated glomerular filtration rate , RIFLE , AKIN , or KDIGO-defined AKI , and serum creatinine , the evidence for RIC is not robust . Finally , recent large-scale RCTs of RIC focusing on patient-centered outcomes do not support the wider application of RIC
MS213898	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: Prognosis studies are investigations of future events or the evaluation of associations between risk factors and health outcomes in population s of patients ( 1 ) . The results of such studies improve our underst and ing of the clinical course of a disease and assist clinicians in making informed decisions about how best to manage patients . Prognostic research also informs the design of intervention studies by helping define subgroups of patients who may benefit from a new treatment and by providing necessary information about the natural history of a disorder ( 2 ) . There has recently been a rapid increase in the use of systematic review methods to synthesize the evidence on research questions related to prognosis . It is essential that investigators conducting systematic review s thoroughly appraise the method ologic quality of included studies to be confident that a study 's design , conduct , analysis , and interpretation have adequately reduced the opportunity for bias ( 3 , 4 ) . Caution is warranted , however , because inclusion of method ologically weak studies can threaten the internal validity of a systematic review ( 4 ) . This follows abundant empirical evidence that inadequate attention to biases can cause invalid results and inferences ( 5 - 9 ) . However , there is limited consensus on how to appraise the quality of prognosis studies ( 1 ) . A useful framework to assess bias in such studies follows the basic principles of epidemiologic research ( 10 , 11 ) . We focus on 6 areas of potential bias : study participation , study attrition , prognostic factor measurement , confounding measurement and account , outcome measurement , and analysis . The main objectives of our review of review s are to describe methods used to assess the quality of prognosis studies and to describe how well current practice s assess potential biases . Our secondary objective is to develop recommendations to guide future quality appraisal , both within single studies of prognostic factors and within systematic review s of the evidence . We hope this work facilitates future discussion and research on biases in prognosis studies and systematic review s. Methods Literature Search and Study Selection We identified systematic review s of prognosis studies by search ing MEDLINE ( 1966 to October 2005 ) using the search strategy recommended by McKibbon and colleagues ( 12 ) . This strategy combines broad search terms for systematic review s ( systematic review .mp ; meta- analysis .mp ) and a sensitive search strategy for prognosis studies ( cohort , incidence , mortality , follow-up studies , prognos * , predict * , or course ) . We also search ed the reference lists of included review s and method ologic papers to identify other relevant publications . We restricted our search to English- language publications . One review er conducted the search and selected the studies . Systematic review s , defined as review s of published studies with a comprehensive search and systematic selection , were included if they assessed the method ologic quality of the included studies by using 1 or more explicit criteria . We excluded studies if they were meta-analyses of independent patient data only , if their primary goal was to investigate the effectiveness of an intervention or specific diagnostic or screening tests , or if they included studies that were not done on humans . Data Extraction and Synthesis Individual items included in the quality assessment of the systematic review s were recorded as they were reported in the publication ( that is , the information that would be available to readers and future review ers ) . We review ed journal Web sites and contacted the authors of the systematic review s for additional information when authors made such an offer in their original papers . When review s assessed different study design s by using different sets of quality items , we extracted only those items used to assess cohort studies . We constructed a comprehensive list of distinct items that the review s used to assess the quality of their included studies . The full text of each review was screened . All items used by the review authors to assess the quality of studies were extracted into a computerized spreadsheet by 1 review er . Two experienced review ers , a clinical epidemiologist and an epidemiologist , independently synthesized the quality items extracted from the prognosis review s to determine how well the systematic review s assessed potential biases . We did this in 3 steps : 1 ) identified distinct concepts or domains addressed by the quality items ; 2 ) grouped each extracted quality item into the appropriate domain or domains ; and 3 ) identified the domains necessary to assess potential biases in prognosis studies . We then used this information to assess how well the review s ' quality assessment included items from the domains necessary to assess potential biases . After completing each of the first 3 steps , the review ers met to attempt to reach a consensus . The consensus process involved each review er presenting his or her observations and results , followed by discussion and debate . A third review er was available in cases of persistent disagreement or uncertainty . In the first step , all domains addressed by the quality items were identified . The first review er iteratively and progressively defined the domains as items were extracted from the included review s. The second review er defined domains from a r and om list of all extracted quality items . Limited guidance was provided to the review ers so that their assessment s and definitions of domains would be independent . The review ers agreed on a final set of domains that adequately and completely defined all of the extracted items . In the second step , review ers independently grouped each extracted item into the appropriate domains . Review ers considered each extracted item by asking , What is each particular quality item addressing ? or What are the review 's authors getting at with the particular quality assessment item ? . Items were grouped into the domain or domains that best represented the concepts being addressed . For example , the extracted items at least 80 % of the group originally identified was located for follow-up and follow-up was sufficiently complete or does n't jeopardize validity were each independently classified by both review ers as assessing the domain completeness of follow-up adequate , whereas the extracted item quantification and description of all subjects lost to follow-up was classified as assessing the domain completeness of follow-up described . In the third step , we identified the domains necessary to assess potential biases . Each review er considered the ability of the identified domains to adequately address , at least in part , 1 of the following 6 potential biases : 1 ) study participation , 2 ) study attrition , 3 ) prognostic factor measurement , 4 ) confounding measurement and account , 5 ) outcome measurement , and 6 ) analysis . Domains were considered to adequately address part of the framework if information garnered from that domain would inform the assessment of potential bias . For example , both review ers judged that the identified domain study population represents source population or population of interest assessed potential bias in a prognosis study , whereas the domain research question definition did not , although the latter is an important consideration in assessing the inclusion of studies in a systematic review . Finally , on the basis of our previous ratings , we looked at whether each review included items from the domains necessary to assess the 6 potential biases . We calculated the frequency of systematic review s by assessing each potential bias and the number of review s that adequately assessed bias overall . From this systematic synthesis , we developed recommendations for improving quality appraisal in future systematic review s of prognosis studies . We used Microsoft Access and Excel 2002 ( Microsoft Corp. , Redmond , Washington ) for data management and SAS for Windows , version 9.1 ( SAS Institute , Inc. , Cary , North Carolina ) for descriptive statistics . Role of the Funding Sources The funding sources , the Canadian Institutes of Health Research , the Canadian Chiropractic Research Foundation , the Ontario Chiropractic Association , and the Ontario Ministry of Health and Long Term Care , did not have a role in the collection , analysis , or interpretation of the data or in the decision to su bmi t the manuscript for publication . Results We identified 1384 potentially relevant articles . Figure 1 shows a flow chart of studies that were included and excluded . Figure 2 shows the number of review s identified by year of publication . We excluded 131 systematic review s of prognosis studies that did not seem to include any quality assessment of the included studies ; this represented 44 % of prognosis review s. We included 163 review s of prognosis studies in our analysis ( 13 - 175 ) . The most common topics were cancer ( 15 % ) , musculoskeletal disorders and rheumatology ( 13 % ) , cardiovascular ( 10 % ) , neurology ( 10 % ) , and obstetrics ( 10 % ) . Other review s included a wide range of health and health care topics . Sixty-three percent of the review s investigated the association between a specific prognostic factor and a particular outcome ; the remainder investigated multiple prognostic factors or models . The number of primary studies included in each systematic review ranged from 3 to 167 ( median , 18 [ interquartile range , 12 to 31 ] ) . A complete description of the included review s is available from the authors on request . Figure 1 . Flow diagram of inclusion and exclusion criteria of systematic review s. Figure 2 . Number of systematic review s of prognosis studies identified over time . Quality Items One hundred fifty-three review s provided adequate detail to allow extraction of quality items . Eight hundred eighty-two distinct quality items were extracted from the review s. Most review s developed their own set of quality items , with only a few applying criteria from previous review s. Most quality items Purpose : To compare percutaneous coronary intervention ( PCI ) using stent implantation versus coronary artery bypass graft ( CABG ) in patients with multiple vessel disease with involvement of the proximal left anterior descending coronary artery ( LAD ) . Methods : 230 patients with multiple vessel disease and severe stenosis of the proximal LAD ( 113 with PCI , 117 with CABG ) . They were a cohort of patients from the r and omised ERACI ( Argentine r and omized trial of percutaneous transluminal coronary angioplasty versus coronary artery bypass surgery in multivessel disease ) II study . Results : Both groups had similar baseline characteristics . There were no significant differences in 30 day major adverse cardiac events ( death , myocardial infa rct ion , stroke , and repeat procedures ) between the strategies ( PCI 2.7 % v CABG 7.6 % , p = 0.18 ) . There were no significant differences in survival ( PCI 96.4 % v CABG 95 % , p = 0.98 ) and survival with freedom from myocardial infa rct ion ( PCI 92 % v CABG 89 % , p = 0.94 ) at 41.5 ( 6 ) months ’ follow up . However , freedom from new revascularisation procedures ( CABG 96.6 % v PCI 73 % , p = 0.0002 ) and frequency of angina ( CABG 9.4 % v PCI 22 % , p = 0.025 ) were superior in the CABG group . Conclusion : Patients with multivessel disease and significant disease of the proximal LAD r and omly assigned in the ERACI II trial to PCI or CABG had similar survival and survival with freedom from myocardial infa rct ion at long term follow up . Repeat revascularisation procedures were higher in the PCI group Background —R and omized trials comparing coronary artery bypass graft surgery ( CABG ) with percutaneous coronary interventions ( PCIs ) for patients with multivessel coronary disease ( MVD ) report similar long-term survival for CABG and PCI . These studies used a highly selected population of patients and providers , and their results may not be generalizable to actual care . Our goal in this study was to compare long-term survival of MVD patients treated with CABG vs PCI in contemporary practice . Methods and Results —From our northern New Engl and registries of consecutive coronary revascularizations , we identified 10 198 CABG and 4295 PCI patients with MVD who may have been eligible for either procedure between 1994 and 2001 . Vital status was obtained by linkage to the National Death Index . Proportional-hazards regression was used to calculate hazard ratios ( HRs ) for survival in CABG vs PCI patients after adjustment for comorbidities and disease characteristics . CABG patients were older ; had more comorbidities , more 3-vessel disease , and lower ejection fractions ; and were more completely revascularized . Adjusted long-term survival for patients with 3-vessel disease was better after CABG than PCI ( HR , 0.60 ; P<0.01 ) but not for patients with 2-vessel disease ( HR , 0.98 ; P=0.77 ) . The survival advantage of CABG for 3-vessel disease patients was present in all patient population s , including women , diabetics , and the elderly and in the era of high stent utilization . Conclusions —In contemporary practice , survival for patients with 3-vessel coronary disease is better after CABG than PCI , an observation that patients and physicians should carefully consider when deciding on a revascularization strategy Background —The optimal method of coronary revascularization in dialysis patients is controversial . The purpose of this study was to compare the long-term survival of dialysis patients in the United States after PTCA , coronary stenting , or CABG . Methods and Results —Dialysis patients hospitalized from 1995 to 1998 for first coronary revascularization procedures after renal replacement therapy initiation were identified from the US Renal Data System data base . All-cause and cardiac survival was estimated by the life-table method and compared by the log-rank test . The impact of independent predictors on survival was examined in a Cox regression model . The in-hospital mortality was 8.6 % for 6668 CABG patients , 6.4 % for 4836 PTCA patients , and 4.1 % for 4280 stent patients . The 2-year all-cause survival ( mean±SEM ) was 56.4±1.4 % for CABG patients , 48.2±1.5 % for PTCA patients , and 48.4±2.0 % for stent patients ( P < 0.0001 ) . After comorbidity adjustment , the relative risk ( RR ) for CABG ( versus PTCA ) patients was 0.80 ( 95 % CI 0.76 to 0.84 , P < 0.0001 ) for all-cause death and 0.72 ( 95 % CI 0.67 to 0.77 , P < 0.0001 ) for cardiac death . For stent ( versus PTCA ) patients , the RR was Output:	In an exploratory meta- analysis , short-term mortality was higher after CABG compared to PCI . A substantial number of patients died over a subsequent 1 to 5 yr , with no difference in mortality after CABG compared to PCI .
MS213899	*TASK* the task is to summarize an input biomedical literature in six sentences *INPUT* the input is a biomedical literature *OUTPUT* the output is the summary of an input biomedical literature in six sentences *DOCUMENTATION* *EXAMPLES* Input: The effect of intravenous infusion of labetalol and of dihydralazine in increasing doses was compared in 12 women with severe hypertension in pregnancy . In 5 our of 6 women labetalol produced a smooth , progressive fall in blood pressure to normal levels with minimal side effects . In 2 our of 6 women on dihydralazine the blood pressure control was satisfactory but in the remaining 4 patients treatment had to by discontinued because of unpredictable , sudden falls in blood pressure . One of the 6 infants of mothers treated with labetalol manifested signs of adrenergic blockade . Continuous infusion of labetalol appears to offer significant advantages in the management of severe hypertension in pregnancy and merits further trial Summary : The results of a prospect i ve trial to evaluate the use of diazoxide and labetalol given intravenously in the management of severe hypertensive disease in pregnancy are presented OBJECTIVE Determine the definitive position of ketanserin and dihydralazine for treatment of severe hypertension in pregnancy . STUDY DESIGN A single centre double blind r and omized controlled trial was performed at the obstetrical tertiary high care unit of the University Medical Centre in Rotterdam , the Netherl and s. Women with severe hypertension in pregnancy ( diastolic blood pressure (DBP)≥110mmHg ) , and significant proteinuria ( ≥300mg/24h ) , and gestational age≤32 weeks were eligible for the study . All patients ( n=30 ) received two infusions ( double dummy technique ) : one contained the active ingredient ( ketanserin or dihydralazine ) , the other was used for placebo . Nicardipine was used as rescue medication . The main outcome measures were persistent severe hypertension ( DBP>100mmHg>120min ) despite maximum dosage of study medication and prolongation of pregnancy . RESULTS Dihydralazine was significantly more effective in lowering blood pressure than ketanserin . No significant difference in prolongation of pregnancy was seen between the two groups . After 30 inclusion s , the study was stopped because of the high rate of persistent hypertension using ketanserin and the high rate of maternal side effects using dihydralazine and the apparent succesful use of the rescue drug nicardipine . CONCLUSIONS Our results do not support the use of either dihydralazine or ketanserin for the treatment of severe hypertension in pregnancy . Future research is needed to compare nicardipine with other antihypertensive drugs currently in use for treatment of severe hypertension in pregnancy OBJECTIVES The purpose s of this study were to compare the efficacy of sublingual nifedipine with intravenous hydrallazine in the control of acute hypertension of pregnancy and to make a preliminary assessment whether sublingual nifedipine could be recommended for use by midwives faced with severe hypertension in pregnancy in a rural setting . METHODS Subjects were 200 consecutive patients admitted to Kuala Tereng-ganu General Hospital , Malaysia with severe hypertension in pregnancy between August 1989 and June 1990 . Admission criteria were an ongoing viable pregnancy more than 28 weeks and diastolic blood pressure ( DBP ) more than 120 mmHg . The patients were r and omly divided into 2 groups . In group I , sublingual nifedipine 5 mg was administered and repeated after 15 minutes if DBP > 120 mmHg ; and in group II hydrallazine 5 mg was intravenously injected and repeated after 15 minutes if DBP > 120 mmHg . Both groups were put on hydrallazine infusion if DBP > 120 mmHg after 30 minutes . The Chi-square test was used for analysis with significance at p < 0.05 . RESULTS There was no statistical difference in the efficacy of therapy for decreasing blood pressure between the 2 groups . The groups were comparable by age , parity , gestational age at presentation , birth weight of infants , incidence of postpartum haemorrhage and fetal distress . Caesarian section rates were similar . In the observational studies on nurses administering the drugs , no significant difficulties were observed . CONCLUSION Sublingual nifedipine was comparable to IV hydrallazine in the treatment of acute hypertension of pregnancy . Nurses were able to administer lingual nifedipine without difficulty Objective Preeclampsia ( PE ) is a complication affecting pregnant women worldwide , which usually manifests as severe maternal hypertension . Resveratrol ( RESV ) , a naturally existing polyphenol , is known to exhibit beneficial effects in cardiovascular disease including hypertension . We evaluated the outcome of treatment combining oral nifedipine ( NIFE ) and RESV against PE . Design and methods Using a r and omized group assignment , 400 PE patients were enrolled and received oral treatments of either NIFE + RESV or NIFE + placebo . Primary endpoints were defined as time to control blood pressure and time before a new hypertensive crisis . Secondary endpoints were defined as the number of doses needed to control blood pressure , maternal and neonatal adverse effects . Results Compared with the NIFE + placebo group , the time needed to control blood pressure was significantly reduced in NIFE + RESV group , while time before a new hypertensive crisis was greatly delayed in NIFE + RESV group . The number of treatment doses needed to control blood pressure was also categorically lower in NIFE + RESV group . No differences in maternal or neonatal adverse effects were observed between the two treatment groups . Conclusion Our data support the potential of RESV as a safe and effective adjuvant of oral NIFE to attenuate hypertensive symptoms among PE patients AIMS Diazoxide is one of few available agents for treatment of hypertensive emergencies in pregnancy . From previous studies , there is a question concerning safety after moderate-dose administration caused episodes of hypotension . Rapid control of severe hypertension is necessary to reduce maternal morbidity , for example , stroke and placental abruption . This study was design ed to compare the efficacy of mini-bolus diazoxide with intravenous ( i.v . ) hydralazine . DESIGN A r and omised controlled trial . SETTING Tertiary referral maternity hospital , Royal Prince Alfred Women and Babies , Sydney Australia . POPULATION Antenatal and postnatal women with severe hypertension . METHODS One hundred and twenty-four hypertensive women were r and omised to either i.v . hydralazine ( 5 mg doses ) or mini-bolus diazoxide ( 15 mg doses ) . PRIMARY OUTCOME MEASURE Achievement of target blood pressure reduction ; secondary measures included requirement for Caesarean section because of fetal deterioration as determined by non-reassuring cardiotocograph ( CTG ) . RESULTS Reduction in systolic and diastolic blood pressure was 34 min for hydralazine and 19 min for diazoxide ( P < 0.001 ) . There were no episodes of hypotension after diazoxide and one after hydralazine ( after epidural ) . Episodes of persistent severe hypertension were more common with hydralazine ( 38 % ) than with diazoxide ( 16 % ) , P < 0.01 . The Caesarean section rate for no-reassuring CTG was no different between the two groups . Neonatal outcomes were similar . CONCLUSION Diazoxide and hydralazine are safe and effective antihypertensives , showing a controlled and comparable blood pressure reduction in women with hypertensive emergencies in pregnancy . The mini-bolus doses of 15 mg of diazoxide did not precipitate maternal hypotension as previously described and reduces episodes of persistent severe hypertension Vitamin D ( VD ) has exhibited immunomodulatory role in the pathogenesis of preeclampsia . We hypothesize VD potentiate nifedipine treatment for preeclampsia by shortened the time to control blood pressure and prolong time before subsequent hypertensive crisis . We conduct a r and omized trial of 683 primigravid women with preeclampsia , who were assigned to different treatment groups , either nifedipine+placebo or nifedipine+VD orally , by r and om after screening . Primary endpoints include time to control hypertension and time before another hypertensive crisis . Maternal adverse effects including nausea , vomiting , chest pain , mild headache , dizziness , maternal tachycardia , hypotension or shortness of breath , and neonatal parameters including birth weight and Apgar scores , as well as the minimum number of dosages needed to control hypertension were defined as secondary endpoints . Serum levels of cytokines tumor necrosis factor-α ( TNF-α ) and interleukin-10 ( IL-10 ) were also examined . There was a marked reduction of the time required to control hypertension and a significant lengthening ( p = 0.013 ) of the time before a new hypertensive crisis in participants received nifedipine+VD treatments ( 41.8 ± 18.3 min ) , in comparison with the nifedipine+placebo controls ( 61.1 ± 15.9 min ) . In women treated with nifedipine+VD , the minimum number of dosages needed to control hypertension was also lower . With regard to adverse effects , no statistical difference was observed between the two treatment groups . Moreover , treatment with VD increased IL-10 and reduced TNF-α serum levels . VD possesses the potential of serving as a safe and effective adjuvant to oral nifedipine in treating women with preeclampsia against hypertension , possibly through the upregulation of IL-10 and the downregulation of TNF-α OBJECTIVE The objective was to compare the safety and efficacy of intravenous labetalol and intravenous hydralazine for acutely lowering blood pressure in pregnancy . STUDY DESIGN Two hundred women with severe hypertension in pregnancy were r and omized to receive hydralazine ( 5 mg as a slow bolus dose given intravenously , and repeated every 20 min up to a maximum of five doses ) or labetalol ( 20-mg intravenous bolus dose followed by 40 mg if not effective within 20 min , followed by 80 mg every 20 min up to a maximum dose of 300 mg ) . The primary end point was successful lowering of blood pressure and maternal hypotension . RESULTS Women were similar with respect to characteristics at r and omization . No significant differences were observed for maternal hypotension or persistent severe hypertension ; only two patients in the hydralazine group presented with hypotension . Palpitations ( p=0.01 ) and maternal tachycardia ( p=0.05 ) occurred significantly more often in patients treated with hydralazine . The main neonatal outcomes were very similar per group ; however , hypotension and bradycardia were significantly more frequent in the labetalol group . There were two neonatal deaths per antihypertensive drug group . CONCLUSIONS This r and omized clinical trial shows that labetalol and hydralazine fulfill the criteria required for an antihypertensive drug to treat severe hypertension in pregnancy Abstract Objective : Using noninvasive bedside impedance cardiography ( ICG ) , we compared the effectiveness and the hemodynamic impact of intravenous labetalol versus hydralazine for the reduction of acute-onset severe hypertension to ACOG-recommended blood pressure levels ( ACOG Committee Opinion 514 ) . Study design : In this prospect i ve r and omized pilot study of acutely severe systolic hypertension ( ≥160 mmHg ) , pregnant women received either labetalol ( L ) or hydralazine ( H ) intravenously and underwent thoracic ICG before and after treatment . Data analysis were performed using STATA software ( StataCorp LP , College Station , TX ) ; data are expressed as mean ± SD . Results : About 29 patients completed the study . There was no significant difference in mean arterial pressure ( MAP ) between groups [ H = 119.4 mmHg , L = 117.7 mmHg , mean difference ( MD ) = 1.73 ) ; the estimated MD between baseline and follow-up ICG was −9.17 ( p = 0.001 , 95 % CI : −14.39 to −3.95 ) . There were no significant differences in total peripheral resistance ( TPR ) between groups ( H = 1771.3 , L = 1976.97 , MD = 205.62 ) or cardiac output ( CO ) between groups ( H = 5.7 , L = 5.1 , MD = 0.64 ) or a significant MD between these at baseline and follow-up . Conclusion : Both drugs performed similarly to achieve ACOG-recommended initial blood pressure reduction safely without side effects or excessive acute hemodynamic profile correction toward normal pregnancy values OBJECTIVE This executive summary presents in brief the current evidence assessed in the clinical practice guideline prepared by the Canadian Hypertensive Disorders of Pregnancy Working Group and published by Pregnancy Hypertension ( http://www.pregnancyhypertension.org/article/S2210-7789(14)00004-X/fulltext ) to provide a reasonable approach to the diagnosis , evaluation , and treatment of the hypertensive disorders of pregnancy . EVIDENCE Published literature was retrieved through search es of Medline , CINAHL , and The Cochrane Library in March 2012 using appropriate controlled vocabulary ( e.g. , pregnancy , hypertension , pre-eclampsia , pregnancy toxemias ) and key words ( e.g. , diagnosis , evaluation , classification , prediction , prevention , prognosis , treatment , postpartum follow-up ) . Results were restricted to systematic review s , r and omized control trials , controlled clinical trials , and observational studies published in French or English between January 200 Output:	Diazoxide [ -15 ( -20.6 , -9.4 ) ] , nicardipine [ -11.8 ( -22.3 , -1.2 ) ] , nifedipine/celastrol [ -19.3 ( -27.4 , -11.1 ) ] , nifedipine/vitamin D [ -17.1 ( -25.7 , -9.7 ) ] , nifedipine/resveratrol [ -13.9 ( -22.6 , -5.2 ) ] and glyceryl trinitrate [ -33.8 ( -36.7 , -31 ) ] were observed to achieve the target BP ( in minutes ) more rapidly than hydralazine . Nifedipine required fewer doses than hydralazine for achieving the target BP . Glyceryl trinitrate and labetalol were associated with fewer incidences of tachycardia and palpitation respectively than hydralazine . Trial sequential analysis concluded adequate evidence for hydralazine and nifedipine compared with labetalol . The present evidence suggests similar efficacy between nifedipine , hydralazine and labetalol in the treatment of severe hypertension in pregnancy . Subtle differences may exist in their safety profile .

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