***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 Current Medical Research Council ( MRC ) guidance on complex interventions advocates pilot trials and feasibility studies as part of a phased approach to the development , testing , and evaluation of healthcare interventions . In this paper we discuss the results of a recent feasibility study and pilot trial for a r and omized controlled trial ( RCT ) of pelvic floor muscle training for prolapse ( Clinical Trials.gov : NCT01136889 ) . The ways in which research ers decide to respond to the results of feasibility work may have significant repercussions for both the nature and degree of tension between internal and external validity in a definitive trial . Methods We used method ological issues to classify and analyze the problems that arose in the feasibility study . Four centers participated with the aim of r and omizing 50 women . Women were eligible if they had prolapse of any type , of stage I to IV , and had a pessary successfully fitted .  Postal question naires were administered at baseline , 6 months , and 7 months post-r and omization . After identifying problems arising within the pilot study we then sought to locate potential solutions that might minimize the trade-off between a subsequent explanatory versus pragmatic trial . Results The feasibility study pointed to significant potential problems in relation to participant recruitment , features of the intervention , acceptability of the intervention to participants , and outcome measurement . Finding minimal evidence to support our decision-making regarding the transition from feasibility work to a trial , we developed a systematic process ( A process for Decision-making after Pilot and feasibility Trials ( ADePT ) ) which we subsequently used as a guide . The process sought to : 1 ) encourage the systematic identification and appraisal of problems and potential solutions ; 2 ) improve the transparency of decision-making processes ; and 3 ) reveal the tensions that exist between pragmatic and explanatory choices . Conclusions We have developed a process that may aid research ers in their attempt to identify the most appropriate solutions to problems identified within future pilot and feasibility RCTs . The process includes three key steps : a decision about the type of problem , the identification of all solutions ( whether addressed within the intervention , trial design or clinical context ) , and a systematic appraisal of these solutions Background Animal experimental studies and previous r and omized trials suggest an improvement in mortality and neurological function with temperature regulation to hypothermia  after cardiac arrest . According to a systematic review , previous trials were small , had a risk of bias , evaluated select population s , and did not treat hyperthermia in the control groups . The optimal target temperature management ( TTM ) strategy is not known . To prevent outcome reporting bias , selective reporting and data -driven results , we present the a priori defined detailed statistical analysis plan as an up date to the previously published outline of the design and rationale for the TTM trial . Methods The TTM trial is an investigator-initiated , multicenter , international , r and omized , parallel-group , and assessor-blinded clinical trial of temperature management in 950 adult unconscious patients resuscitated after out-of-hospital cardiac arrest of a presumed cardiac cause . The patients are r and omized to a TTM of either 33 ° C or 36 ° C after return of spontaneous circulation . The primary outcome is all-cause mortality at maximal follow-up ( until end of the trial and a minimum of 180 days ) . The main secondary outcomes are the composite outcome of all-cause mortality and poor neurological function ( Cerebral Performance Category ( CPC ) 3 and 4 , and modified Rankin Scale ( mRS ) 4 and 5 ) at hospital discharge and at 180 days ; and assessment of safety and harm : bleeding , infections , electrolyte and metabolic disorders , seizures , cardiac arrhythmia , and renal replacement therapy . Conclusion The TTM trial investigates potential benefit and harm of two target temperature strategies , both avoiding hyperthermia in a large proportion of the out-of-hospital cardiac arrest population .Trial registration Clinical Trials.gov identifier : BACKGROUND Efficient trials of interventions for patients with out-of-hospital cardiac arrest ( OHCA ) should have adequate but not excess power to detect a difference in outcomes . The minimum clinical ly important difference ( MCID ) is the threshold value in outcomes observed in a trial at which providers should choose to adopt a treatment . There has been limited assessment of MCID for outcomes after OHCA . Therefore , we conducted an international survey of individuals interested in cardiac resuscitation to define the MCID for a range of outcomes after OHCA . METHODS A brief survey instrument was developed and modified by consensus . Included were open-ended responses . The survey included an illustrative example of a hypothetical r and omized study with distributions of outcomes based on those in a public use data file from a previous trial . Elicited information included the minimum significant difference required in an outcome to change clinical practice . The population of interest was emergency physicians or other practitioners of acute cardiovascular research . RESULTS Usable responses were obtained from 160 respondents ( 50 % of surveyed ) in 46 countries ( 79 % of surveyed ) .  MCIDs tended to increase as baseline outcomes increased . For a population of patients with 25 % survival to discharge and 20 % favorable neurologic status at discharge , the MCID were median 5 ( interquartile range [ IQR ] 3 , 10 ) percent for survival to discharge ; median 5 ( IQR 2 , 10 ) percent for favorable neurologic status at discharge , median 4 ( IQR 2 , 9 ) days of ICU-free survival and median 4 ( IQR 2 , 8) days of hospital-free survival . CONCLUSION Reported MCIDs for outcomes after OHCA vary according to the outcome considered as well as the baseline rate of achieving it . MCIDs of ICU-free survival or hospital-free survival may be useful to accelerate the rate of evidence -based change in resuscitation care R and omised control trials have sought to seek to improve mechanical ventilation  treatment . However , few trials to date have shown clinical significance . It is hypothesised that aside from effective treatment , the outcome metrics and sample sizes of the trial also affect the significance , and thus impact trial design . In this study , a Monte-Carlo simulation method was developed and used to investigate several outcome metrics of ventilation treatment , including 1 )  length of mechanical ventilation ( LoMV ) ;  2 )  Ventilator Free Days ( VFD ) ;  and 3 )  LoMV-28  , a combination of the other metrics . As these metrics have highly skewed distributions , it also investigated the impact of imposing clinical ly relevant exclusion criteria on study power to enable better design for significance . Data from invasively ventilated patients from a single intensive care unit were used in this analysis to demonstrate the method . Use of LoMV as an outcome metric required 160 patients /arm to reach 80 % power with a clinical ly expected intervention difference of 25 % LoMV if clinical ly relevant exclusion criteria were applied to the cohort , but 400 patients /arm if they were not . However , only 130 patients /arm would be required for the same statistical significance at the same intervention difference if VFD was used . A Monte-Carlo simulation approach using local cohort data combined with objective patient selection criteria can yield better design of ventilation studies to desired power and significance , with fewer patients per arm than traditional trial design methods , which in turn reduces patient risk . Outcome metrics , such as VFD , should be used when a difference in mortality is also expected between the two cohorts . Finally , the non-parametric approach taken is readily generalisable to a range of trial types where outcome data is similarly skewed BACKGROUND Heart failure ( HF )  treatment guided by amino-terminal pro-B type natriuretic peptide ( NT-proBNP ) may reduce cardiovascular event rates compared to st and ard-of-care ( SOC ) management . Comprehensive underst and ing regarding effect of NT-proBNP guided care on patient-reported quality of life ( QOL ) remains unknown . METHODS One hundred fifty-one subjects with HF due to left ventricular systolic dysfunction were r and omized to either SOC HF management or care with a goal to reduce NT-proBNP values ≤1000 pg/mL. Effects of HF on QOL were assessed using the  Minnesota Living with HF Question naire ( MLHFQ ) quarterly , with change ( Δ ) in score assessed across study procedures and as a function of outcome . RESULTS Overall , baseline MLHFQ score was 30 . Across study visits , QOL improved in both arms , but was more improved and sustained in the NT-proBNP arm ( repeated measures P = .01 ) ; NT-proBNP patients showing greater reduction in MLHFQ score ( -10.0 vs -5.0 ; P = .05 ) , particularly in the physical scale of the question naire . Baseline MLHFQ scores did not correlate with NT-proBNP ; in contrast , ∆MLHFQ scores modestly correlated with ∆NT-proBNP values ( ρ = .234 ; P = .006 ) as did relative ∆ in MLHFQ score and NT-proBNP ( ρ = .253 ; P = .003 ) . Considered in tertiles , less improvement in MLHFQ scores was associated with a higher rate of HF hospitalization , worsening HF , and cardiovascular death ( P = .001 ) . CONCLUSIONS We describe novel associations between NT-proBNP concentrations and QOL scores among patients treated with biomarker guided care .  Compared to SOC HF management , NT-proBNP guided care was associated with greater and more sustained improvement in QOL ( Clinical Trial Registration : www . clinical trials.govNCT00351390 ) AIM OF THE STUDY To investigate whether there were any changes in and correlations between anxiety , depression and health-related quality of life ( HRQoL ) over time , between hospital discharge and one and six months after cardiac arrest ( CA ) , in patients treated with therapeutic hypothermia ( TH ) .  METHOD During a 4-year period at three hospitals in Sweden , 26 patients were prospect ively included after CA treated with TH .  All patients completed the question naires Hospital Anxiety and Depression Scale ( HADS ) , Euroqol ( EQ5D ) , Euroqol visual analogue scale ( EQ-VAS ) and Short Form 12 ( SF12 ) at three occasions , at hospital discharge , and at one and 6 months after CA . RESULT There was improvement over time in HRQoL , the EQ5D index ( p=0.002 ) and the SF12 physical component score ( PCS ) ( p=0.005 ) . Changes over time in anxiety and depression were not found . Seventy-three percent of patients had an EQ-VAS score below 70 ( scale 0 - 100 ) on overall health status at discharge from hospital ; at 6 months the corresponding figure was 41 % . Physical problems were the most common complaint affecting HRQoL. A correlation was found between depression and HRQoL , and this was strongest at six months ( rs=-0.44 to -0.71 , p≤0.001 ) . CONCLUSION HRQoL improves over the first 6 months after a CA . Patients reported lower levels of HRQoL on the physical as compared to mental component . The results indicate that the less anxiety and depression patients perceive , the better HRQoL they have and that time can be an important factor in recovery after CA BACKGROUND During cardiopulmonary resuscitation ( CPR ) in patients with out-of-hospital cardiac arrest , the interruption of manual chest compressions for rescue breathing reduces blood flow and possibly survival . We assessed whether outcomes after continuous compressions with positive-pressure ventilation differed from those after compressions that were interrupted for ventilations at a ratio of 30 compressions to two ventilations . METHODS This cluster-r and omized trial with crossover included 114 emergency medical service ( EMS ) agencies . Adults with non-trauma-related cardiac arrest who were treated by EMS providers received continuous chest compressions ( intervention group ) or interrupted chest compressions ( control group ) . The primary outcome was the rate of survival to hospital discharge . Secondary outcomes included the modified Rankin scale score ( on a scale from 0 to 6 , with a score of ≤3 indicating favorable neurologic function ) . CPR process was measured to assess compliance . RESULTS Of 23,711 patients included in the primary analysis , 12,653 were assigned to the intervention group and 11,058 to the control group . A total of 1129 of 12,613 patients with available data ( 9.0 % ) in the intervention group and 1072 of 11,035 with available data ( 9.7 % ) in the control group survived until discharge ( difference , -0.7 percentage points ; 95 % confidence interval [ CI ] , -1.5 to 0.1 ; P=0.07 ) ; 7.0 % of the patients in the intervention group and 7.7 % of those in the control group survived with favorable neurologic function at discharge ( difference , -0.6 percentage points ; 95 % CI , -1.4 to 0.1 , P=0.09 ) . Hospital-free survival was significantly shorter in the intervention group than in the control group ( mean difference , -0.2 days ; 95 % CI , -0.3 to -0.1 ; P=0.004 ) . CONCLUSIONS In patients with out-of-hospital cardiac arrest , continuous chest compressions during CPR performed by EMS providers did not result in significantly higher rates of survival or favorable neurologic function than did interrupted chest compressions . ( Funded by the National Heart , Lung , and Blood Institute and others ; ROC CCC Clinical Trials.gov number , NCT01372748 . ) Background : Little evidence guides the appropriate duration of resuscitation in out-of-hospital cardiac arrest , and case features justifying longer or shorter duration s are ill defined . We estimated the impact 
    Output:
    
Consensus emerged that a core outcome set for reporting on effectiveness studies of cardiac arrest ( COSCA ) in adults should include survival , neurological function , and health-related quality of life .