***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 Platelet activation has been implicated in the pathogenesis of sickle cell disease ( SCD ) suggesting antiplatelet agents may be therapeutic . To evaluate the safety of prasugrel , a thienopyridine antiplatelet agent , in adult patients with SCD , we conducted a double-blind , r and omized , placebo-controlled study . Methods The primary endpoint , safety , was measured by hemorrhagic events requiring medical intervention . Patients were r and omized to prasugrel 5 mg daily ( n = 41 ) or placebo ( n = 21 ) for 30 days .  Platelet function by VerifyNow ® P2Y12 and vasodilator-stimulated phosphoprotein assays at days 10 and 30 were significantly inhibited in prasugrel- compared with placebo-treated SCD patients . Results There were no hemorrhagic events requiring medical intervention in either study arm . Mean pain rate ( percentage of days with pain ) and intensity in the prasugrel arm were decreased compared with placebo . However , these decreases did not reach statistical significance . Platelet surface P-selectin and plasma soluble P-selectin , biomarkers of in vivo platelet activation , were significantly reduced in SCD patients receiving prasugrel compared with placebo . In sum , prasugrel was well tolerated and not associated with serious hemorrhagic events . Conclusions Despite the small size and short duration of this study , there was a decrease in platelet activation biomarkers and a trend toward decreased pain The effects of low doses of aspirin on the frequency and severity of painful vaso-occlusive crises were evaluated in children with sickle hemoglobinopathies .  Aspirin was compared with placebo in 49 patients in a double-blind crossover study . Careful monitoring of patients revealed an average of 1.1 painful crises per patient year . During the 21 months of study , 70 % of patients had a maximum of two painful crises , and 25 % experienced four or more . The frequency and severity of crises were not affected by aspirin therapy . In view of aspirin 's demonstrated effect on platelet function , we suggest that platelets do not contribute to the initiation or progression of the vaso-occlusive process BACKGROUND Systematic review s may be compromised by selective inclusion and reporting of outcomes and analyses . Selective inclusion occurs when there are multiple effect estimates in a trial report that could be included in a particular meta- analysis ( e.g. from multiple measurement scales and time points ) and the choice of effect estimate to include in the meta- analysis is based on the results ( e.g. statistical significance , magnitude or direction of effect ) . Selective reporting occurs when the reporting of a subset of outcomes and analyses in the systematic review is based on the results ( e.g. a protocol -defined outcome is omitted from the published systematic review ) . OBJECTIVES To summarise the characteristics and synthesis e the results of empirical studies that have investigated the prevalence of selective inclusion or reporting in systematic review s of r and omised controlled trials ( RCTs ) , investigated the factors ( e.g. statistical significance or direction of effect ) associated with the prevalence and quantified the bias . SEARCH METHODS We search ed the Cochrane Methodology Register ( to July 2012 ) , Ovid MEDLINE , Ovid EMBASE , Ovid PsycINFO and ISI Web of Science ( each up to May 2013 ) , and the US Agency for Healthcare Research and Quality ( AHRQ ) Effective Healthcare Program 's Scientific Re source Center ( SRC ) Methods Library ( to June 2013 ) . We also search ed the abstract books of the 2011 and 2012 Cochrane Colloquia and the article alerts for method ological work in research synthesis published from 2009 to 2011 and compiled in Research Synthesis Methods . SELECTION CRITERIA We included both published and unpublished empirical studies that investigated the prevalence and factors associated with selective inclusion or reporting , or both , in systematic review s of RCTs of healthcare interventions . We included empirical studies assessing any type of selective inclusion or reporting , such as investigations of how frequently RCT outcome data is selectively included in systematic review s based on the results , outcomes and analyses are discrepant between protocol and published review or non-significant outcomes are partially reported in the full text or summary within systematic review s. DATA COLLECTION AND ANALYSIS Two review authors independently selected empirical studies for inclusion , extracted the data and performed a risk of bias assessment . A third review author resolved any disagreements about inclusion or exclusion of empirical studies , data extraction and risk of bias . We contacted authors of included studies for additional unpublished data . Primary outcomes included overall prevalence of selective inclusion or reporting , association between selective inclusion or reporting and the statistical significance of the effect estimate , and association between selective inclusion or reporting and the direction of the effect estimate . We combined prevalence estimates and risk ratios ( RRs ) using a r and om-effects meta- analysis model . MAIN RESULTS Seven studies met the inclusion criteria . No studies had investigated selective inclusion of results in systematic review s , or discrepancies in outcomes and analyses between systematic review registry entries and published systematic review s. Based on a meta- analysis of four studies ( including 485 Cochrane Review s ) , 38 % ( 95 % confidence interval ( CI ) 23 % to 54 % ) of systematic review s added , omitted , up grade d or down grade d at least one outcome between the protocol and published systematic review . The association between statistical significance and discrepant outcome reporting between protocol and published systematic review was uncertain . The meta-analytic estimate suggested an increased risk of adding or upgrading ( i.e. changing a secondary outcome to primary ) when the outcome was statistically significant , although the 95 % CI included no association and a decreased risk as plausible estimates ( RR 1.43 , 95 % CI 0.71 to 2.85 ; two studies , n = 552 meta-analyses ) . Also , the meta-analytic estimate suggested an increased risk of downgrading ( i.e. changing a primary outcome to secondary ) when the outcome was statistically significant , although the 95 % CI included no association and a decreased risk as plausible estimates ( RR 1.26 , 95 % CI 0.60 to 2.62 ; two studies , n = 484 meta-analyses ) . None of the included studies had investigated whether the association between statistical significance and adding , upgrading or downgrading of outcomes was modified by the type of comparison , direction of effect or type of outcome ; or whether there is an association between direction of the effect estimate and discrepant outcome reporting . Several secondary outcomes were reported in the included studies . Two studies found that reasons for discrepant outcome reporting were infrequently reported in published systematic review s ( 6 % in one study and 22 % in the other ) . One study ( including 62 Cochrane Review s ) found that 32 % ( 95 % CI 21 % to 45 % ) of systematic review s did not report all primary outcomes in the abstract . Another study ( including 64 Cochrane and 118 non-Cochrane review s ) found that statistically significant primary outcomes were more likely to be completely reported in the systematic review abstract than non-significant primary outcomes ( RR 2.66 , 95 % CI 1.81 to 3.90 ) . None of the studies included systematic review s published after 2009 when reporting st and ards for systematic review s ( Preferred Reporting Items for Systematic review s and Meta-Analyses ( PRISMA ) Statement , and Method ological Expectations of Cochrane Intervention Review s ( MECIR ) ) were disseminated , so the results might not be generalisable to more recent systematic review s. AUTHORS ' CONCLUSIONS Discrepant outcome reporting between the protocol and published systematic review is fairly common , although the association between statistical significance and discrepant outcome reporting is uncertain . Complete reporting of outcomes in systematic review abstract s is associated with statistical significance of the results for those outcomes . Systematic review outcomes and analysis plans should be specified prior to seeing the results of included studies to minimise post-hoc decisions that may be based on the observed results . Modifications that occur once the review has commenced , along with their justification , should be clearly reported . Effect estimates and CIs should be reported for all systematic review outcomes regardless of the results . The lack of research on selective inclusion of results in systematic review s needs to be addressed and studies that avoid the method ological weaknesses of existing research are also needed This article introduces the approach of GRADE to rating  quality of evidence .  GRADE specifies four categories-high , moderate , low , and very low-that are applied to a body of evidence , not to individual studies . In the context of a systematic review , quality reflects our confidence that the estimates of the effect are correct . In the context of recommendations , quality reflects our confidence that the effect estimates are adequate to support a particular recommendation . R and omized trials begin as high- quality evidence , observational studies as low quality . " Quality " as used in GRADE means more than risk of bias and so may also be compromised by imprecision , inconsistency , indirectness of study results , and publication bias . In addition , several factors can increase our confidence in an estimate of effect . GRADE provides a systematic approach for considering and reporting each of these factors . GRADE separates the process of assessing quality of evidence from the process of making recommendations . Judgments about the strength of a recommendation depend on more than just the quality of evidence AIMS To illustrate how Bayes factors are important for determining the effectiveness of interventions . METHOD We consider a case where inappropriate conclusions were drawn publicly based on significance testing , namely the SIPS project ( Screening and Intervention Programme for Sensible drinking ) , a pragmatic , cluster-r and omized controlled trial in each of two health-care setting s and in the criminal justice system . We show how Bayes factors can disambiguate the non-significant findings from the SIPS project and thus determine whether the findings represent evidence of absence or absence of evidence . We show how to model the sort of effects that could be expected , and how to check the robustness of the Bayes factors . RESULTS The findings from the three SIPS trials taken individually are largely uninformative but , when data from these trials are combined , there is moderate evidence for a null hypothesis ( H0 ) and thus for a lack of effect of brief intervention compared with simple clinical feedback and an alcohol information leaflet ( B = 0.24 , P = 0.43 ) . CONCLUSION Scientists who find non-significant results should suspend judgement-unless they calculate a Bayes factor to indicate either that there is evidence for a null hypothesis ( H0 ) over a ( well-justified ) alternative hypothesis ( H1 ) , or that more data are needed BACKGROUND This study describes how painful events affect the health-related quality of life ( HRQL ) of children with sickle cell disease ( SCD ) and determines the responsiveness of a generic HRQL measure in SCD . Our hypotheses were twofold : ( 1 ) HRQL is significantly impaired at presentation to the emergency department for a painful event and ( 2 ) PedsQL 4.0 Acute Version Generic Core Scales is responsive to change in the evolution of a painful event . PROCEDURE This prospect i ve cohort study included 57 children with SCD .  HRQL was measured with the Acute Version of the PedsQL 4.0 Generic Core Scales , completed by child ( self-report ) and caregiver ( proxy report ) at presentation and 7 days post-discharge . Independent comparisons of HRQL scores were made between children in the study cohort and a published reference sample of children with SCD in baseline health ( historical SCD controls ) . RESULTS Median PedsQL scores at presentation were significantly lower than historical SCD controls in all domains for child self-report and all domains except social and school functioning in parent-proxy . Clinical ly and statistically significant changes in HRQL between presentation and post-discharge result ed in similar HRQL scores at 7 days post-discharge to historical SCD controls . CONCLUSIONS The PedsQL is responsive to change ; thus a useful tool to measure the impact of interventions in future SCD clinical trials . Painful events significantly diminish all domains of HRQL and this improves 7 days post-discharge Baseline studies of 111Indium oxine labelled platelet life-span , platelet alpha-granule release products , beta-thromboglobulin ( beta TG ) and platelet factor 4 ( PF4 ) , and factor VIII related activities were performed on 9 asymptomatic patients with sickle cell disease , who were subsequently r and omised in a prospect i ve double-blind trial of ticlopidine ( 250 mg . b. d. )  or placebo for one month and the investigations repeated . Control studies indicated that 5 of the 9 patients had shortened platelet survivals : mean beta TG ( 50.8 ng/ml ) and PF4 ( 19.5 ng/ml ) , factor VIII : C ( 283.4 i.u./dl ) and factor VIIIR : AG ( 168.7 u/dl ) levels were raised . Ticlopidine treatment did not significantly improve platelet life-span or factor VIII levels , though it was associated with reduced values of beta TG and PF4 . One patient taking ticlopidine developed an infa rct i ve sickle crisis . Although ticlopidine blocked platelet activation , this alone did not improve platelet survival or prevent sickle crisis : in view of evidence of platelet activation in sickle cell disease , however , a longer trial of prophylactic antiplatelet drugs might be warranted OBJECTIVES By removing systematic differences across treatment groups , simple r and omization is assumed to protect against bias . However , r and om differences may remain if the sample size is insufficiently large . We sought to determine the minimal sample size required to eliminate r and om differences , thereby allowing an unbiased estimation of the treatment effect . STUDY DESIGN AND SETTING We reanalyzed two published multicenter , large , and simple trials : the International Stroke Trial ( IST ) and the Coronary Artery Bypass Grafting ( CABG ) Off- or On-Pump Revas 
    Output:
    
No difference in VOEs was found in studies that compared either ticagrelor in children or prasugrel in adults vs placebo .
The overall incidence of harms in any intervention did not differ from that in the control .
The current evidence does not support or reject the use of any antiplatelet agent for preventing VOEs in people with SCD .