***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: & NA ; Adverse events in r and omized controlled trials of noninvasive , pharmacologic analgesics are frequently incompletely or inconsistently reported . A comprehensive reporting checklist is proposed to improve disclosure of adverse effects . & NA ; The development of valid and informative treatment risk – benefit profiles requires consistent and thorough information about adverse event ( AE ) assessment and participants ’ AEs during r and omized controlled trials ( RCTs ) . Despite a 2004 extension of the Consoli date d St and ards of Reporting Trials ( CONSORT ) statement recommending the specific AE information that investigators should report , there is little evidence that analgesic RCTs adequately adhere to these recommendations . This systematic review builds on prior recommendations by describing a comprehensive checklist for AE reporting developed to capture clinical ly important AE information . Using this checklist , we coded AE assessment methods and reporting in all 80 double‐blind RCTs of noninvasive pharmacologic treatments published in the European Journal of Pain , Journal of Pain , and PAIN ® from 2006 to 2011 . Across all trials , reports of AEs were frequently incomplete , inconsistent across trials , and , in some cases , missing . For example , > 40 % of trials failed to report any information on serious adverse events . Trials of participants with acute or chronic pain conditions and industry‐sponsored trials typically provided more and better‐ quality AE data than trials involving pain‐free volunteers or trials that were not industry sponsored . The results of this review suggest that improved AE reporting is needed in analgesic RCTs . We developed an ACTTION ( Analgesic , Anesthetic , and Addiction Clinical Trial Translations , Innovations , Opportunities , and Networks ) AE reporting checklist that is intended to assist investigators in thoroughly and consistently capturing and reporting these critically important data in publications 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 Postoperative pain can have a significant effect on patient recovery . An underst and ing of patient attitudes and concerns about postoperative pain is important for identifying ways health care professionals can improve postoperative care . To assess patients ’ postoperative pain experience and the status of acute pain management , we conducted a national study by using telephone question naires . A r and om sample of 250 adults who had undergone surgical procedures recently in the United States was obtained from National Family Opinion . Patients were asked about the  severity of postsurgical pain , treatment , satisfaction with pain medication , patient education , and perceptions about postoperative pain and pain medications .  Approximately 80 % of patients experienced acute pain after surgery . Of these patients , 86 % had moderate , severe , or extreme pain , with more patients experiencing pain after discharge than before discharge . Experiencing postoperative pain was the most common concern ( 59 % ) of patients . Almost 25 % of patients who received pain medications experienced adverse effects ; however , almost 90 % of them were satisfied with their pain medications . Approximately two thirds of patients reported that a health care professional talked with them about their pain . Despite an increased focus on pain management programs and the development of new st and ards for pain management , many patients continue to experience intense pain after surgery . Additional efforts are required to improve patients ’ postoperative pain experience OBJECTIVE To assess how information about adverse events is included in systematic review s. STUDY DESIGN AND SETTING We included all new Cochrane review s published in the Cochrane Data base of Systematic Review s ( CDSRs ) and all new review s ( 2003 - -2004 ) in the Data base of Abstract s of Review s of Effects ( DAREs ) in Issue 1 2005 of The Cochrane Library . RESULTS More than half of Cochrane ( 44/78 ) and DARE ( 46/79 ) review s assessed drug interventions . The rest assessed surgery ( Cochrane [ 12 ] ; DARE [ 10 ] ) , psychosocial , educational , or physiotherapy interventions ( 22 ; 23 ) . Seventy-six percent ( 59/78 ) of Cochrane review s mentioned adverse events as an outcome compared with 48 % ( 38/79 ) of DARE review s. Most review s mentioning adverse events were of drug interventions ( Cochrane [ 41/59 ] ; DARE review s [ 29/38 ] ) . Considering review s that mentioned adverse events , 95 % ( 56/59 ) of Cochrane review s included only r and omized trials and 73 % ( 43/59 ) included an analysis of adverse events . For 10 Cochrane review s , adverse events had not been reported by the included trials . In contrast , 58 % ( 22/38 ) of DARE review s mentioning adverse events included only r and omized trials , the rest included both r and omized and nonr and omized studies . CONCLUSIONS Most Cochrane review s of drug interventions considered adverse events . This was not the case for DARE review s and for Cochrane review s of nondrug interventions . This could be improved The nocebo effect is the onset of untoward reactions following the administration of an indifferent substance . The oral challenge with alternative drugs plays a central role in the management of drug allergy and the use of inert substances is part of this procedure . We evaluated the occurrence and clinical characteristics of nocebo effect in patients with adverse drug reactions . Six hundred patients , seen in three different centres ( Genoa , Naples and Verona ) with a history of reactions to drugs , underwent a blind oral challenge with the administration of an indifferent substance and active drugs . The administration of an inert substance provoked untoward reactions in 54 patients ( 27 % ) in Verona , 60 ( 30 % ) in Naples and 48 ( 24 % ) in Genoa . The overall occurrence of nocebo effect was 27 % . The majority of reactions were subjective symptoms ( itching , malaise , headache etc ) , perceived as troublesome by all subjects . The occurrence was significantly higher in women than in men . Our data , collected in a large population , confirm that the nocebo effect occurs frequently in clinical practice . In managing adverse drug reactions through oral challenge the nocebo effect is m and atory to recognize false positive responses Objectives To compare the efficacy and safety of single versus combination non-prescription oral analgesics in community-derived people aged 40 years and older with chronic knee pain . Methods A r and omised , double-blind , four-arm , parallel-group , active controlled trial investigating short-term ( day 10 ) and long-term ( week 13 ) benefits and side-effects of four regimens , each taken three times a day : ibuprofen ( 400 mg ) ; paracetamol ( 1000 mg ) ; one fixed-dose combination tablet ( ibuprofen 200 mg/paracetamol 500 mg ) ; two fixed-dose combination tablets ( ibuprofen 400 mg/paracetamol 1000 mg ) . Results There were 892 participants ( mean age 60.6 , range 40–84 years ) ; 63 % had radiographic knee osteoarthritis and 85 % fulfilled American College of Rheumatology criteria for osteoarthritis . At day 10 , two combination tablets were superior to paracetamol ( p<0.01 ) for pain relief ( determined by mean change from baseline in WOMAC pain ; n=786 ) . At 13 weeks , significantly more participants taking one or two combination tablets rated their treatment as excellent/good  compared with paracetamol ( p=0.015 , p=0.0002 , respectively ; n=615 ) . The frequency of adverse events was comparable between groups . However , by 13 weeks , decreases in haemoglobin ( ≥1 g/dl ) were observed in some participants in all groups . Twice as many participants taking two combination tablets had this decrease compared with those on monotherapy ( p<0.001 ; paracetamol , 20.3 % ; ibuprofen , 19.6 % ; one or two combination tablets , 24.1 % , 38.4 % , respectively ) . Conclusions Ibuprofen/paracetamol combination analgesia , at non-prescription doses , confers modest short-term benefits for knee pain/osteoarthritis . However , in this population , paracetamol 3 g/day may cause similar degrees of blood  loss as ibuprofen 1200 mg/day , and the combination of the two appears to be additive . Study no IS RCT CONTEXT R and omized trials with adequate sample size offer an opportunity to assess the safety of new medications in a controlled setting ; however , generalizable data on drug safety reporting are sparse . OBJECTIVE To scrutinize the completeness of safety reporting in r and omized trials .  DESIGN , SETTING , AND PATIENTS Survey of safety reporting in 192 r and omized drug trials 7 diverse topics with sample sizes of at least 100 patients and at least 50 patients in a study arm ( N = 130074 patients ) . Trial reports were identified from comprehensive meta-analyses in 7 medical areas . MAIN OUTCOME MEASURES Adequate reporting of specific adverse effects and frequency and reasons for withdrawals due to toxic effects ; article space allocated to safety reporting and predictors of such reporting . RESULTS Severity of clinical adverse effects and laboratory-determined toxicity was adequately defined in only 39 % and 29 % of trial reports , respectively . Only 46 % of trials stated the frequency of specific reasons for discontinuation of study treatment due to toxicity . For these 3 parameters , there was significant heterogeneity in rates of adequate reporting across topics ( P = .003 , P<.001 , and P = .02 , respectively ) . Overall , the median space allocated to safety results was 0.3 page . A similar amount of space was devoted to contributor names and affiliations ( P = .16 ) . On average , the percentage of space devoted to safety in the results section was 9.3 % larger in trials involving dose comparisons than in those that did not ( P<.001 ) and 3.8 % smaller in trials reporting statistically significant results for efficacy outcomes ( P = .047 ) . CONCLUSIONS The quality and quantity of safety reporting vary across medical areas , study design s , and setting s but they are largely inadequate . Current st and ards for safety reporting in r and omized trials should be revised to address this inadequacy Background Although the methods for conducting systematic review s of efficacy are well established , there is much less guidance on how systematic review s of adverse effects should be performed . Methods In order to determine where method ological research is most needed to improve systematic review s of adverse effects of health care interventions , we conducted a descriptive analysis of systematic review s published between 1994 and 2005 . We search ed the Data base of Abstract s of Review s of Effects ( DARE ) and The Cochrane Data base of Systematic Review s ( CDSR ) to identify systematic review s in which the primary outcome was an adverse effect or effects . We then extracted data on many of the elements of the systematic review process including : types of interventions studied , adverse effects of interest , re sources search ed , search strategies , data sources included in review s , quality assessment of primary data , nature of the data analysis , and source of funding . Results 256 review s were included in our analysis , of which the majority evaluated drug interventions and pre-specified the adverse effect or effects of interest . A median of 3 re sources were search ed for each review and very few review s ( 13/256 ) provided sufficient information to reproduce their search strategies . Although more than three quarters ( 185/243 ) of the review s sought to include data from sources other than r and omised controlled trials , fewer than half ( 106/256 ) assessed the quality of the studies that were included . Data were pooled quantitatively in most 
    Output:
    
For aspirin 1000 mg and diflunisal 1000 mg , opioids , or fixed-dose combination drugs containing opioids , participants typically experienced significantly more adverse events than with placebo .
Studies of combinations of ibuprofen and paracetamol reported significantly fewer adverse events .
Serious adverse events were rare , occurring a rate of about 1 in 3200 participants .Most review s did not report specific adverse events .
AUTHORS ' CONCLUSIONS Despite ongoing problems with the measurement , recording , and reporting of adverse events in clinical trials and in systematic review s , the large amount of information available for single oral doses of analgesics provides evidence that adverse events rates are generally similar with active drug and placebo in these circumstances , except at higher doses of some drugs , and in combinations including opioids