***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 
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    Input: 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 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 Renal prostagl and in inhibition by nonsteroidal antiinflammatory drugs ( NSAIDs ) may decrease renal function , especially under conditions of low effective circulating volume . To evaluate the risk of important deterioration of renal function due to this effect , the authors performed a nested case-control study using Tennessee Medicaid enrollees aged > or = 65 years in 1987 - 1991 . Cases were patients who had been hospitalized with community-acquired acute renal failure ; they were selected on the basis of medical record review of Medicaid enrollees with selected discharge diagnoses . Information on the timing , duration , and dose of prescription NSAIDs used , demographic factors , and comorbidity was gathered from computerized Medicaid-Medicare data files . Of the 1,799 patients with acute renal failure ( 4.51 hospitalizations per 1,000 person-years ) , 18.1 % were current users of prescription NSAIDs  as compared with 11.3 % of 9,899 r and omly selected population controls . After control for demographic factors and comorbidity , use of NSAIDs increased the risk of acute renal failure 58 % ( adjusted odds ratio = 1.58 ; 95 % confidence interval ( CI ) : 1.34 , 1.86 ) . For ibuprofen , which accounted for 35 % of NSAID use , odds ratios associated with dosages of < or = 1,200 mg/day , > 1,200-<2,400 mg/day , and > or = 2,400 mg/day were 0.94 ( 95 % CI : 0.58 , 1.51 ) , 1.89 ( 95 % CI : 1.34 , 2.67 ) , and 2.32 ( 95 % CI : 1.45 , 3.71 ) , respectively ( test for linear trend : p = 0.009 ) . Prescription NSAID use result ed in an estimated 25 excess hospitalizations associated with renal failure per 10,000 years of use . Thus , NSAIDs represent a relatively uncommon but avoidable cause of acute renal failure in frail elderly persons & NA ; The objective was to investigate the relationship between pain relief scores produced by placebo and by active interventions in r and omised controlled trials ( RCTs ) . Individual patient categorical pain relief scores from 5 placebo‐controlled single‐dose parallel‐group RCTs in acute postoperative pain were used to calculate the percentage of the maximum possible pain relief score ( % maxTOTPAR ) for the different treatments . One hundred and thirty of the 525 patients in the 5 trials had a placebo .  Individual patients ' scores with placebo varied from 0 to 100 % of the maximum possible pain relief . The proportion who obtained more than 50 % of the maximum possible pain relief with placebo varied from 7 % to 37 % across the trials ; with the active drugs the variation was from 5 to 63 % . Mean placebo scores were related to the mean score for the active treatments in each study ; the higher the mean active score , the higher the mean placebo score . This relationship disappeared when median values were used . Medical folklore has it that the amount of relief obtained with placebo is one‐third of the maximum possible ( and does not vary ) , and that one‐third of patients respond to placebo . The results show that the amount of relief obtained with placebo varies considerably between patients , that 38 % of patients obtained more than 10 % of the maximum possible relief , and 16 % obtained greater than 50 % . In double‐blind , r and omised parallel‐group studies of high quality placebo scores should not vary . Despite these conditions being met the placebo scores did vary . The previous explanation , of a relationship between the mean placebo scores and the mean scores for the active treatments was not supported BACKGROUND In recent studies of acute pain and primary dysmenorrhea , rofecoxib , a nonsteroidal anti-inflammatory drug that selectively targets the cyclooxygenase-2 enzyme , was found to be similar in efficacy to ibuprofen and naproxen sodium . OBJECTIVE The purpose of this study was to determine the analgesic efficacy of a single oral dose of rofecoxib 50 mg compared with the combination of codeine 60 mg/acetaminophen 600 mg in a model of postsurgical dental pain . METHODS In this double-blind , placebo- and active comparator-controlled , parallel-group study , patients experiencing moderate or severe pain after the surgical extraction of > or = 2 third molars , at least 1 of which was a m and ibular impaction , were r and omized to receive placebo , rofecoxib 50 mg , or codeine 60 mg/acetaminophen 600 mg . Patient evaluations of pain intensity , pain relief , and global assessment s were recorded throughout the 24-hour period after dosing . The 2-stopwatch method was used to determine time to confirmed perceptible pain relief . The primary end point assessing overall analgesic effect was total pain relief over 6 hours ( TOPAR6 ) . Secondary end points were patient global assessment of response to therapy ( PGART ) at 6 hours , onset of analgesia , peak analgesic effect , and duration of analgesia . RESULTS A total of 393 patients were enrolled ; 182 received rofecoxib , 180 received codeine/acetaminophen , and 31 received placebo . The overall analgesic effect of rofecoxib 50 mg was greater than that of codeine 60 mg/acetaminophen 600 mg for TOPAR6 ( 12.4 vs 7.0 ; P < 0.001 ) and PGART at 6 hours ( P < 0.001 ) . The onset of analgesic effect was similar for rofecoxib and codeine/acetaminophen .  Peak analgesic effect as measured by peak pain relief scores during the first 6 hours was significantly greater in the rofecoxib group compared with the codeine/acetaminophen group ( P < 0.001 ) , as was the duration of analgesic effect measured by the time to rescue analgesia ( 9.6 hours vs 2.3 hours , P < 0.001 ) . Adverse events were reported in 33.0 % , 46.1 % , and 32.3 % of patients treated with rofecoxib , codeine/acetaminophen , and placebo , respectively . The most common adverse events were nausea ( 6.0 % , 25.0 % , and 9.7 % , respectively ) and vomiting ( 3.8 % , 18.3 % , and 6.5 % , respectively ) . Significantly more patients in the codeine/acetaminophen group than in the rofecoxib group experienced adverse events overall ( P < 0.050 ) and nausea in particular ( P < 0.001 ) . CONCLUSION In this study of moderate to severe postoperative dental pain , the analgesic efficacy of rofecoxib 50 mg was greater than that of codeine/acetaminophen , with a lower incidence of adverse events and nausea Nonsteroidal anti‐inflammatory drugs ( NSAIDs ) such as aspirin , ibuprofen , and indomethacin ( INN , indometacin ) inhibit both the constitutive ( COX‐1 ) and inducible ( COX‐2 ) isoforms of cyclooxygenase . The induction of COX‐2 after inflammatory stimuli has led to the hypothesis that COX‐2 inhibition primarily accounts for the therapeutic properties of NSAIDs 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 data in acute pain studies enables data published as means to be used for quantitative systematic review s which require data in dichotomous form We assessed the quality of assessment and reporting of adverse effects in r and omized , double-blind clinical trials of single-dose acetaminophen or ibuprofen compared with placebo in moderate to severe postoperative pain . Reports were identified by systematic search ing of a number of bibliographic data bases ( e.g. , MEDLINE ) . Information on adverse effect assessment , severity and reporting , patient withdrawals , and anesthetic used was extracted . Compliance with former guidelines for adverse effect reporting was noted . Fifty-two studies were included ; two made no mention of adverse effects . No method of assessment was given in 19 studies . Twenty trials failed to report the type of anesthetic used , eight made no mention of patient withdrawals , and nine did not state the severity of reported adverse effects . Only two studies described the method of assessment of adverse effect severity . When all adverse effect data were pooled , significantly more adverse effects were reported with active treatment than with placebo . For individual adverse effects , there was no difference between active ( acetaminophen 1000 mg or ibuprofen 400 mg ) and placebo ; the exception was significantly more somnolence/drowsiness with ibu 
    Output:
    
Conclusion Rofecoxib at 2–4 times the st and ard daily dose for chronic pain is an effective single dose oral analgesic in acute pain .