***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 study was conducted to compare the analgesic activity of single oral doses of etodolac ( 25 , 50 , 100 , 200 , and 400 mg ) with 650 mg aspirin and placebo . A total of 146 patients with moderate or severe pain from orthopedic or urologic interventions received one of the test medications 13 - 25 h after the beginning of surgery and according to a r and omized allocation balanced as to initial pain intensity . Data for pain intensity and pain relief were collected at 1/2 h and then hourly for 8 h. Vital signs and adverse reactions were also recorded . One hundred and forty-two patients completed the study : four were excluded because of protocol deviations . The average response to 100 , 200 , and 400 mg of etodolac was superior to that of placebo . On the basis of SPID , TOTPAR , and duration of analgesia , 400 mg etodolac was also significantly more effective than 650 mg aspirin .  Mild side effects probably or possibly related to etodolac were reported by three patients . This study provides evidence that etodolac in doses of 100 mg and higher is an effective and well-tolerated analgesic 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 Etodolac is a new nonsteroidal anti-inflammatory drug ( NSAID ) . Published and unpublished data on etodolac in pain management are review ed to assess the analgesic effectiveness of this drug . Data are presented from four representative studies that showed the analgesic activity of etodolac in postsurgical pain models . These results suggest that the drug would have analgesic utility in other painful conditions such as gout and musculoskeletal disorders . The efficacy of etodolac in such conditions is confirmed by the results from eight controlled clinical studies in patients with gouty arthritis , tendinitis and bursitis , and acute sports injuries .  Etodolac 200 or 300 mg twice a day ( b.i.d . ) or 200 mg three times a day ( t.i.d . ) was compared with naproxen 500 mg b.i.d . and diclofenac 50 mg b.i.d . or 50 mg t.i.d . All three NSAIDs provided analgesia , and etodolac was comparable in efficacy to the comparators . The data presented in this review suggest a future role for etodolac as an analgesic as well as an anti-inflammatory agent This controlled , single dose study has demonstrated that compared with placebo , substantial analgesia is obtained with 200 and 400 mg doses of etodolac . The analgesic effects of both doses of etodolac were not notably different from each other or significantly different from zomepirac , a proven analgesic . With respect to safety , both doses of etodolac were well tolerated , with no reports of serious or dose related adverse side effects A double-blind , r and omized study of 137 patients compared the effectiveness of single doses of etodolac , 200 and 400 mg , zomepirac , 100 mg , and placebo in relieving moderate to severe pain following third molar extraction s. Throughout the 12-hour evaluation period , doses of both etodolac and zomepirac were significantly superior to placebo for total analgesic effect , as measured by the sum of pain intensity difference ( SPID ) and sum of pain relief ( TOTPAR ) scores . However , there were no significant differences among the active drugs . It was concluded that etodolac , 200 and 400 mg , provides analgesic efficacy comparable to that of zomepirac , 100 mg , and superior to that of placebo 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 ibuprofen 400 mg . Ninety percent of trials reporting somnolence/drowsiness with ibuprofen 400 mg were in dental pain . All studies published after 1994 complied with former guidelines for adverse effect reporting . Different methods of assessing adverse effects produce different reported incidence : patient diaries yielded significantly more adverse effects than other forms of assessment . We recommend guidelines for reporting adverse effect information in clinical trials BACKGROUND Ketorolac is approved for the relief of postoperative pain but concerns have been raised over a possible risk of serious adverse effects and death . Two regulatory review s in Europe on the safety of ketorolac found the data were inconclusive and lacked comparison with other non-steroidal anti-inflammatory drugs . The aim of this study was to compare the risk of serious adverse effects with ketorolac vs diclofenac or ketoprofen in adult patients after elective major surgery . METHODS This prospect i ve , r and omized multicentre trial evaluated the risks of death , increased surgical site bleeding , gastrointestinal bleeding , acute renal failure , and allergic reactions , with ketorolac vs diclofenac or ketoprofen administered according to their approved parenteral and oral dose and duration of treatment . Patients were followed for 30 days after surgery . RESULTS A total of 11,245 patients completed the trial at 49 European hospitals . Of these , 5634 patients received ketorolac and 5611 patients received one of the comparators . 155 patients ( 1.38 % ) had a serious adverse outcome , with 19 deaths ( 0 . 17 % ) , 117 patients with surgical site bleeding ( 1.04 % ) , 12 patients with allergic reactions ( 0.12 % ) , 10 patients with acute renal failure ( 0.09 % ) , and four patients with gastrointestinal bleeding ( 0.04 % ) . There were no differences between ketorolac and ketoprofen or diclofenac . Postoperative anticoagulants increased the risk of surgical site bleeding equally with ketorolac ( odds ratio=2.65 , 95 % CI=1.51 - 4.67 ) and the comparators ( odds ratio=3.58 , 95 % CI=1.93 - 6.70 ) . Other risk factors for serious adverse outcomes were age , ASA score , and some types of surgery ( plastic/ear , nose and throat , gynaecology , and urology ) . CONCLUSION We conclude that ketorolac is as safe as ketoprofen and diclofenac for the treatment of pain after major surgery Purpose The present study was design ed to evaluate the efficacy of a cyclooxygenase (COX)-2 inhibitor , etodolac , on postoperative pain after fast-track cardiac surgery , and to examine the changes in plasma etodolac concentration after oral administration . Methods Thirty patients scheduled for elective coronary artery bypass grafting ( CABG ) surgery were r and omly assigned preoperatively in a double-blind fashion to receive either vehicle ( n = 15 ) or etodolac 400 mg ( n = 15 ) via a gastric tube at the end of the surgery . St and ardized fast-track cardiac anesthesia was used . In both groups , postoperative pain was treated with buprenorphine suppository . Visual analogue pain scores ( VASs ) were recorded immediately after extubation and at 24 h after surgery . Plasma etodolac concentration was measured at 1 , 2 , and 6 h after administration ( n = 8) . Results No difference was detected in time to extubation between the etodolac group ( 209 ± 85 min , mean ± SD ) and the vehicle group ( 207 ± 98 min ) . VASs were significantly lower in the etodolac ( 2.3 ± 2.1 ) vs the vehicle group ( 5.8 ± 2.0 ) immediately after extubation ( P = 0.009 ) , but no difference was detected in pain scores at 24 h after surgery , or in the amount of buprenorphine administered in the intensive care unit ( ICU ) , or in the incidence of side effects . Plasma etodolac concentration was within the pharmaceutically recommended range at 1 h , 2 h , and 6 h after administration . Conclusion The oral use of etodolac with rectal buprenorphine reduces pain scores immediately after cardiac surgery without an increase in side effects & NA ; 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 , at least in acute pain models , indicates that more meaningful overviews or meta‐ analysis may be possible . This study investigated the relationship between continuous and dichotomous analgesic measures in a set of individual patient data , and then used that relationship to derive dichotomous from continuous information in r and omised controlled trials ( RCTs ) of analgesics .  Individual patient information from 13 RCTs of parallel‐group and crossover design in acute postoperative pain was used to calculate the percentage of the maximum possible pain relief score ( % maxTOTPAR ) and the proportion of 
    Output:
    
Adverse events were uncommon , and not significantly different form placebo .
AUTHORS ' CONCLUSIONS Etodolac 200 mg may be a useful analgesic in postoperative pain , with efficacy similar to paracetamol 1000 mg and celecoxib 200 mg .
Higher doses may provide analgesia equivalent to more commonly used drugs , such as ibuprofen 400 mg , naproxen 500 mg and diclofenac 50 mg