***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: 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 Objective : To assess the time of onset and difference in analgesic efficacy of oral dexketoprofen compared with oral diclofenac in patients with acute lower limb injury . Design : A prospect i ve , double blind , r and omised controlled trial . Interventions : Patients who fitted the study criteria were given either 25 mg oral dexketoprofen trometamol or 50 mg sodium diclofenac immediately after triage ; baseline and 15 minute pain scores were then recorded for one hour . Results : 122 patients were studied ( diclofenac = 57 and dexketoprofen = 65 ) . There were no significant differences in age , sex , type of injury , or baseline pain scores between the two groups . The differences in group mean pain scores between diclofenac and dexketoprofen at 15 , 30 , 45 , and 60 minutes were ; 0.53 ( 95 % confidence intervals −0.03 to 1.09 ) , 0.70 ( 0.16 to 1.24 ) , 0.89 ( 0.32 to 1.47 ) , and 0.83 ( 0.21 to 1.45 ) . Odds ratios for a decrease in pain score of at least 1 from baseline ( on the 11 point scale ) when given dexketoprofen rather than diclofenac at 15 , 30 , 45 , and 60 minutes were ; 2.66 ( 1.19 to 5.98 ) , 3.52 ( 1.60 to 7.73 ) , 4.48 ( 1.72 to 11.65 ) , and 5.54 ( 1.90 to 16.15 ) . Corresponding odds ratios for a decrease in pain score of ⩾2 were ; 6.88 ( 1.48 to 32.0 ) , 3.79 ( 1.59 to 9.01 ) , 5.19 ( 2.29 to 11.78 ) , and 5.87 ( 2.68 to 12.88 ) . Conclusions : Dexketoprofen trometamol is an effective and rapidly acting analgesic for the treatment of acute musculoskeletal injuries Background Differences between gastrointestinal and cardiovascular effects of traditional NSAID or cyclooxygenase-2 selective inhibitor ( coxib ) are affected by drug , dose , duration , outcome definition , and patient gastrointestinal and cardiovascular risk factors . We calculated the absolute risk for each effect . Methods We sought studies with large amounts of information to calculate annualised rates for clearly defined  gastrointestinal ( complicated upper gastrointestinal perforations , ulcers , or bleeds  , but not  symptomatic  or  endoscopic ulcers ) and  serious cardiovascular outcomes ( antiplatelet trial collaborators – APTC – outcome of fatal or nonfatal myocardial infa rct ion or stroke , or vascular death ) . Results Meta-analyses and large r and omised trials specifically analysing serious gastrointestinal bleeding or cardiovascular events occurring with five different coxibs had appropriate data . In total there were 439 complicated upper gastrointestinal events in 49,006 patient years of exposure and 948 serious cardiovascular events in 99,400 patient years of exposure .  Complicated gastrointestinal events occurred less frequently with coxibs than NSAIDs ;  serious cardiovascular events occurred at approximately equal rates . For each coxib , the reduction in complicated upper gastrointestinal events was numerically greater than any increase in APTC events . In the overall comparison , for every 1000 patients treated for a year with coxib rather than NSAID , there would be eight fewer complicated upper gastrointestinal events , but one more fatal or nonfatal heart attack or stroke . Three coxib-NSAID comparisons had sufficient numbers of events for individual comparisons . For every 1000 patients treated for a year with celecoxib rather than an NSAID there would be 12 fewer upper gastrointestinal complications , and two fewer fatal or nonfatal heart attacks or strokes . For rofecoxib there would be six fewer upper gastrointestinal complications , but three more fatal or nonfatal heart attacks or strokes . For lumiracoxib there would be eight fewer upper gastrointestinal complications , but one more fatal or nonfatal heart attack or stroke . Conclusion Calculating annualised event rates for gastrointestinal and cardiovascular harm shows that while complicated gastrointestinal events occur more frequently with NSAIDs than coxibs , serious cardiovascular events occur at approximately equal rates . For each coxib , the reduction in complicated upper gastrointestinal events was numerically greater than any increase in APTC events BACKGROUND In this double-blind , r and omized , placebo-controlled trial , the safety and analgesic efficacy of perioperative dexketoprofen were evaluated . METHODS Thirty ASA I or II patients undergoing elective hip arthroplasty were r and omized to one of two groups . One group ( D ) received dexketoprofen 25 mg tds for 24 h before and 48 h after surgery ; the second group ( P ) received placebo tablets at equivalent times . Hyperbaric 0.5 % bupivacaine ( 17.5 mg if greater than 70 kg and 15 mg if less than 70 kg ) and preservative-free morphine ( 0.6 mg ) were administered intrathecally . Postoperatively , PCA was provided ( bolus morphine sulphate 1 mg ; lockout 5 min ; no continuous infusion ) . RESULTS The two groups were similar in terms of age , gender , weight , height , ASA class , duration of operation , and level of sensory block on arrival to the recovery room . Groups were also similar in terms of blood loss , transfusion requirements , ventilatory frequency , and haemodynamic variables . According to visual analogue pain scores patients in group D experienced less pain at 15 h ( P=0.02 ) postoperatively . Cumulative morphine consumption was also less in group D compared with group P at 6 ( 0.06 ( 0.2 ) vs 0.85 ( 1.4 ) mg , P=0.04 ) and 48 h postoperatively ( 10.1 ( 8) vs 26.2 ( 20 ) mg , P<0.01 ) . Plasma interleukin 6 concentrations increased postoperatively to a significantly lesser extent in group D than in group P ( P=0.02 ) . Nausea and vomiting were less ( P<0.01 ) in group D compared with group P at 18 h postoperatively . Sedation scores were less ( P=0.03 ) in group D. CONCLUSIONS Perioperative administration of dexketoprofen 25 mg 8 hourly markedly improves analgesia and decreases opioid requirements ( and associated adverse effects ) following hip arthroplasty . It appears that this regimen decreases the postoperative pro-inflammatory response 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 & 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 patients with greater than 50 % pain relief ( > 50%maxTOTPAR ) for the different treatments . The relationship between the measures was investigated in 45 actual treatments and 10 000 treatments simulated using the underlying actual distribution ; 1283 patients had 45 separate treatments . Mean % maxTOTPAR correlated with the proportion of patients with > 50%maxTOTPAR ( r2 = 0.90 ) . The relationship calculated from all the 45 treatments predicted to within three patients the number of patients with more than 50 % pain relief in 42 of 45 treatments , and 98.8 % of 10 000 simulated treatments . For seven effective treatments , actual numbers‐needed‐to‐treat ( NNT ) to achieve > 50%maxTOTPAR compared with placebo were very similar to those derived from calculated data BACKGROUND 
    Output:
    
Adverse event withdrawal rates were low in postoperative pain and somewhat higher in trials of longer duration ; no serious adverse events were reported .
Conclusion Dexketoprofen was at least as effective as other NSAIDs and paracetamol/opioid combinations .
Exposure was limited , and no conclusions could be drawn about safety in terms of serious adverse events like gastrointestinal bleeding or cardiovascular events