***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 Two bioavailability studies of S(+)-ibuprofen ( dexibuprofen ) were conducted in healthy volunteers to define the relationship between the bioavailability of the drug after administration of dexibuprofen alone or as part of ibuprofen racemate . Enantioselective plasma drug analysis was used throughout . In the first study , the bioavailability of dexibuprofen from a 400 mg tablet formulation was compared with that from 400 mg in aqueous solution . The tablet formulation did not influence the bioavailability of the drug and dexibuprofen was well absorbed from the gastro-intestinal tract . The second study was divided into three identical parts . Bioavailability of dexibuprofen 200 , 400 and 600 mg was compared with its bioavailability from ibuprofen racemate 400 , 800 and 1200 mg . The second study showed that the mean relative bioavailability of dexibuprofen  to ibuprofen racemate was 0.66 , thus enabling the estimation of clinical ly useful dexibuprofen doses from the usual doses of the racemate . The 95 % confidence interval limits did not include 0.5 , leading to the conclusion that administering half of the racemate dose would not provide patients with an adequate amount of therapeutically active drug OBJECTIVE Treatment with non-steroidal anti-inflammatory drugs is the most common pharmacological therapy of rheumatic diseases . For the symptomatic treatment of painful disorders a dose-response relationship of the NSAID should be a basic requirement , which is difficult to be proven in studies because rheumatic diseases are heterogenous in terms of clinical involvement . The aim of this double-blind r and omized trial was to compare the isolated active enantiomer dexibuprofen ( S(+)-ibuprofen ) with the double dose of racemic ibuprofen and to show a dose-response relationship of dexibuprofen in painful osteoarthritis of the hip . METHODS 178 patients were r and omly assigned to dexibuprofen 600/1,200 mg or racemic ibuprofen 2,400 mg daily . The primary endpoint was the improvement of the WOMAC osteoarthritis index after 15 days of therapy . The analysis was by intention to treat . RESULTS The evaluation of the WOMAC OA index showed statistically significant equivalence of dexibuprofen 400 mg t.i.d . compared with racemic ibuprofen 800 mg t.i.d . by a Mann-Whitney statistic of 0.578 and the corresponding lower bound of the 95 % confidence interval of 0.498 . The test for superiority of dexibuprofen was borderline significant with p = 0.055 . Dexibuprofen 400 mg t.i.d . and dexibuprofen 200 mg t.i.d . showed a statistically significant dose-response relationship in improving the WOMAC OA index ( p = 0.023 ) . Patients suffered from adverse drug reactions , mainly gastrointestinal disorders , 13.34 % on dexibuprofen 200 mg , 15.25 % on dexibuprofen 400 mg and 16.94 % on racemic ibuprofen 800 mg . CONCLUSIONS The active enantiomer dexibuprofen ( S(+)-ibuprofen ) proved to be an effective non-steroidal anti-inflammatory drug with a significant dose-response relationship in patients with painful osteoarthritis of the hip . Compared with racemic ibuprofen half of the daily dose of dexibuprofen shows at least equivalent efficacy . In contrast to pharmacokinetic data , the additional administration of R(-)-ibuprofen in form of racemate does not contribute to the clinical efficacy of racemic ibuprofen 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 Summary A rapid , sensitive and stereoselective HPLC method based on chiral column analysis was developed and fully vali date d for the simultaneous determination of the two enantiomers of ibuprofen in human plasma . Using this method , a chiral pharmacokinetic study of two different ibuprofen tablets , i.e. dexibuprofen tablets and racemic ibuprofen tablets , was carried out on 20 healthy Chinese male volunteers according to a single-dose ( 400 mg ) , two-way , cross-over r and omized design . When a ‘ non-chiral calculation method ’ was used , the statistical analysis showed no significant difference for the pharmacokinetic parameters ( AUC0–∞ , AUC0-t , Cmax , and tmax ) between the two oral formulations , suggesting that they were pharmaceutically bioequivalent . Considering that the pharmacological activity of ibuprofen resides exclusively in the S(+)-enantiomer , and that the unidirectional inversion of the R(− ) to the S(+)-enantiomer is incomplete and might be race-dependent , the pharmacokinetic parameters for only the S(+)-enantiomer were further compared and the inversion ratio calculated . It was found that only 25 % of R(−)-ibuprofen in the racemic ibuprofen tablets was inverted into S(+)-ibuprofen in the Chinese population , which suggested that dexibuprofen might possess a much stronger pharmacological activity than that of racemic ibuprofen when administered at the same dose CONTEXT Osteoarthritis ( OA ) is often treated with nonsteroidal anti-inflammatory drugs ( NSAIDs ) or selective inhibitors of cyclooxygenase-2 ( COX-2 ) . OBJECTIVE This clinical trial aim ed to assess directly the relative therapeutic efficacy of the isolated active enantiomer of ibuprofen , named dexibuprofen ( S(+)-ibuprofen ) in a special crystal form , and the selective COX-2 inhibitor celecoxib in adults with OA of the hip . Moreover , the hypothesis that the tolerability/safety profile of dexibuprofen is comparable to celecoxib is to be tested . METHODS The investigation was a r and omized , parallel-group , double-blind , active controlled clinical trial , conducted from January 2001 to February 2002 in 4 rehabilitation centers in Austria . 148 in patients were r and omly assigned to dexibuprofen 800 mg or celecoxib 200 mg daily . The primary criterion was the improvement in the Western Ontario and ' McMasters osteoarthritis index ( WOMAC OA index ) after 15 days of therapy . RESULTS Evaluation of the WOMAC OA index proved that dexibuprofen 400 mg b.i.d . is not inferior to celecoxib 100 mg b.i.d . with the Mann-Whitney estimator equal to 0.5129 and the corresponding lower boundary of the 95 % confidence interval equal to 0.4409 . The overall incidence of adverse drug reactions was 12.16 % in the dexibuprofen group and 13.51 % in the celecoxib group . 8.1 % of patients on dexibuprofen and 9.5 % on celecoxib suffered from gastrointestinal disorders . CONCLUSION In the presented clinical trial dexibuprofen has at least equal efficacy and a comparable safety/tolerability profile as celecoxib in adult patients suffering from osteoarthritis of the hip Background : Primary dysmenorrhea is estimated to affect 40–50 % of menstruating young women . Methods : R and omized , double-blind , 3-cycle crossover , active-controlled clinical trial conducted in 102 out patients . Results : 102 patients entered the study and 77 were eligible for analyses . The mean ( SD ) age was 31.1 ( 7.0 ) years , and the mean cycle duration was 28.1 days ( 1.89 ) with a mean menstrual phase of 5.3 days ( 1.28 ) . 40.26 % of patients reported moderate pain from dysmenorrhea , and the remaining 59.74 % reported severe pain . Compared to ibuprofen 400 mg , both dexibuprofen doses ( 200 and 300 mg ) showed a trend towards superiority for sum of 
    Output:
    
Adverse events were generally of mild or moderate intensity and consistent with events normally associated with anaesthesia and surgery .
The information from these two studies in acute postoperative pain suggested that dexibuprofen may be a useful analgesic , but at doses not very different from racemic ibuprofen , for which considerably more evidence exists