***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 ; Tramadol hydrochloride is a synthetic & mgr;‐opioid agonist with additional monoaminergic activity . Tramadol 's analgesic effect has been equated with that of pethidine , with a more favourable side‐effect profile . Tramadol has been the most‐selling prescription analgesic in Germany for several years , and it is now available in many other European countries , but still there is a lack of adequately controlled clinical studies of its analgesic properties . The purpose of this study was to compare the analgesic efficacy of 50 and 100 mg oral tramadol with our st and ard analgesic for postoperative pain treatment , 1000 mg paracetamol + 60 mg codeine , and placebo . A single‐dose , parallel group , double‐blind design was used . One hundred forty‐four patients were enrolled the day after total hip replacement if they had a pain intensity of 60 mm or more on a 0–100 mm visual analogue scale . Treatments were compared on the basis of pain intensity and derived variables ( pain intensity difference , and summed pain intensity differences ) , the need of rescue medication , and a global evaluation . Serum concentrations confirmed rapid and good absorption comparable with the reported in healthy volunteers . The active drug control , paracetamol + codeine , was significantly superior to placebo for all efficacy variables ( P = 0.0002–0.004 ) , confirming good assay sensitivity .  Paracetamol + codeine  was also significantly superior to both 50 mg tramadol ( P = 0.002–0.03 ) and 100 mg tramadol ( P = 0.002–0.02 ) . There was no difference between placebo and 50 and 100 mg tramadol for any of the efficacy variables . Adverse events were more common with tramadol than with the active control ( P < 0.02 ) , with significantly more emetic episodes after 50 and 100 mg tramadol ( P < 0.05 ) . Thus , this double‐blind , placebo‐ and active drug‐controlled study after orthopaedic surgery shows that 50 and 100 mg oral tramadol is well absorbed but has no significant analgesic effect in doses that are tolerable as single doses by mouth . We emphasize the importance of proper study design with documented assay sensitivity and sufficiently high initial pain intensity for differentiation between analgesics of different potencies A single-blind , parallel-group study was carried out to evaluate the efficacy and safety of an analgesic combining 650 mg of acetaminophen and 25 mg of pentazocine in 129 patients with moderate postoperative pain .  Comparisons were made with a combination containing acetaminophen ( 300 mg ) and codeine ( 30 mg ) , a combination containing acetaminophen ( 650 mg ) and propoxyphene napsylate ( 100 mg ) , and a placebo . A nurse observer queried patients at regular intervals over a six-hour period concerning the intensity of pain and the degree of pain relief . The scores obtained were used in the calculation of st and ard measures of analgesic efficacy .  Acetaminophen/pentazocine proved to be significantly superior to placebo and equivalent to the other active analgesic combinations . No side effects were reported with acetaminophen/pentazocine , acetaminophen/propoxyphene napsylate , or placebo . One mild side effect was question ably associated with acetaminophen/codeine . This study demonstrates that the combination of acetaminophen and pentazocine is as safe and effective in controlling postoperative pain of moderate severity as other commonly used analgesics 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 In a double‐blind , r and omized , single‐dose trial the analgesic contribution of acetaminophen , 1000 mg , and codeine , 60 mg , was determined . The study was a 2 × 2 factorial experiment in which 120 patients suffering from pain as a result of oral surgery rated their pain intensity and pain relief for up to 5 hours after a single dose of one of : 1000 mg acetaminophen , 60 mg codeine , 1000 mg acetaminophen plus 60 mg codeine , or placebo . The factorial analysis showed that both 1000 mg acetaminophen and 60 mg codeine made a statistically significant ( P < 0.05 ) contribution to the analgesic effectiveness of the combination on all measures of efficacy ( sum of pain intensity differences , largest pain intensity difference , total pain relief , largest pain relief , and time to remedication ) . The incidence of adverse effects did not appear to differ among the treatments , including placebo One hundred sixty-one patients with postoperative pain were treated at a single center in a double-blind , r and omized , parallel study design ed to compare the efficacy and safety of single oral doses of ketoprofen ( 50 and 150 mg ) , an acetaminophen ( 650 mg ) plus codeine ( 60 mg ) combination , and placebo . From 1 through 4 hours after administration of the study drugs , the mean summed pain intensity difference ( SPID ) and time-weighted total pain relief ( TOPAR ) scores for the three active treatments generally were significantly ( P less than 0.05 ) higher than those for placebo but not significantly different from each other . At the 6-hour evaluation , the ketoprofen groups , but not the acetaminophen-codeine group , had higher ( P less than 0.05 ) mean SPID and TOPAR scores than the placebo group , as a result of a shorter duration of pain relief in the acetaminophen-codeine group . The 6-hour TOPAR scores were significantly ( P less than 0.05 ) higher for both ketoprofen groups than for the acetaminophen-codeine group ; the ketoprofen 150 mg group also had significantly ( P less than 0.05 ) higher mean 6-hour SPID and global subjective assessment scores . As a result of a higher frequency of somnolence , there was a significantly ( P less than 0.05 ) greater incidence of central nervous system adverse drug reactions among patients treated with acetaminophen plus codeine than among those treated with 150 mg of ketoprofen . These results indicate that the analgesic efficacy of both 50 and 150 mg doses of ketoprofen equals that of acetaminophen 650 mg plus codeine 60 mg and the duration of the analgesic effect of ketoprofen is significantly longer Background : A r and omized , double‐blind , placebo‐controlled single oral dose study was done in order to examine whether codeine has an additive analgesic effect to that of paracetamol for moderate and strong postoperative pain after abdominal surgery . The maximum recommended single dose of paracetamol 1000 mg ( Paracet ® ) was compared with a combination of a submnximal dose of paracetamol 800 mg plus codeine 60 mg ( Paralgin forte ® ) and placebo for pain relief  after Caesarean section in 125 patients & 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 The efficacy of diclofenac sodium ( Voltarol ) with and without paracetamol in the control of post-surgical dental & NA ; Ibuprofen , 400 mg , was compared with 300 mg acetaminophen plus 30 mg of codeine and placebo in 120 post‐orthopedic surgery patients with moderate to severe pain . The study was design ed as a double‐blind , single‐dose , parallel‐group analgesic efficacy assay . Estimates of analgesia were obtained up to 6 h using categorical and visual analog measures of pain intensity and pain relief . Estimates of selected elements of mood and of sensory and affective components of pain were obtained at 0 and 2 h using contrasting mood word/phrase pairs and a portion of the McGill Pain Question naire , respectively . Drugs were distinguishable from placebo in total analgesic effect and ibuprofen was more effective than acetaminophen plus codeine , especially in terms of duration . While peak effects were comparable , they occurred 1 h later following ibuprofen . Differences among treatments were more discernible using visual analog measures . Side effects were minimal . Ibuprofen provided greater improvement in selected elements of mood  than acetaminophen plus codeine at comparable levels of pain relief . While decreases in the sensory component of pain were most highly associated with pain relief provided by ibuprofen , decreases in the affective component were most highly associated with pain relief  following acetaminophen plus codeine . These latter results indicate that mood assessment and the discrimination between sensory and effective components of pain could be particularly useful within analgesic drug assays , especially when comparing analge‐sics of differing pharmacologic class when comparing the result of such assays in pain syndromes characterised by differing pain quality Summary Acetylsalicylic acid(ASA ) was compared with paracetamol(P ) in a double-blind crossover study , in which essentially the same operation was performed on two separate occasions in 32 healthy patients , who required surgical removal of bilateral “ identically ” impacted wisdom teeth . Sixteen patients were given the drugsboth before and after(b & a-group ) the operations ( 0.5 g on the pre-operative evening , followed by 0.5 g × 4 for 3 days ) ; the other 16 patients did not start treatment until 2 hoursafter(a-group ) the operations . A number of objective and subjective factors were assessed , including swelling , bleeding , pain and preference , and were used to make comparisons of the pre- , per- and post-operative courses . About 50 % greater post-operative swelling was associated withASA compared toP , either if medication was begun prior to surgery or if the drugs were given only after operation . In theb & a-group , interference with platelet function and prolonged pre-operative bleeding time were produced byASA ( 8.9 vs 6.5 min ) , but the per-operative blood loss was not significantly increased ( 7.8 vs 7.4 ml ) . In both groupsASA tended to increase post-operative bleeding and the formation of haematomas and ecchymoses . There was no noticeable difference betweenASA and P with respect to pain score , but the preference scores showed a tendency to favourP in both groups . It appears that in 
    Output:
    
New information for remedication shows that the combination extended the duration of analgesia by about one hour compared to treatment with the same dose of paracetamol alone .