***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: Ketoprofen , 25 , 50 , and 100 mg , was compared with 90 mg codeine and placebo for relief of pain due to removal of impacted third molar teeth . Treatment was self-administered as a single oral dose under double-blind conditions in five parallel groups established by a r and om code in healthy young adults . Based on 129 patient evaluations of pain experience and pain relief , ketoprofen was shown to have a more rapid onset and longer duration of action than codeine . In the derived variables of SPID ( Sum of Pain Intensity Differences ) and TOPAR ( Total Pain Relief ) , all three doses of ketoprofen , with no dose-related differences among them , were found to provide statistically superior analgesia to codeine and placebo . All five treatments were associated with some adverse reactions Summary The efficacy and safety of ciramadol ( Cir ) as an analgesic in relieving moderate  to severe pain after oral surgery has been studied in 79 patients r and omly assigned to receive single oral doses of Cir 15 , 30 or 60 mg , codeine 60 mg or placebo .  During the 6-hour observation period , the three ciramadol-treated groups indicated greater pain relief than the codeine 60 mg or placebo groups . In general , Cir 60 mg was significantly more effective than codeine 60 mg , and all doses of Cir were superior to placebo . The proportion of patients in each Cir group reporting adverse experiences was significantly higher than in either the placebo or codeine groups . The experimental system proved very effective in demonstrating analgesic potency of Cir . The very high incidence of side-effects in the three ciramadol-treated groups makes it unfit for further clinical use in ambulant patients Meclofenamate sodium , a nonsteroidal anti-inflammatory drug with proven analgesic effects , was compared at two dose levels ( 200 mg and 100 mg ) with codeine ( 60 mg ) and placebo in a double-blind , r and omized study of 327 women experiencing episiotomy pain after normal delivery .  Meclofenamate sodium at either dose was significantly better than codeine or placebo in reducing pain intensity and increasing pain relief , and it had a longer duration of action . Adverse effects were minimal , and their frequency did not differ significantly among treatment groups . Meclofenamate sodium appears to be as safe as and more effective than codeine for the management of episiotomy pain 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 Tramadol hydrochloride is a novel , central ly acting analgesic with two complementary mechanisms of action : opioid and aminergic . Relative to codeine , tramadol has similar analgesic properties but may have fewer constipating , euphoric , and respiratory depressant effects . A two-center r and omized double-blind controlled clinical trial was performed to assess the analgesic efficacy and reported side effects of tramadol 100 mg , tramadol 50 mg , codeine 60 mg , aspirin ( ASA ) 650 mg with codeine 60 mg , and placebo .  Using a third molar extraction pain model , 200 healthy subjects were enrolled in a 6-hour evaluation after a single dose of drug . Of the 200 patients enrolled , seven provided incomplete efficacy data or discontinued prematurely and one was lost to follow-up . Using st and ard measures of analgesia , including total pain relief score ( TOTPAR ) , maximum pain relief score ( MaxPAR ) , sum of pain intensity difference scores ( SPID ) , peak pain intensity difference ( Peak PID ) , remedication , and global evaluations , all active treatments were found to be numerically superior to placebo . ASA/codeine was found to be statistically superior to placebo for all measures of efficacy .  Tramadol 100 mg was statistically superior to placebo for TOTPAR , SPID , and time of remedication , whereas tramadol 50 mg was statistically superior to placebo onlyfor remedication time .  Codeine was not found to be statistically superior to placebo for any efficacy measure . A greater TOTPAR response compared with all other active measures was seen for ASA/codeine during the first 3 hours of study . The 6-hour TOTPAR scores for the tramadol groups and ASA/ codeine group were not significantly different . Gastrointestinal side effects ( nausea , dysphagia , vomiting ) were reported more frequently with tramadol 100 mg , ASA/ codeine , and codeine 60 mg than with placebo 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 & NA ; There is uncertainty over whether the patient group in which acute pain studies are conducted ( pain model ) has any influence on the estimate of analgesic efficacy . Data from four recently up date d systematic review s of aspirin 600/650 mg , paracetamol 600/650 mg , paracetamol 1000 mg and ibuprofen 400 mg were used to investigate the influence of pain model . Area under the pain relief versus time curve equivalent to at least 50 % maximum pain relief over 6 h was used as the outcome measure . Event rates with treatment and placebo , and relative benefit ( RB ) and number needed to treat ( NNT ) were used as outputs from the meta‐analyses . The event rate with  placebo was systematic ally statistically lower for dental than postsurgical pain for all four treatments . Event rates with analgesics , RB and NNT were infrequently different between the pain models . Systematic difference in the estimate of analgesic efficacy between dental and postsurgical pain models remains unproven , and , on balance , no major difference is likely To evaluate the analgesic efficacy of orally administered 50 mg propiram fumarate , 650 mg aspirin , 60 mg codeine phosphate , and placebo in acute post-impaction dental pain , 159 patients with moderate or severe pain were r and omly allocated to the four treatments in this single-dose double-blind , stratified , parallel-group study . A research nurse question ed the patients at 1/2 hour and hourly for 6 hours after medicating . A st and ard format was used to question subjects about their pain intensity and relief from the starting pain . Propiram , 50 mg , produced a level of analgesia approaching that of 650 mg aspirin in peak effect , total effect , and duration of action and was statistically superior to 60 mg codeine and placebo for every measure of analgesic efficacy . Several mild adverse effects were observed ; however , they appeared to be evenly distributed among the active treatments In a double-blind study , 198 out patients with pain after oral surgery were r and omly assigned to treatment with a single oral dose of naproxen sodium 550 mg , codeine sulfate 60 mg , a combination of naproxen sodium 550 mg with codeine sulfate 60 mg , aspirin 650 mg or placebo . Using a self-rating record , subjects rated their pain and its relief hourly for 12 hours after medication . Orthogonal contrasts for the four treatments making up the factorial component showed that the naproxen effect was significant for every measurement of total and peak analgesia ; the codeine effect was significant for total and peak pain relief and patients ' overall evaluation . The naproxen-codeine interaction was not statistically significant for any measure , which suggests that the analgesic effect of the combination represents the additive effect of its constituents . Based on pairwise comparisons , aspirin was significantly superior to placebo for most measures of effect , naproxen was significantly superior to both aspirin and codeine for all measures and the combination was significantly superior to naproxen for patients ' overall evaluation . No more patients experienced adverse effects with aspirin or naproxen than with placebo , but significantly more patients receiving the codeine-containing treatments experienced adverse effects than those receiving aspirin and naproxen 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 The purpose of this study was to evaluate the contribution of endogenous opiates to the analgesic response after treatment with placebo , codeine , and ibuprofen  after oral surgery . Eighty-one patients undergoing complicated dental extraction s were pretreated with either a placebo or the narcotic antagonist naltrexone 50 mg , 30 minutes before surgery . After surgery , patients self administered one of three possible postsurgical medications , which included placebo , codeine 60 mg , and ibuprofen 400 mg , when their pain reached a moderate or severe intensity . The study was double-blind with the three postsurgical treatments being r and omly allocated within each presurgical treatment block . Pain intensity , pain relief , pain half gone , and overall evaluations were assessed for up to 6 hours . Ibuprofen was significantly more efficacious ( p < .05 ) than codeine or placebo for most analgesic measures . The administration of naltrexone before surgery reduced the analgesic response to both placebo and codeine . Pretreatment with naltrexone did not diminish the peak analgesic response to ibuprofen  , but surprisingly prolonged ( p < .05 ) the duration of its action . The results suggest that a blockade of endogenous opiates by naltrexone diminished the placebo response , but that naltrexone may prolong ibuprofen analgesia by some unknown mechanism & 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 
    Output:
    
More participants experienced adverse events with codeine 60 mg than placebo ; the difference was not significant and none were serious .
Single dose codeine 60 mg provides good analgesia to few individuals , and does not compare favourably with commonly used alternatives such as paracetamol , NSAIDs and their combinations with codeine , especially after dental surgery ; the large difference between dental and other surgery was unexpected .