***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: 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 & 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 analgesic efficacy of single 500 and 1,000 mg doses of diflunisal , a new nonsteroidal antiinflammatory analgesic , was compared in a double-blind study with acetaminophen 600 mg , the combination of acetaminophen 600 mg with codeine 60 mg , and placebo in 132 in patients with postoperative pain . Using a self-rating record , patients rated their pain and its relief hourly for up to 12 hours after medication . Diflunisal 500 and 1,000 mg were significantly superior to placebo for every measure of total and peak analgesia , and a significant analgesic effect persisted for 8 hours . Acetaminophen alone and the acetaminophen-codeine combination were significantly superior to placebo for most measures of analgesia , and their effects were significant for 4 and 5 hours respectively . Differences among the active medications were not statistically significant for measures of total or peak analgesia 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 Two-hundred six out patients with postoperative pain after the surgical removal of impacted third molars were r and omly assigned on a double-blind basis to receive oral doses of ketorolac tromethamine 10 and 20 mg , ibuprofen 400 mg , acetaminophen 600 mg , a combination of acetaminophen 600 mg plus codeine 60 mg , or placebo . Using a self-rating record , subjects rated their pain and its relief hourly for 6 hours after medicating . All active medications were significantly superior to placebo .  Analgesia was similar for ketorolac 10 and 20 mg and ibuprofen 400 mg ; however , these treatments were superior to acetaminophen alone and the acetaminophen-codeine combination . The analgesic effect of each active medication was significant by hour 1 and persisted for 5 - 6 hours . The data suggest a plateau in  ketorolac 's analgesic efficacy at the 10-mg level . Repeat-dose data indicated that on the day of surgery ketorolac 10 and 20 mg and ibuprofen 400 mg were superior to acetaminophen 600 mg ; ketorolac 20 mg was also superior to acetaminophen-codeine . Differences among active medications were not significant when data for the entire postoperative period ( days 0 - 6 ) were evaluated . The frequency of adverse effects was similar for the active medications A double-blind , r and omized , single-dose study was performed to compare the efficacy and safety of two commonly prescribed combination analgesic products to placebo . The combinations were acetaminophen 300 mg/codeine 30 mg(† ) , and aspirin 325 mg/butalbital 50 mg/caffeine 40 mg/codeine 30 mg(†† ) . One hundred twenty-three ( 123 ) oral surgery out patients took study medications when their pain became moderate to severe and recorded the levels of pain intensity , pain relief , anxiety and relaxation at 30 minutes and hourly for 6 hours after dosing . Remedication was permitted if study medications did not provide adequate pain relief . Time to remedication , and the number of observations with 50 % or better relief , were noted as were any side effects . An overall evaluation was obtained from each patient . Results of the study showed that the aspirin/butalbital/caffeine/codeine combination was significantly more effective than placebo  for total pain relief , peak relief and global evaluation . While the acetaminophen/codeine combination was numerically superior to placebo , it achieved statistical significance only for global evaluation . The aspirin/butalbital/caffeine/codeine combination was numerically superior to acetaminophen/codeine for every measure of analgesic efficacy but the differences did not achieve statistical significance . Both active treatment groups experienced significantly less total anxiety than did the placebo group . Only 11 patients reported mild , transient adverse effects ; the most common was drowsiness . The adverse effects occurred equally among the three treatment groups . In this study , the aspirin/butalbital/caffeine/codeine combination was significantly superior to placebo and somewhat better than acetaminophen/codeine & 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 The analgesic efficacy of single 500- and 1,000-mg doses of diflunisal ( Dolobid ) , a new nonsteroidal anti-inflammatory analgesic , was compared in a double-blind study with that of acetaminophen , 600 mg , the combination of acetaminophen , 600 mg , with codeine phosphate , 60 mg , and placebo in 159 oral surgery out patients . Using a self-rating record , patients rated their pain and its relief hourly for 12 hours after medication . Both doses of diflunisal were significantly more effective than acetaminophen alone and produced peak analgesia comparable to that of the acetaminophen-codeine combination . Diflunisal proved to have an unusually long duration of analgesic action .  Acetaminophen and the combination were significantly superior to placebo through hours 2 and 5 , respectively ; both doses of diflunisal were significantly superior through the end of the 12-hour observation period . None of the active treatments produced more side effects than the placebo The analgesic efficacy and duration of action of naproxen sodium 440 mg ( n = 92 ) , acetaminophen 1000 mg ( n = 89 ) , and placebo ( n = 45 ) were compared in a single-dose , r and omized , double-blind , 12-hour study of patients with at least moderate pain secondary to extraction of three or four third molars .  Time to remedication , a measure of duration of analgesic effect , was significantly longer ( P < 0.001 ) with naproxen sodium ( median , 9.9 hours ) than with either acetaminophen ( median , 3.1 hours ) or placebo ( median , 2.0 hours ) . Naproxen sodium was also superior to acetaminophen for peak pain intensity difference ( visual analog scale ) , summed pain intensity differences , total pain relief , peak pain relief , time to reduction 
    Output:
    
The results confirm that paracetamol is an effective analgesic , and that codeine 60 mg added to paracetamol produces worthwhile additional pain relief even in single oral doses