***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 Background Dexketoprofen trometamol plus tramadol hydrochloride is a new oral combination of two analgesics , which have different mechanisms of action for the treatment of moderate to severe acute pain . Methods R and omised , double-blind , parallel , placebo and active-controlled , single and multiple-dose study to evaluate the analgesic efficacy and safety of dexketoprofen/tramadol 25 mg/75 mg in comparison with the single agents ( dexketoprofen 25 mg and tramadol 100 mg ) in moderate to severe acute pain after abdominal hysterectomy . Patients received seven consecutive doses of study drug within a 3-day period , each dose separated by an 8-hour interval . A placebo arm was included during the single-dose phase to vali date the pain model . Efficacy assessment s included pain intensity , pain relief , patient global evaluation and use of rescue medication . The primary endpoint was the mean sum of pain intensity differences over the first 8 h ( SPID8 ) . Results The efficacy analysis included 606 patients , with a mean age of 48 years ( range 25–73 ) . The study results confirmed the superiority of the combination over the single agents in terms of the primary endpoint ( p < 0.001 ) . Secondary endpoints were generally supportive of the superiority of the combination for both single and multiple doses . Most common adverse drug reactions ( ADRs ) were nausea ( 4.6 % ) and vomiting ( 2.3 % ) . All other ADRs were experienced by less than 2 % of patients . Conclusions The study results provided robust evidence of the superiority of dexketoprofen/tramadol 25 mg/75 mg over the single components in the management of moderate to severe acute pain , as confirmed by the single-dose efficacy , repeated-dose sustained effect and good safety profile observed . Trial registration EU Clinical Trials Register ( EudraCT number 2012 - 004545 - 32 , registered 04 October 2012 ) ; Clinical trials.gov ( NCT01904149 , registered 17 July 2013 ) 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 . The aim was to evaluate the analgesic efficacy and safety of the dexketoprofen/tramadol 25 mg/75 mg fixed-dose combination vs dexketoprofen ( 25 mg ) and tramadol ( 100 mg ) in moderate-to-severe acute pain after total hip arthroplasty . Methods . This was a r and omized , double-blind , parallel-group study in patients experiencing pain of at least moderate intensity on the day after surgery , compared with placebo  at first administration to vali date the pain model . The study drug was administered orally every 8 h throughout a 5 day period . Rescue medication , metamizole 500 mg , was available during the treatment period . The evaluation of efficacy was based on patient assessment s of pain intensity and pain relief . The primary end point was the mean sum of the pain intensity difference values throughout the first 8 h ( SPID8 ) . Results . Overall , 641 patients , mean age 62 ( range 29–80 ) yr , were analysed ; mean ( sd ) values of SPID8 were 247 ( 157 ) for dexketoprofen/tramadol , 209 ( 155 ) for dexketoprofen , 205 ( 146 ) for tramadol , and 151 ( 159 ) for placebo . The primary analysis confirmed the superiority of the combination over dexketoprofen 25 mg ( P=0.019 ; 95 % confidence interval 6.4–73 ) and tramadol 100 mg ( P=0.012 ; 95 % confidence interval 9.5–76 ) . The single components were superior to placebo ( P<0.05 ) , confirming model sensitivity . Most secondary analyses supported the superiority of the combination . The incidence of adverse drug reactions was low and similar among active treatment groups . Conclusion . The efficacy results confirmed the superiority of dexketoprofen/tramadol over its single components , even at higher doses ( tramadol ) , with a safety profile fully in line with that previously known for these agents in monotherapy . Clinical trial registration . EudraCT 2012 - 004548 - 31 ( https://www . clinical trialsregister.eu/ctr- search / search ? query = eudract_number:2012 - 004548 - 31 ) ; Clinical Trials.gov NCT01902134 ( https://www . clinical trials.gov/ct2/show/NCT01902134?term=NCT01902134&rank=1 ) 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 Combination analgesics are effective in acute pain , and a theoretical framework predicts efficacy for combinations . The combination of dexketoprofen and tramadol is untested , but predicted to be highly effective . Methods This was a r and omised , double-blind , double-dummy , parallel-group , placebo-controlled , single-dose trial in patients with moderate or severe pain following third molar extraction . There were ten treatment arms , including dexketoprofen trometamol ( 12.5 mg and 25 mg ) and tramadol hydrochloride ( 37.5 mg and 75 mg ) , given as four different fixed combinations and single components , with ibuprofen 400 mg as active control as well as a placebo control . The study objective was to evaluate the superior analgesic efficacy and safety of each combination and each single agent versus placebo . The primary outcome was the proportion of patients with at least 50 % max TOTPAR over six hours . Results 606 patients were r and omised and provided at least one post-dose assessment . All combinations were significantly better than placebo . The highest percentage of responders ( 72 % ) was achieved in the dexketoprofen trometamol 25 mg plus tramadol hydrochloride 75 mg group ( NNT 1.6 , 95 % confidence interval 1.3 to 2.1 ) . Addition of tramadol to dexketoprofen result ed in greater peak pain relief and greater pain relief over the longer term , particularly at times longer than six hours ( median duration of 8.1 h ) . Adverse events were unremarkable . Conclusions Dexketoprofen trometamol 25 mg combined with tramadol hydrochloride 75 mg provided good analgesia with rapid onset and long duration in a model of moderate to severe pain . The results of the dose finding study are consistent with pre-trial calculations based on empirical formulae . Trial registration EudraCT ( 2010 - 022798 - 32 ) ; Clinical trials.gov ( NCT01307020 ) Our purpose was to evaluate the analgesic efficacy of single oral doses of ketoprofen 25 , 50 , and 100 mg compared with aspirin 650 mg and placebo in the relief of moderate to severe postepisiotomy , uterine cramping , or cesarean section pain . One hundred and fifty-six patients participated in a r and omized , double-blind , stratified , parallel-group study . They were observed over a six-hour period by one nurse-observer . Several of the st and ard summary measures of analgesia were derived from the interview data , including the sum of pain intensity differences ( SPID ) and the sum of the hourly relief values ( TOTAL ) . The study showed significant differences between aspirin and placebo for four-hour SPID and several other parameters and between ketoprofen at all dose levels and placebo for the four- and six-hour SPID and many other parameters . The two higher doses of ketoprofen were significantly more effective than aspirin as as assessed by the four- and six-hour SPID , TOTAL , and other summary measures . The low dose of ketoprofen , although not significantly different from aspirin for SPID and TOTAL , showed a significantly faster onset of relief and had a better global rating . This study suggests that 50 mg of ketoprofen may be the clinical dose of choice as an analgesic . There were no adverse effects reported & 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 
    Output:
    
Differential efficacy between dental surgery and other types of surgery seen for both drugs is unusual .
Both drugs were well tolerated in single doses