***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 Objective This study was conducted to evaluate the dose range of etoricoxib in acute pain using the postoperative dental pain model further . Methods This double-blind , r and omized controlled study evaluated etoricoxib ( 90 and 120 mg ) , ibuprofen ( 600 mg ) , and acetaminophen ( 600 mg/codeine ) ( 60 mg , ( A/C ) ) in patients aged ≥18 years with moderate or severe pain after surgical extraction of ≥2 third molars ( ≥1 impacted ) . The patients reported pain intensity and pain relief over 24 hours . The primary efficacy endpoint was total pain relief over 6 hours ( TOPAR6 ) . Adverse events were evaluated throughout the study . Results There were 588 patients r and omized to placebo  ( n=46 ) , etoricoxib ( 90 mg ( n=191 ) ) , etoricoxib ( 120 mg ( n=97 ) ) , ibuprofen ( 2400 mg ( n=192 ) ) , and A/C ( n=62 ) . The overall analgesic effect ( TOPAR6 ) of etoricoxib ( 90 , 120 mg ) was significantly greater than that of placebo ( P⩽0.001 ) , and not inferior to that of ibuprofen ; no discernible difference was observed between etoricoxib 90 and 120 mg . Both etoricoxib doses were superior to A/C ( P⩽0.001 ) . Etoricoxib ( 90 and 120 mg ) and ibuprofen ( 2400 mg ) were generally well tolerated and had a similar incidence of adverse events ( AEs ) . A/C was associated with significantly more AEs that led to discontinuation ( ie , nausea and vomiting ) . Conclusions Etoricoxib ( 90 and 120 mg ) showed similar efficacy in the postoperative dental pain model , which was noninferior to ibuprofen and superior to A/C. A higher number of tooth extraction s or a higher mean impaction score may have led to a greater separation in efficacy between the 2 etoricoxib doses & 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 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 BACKGROUND Patients experiencing acute pain after surgery , including dental surgery , often require analgesia . Ideally , the chosen analgesic should have a rapid onset and sustained effect . Etoricoxib is a new cyclooxygenase-2-selective inhibitor that has demonstrated analgesic efficacy in the treatment of acute pain with a rapid onset and long-lasting pain relief . OBJECTIVE The goal of this study was to determine the analgesic effect of single oral doses of etoricoxib 60 , 120 , 180 , and 240 mg compared with placebo in the treatment of pain after dental surgery .  Ibuprofen was used as an active control . METHODS This was a r and omized , double-blind , parallel-group , single-dose , placebo- and active comparator-controlled study performed at a single center . It consisted of 3 visits ( pre study , treatment , and post study ) . Eligible patients were aged > or = 16 years with moderate or severe pain after surgical extraction of > or = 2 third molars , of which > or = 1 was an impacted m and ibular molar . Patients were assessed over 24 hours and reported pain intensity and pain relied at 14 predefined time points . Plasma sample s for a pharmacokinetic/pharmacodynamic analysis were collected from a subset of patients at baseline and the 14 predefined time points . The end points included total pain relief over 8 hours ( TOPAR8 , the primary end point ) , sum of pain intensity difference over 8 hours , patient 's global evaluation of treatment , median time to onset of pain relief ( 2-stopwatch method ) , peak pain relief , and duration of analgesic effect ( median time to use of rescue medication ) . Adverse events were collected up to 14 days postdose . RESULTS Three hundred ninety-eight ( 63.1 % women , 36.9 % men ; mean age , 21.1 years ; 72.1 % white , 27.9 % other ; mean number of third molars removed , 3.5 ; 65.2 % experiencing moderate pain ) were r and omly allocated to receive etoricoxib 60 mg ( n = 75 ) , etoricoxib 120 mg ( n = 76 ) , etoricoxib 180 mg ( n = 74 ) , etoricoxib 240 mg ( n = 76 ) , ibuprofen 400 mg ( n = 48 ) , and placebo ( n = 49 ) . All active treatments had significantly greater overall analgesic effect ( TOPAR8 ) compared with placebo ( P < or 0.001 ) . Patients who received etoricoxib 120 and 180 mg had significantly higher TOPAR8 scores than those who received etoricoxib 60 mg ( P < = 0.001 ) and ibuprofen ( P < 0.05 etoricoxib 120 mg ; P < or = 0.001 etoricoxib 180 mg ) . Least-squares mean TOPAR8 scores for etoricoxib 60 , 120 , 180 , and 240 mg , ibuprofen , and placebo were 16.0 , 22.0 , 23.5 , 20.7 , 18.6 , and 5.2 , respectively . The median time to onset of analgesia was 24 minutes for etoricoxib 120 , 180 , and 240 mg , and 30 minutes for etoricoxib 60 mg and ibuprofen . There were no significant differences in the onset of analgesia between etoricoxib 120 , 180 , and 240 mg and ibuprofen . The duration of analgesic effect was > 24 hours for etoricoxib 120 , 180 , and 240 mg , and 12.1 hours for etoricoxib 60 mg . The duration of effect was significantly longer with all 4 etoricoxib doses compared with ibuprofen ( 10.1 hours ; P < 0.05 etoricoxib 60 mg ; < or = 0.001etoricoxib 120 , 180 , and 240 mg ) and compared with placebo ( 2.1 hours ; P < = 0.001 ) . In the pharmacokinetic/pharmacodynamic analysis ( n approximately 120 ) , there was a linear relationship between plasma etoricoxib concentrations and pain relief scores up to the maximum observed concentration , followed by a decline in plasma concentrations with persistent analgesia . The most common adverse events were post extraction alveolitis and nausea . CONCLUSIONS In this dose-ranging study , etoricoxib 120 mg was determined to be the minimum dose that had maximal efficacy in patients with moderate to severe acute pain associated with dental surgery . Both etoricoxib and ibuprofen were generally well tolerated We assessed the quality of assessment and reporting of adverse effects in r and omized , double-blind clinical trials of single-dose acetaminophen or ibuprofen compared with placebo in moderate to severe postoperative pain . Reports were identified by systematic search ing of a number of bibliographic data bases ( e.g. , MEDLINE ) . Information on adverse effect assessment , severity and reporting , patient withdrawals , and anesthetic used was extracted . Compliance with former guidelines for adverse effect reporting was noted . Fifty-two studies were included ; two made no mention of adverse effects . No method of assessment was given in 19 studies . Twenty trials failed to report the type of anesthetic used , eight made no mention of patient withdrawals , and nine did not state the severity of reported adverse effects . Only two studies described the method of assessment of adverse effect severity . When all adverse effect data were pooled , significantly more adverse effects were reported with active treatment than with placebo . For individual adverse effects , there was no difference between active ( acetaminophen 1000 mg or ibuprofen 400 mg ) and placebo ; the exception was significantly more somnolence/drowsiness with ibuprofen 400 mg . Ninety percent of trials reporting somnolence/drowsiness with ibuprofen 400 mg were in dental pain . All studies published after 1994 complied with former guidelines for adverse effect reporting . Different methods of assessing adverse effects produce different reported incidence : patient diaries yielded significantly more adverse effects than other forms of assessment . We recommend guidelines for reporting adverse effect information in clinical trials Objective . Patients with arthritis frequently are at increased risk for future cardiovascular ( CV ) events . We investigated the performance of the cardiac biomarkers N-terminal pro-B-type natriuretic peptide ( NT-proBNP ) and high sensitivity C-reactive protein ( hsCRP ) for predicting CV events in patients with arthritis taking chronic nonsteroidal antiinflam 
    Output:
    
Adverse events were reported at a similar rate to placebo ( moderate- quality evidence ) , with no serious events .
Single-dose oral etoricoxib produces high levels of good quality pain relief after surgery , and adverse events did not differ from placebo in these studies .
The 120 mg dose is as effective as , or better than , other commonly used analgesics