***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 We studied the effects of various nonmorphine pain medications  as well as rheumatoid arthritis and osteoarthritis on  fracture risk  in a nationwide case-control study . Cases were all subjects with any fracture sustained during the year 2000 ( n = 124,655 ) in Denmark . For each case , three controls ( n = 373,962 ) matched on age and gender were r and omly drawn from the background population . The primary exposure variables were use of acetaminophen , nonsteroidal anti-inflammatory drugs ( NSAIDs ) , or acetylsalicylic acid ( ASA ) . Adjustments were made for several confounders . The effect of dose was examined by stratifying for cumulated dose ( defined daily dose , DDD ) . For acetaminophen , a small increase in overall fracture risk was observed with use within the last year ( odds ratio [ OR ] = 1.45 , 95 % confidence interval [ CI ] 1.41–1.49 ) . For ASA , no increase in overall fracture risk was present with recent use . Significant heterogeneity was present for the NSAIDs ; e.g. , ibuprofen was associated with an increased overall fracture risk ( OR = 2.09 , 95 % CI 2.00–2.18 for < 20 DDD ) , while celecoxib was not ( OR = 0.76 , 95 % CI 0.51–1.13 for < 20 DDD , 2P < 0.01 for comparison ) . Osteoarthritis was associated with a decreased risk of any fracture if the diagnosis had been made more than 1 year ago ( OR = 0.70 , 95 % CI 0.67–0.72 ) . Rheumatoid arthritis was associated with an increase in overall fracture risk if the diagnosis had been made within the last year ( OR = 1.86 , 95 % CI 1.68–2.07 ) . Weak analgesics may be associated with fracture risk in a varying way . The effects in most cases were small . Falls may be one reason for the increase in fracture risk with some NSAIDs Renal prostagl and in inhibition by nonsteroidal antiinflammatory drugs ( NSAIDs ) may decrease renal function , especially under conditions of low effective circulating volume . To evaluate the risk of important deterioration of renal function due to this effect , the authors performed a nested case-control study using Tennessee Medicaid enrollees aged > or = 65 years in 1987 - 1991 . Cases were patients who had been hospitalized with community-acquired acute renal failure ; they were selected on the basis of medical record review of Medicaid enrollees with selected discharge diagnoses . Information on the timing , duration , and dose of prescription NSAIDs used , demographic factors , and comorbidity was gathered from computerized Medicaid-Medicare data files . Of the 1,799 patients with acute renal failure ( 4.51 hospitalizations per 1,000 person-years ) , 18.1 % were current users of prescription NSAIDs  as compared with 11.3 % of 9,899 r and omly selected population controls . After control for demographic factors and comorbidity , use of NSAIDs increased the risk of acute renal failure 58 % ( adjusted odds ratio = 1.58 ; 95 % confidence interval ( CI ) : 1.34 , 1.86 ) . For ibuprofen , which accounted for 35 % of NSAID use , odds ratios associated with dosages of < or = 1,200 mg/day , > 1,200-<2,400 mg/day , and > or = 2,400 mg/day were 0.94 ( 95 % CI : 0.58 , 1.51 ) , 1.89 ( 95 % CI : 1.34 , 2.67 ) , and 2.32 ( 95 % CI : 1.45 , 3.71 ) , respectively ( test for linear trend : p = 0.009 ) . Prescription NSAID use result ed in an estimated 25 excess hospitalizations associated with renal failure per 10,000 years of use . Thus , NSAIDs represent a relatively uncommon but avoidable cause of acute renal failure in frail elderly persons & 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 BACKGROUND Cyclo-oxygenase 2 (COX2)-selective inhibitors should reduce ulcer complications compared with non-selective non-steroidal anti-inflammatory drugs , but evidence is limited , and the possibility that these inhibitors increase cardiovascular events has been raised . The Therapeutic Arthritis Research and Gastrointestinal Event Trial ( TARGET ) aim ed to assess gastrointestinal and cardiovascular safety of the COX2 inhibitor lumiracoxib compared with two non-steroidal anti-inflammatory drugs , naproxen and ibuprofen . METHODS 18325 patients age 50 years or older with osteoarthritis were r and omised to lumiracoxib 400 mg once daily ( n=9156 ) , naproxen 500 mg twice daily ( 4754 ) , or ibuprofen 800 mg three times daily ( 4415 ) for 52 weeks , in two sub studies of identical design ( lumiracoxib vs ibuprofen or naproxen ) . R and omisation was stratified for low-dose aspirin use and age . The primary endpoint was the difference in time-to-event distribution of upper gastrointestinal ulcer complications ( bleeding , perforation , or obstruction ) ; analysis was by modified intention to treat . The principle measure of adverse cardiovascular events was the Antiplatelet Trialists ' Collaboration endpoint ( myocardial infa rct ion , stroke , or cardiovascular death ) ; this analysis was intention to treat . FINDINGS 81 ( 0.44 % ) patients did not start treatment and 7120 ( 39 % ) did not complete the study . In patients not taking aspirin , the cumulative 1-year incidence of ulcer complications was 1.09 % ( 95 % CI 0.82 - 1.36 ) with non-steroidal anti-inflammatory drugs ( 64 events ) versus 0.25 % ( 95 % CI 0.12 - 0.39 ) with lumiracoxib ( 14 events ; hazard ratio 0.21 [ 95 % CI 0.12 - 0.37 ] , p<0.0001 ) . Reductions in ulcer complications were also significant in the overall population ( 0.34 [ 0.22 - 0.52 ] , p<0.0001 ) but not in those taking aspirin ( 0.79 [ 0.40 - 1.55 ] , p=0.4876 ) . In the overall population , 0.55 % ( 50/9127 ) of those on non-steroidal anti-inflammatory drugs and 0.65 % ( 59/9117 ) of those on lumiracoxib reached the cardiovascular endpoint ( 1.14 [ 0.78 - 1.66 ] , p=0.5074 ) . INTERPRETATION Lumiracoxib showed a three to four-fold reduction in ulcer complications compared with non-steroidal anti-inflammatory drugs without an increase in the rate of serious cardiovascular events , suggesting that lumiracoxib is an appropriate treatment for patients with osteoarthritis Background : Valdecoxib and its intravenous prodrug parecoxib are reported to increase thromboembolic risk after coronary artery bypass grafting . The authors conducted a r and omized trial to examine their safety and analgesic efficacy in patients recovering from major noncardiac surgical procedures . Methods : The trial was r and omized and double-blind , with 10 days of treatment and 30 days of follow-up . Patients ( n = 1,062 ) received either parenteral parecoxib for 3 days and oral valdecoxib for the rest of the treatment period or placebo medications throughout . The frequency of predefined adjudicated postr and omization adverse events , including cardiovascular thromboembolism , renal dysfunction , gastroduodenal ulceration , and wound-healing complications , was assessed in each group . Secondary efficacy endpoints included patients ' pain ratings , opioid analgesic consumption ( recorded as morphine equivalents ) , and reports of opioid-related adverse effects . Results : Predefined adjudicated adverse events had similar frequencies among patients who received parecoxib and valdecoxib ( 2.7 % ) and placebo patients ( 3.2 % ) ( P = 0.58 ) , including cardiovascular thromboembolic events ( 1.0 % in each group ; P = 1.0 ) . Placebo patients consumed more morphine equivalents ( 66.2 ± 92.4 mg ) than did patients receiving parecoxib and valdecoxib ( 43.2 ± 65.7 mg ) ( P < 0.001 ) . Placebo patients had higher mean pain ratings on each of study days 2–10 ( P < 0.01 ) and reported more opioid-related symptom distress on days 2–6 ( P < 0.01 ) . Conclusions : Parecoxib and valdecoxib are useful adjuncts to opioids for the treatment of postoperative pain in noncardiac surgical patients . Further study will be required to determine the safety profile of parecoxib and valdecoxib administered to patients with known atherosclerotic disease after noncardiac surgery 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 
    Output:
    
Lumiracoxib 400 mg given as a single oral dose , is an effective analgesic for acute postoperative pain