***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: BACKGROUND Paracetamol is a recommended symptomatic treatment of osteoarthritis ( OA ) , but in clinical trials sample sizes have been relatively small and variable daily doses of paracetamol have been used . OBJECTIVES To determine the therapeutic efficacy of paracetamol in OA of the knee and identify predictive factors of clinical response to treatment . METHODS A double blind , parallel group , placebo controlled trial of analgesic efficacy and safety of paracetamol versus placebo including 779 patients with OA of the knee . Patients were r and omly assigned to receive paracetamol 4 g/day ( n = 405 ) or placebo ( n = 374 ) for 6 weeks . Symptomatic OA of the knee was required at inclusion with global pain intensity of the knee during physical activities for the past 24 hours of > or=30 mm on a 100 mm visual analogue scale . The primary end point was a 30 % decrease of global pain intensity of the knee . Intention to treat analyses were performed . RESULTS The percentage of responders did not differ significantly between groups : 52.6 % and 51.9 % in paracetamol and placebo groups , respectively ( p = 0.840 ) . In a subgroup of patients with chronic mechanical knee pain without signs of inflammation ( n = 123 ) , the mean change in pain intensity from baseline was 25.2 mm v 15.2 mm , in the paracetamol ( n = 63 ) and placebo ( n = 60 ) groups , respectively-mean difference 10.0 mm ; 95 % CI 1.0 to 19.0 ; p = 0.0294 . No serious adverse events were attributable to treatment . CONCLUSION A statistically significant symptomatic effect of oral paracetamol 4 g/day over placebo was not found , suggesting that paracetamol use in symptomatic OA of the knee should be further explored . The tolerability and safety of paracetamol , at the recommended maximum dose of 4 g/day , was confirmed over 6 weeks 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 SUMMARY Objectives : To compare patient and physician attitudes to osteoarthritis ( OA ) treatment with rofecoxib or traditional non-steroidal anti-inflammatory drugs ( tNSAIDs ) . Methods : A 6-month prospect i ve study involving 562 OA patients enrolled at 29 Spanish primary -care centres . Patients were continued on established tNSAID therapy for the first 3 months then switched to rofecoxib 12.5 or 25 mg/day . Results : Both patients and physicians were significantly more likely to be satisfied with rofecoxib treatment than with tNSAIDs ( p < 0.001 ) and assessment s of overall health status improved significantly during rofecoxib therapy ( p < 0.001 ) . Adherence to therapy was significantly better with rofecoxib than during tNSAID treatment ( p < 0.001 ) . Use of rofecoxib was associated with a significant reduction in the proportion of discontinuations attributed to lack of effectiveness ( p < 0.001 ) or gastrointestinal ( GI ) adverse events ( p < 0.001 compared with tNSAIDs ) . Rofecoxib was also associated with a > 60 % reduction in the proportion of patients experiencing a GI adverse event and a halving in the proportion of patients who received GI co-medications ; concomitant analgesic use decreased by one-third during rofecoxib therapy . Conclusions : Use of rofecoxib was associated with marked improvements in several indices of treatment effectiveness and tolerability , and in patient and physician satisfaction and perception of general health status compared with tNSAIDs . Rofecoxib is a valuable additional medication for relieving the symptoms of OA and its use in place of tNSAIDs may lead to a reduction in the prescription of concomitant medications BACKGROUND Chronic pain is recognised as an important problem in the community but our underst and ing of the epidemiology of chronic pain remains limited . We undertook a study design ed to quantify and describe the prevalence and distribution of chronic pain in the community . METHODS A r and om sample of 5036 patients , aged 25 and over , was drawn from 29 general practice s in the Grampian region of the UK and surveyed by a postal self-completion question naire . The question naire included case-screening questions , a question on the cause of the pain , the chronic pain grade question naire , the level of expressed needs question naire , and sociodemographic questions . FINDINGS 3605 question naires were returned completed . 1817 ( 50.4 % ) of patients self reported chronic pain , equivalent to 46.5 % of the general population . 576 reported back pain and 570 reported arthritis ; these were the most common complaints and accounted for a third of all complaints . Backward stepwise logistic-regression modelling identified age , sex , housing tenure , and employment status as significant predictors of the presence of chronic pain in the community . 703 ( 48.7 % ) individuals with chronic pain had the least severe grade of pain , and 228 ( 15.8 % ) the most severe grade . Of those who reported chronic pain , 312 ( 17.2 % ) reported no expressed need , and 509 ( 28.0 % ) reported the highest expressed need . INTERPRETATION Chronic pain is a major problem in the community and certain groups within the population are more likely to have chronic pain . A detailed underst and ing of the epidemiology of chronic pain is essential for efficient management of chronic pain in primary care CONTEXT Conventional nonsteroidal anti-inflammatory drugs ( NSAIDs ) are associated with a spectrum of toxic effects , notably gastrointestinal ( GI ) effects , because of inhibition of cyclooxygenase (COX)-1 . Whether COX-2-specific inhibitors are associated with fewer clinical GI toxic effects is unknown . OBJECTIVE To determine whether celecoxib , a COX-2-specific inhibitor , is associated with a lower incidence of significant upper GI toxic effects and other adverse effects compared with conventional NSAIDs . DESIGN The Celecoxib Long-term Arthritis Safety Study ( CLASS ) , a double-blind , r and omized controlled trial conducted from September 1998 to March 2000 . SETTING Three hundred eighty-six clinical sites in the United States and Canada . PARTICIPANTS A total of 8059 patients ( > /=18 years old ) with osteoarthritis ( OA ) or rheumatoid arthritis ( RA ) were enrolled in the study , and 7968 received at least 1 dose of study drug . A total of 4573 patients ( 57 % ) received treatment for 6 months . INTERVENTIONS Patients were r and omly assigned to receive celecoxib , 400 mg twice per day ( 2 and 4 times the maximum RA and OA dosages , respectively ; n = 3987 ) ; ibuprofen , 800 mg 3 times per day ( n = 1985 ) ; or diclofenac , 75 mg twice per day ( n = 1996 ) . Aspirin use for cardiovascular prophylaxis ( < /=325 mg/d ) was permitted . MAIN OUTCOME MEASURES Incidence of prospect ively defined symptomatic upper GI ulcers and ulcer complications ( bleeding , perforation , and obstruction ) and other adverse effects during the 6-month treatment period . RESULTS For all patients , the annualized incidence rates of upper GI ulcer complications alone and combined with symptomatic ulcers for celecoxib vs NSAIDs were 0.76 % vs 1.45 % ( P = .09 ) and 2 . 08 % vs 3.54 % ( P = .02 ) , respectively . For patients not taking aspirin  , the annualized incidence rates of upper GI ulcer complications alone and combined with symptomatic ulcers for celecoxib vs NSAIDs were 0.44 % vs 1.27 % ( P = .04 ) and 1.40 % vs 2.91 % ( P = .02 ) . For patients taking aspirin  , the annualized incidence rates of upper GI ulcer complications alone and combined with symptomatic ulcers for celecoxib vs NSAIDs were 2.01 % vs 2.12 % ( P = .92 ) and 4.70 % vs 6.00 % ( P = .49 ) . Fewer celecoxib-treated patients than NSAID-treated patients experienced chronic GI blood loss , GI intolerance , hepatotoxicity , or renal toxicity . No difference was noted in the incidence of cardiovascular events between celecoxib and NSAIDs , irrespective of aspirin use . CONCLUSIONS In this study , celecoxib , at dosages greater than those indicated clinical ly , was associated with a lower incidence of symptomatic ulcers and ulcer complications combined , as well as other clinical ly important toxic effects , compared with NSAIDs at st and ard dosages . The decrease in upper GI toxicity was strongest among patients not taking aspirin concomitantly . JAMA . 2000;284:1247 - 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 Abstract Objective : To compare rates of upper gastrointestinal haemorrhage among elderly patients given selective cyclo-oxygenase-2 ( COX 2 ) inhibitors and non-selective non-stero 
    Output:
    
Compared with placebo , celecoxib had fewer discontinuations for any cause or for lack of efficacy , fewer serious adverse events , and less nausea .
It had more patients with dyspepsia , diarrhoea , oedema , more adverse events that were gastrointestinal or treatment related , and more patients experiencing an adverse event .
There were no differences for hypertension , gastrointestinal tolerability , or discontinuations for adverse events .
Compared with paracetamol , celecoxib had fewer discontinuations for any cause , for lack of efficacy , or diarrhoea , but no other differences .
Compared with rofecoxib , celecoxib had fewer patients with abdominal pain and oedema , but no other differences .
Compared with NSAIDs , celecoxib had fewer symptomatic ulcers and bleeds , endoscopically detected ulcers , and discontinuations for adverse events or gastrointestinal adverse events .
Fewer patients had any , or a gastrointestinal , or a treatment-related adverse event , or vomiting , abdominal pain , dyspepsia , or reduced haemoglobin or haematocrit .
Discontinuations for lack of efficacy were higher .
No differences were found for all-cause discontinuations , serious adverse events , hypertension , diarrhoea , nausea , oedema , myocardial infa rct ion , cardiac failure , or raised creatinine .