***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 Bodily pain and physical disability can negatively impact health-related quality of life ( HRQL ) in patients with osteoarthritis ( OA ) . OBJECTIVE To assess the effects of treatment with a new agent , rofecoxib , on HRQL in patients with OA . STUDY DESIGN R and omized , double-blind , 6-week clinical trial comparing treatment with rofecoxib , 5 to 50 mg , with placebo in 672 patients with OA of the hip or knee . MAIN OUTCOME MEASURE Patient HRQL was assessed at baseline and at the end of treatment using the Medical Outcomes Study 36-Item Short-Form Health Survey ( SF-36 ) . RESULTS At 6 weeks , mean change from baseline in all SF-36 mental and physical health domain scores demonstrated significant improvement with rofecoxib use ( P < .05 for all doses for all SF-36 domains ) , with evidence of a dose-response relation . Improvements in mental and physical HRQL domains with rofecoxib treatment were significantly greater than those with placebo treatment ( P < .05 for each dose of rofecoxib vs placebo for all domains except general health ) and highly correlated with improvements observed using disease-specific OA outcome measures such as the Western Ontario and McMaster Universities Osteoarthritis Index-visual Analog 3.0 OA index pain and physical function subscales . The effect of rofecoxib vs placebo treatment on mental health largely disappeared after adjustment for improvement in OA disease-specific measures . CONCLUSIONS Rofecoxib treatment increased physical and mental HRQL domain scores on the SF-36 . Improvements in mental health with rofecoxib use primarily result ed from effective treatment of OA ( i.e. , reduction in pain and improvement in physical function ) BACKGROUND Acetaminophen ( paracetamol ) is recommended as the initial pharmacological treatment for knee or hip osteoarthritis . However , survey and clinical trial data indicate greater efficacy for non-steroidal anti-inflammatory drugs and cyclo-oxygenase-2 specific inhibitors . DESIGN Two r and omised , double blind , placebo controlled , crossover multicentre clinical trials , Patient Preference for  Placebo , Acetaminophen or Celecoxib Efficacy Studies ( PACES ) . PATIENTS Osteoarthritis of knee or hip . INTERVENTION " Wash out " of treatment ; r and omisation ; 6 weeks of celecoxib 200 mg/day , acetaminophen 1000 mg four times a day , or placebo ; second " wash out ; " crossover to 6 weeks of second treatment . MEASUREMENTS Western Ontario McMaster Osteoarthritis Index ( WOMAC ) , visual analogue pain scale , patient preference between two treatments . RESULTS Celecoxib was more efficacious than acetaminophen in both periods in both studies ; WOMAC and pain scale scores differed at p<0.05 in period II and both periods combined of PACES-a and in periods I and II and both periods combined in PACES-b , but not in period I of PACES-a . Acetaminophen was more efficacious than placebo , generally p<0.05 in PACES-b , and > 0.05 in PACES-a . Patient preferences were 53 % celecoxib v 24 % acetaminophen in PACES-a ( p<0.001 ) and 50 % v 32 % in PACES-b ( p = 0.009 ) ; 37 % acetaminophen v 28 % placebo in PACES-a ( p = 0.340 ) and 48 % v 24 % in PACES-b ( p = 0.007 ) . No clinical ly or statistically significant differences were seen in adverse events or tolerability among the three treatment groups . CONCLUSIONS Greater efficacy was seen for celecoxib v acetaminophen v placebo , while adverse events and tolerability were similar . Variation in results and statistical significance in the two different trials are of interest Background — Although r and omized trials of cyclooxygenase-2 ( COX-2 ) inhibitors have shown increased cardiovascular risk , studies of nonselective , nonsteroidal antiinflammatory drugs ( NSAIDs ) and acetaminophen have been inconsistent . Methods and Results — We examined the influence of NSAIDs and acetaminophen on the risk of major cardiovascular events ( nonfatal myocardial infa rct ion , fatal coronary heart disease , nonfatal and fatal stroke ) in a prospect i ve cohort of 70 971 women , aged 44 to 69 years at baseline , free of known cardiovascular disease or cancer , who provided medication data biennially since 1990 . During 12 years of follow-up , we confirmed 2041 major cardiovascular events . Women who reported occasional ( 1 to 21 d/mo ) use of NSAIDs or acetaminophen did not experience a significant increase in the risk of cardiovascular events . However , after adjustment for cardiovascular risk factors , women who frequently ( ≥22 d/mo ) used NSAIDs had a relative risk ( RR ) for a cardiovascular event of 1.44 ( 95 % CI , 1.27 to 1.65 ) compared with nonusers , whereas those who frequently consumed acetaminophen had a RR of 1.35 ( 95 % CI , 1.14 to 1.59 ) . The elevated risk associated with frequent NSAID use was particularly evident among current smokers ( RR=1.82 ; 95 % CI , 1.38 to 2.42 ) and was absent among never smokers ( Pinteraction=0.02 ) . Moreover , we observed significant dose-response relations : Compared with nonusers , the RRs for a cardiovascular event among women who used ≥15 tablets per week were 1.86 ( 95 % CI , 1.27 to 2.73 ) for NSAIDs and 1.68 ( 95 % CI , 1.10 to 2.58 ) for acetaminophen . Conclusions — Use of NSAIDs or acetaminophen at high frequency or dose is associated with a significantly increased risk for major cardiovascular events , although more moderate use did not confer substantial risk OBJECTIVE This multicentre , r and omized , double-blind , placebo-controlled parallel-group study was undertaken to investigate the efficacy , safety and tolerability of lumiracoxib ( Prexige ) , a cyclooxygenase-2 selective inhibitor , in patients with primary osteoarthritis ( OA ) of the h and . METHODS The study r and omized 594 patients aged > or = 18 years with symptomatic OA of the h and . Patients underwent a 3 to 7-day washout for previous nonsteroidal anti-inflammatory drugs and those with pain intensity > or = 40 mm on a 100 mm Visual Analogue Scale ( VAS ) in the target h and during the 24 hours prior to baseline and an increase in pain intensity of either > or = 20 % or > or = 10 mm VAS since screening ( whichever was greater ) were r and omized to lumiracoxib 200 mg once daily ( od ) ( n=205 ) , lumiracoxib 400 mg od ( n=193 ) or placebo ( n=196 ) . The primary efficacy variable was overall OA pain intensity ( VAS mm ) in the target h and after 4 weeks of treatment . Safety and tolerability assessment s were performed . RESULTS After 4 weeks of treatment , overall OA pain intensity in the target h and was significantly lower for patients treated with lumiracoxib compared with patients treated with placebo ( both doses p<0.001 ) . There was no significant difference between lumiracoxib doses in terms of the reduction in overall OA pain intensity . Lumiracoxib was well tolerated . The incidence of adverse events was similar for active treatment groups and placebo . CONCLUSIONS Lumiracoxib 200 and 400 mg od were effective and well tolerated treatments for OA of the h and . Lumiracoxib significantly improved overall OA pain intensity in the target h and versus placebo , with a tolerability profile similar to placebo Background Etoricoxib is a highly selective COX-2 inhibitor which was evaluated for the treatment of rheumatoid arthritis ( RA ) . Methods Double-blind , r and omized , placebo and active comparator-controlled , 12-week study conducted at 67 sites in 28 countries . Eligible patients were chronic NSAID users who demonstrated a clinical worsening of arthritis upon withdrawal of pre study NSAIDs . Patients received either placebo , etoricoxib 90 mg once daily , or naproxen 500 mg twice daily ( 2:2:1 allocation ratio ) . Primary efficacy measures included direct assessment of arthritis by counts of tender and swollen joints , and patient and investigator global assessment s of disease activity . Key secondary measures included the Stanford Health Assessment Question naire , patient global assessment of pain , and the percentage of patients who achieved ACR20 responder criteria response ( a composite of pain , inflammation , function , and global assessment s ) . Tolerability was assessed by adverse events and routine laboratory evaluations . Results 1171 patients were screened , 891 patients were r and omized ( N = 357 for placebo , N = 353 for etoricoxib , and N = 181 for naproxen ) , and 687 completed 12 weeks of treatment ( N = 242 for placebo , N = 294 for etoricoxib , and N = 151 for naproxen ) . Compared with patients receiving placebo , patients receiving etoricoxib and naproxen showed significant improvements in all efficacy endpoints ( p<0.05 ) . Treatment responses were similar between the etoricoxib and naproxen groups for all endpoints . The percentage of patients who achieved ACR20 responder criteria response was 41 % in the placebo group , 59 % in the etoricoxib group , and 58 % in the naproxen group . Etoricoxib and naproxen were both generally well tolerated . Conclusions In this study , etoricoxib 90 mg once daily was more effective than placebo and similar in efficacy to naproxen 500 mg twice daily for treating patients with RA over 12 weeks . Etoricoxib 90 mg was generally well tolerated in RA patients SUMMARY Objective : To evaluate and compare the efficacy and tolerability of etoricoxib and diclofenac in patients with osteoarthritis of the knee or hip . Methods : In this 6-week double-blind , active comparator controlled , parallel-group study eligible osteoarthritis patients were r and omised to receive either etoricoxib 60 mg once daily ( n = 256 ) or diclofenac 50 mg three times daily ( n = 260 ) . The primary study endpoint was the Western Ontario McMaster osteoarthritis index ( WOMAC ) pain subscale . Other endpoints included were the WOMAC stiffness and physical function subscales , and the Patient 's Global Assessment of Response to Therapy ( PGART ) question naire . Early efficacy was evaluated using WOMAC first question ( pain walking on a flat surface ) and PGART 4 h after the morning dose of each drug on days 1 and 2 . Rescue medication ( paracetamol ) used was also recorded . The study was design ed to show comparable efficacy between etoricoxib 60 mg once daily and diclofenac 50 mg three times daily with respect to the primary endpoint and was conducted outside the United States at 67 centres in 29 countries . Results : Etoricoxib ( 60 mg once daily ) was comparable in efficacy to diclofenac ( 150 mg daily ) on all the above parameters . The one exception was in the assessment of early efficacy where etoricoxib demonstrated significantly greater benefit within 4 h of taking the first dose on the first day of therapy ( p = 0.007 ) as evaluated by the percentage of patients with good or excellent ( PGART ) responses . The treatment effects of both drugs were similar by the time day 2 was reached and were sustained throughout the 6 weeks of therapy . Both treatments were generally well tolerated . Conclusions : Etoricoxib is clinical ly effective in the therapy of osteoarthritis providing a magnitude of effect comparable to that of the maximum recommended daily dose of diclofenac . The onset of clinical benefit with etoricoxib on day one is more rapid than that of diclofenac . Both drugs were generally well tolerated OBJECTIVE To compare the efficacy of the cyclooxygenase 2 (COX-2)-specific inhibitors celecoxib and rofecoxib in treating the signs and symptoms of  osteoarthritis ( OA ) . METHODS In this r and omized , placebo-controlled , double-blind , multicenter study , 475 patients with OA of the knee received either celecoxib 200 mg/day ( n = 189 ) , rofecoxib 25 mg/day ( n = 190 ) , or placebo ( n = 96 ) for 6 weeks . Arthritis assessment s were performed at baseline , week 3 , and week 6 ( or at the time of early termination ) . RESULTS In primary measures of efficacy ( OA pain score on a 100-mm visual analog scale [ VAS ] and total domain score on the Western Ontario and McMaster Universities Osteoarthritis Index ) , celecoxib 
    Output:
    
The overall risk of MI with NSAIDs and cyclo-oxygenase-2-specific drugs was small ; rofecoxib showed the highest risk .
There was an increased MI risk with cyclo-oxygenase-2-specific drugs compared with NSAIDs , but less serious upper gastrointestinal toxicity