***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: OBJECTIVE To compare the efficacy and safety of celecoxib , a cyclooxygenase-2 ( COX-2 ) inhibitor , with those of naproxen , a nonsteroidal anti-inflammatory drug ( NSAID ) , and placebo in the treatment of osteoarthritis of the knee . METHODS In this multicenter , r and omized , double-blind , placebo-controlled trial , 1003 patients with symptomatic osteoarthritis of the knee were r and omly assigned to receive celecoxib at doses of 50 , 100 , or 200 mg twice a day ; naproxen , 500 mg twice a day ; or placebo for 12 weeks . Patients were evaluated with st and ard measures of efficacy 2 to 7 days after discontinuing previous NSAID or analgesic therapy and after 2 , 6 , and 12 weeks of treatment with the study drug . RESULTS Celecoxib treatment led to significant improvement in the signs and symptoms of osteoarthritis as determined by all efficacy measures . Significant pain relief occurred within 2 days of the initiation of treatment , and maximum anti-inflammatory and analgesic activity , evident within 2 weeks , was sustained throughout the 12-week study . All celecoxib doses were efficacious compared with placebo , although the 50-mg twice-daily dosage regimen was minimally effective . The higher doses of celecoxib ( 100 and 200 mg twice a day ) were similarly efficacious , and the magnitude of improvement observed with these dosing regimens was comparable to that seen with naproxen at a dose of 500 mg twice a day . All doses of celecoxib and naproxen were well tolerated . CONCLUSION COX-2 inhibition with celecoxib is an effective approach for the treatment of osteoarthritis , as seen by clinical improvement in signs and symptoms comparable to treatment with naproxen One hundred subjects with arthritis were r and omized into lay-taught , or professional-taught 12-h arthritis self-management courses , or a control group .  Outcomes , knowledge , exercise , relaxation , disability , pain , and number of physician visits were measured aat baseline and 4 months . Professional-taught groups demonstrated greater knowledge gain while lay-taught groups had greater changes in relaxation ( p less than .01 ) and a tendency toward less disability . Although it is impossible to draw definitive conclusions , this study suggests that lay leaders can teach arthritis self-management courses with results similar to those achieved by professionals 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 - Approximately 14 million patients in the United States regularly take nonsteroidal anti-inflammatory drugs(NSAIDs ) for various types of arthritis [ 1 ] for relief of pain , stiffness , and other symptoms . However , these benefits are obtained at a price . Use of NSAIDs is associated with various gastrointestinal side effects . Minor side effects such as nausea , dyspepsia , anorexia , abdominal pain , flatulence , and diarrhea may affect 10 % to 60 % of patients [ 2 ] . Symptomatic ulcers and potentially life-threatening ulcer complications such as upper gastrointestinal bleeding , perforation , and gastric outlet obstruction are reported in 2 % to 4 % of patients who take NSAIDs for a year [ 3 ] . The chance of hospitalization or death from a gastrointestinal adverse event is 1.3 % to 1.6 % per year in patients with rheumatoid arthritis [ 4 ] . These infrequent but potentially serious gastrointestinal side effects of NSAIDs have become a major health care problem because of the many patients at risk [ 5 ] . General physicians and rheumatologists caring for patients with symptoms of chronic arthritis may be reluctant to ab and on using NSAIDs , which help most of these patients , in order to protect the few who may develop serious complications from use of these drugs . On the other h and , gastroenterologists see fewer patients for arthritis but many with serious gastrointestinal complications . Life-threatening events such as perforation or serious hemorrhage from NSAID-induced ulcers , which often develop with little or no warning [ 6 ] , are a real problem because of the many patients at risk . Various agents have been used in attempts to reduce the incidence of NSAID-induced gastrointestinal lesions . In one endoscopic study , cimetidine at a dose of 300 mg four times a day showed no benefit in healing NSAID-related lesions compared with placebo , and 400 mg at bedtime provided no benefit in preventing these lesions compared with placebo [ 7 ] . Antacids ( magnesium-aluminum hydroxide , 10 to 20 mL as needed to a dose as high as 60 mL daily ) and sucralfate have recently been reported to reduce dyspeptic symptoms in arthritic patients receiving NSAIDs in whom gastropathic lesions ( but not ulcers ) were shown endoscopically [ 8 , 9 ] . The surface-active antiulcer drug sucralfate was ineffective in preventing ulcers in persons receiving NSAIDs [ 10 , 11 ] , and the histamine-2-receptor antagonist ranitidine did not prevent gastric ulcers but did reduce the frequency of duodenal ulcers [ 12 , 13 ] . Results of preliminary studies indicate that the effects of omeprazole parallel those of ranitidine [ 14 ] . A recent study [ 15 ] in achlorhydric patients showed that NSAID-induced ulcers develop in the absence of gastric acid . In contrast , several clinical trials have shown that the incidence of endoscopically visible erosions and ulcers associated with NSAID use can be reduced by cotherapy with the synthetic prostagl and in misoprostol [ 16 - 19 ] . However , it was not proved that preventing endoscopic lesions would prevent clinical ly serious complications of NSAID-induced gastrointestinal ulcers [ 20 ] . Our objective was to determine whether concurrent therapy with misoprostol reduces the incidence of serious upper gastrointestinal complications in older patients with chronic rheumatoid arthritis who are taking NSAIDs .  Because most patients taking NSAIDs do not routinely have endoscopy , we investigated the incidence of these complications during clinical care as actually practice d. A second goal was to better define which patients were at increased risk for development of serious NSAID-induced upper gastrointestinal complications . Methods Patients Ambulatory patients at least 52 years of age who had chronic rheumatoid arthritis , defined by American College of Rheumatology criteria [ 21 ] , and who were expected to be taking 1 of 10 specified NSAIDs at predefined minimum doses for 6 months were sought from practice s of family medicine , internal medicine , or rheumatology . Of these practice s , 661 in the United States and 3 in Canada enrolled at least one patient between July 1991 and August 1993 . For all patients , a medical history was elicited , a physical examination was done , and a modified Health Assessment Question naire that included eight items on activities of daily living was administered [ 22 ] . Patients were excluded if they had had active peptic ulcer disease within 30 days of study enrollment ; were taking or expected to need antiulcer medication ( histamine-2 blockers , sucralfate , omeprazole ) or any experimental medication during the study ; had the Zollinger-Ellison syndrome , pyloric or duodenal obstruction , previous gastric resection or vagotomy , gastroesophageal reflux disease , varices , or cirrhosis ; had a history of inflammatory bowel disease , upper gastrointestinal tract malignancies , hepatitis , alcoholism , or bleeding diathesis ; were estimated to have a life expectancy of less than 8 months or had do-not-resuscitate status ; were women of child-bearing potential ; or could not tolerate misoprostol or any prostagl and in . The following were the minimum NSAID doses ( mg/d ) allowed : aspirin , 2000 ; diclofenac , 100 ; flurbiprofen , 200 ; ibuprofen , 1200 ; indomethacin , 75 ; ketoprofen , 150 ; naproxen , 750 ; piroxicam , 20 ; sulindac , 200 ; or tolmetin , 1200 . Patients were allowed to receive more than one NSAID . Intervention Eligible patients were r and omly assigned to receive either misoprostol or placebo in the form of 200- micrograms tablets from coded bottles supplied by the manufacturer . Patients were r and omly assigned in blocks of four , so that in each block , half the patients would receive misoprostol and half would receive placebo . Because blocks were assigned to investigators , patients were r and omly assigned within the individual centers . Investigators were not informed about the r and omization procedure but were told only that the study was r and omized and double-blind . Patients were instructed to begin taking half a tablet with meals and at bedtime each day for 10 days and then , if the drug was tolerated , to increase the dose to a whole tablet four times a day for the rest of the study . If the drug was not tolerated , the patients were instructed to reduce the dose back to half a tablet four times a day . Patients could continue therapy with arthritis disease-modifying agents ( such as gold or corticosteroids ) and were allowed to take antacids that did not contain magnesium . Patients purchased their own arthritis medications or antacids and reported their consumption when seen monthly for examination and counts of study medication tablets . Physicians were instructed to watch closely for clinical signs of gastrointestinal bleeding or other possible gastrointestinal complications , to inquire about symptoms , and to investigate suspicious episodes by appropriate clinical procedures . Outcome Measures All suspicious events , regardless of presumed cause , were to be 
    Output:
    
This signsymptom complex is uncommon in uncomplicated osteoarthritis , however , and its presence raises the possibility that the affected joint may be septic .
Patient Education for Prevalent Disease IF a patient COX has had a diagnosis of symptomatic osteoarthritis for 12 months or longer THEN there should be evidence that the patient was offered education regarding the natural history , treatment , and self-management of the disease at least once since the time of diagnosis BECAUSE such education produces improvements in physical functioning and pain .