***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 assess the efficacy of glucosamine sulfate in knee osteoarthritis ( OA ) . METHODS A 4-center , 6-month , r and omized , double-blind , placebo-controlled glucosamine discontinuation trial was conducted in 137 current users of glucosamine with knee OA who had experienced at least moderate improvement in knee pain after starting glucosamine .  Study medication dosage was equivalent to the dosage of glucosamine taken prior to the study ( maximum 1,500 mg/day ) . Followup continued for 6 months or until disease flare , whichever occurred first . The primary outcome was the proportion of disease flares in the glucosamine and placebo groups using an intent-to-treat analysis . Secondary outcomes included time to disease flare ; analgesic medication use ; severity of disease flare ; and change in pain , stiffness , function and quality of life in the glucosamine and placebo groups . RESULTS Disease flare was seen in 28 ( 42 % ) of 66 placebo patients and 32 ( 45 % ) of 71 glucosamine patients ( difference -3 % ; 95 % confidence interval [ 95 % CI ] -19 , 14 ; P = 0.76 ) . In the Cox regression analysis , after adjustment for sex , study site , and OA radiographic severity , time to disease flare was not significantly different in the glucosamine compared with placebo group ( hazard ratio of flare = 0.8 ; 95 % CI 0.5 , 1.4 ; P = 0.45 ) . At final study visit ,  acetaminophen  was used in 27 % and 21 % of placebo and glucosamine patients , respectively ( P = 0.40 ) , nonsteroidal antiinflammatory drugs were used in 29 % and 30 % ( P = 0.92 ) , and both were used in 20 % and 21 % ( P = 0.84 ) . No differences were found in severity of disease flare or other secondary outcomes between placebo and glucosamine patients . CONCLUSION In patients with knee OA with at least moderate subjective improvement with prior glucosamine use , this study provides no evidence of symptomatic benefit from continued use of glucosamine sulfate ABSTRACT Objectives : Overview of three dose-response studies demonstrating the efficacy of lumiracoxib , a novel COX-2 selective inhibitor , for  chronic pain associated with osteoarthritis ( OA ) , or rheumatoid arthritis ( RA ) and acute pain following dental extraction . Methods : OA and RA : 4-week , r and omized , placebo- and active-controlled studies of similar design . Patients ( OA , n = 583 ; RA , n = 571 ) received lumiracoxib 50 mg , 100 mg or 200 mg twice daily ( bid ) , lumiracoxib 400 mg once daily ( od ) , diclofenac 75 mg bid or placebo . Dental : 12-h , single-center , r and omized , placebo- and active-controlled study . Patients ( n = 202 ) received single oral doses of lumiracoxib 100 mg or 400 mg , ibuprofen 400 mg or placebo . Main outcome measures : OA : pain intensity ( PI ) in the target joint ( visual analogue scale [ VAS ] ) and WOMAC score at Week 4 ; RA : overall PI ( VAS ) and ACR20 response at Week 4 ; Dental : difference ( PID , categorical and VAS ) score over 12 h post dose , time to onset of analgesia . Results : Throughout the OA study , all lumiracoxib doses provided superior reductions in PI versus placebo and at Week 4 , all lumiracoxib doses provided efficacy similar to each other and to diclofenac . In the RA study , lumiracoxib 100 mg bid , 200 mg bid and 400 mg od were significantly better than placebo in PI at Weeks 1 and 2 ( all p < 0.05 ) but demonstrated borderline significance at Week 4 ( lumiracoxib 400 mg od , p = 0.06 ) . In pain following dental surgery , PID scores for both lumiracoxib doses were superior to placebo from 1.5 h onwards and always comparable , or superior , to ibuprofen . Lumiracoxib 400 mg had the fastest onset of analgesia , measured as median time to confirmed first perceptible pain relief using the two-stopwatch method ( 37.4 min , superiority versus placebo , p < 0.001 ) . Lumiracoxib was well tolerated in all studies . Conclusions : These studies provide initial evidence that lumiracoxib is an effective , well-tolerated agent for the treatment of chronic and acute pain BACKGROUND In a flare of osteoarthritis ( OA ) pain , increasing the dose of st and ard anti-inflammatory or routine analgesic drugs may not be practical because of an increased incidence of side effects . In patients achieving inadequate pain relief from traditional non-steroidal anti-inflammatory drugs ( NSAIDs ) or cyclooxygenase (COX)-2-selective inhibitors , it may be appropriate to add an analgesic agent with a different mechanism of action , thereby targeting multiple components of the pain pathway . OBJECTIVE The addition of tramadol/acetaminophen tablets to existing therapy was compared with the addition of placebo in the treatment of OA flare pain . METHODS This was a multicenter , outpatient , r and omized , double-blind , placebo-controlled , parallel-group , add-on study . Patients received 1 or 2 tramadol/acetaminophen ( 37.5 mg/325 mg ) tablets QID or matching placebo for 10 days in addition to ongoing NSAID or COX-2-selective inhibitor therapy . The primary outcome measures were average daily pain intensity and average daily pain relief scores from days 1 through 5 . RESULTS Three hundred eight patients were r and omized to tramadoUacetaminophen ( n = 197 ) or placebo ( n = 111 ) and were followed for up to 10 days . Patients had a mean ( + /-SD ) age of 60.1 + /- 9.87 years , and were predominantly female ( 71.8 % ) and white ( 87.7 % ) . Their mean ( + /- SD ) pain visual analog score at baseline was 73.2 + /- 11.8 mm , and their mean pain intensity score was 2.4 + /- 0.5 ( on a scale from 0 = none to 3 = severe ) . Average daily pain intensity and pain relief scores were significantly improved with tramadol/acetaminophen compared with placebo on the primary assessment of efficacy from days 1 through 5 ( both , P < 0.001 ) and on the assessment of efficacy from days I through 10 ( both , P < 0.001 ) Tramadol/acetaminophen was significantly superior to placebo on the patients ' and physicians ' overall assessment s of medication ( both , P < 0.001 ) and on 3 of 4 subscales ( pain [ P = 0.004 ] , physical function [ P = 0.013 ] , and overall [ P = 0.008 ] ) of the Western Ontario and McMaster Universities Osteoarthritis Index Question naire . The most common treatment-emergent adverse events with tramadol/acetaminophen were nausea , vomiting , and dizziness . No serious adverse events were reported in the tramadol/acetaminophen group . CONCLUSION In this study , addition of tramadol/acetaminophen to NSAID or COX-2-selective inhibitor therapy was well tolerated and effective in the treatment of OA flare pain Background While knee osteoarthritis ( OA ) is characterised as a slowly progressive disease , acute flares , episodes of severe pain , and substantial fluctuations in pain intensity appear to be part of the natural history for some patients . We sought to estimate what proportion of symptomatic community-dwelling adults might be affected , and to identify patient and problem characteristics associated with higher risk of such variability in pain . Methods We analysed data collected at baseline , 18 , 36 , 54 , and 72 month follow-up of a prospect i ve cohort of symptomatic adults aged over 50 years with current/recent knee pain . At each time point we estimated the proportion of participants reporting ' significant pain variability ' ( defined as worst pain intensity in the past 6 months ≥5/10 and ≥2 points higher than average pain intensity during the same 6-month period ) . The associations between significant pain variability and demographic , socioeconomic , lifestyle , clinical , radiographic , and healthcare utilisation factors measured at baseline were estimated by adjusted odds ratios and 95 % confidence intervals ( aOR ; 95%CI ) from multivariable discrete-time survival analysis . Results Seven hundred and nineteen participants were included in the final analysis . At each time point , 23–32 % of participants were classed as reporting significant pain variability . Associated factors included : younger age ( aOR ( per year ) : 0.96 ; 95 % CI 0.94 , 0.97 ) , higher BMI ( per kg/m2:1.03 ; 1.01 , 1.06 ) , higher WOMAC Pain score ( per unit : 1.06 ; 1.03 , 1.10 ) , longer time since onset ( e.g. 1–5 years vs < 1 year : 1.79 ; 1.16 , 2.75 ) and morning stiffness ( ≤30 min vs none : 1.43 ; 1.10 , 1.85 ) . The models accounting for multiple periods of significant symptom variability found similar associations . Conclusions Our findings are consistent with studies showing that , for some patients OA symptoms are significantly variable over time . Future prospect i ve studies on the nature and frequency of flare ups are needed to help determine triggers and their underlying pathophysiology in order to suggest new avenues for effective episode management of OA to complement long-term behaviour change BACKGROUND Nonsteroidal anti-inflammatory drugs ( NSAIDs ) inhibit both cyclooxygenase-1 ( COX-1 ) and cyclooxygenase-2 ( COX-2 ) . It is not known whether a specific inhibitor of COX-2 will provide efficacy in osteoarthritis ( OA ) comparable with NSAIDs . Therefore , we compared the efficacy and safety of the rofecoxib , which specifically inhibits COX-2 , with those of the NSAID ibuprofen in patients with OA . OBJECTIVE To compare the clinical efficacy and tolerability of rofecoxib ( 12.5 and 25 mg once daily ) with ibuprofen ( 800 mg 3 times daily ) . METHODS A r and omized , double-blind trial of 809 adults with OA was conducted . Patients with OA in whom the knee or hip was the primary source of pain were r and omized to 1 of 4 treatment groups on demonstration of disease activity : placebo ; rofecoxib , 12.5 or 25 mg once daily ; or ibuprofen , 800 mg 3 times daily . Clinical efficacy and safety were monitored during a 6-week treatment period . RESULTS Both doses of rofecoxib demonstrated efficacy clinical ly comparable with ibuprofen as assessed by 3 primary end points ( pain walking on a flat surface [ Western Ontario and McMaster Universities Osteoarthritis Index ] , patient global assessment of response to therapy , and investigator global assessment of disease status ) according to predefined comparability criteria . Both rofecoxib doses and the ibuprofen dose provided significantly ( P<.001 ) greater efficacy than placebo on all primary end points . Results from secondary end points were consistent with those of the primary end points . All treatments were well tolerated ; the overall incidence rates of clinical adverse experiences were not significantly different ( P>.05 ) among the treatment groups . CONCLUSION Rofecoxib was well tolerated and provided clinical efficacy comparable with a high dose of the NSAID ibuprofen OBJECTIVE The aim of this study was to evaluate the effect of ibuprofen on the urinary excretion of C-terminal crosslinking telopeptide of type II collagen ( CTX-II ) and urinary glucosyl galactosyl pyridinoline ( Glc-Gal-PYD ) , two new molecular markers of cartilage and synovial tissue metabolism , respectively , in patients with knee osteoarthritis ( OA ) . METHODS We studied 201 patients with knee pain and radiographic evidence of knee OA who were on treatment with non-steroidal anti-inflammatory drugs ( NSAIDs ) prior to study initiation . After an initial screening visit , patients were withdrawn from their pre- study NSAID and , following a flare of their OA symptoms , were r and omised to ibuprofen ( 2400 mg/day ) or placebo .  Urinary CTX-II and Glc-Gal-PYD levels were measured at time of r and omisation ( baseline ) and after 4 - 6 weeks of treatment . RESULTS After 4 to 6 weeks , urinary CTX-II ( + 17 % , p = 0.023 ) and Glc-Gal-PYD ( + 10 % , p = 0.020 ) increased significantly from baseline in the placebo group whereas marginal or no increase was observed in the ibu 
    Output:
    
The concept of OA flare appears in the medical literature but most often in the context of flare design trials ( pain increases observed after stopping usual treatment ) .