***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: Etodolac , a new anti-inflammatory analgesic drug found to be effective in treating arthritis in a dose range of 100 to 300 mg bid , has been shown to induce significantly less gastrointestinal microbleeding in normal men than several other NSAIDs . In this study , the effect on gastrointestinal blood loss of highdose etodolac , 300 and 500 mg bid , versus piroxicam at its normal therapeutic dose of 20 mg qd , was investigated by the 51Cr method in 23 men with osteo- or rheumatoid arthritis .  Placebo periods preceded and followed 28 days of active drug treatment . Blood and stool analyses were performed by an analyst not aware of drug assigment or study design . Patients receiving piroxicam , but not those receiving either dose of etodolac , had a significantly higher mean level of fecal blood loss in the active treatment phase compared with the pretreatment placebo level ( p < 0.01 ) . Further , microbleeding was significantly greater for the piroxicam group during treatment than for either of the etodolac groups ( p < 0.01 ) . There were no significant differences in fecal blood loss between the two groups receiving etodolac compared with pretreatment . Even at doses two to three times those found effective in the treatment of arthritis , etodolac produces no increase in fecal blood loss , in contrast to blood loss seen with the recommended dose of piroxicam .  Fecal blood loss in osteoarthritic patients , not receiving an NSAID , was similar to normal subjects in previous studies Summary The efficacy and safety of a sustained-release ( SR ) formulation of etodolac were compared with those of conventional etodolac in two separate , r and omized , double-blind , multicenter , 6-week trials . This report presents an interim analysis of the data from these studies . One study included 174 patients with rheumatoid arthritis ( RA ) : 58 received etodolac SR 400 mg once daily ( q.d . ) , 59 received etodolac SR 600 mg q.d . , and 57 received etodolac 200 mg twice daily ( b.i.d . ) . The second study included 230 patients with osteoarthritis ( OA ) : 80 patients received etodolac SR 400 mg q.d . , 76 received etodolac SR 600 mg q.d . , and 74 received etodolac 300 mg b.i.d . Efficacy was evaluated by physician 's global and patient 's global assessment s ( both studies ) , number of painful joints ( RA study ) , number of swollen joints ( RA study ) , pain intensity ( OA study ) , and weight-bearing pain ( OA study ) . The interim analyses of the data from the studies indicates that all three regimens produced significant improvements from baseline in all mean efficacy values at each assessment ; there were no significant differences between the treatment groups . The incidence of study events , except for dyspepsia , was comparable among the treatment groups in each study ; dyspepsia occurred at a significantly lower rate in patients treated with etodolac SR than in patients treated with the conventional formulation of etodolac . We conclude that etodolac SR is as effective and safe as conventional etodolac for the treatment of patients with RA or OA Nonselective nonsteroidal anti-inflammatory agents have been shown to attenuate the antihypertensive efficacy of ACE inhibitors with average increases in systolic blood pressure ( BP ) of 5 to 10 mm Hg . Less is known about the specific cyclooxygenase-2 ( COX-2 ) inhibitors now widely used for the treatment of arthritis . The objective of this study was to determine the effects of celecoxib compared with placebo on 24-hour BP levels in ACE inhibitor-treated patients with hypertension . This was a r and omized , double-blind , placebo-controlled , parallel-group clinical trial involving 178 men and women ( mean age , 53 years ) with essential hypertension who were treated and controlled with lisinopril monotherapy ( 10 to 40 mg daily ) .  Baseline BP values were obtained using 24-hour ambulatory recordings . Patients received either celecoxib , 200 mg twice daily ( twice the recommended dose for osteoarthritis ) ( n=91 ) , or placebo ( n=87 ) for 4 weeks , and changes in the 24-hour BP , body weight , and clinical laboratory parameters were assessed . Mean changes from baseline in the 24-hour systolic and diastolic BP were 2.6/1.5±0.9/0.6 mm Hg on celecoxib versus 1.0/0.3±1/0.6 mm Hg on placebo ( P = 0.34 for systolic BP;P = 0.45 for diastolic BP ) . The proportion of patients whose 24-hour BP increased by at least 5 , 10 , 15 , or 20 mm Hg were also similar on celecoxib and placebo . No changes in body weight , serum creatinine , or potassium occurred in either group . Thus , these data demonstrate that high doses of celecoxib have no significant effect on the antihypertensive effect of the ACE inhibitor lisinopril . The placebo-subtracted changes observed in 24-hour BP ( 1.6/1.2 mm Hg ) are less than what has been reported for nonselective nonsteroidal anti-inflammatory agents in ACE inhibitor-treated patients The effects of the new cyclooxygenase (COX)-2 selective inhibitor , valdecoxib ( 40 mg bid ; n = 17 ) , on platelet function were evaluated , along with ibuprofen ( 800 mg tid ; n = 15 ) and placebo ( n = 15 ) , in healthy elderly subjects ( 65 - 85 years ) in this 7.5-day , r and omized , single-center , double-blind study . Platelet aggregation ( to sodium arachidonate , collagen , and adenosine diphosphate ) , bleeding time , and serum thromboxane B2 ( TxB2 ) concentrations were measured up to 8 hours postdose on Days 1 and 8 . Valdecoxib had no platelet effects , while ibuprofen significantly decreased platelet aggregation , significantly increased bleeding time ( 2 - 4 h postdose on each day ) , and significantly decreased TxB2 levels at all time points . In conclusion , unlike ibuprofen , valdecoxib 40 mg bid spares platelet COX-1 function in healthy elderly subjects .  Valdecoxib 's lack of effect on platelet aggregation and bleeding time suggests that it will have an improved clinical profile over nonselective NSAIDs , particularly in patients for whom bleeding complications are a concern BACKGROUND Nonsteroidal anti-inflammatory drugs are the most widely used agents in the symptomatic treatment of osteoarthritis ( OA ) . No data are presently available on the medium-term management of this disease with an on-dem and treatment regimen , which nevertheless reflects medical practice . OBJECTIVES The aim of this study was to compare nimesulide-beta-cyclodextrin and naproxen in terms of short-term ( 2 weeks ) pain control with scheduled dosing and medium-term ( 5.5 months ) pain control with on-dem and dosing in patients with OA . METHODS In this multicenter , r and omized , double-blind , controlled study , we compared 2 weeks of scheduled treatment plus 5.5 months of on-dem and treatment in patients with OA of the hip and /or knee and moderate to severe pain , with no important concomitant disorders . Treatment consisted of nimesulide-beta-cyclodextrin ( 400 mg BID , orally = 100 mg nimesulide BID ) or naproxen ( 500 mg BID ) . The primary outcome measures for scheduled dosing were pain on movement ( measured by visual analog scale ) , morning stiffness score , Lequesne index , and adverse events . For on-dem and dosing , the measures were the same as for scheduled dosing , plus duration of treatment and global assessment of efficacy and tolerability by patient and physician . RESULTS After 2 weeks , there was equivalent reduction from baseline in pain on movement in the 2 treatment groups ( nimesulide-beta-cyclodextrin , -41.5 % ; naproxen , -40.5 % ) ; the reduction was significant after 1 week ( P < 0.001 ) . The findings were also similar for the morning stiffness score and Lequesne index . There were no significant differences in mean duration of on-dem and treatment  ( nimesulide-beta-cyclodextrin , 163.03 days ; naproxen , 166.3 days ) or in mean consumption of study drug  ( nimesulide-beta-cyclodextrin , 0.85 + /- 0.61 sachets/d ; naproxen , 0.74 + /- 0.42 sachets/d ) . Withdrawal due to intolerance occurred in 8 patients given nimesulide-beta-cyclodextrin and 13 patients given naproxen , with no significant difference between groups ; 3 and 12 patients , respectively , withdrew due to gastrointestinal intolerance , a finding that was significantly different between groups ( P < 0.01 ) . Global assessment of efficacy by patient and physician was similar for both drugs . Assessment of tolerability significantly favored nimesulide-beta-cyclodextrin on the physician assessment s ( P < 0.05 ) but was similar for the 2 drugs on the patient assessment s ( physicians , 46.9 % vs 30.9 % ; patients , 43.5 % vs 33.3 % ) . CONCLUSIONS The results suggest that nimesulide-beta-cyclodextrin provides similar pain relief to naproxen in the management of OA of the hip and /or knee and is associated with fewer gastrointestinal adverse reactions . On-dem and dosing may be an effective and well-tolerated low-dose regimen of nonsteroidal anti-inflammatory drugs for the maintenance of pain control in OA in the medium term A prospect i ve , open trial to evaluate the safety and efficacy of oral meloxicam 7.5 mg once daily over a period of 28 days in Thai patients with osteoarthritis was conducted in 3 major hospitals in Bangkok , Thail and . A total of 137 patients were enrolled and completed the study protocol . The mean age of the patients was 57.6 years and 88 per cent were female .  Pain on movement and pain at rest evaluated after treatment by visual analog scale ( VAS ) were significantly improved with respect to the baseline status ( p<0.001 ) . The final efficacy was reported as satisfactory or good in 97 per cent and 94 per cent as determined by patients and physicians respectively . Patient status evaluated at the end of the study reported improvement of their arthritic condition in 84 per cent . Drug tolerability assessed by patients and physicians and was good or satisfactory in 99 per cent and 98 per cent . GI adverse event was reported in 8.8 per cent . Other adverse events were itching/rash in 2.0 per cent and headache/insomnia in 1.5 per cent of patients . No patients withdrew from the study due to adverse events . No GI bleeding or perforation were observed . No hospitalization was observed during the study . There was no significant change of blood chemistry and hematological profile between pre and post treatment examination . Results from this study suggest that oral meloxicam 7.5 mg for 28 days is a safe and effective treatment regimen with high GI tolerability profile for the treatment of osteoarthritis in Thai patients The aim of the study was to assess the efficacy , tolerability and chondroprotection afforded by nimesulide , a selective cyclooxygenase-2 inhibitor and piroxicam in a r and omised , double blind , controlled clinical trial in 90 patients suffering from osteoarthritis of the knee joint . A significant improvement in the osteoarthritis severity index at 2 weeks ( p < 0.01 ) and an improvement in physicians assessment of global arthritic condition at 4 weeks ( p < 0.01 ) was seen with both the treatments . A significant decrease in articular index of joint tenderness ( p < 0.05 ) at 8 weeks and in self assessment of h and icap at 4 weeks ( p < 0.05 ) , in comparison to baseline , was observed only in patients receiving nimesulide .  Rescue therapy was required by a greater percentage of patients being administered piroxicam .  Functional capacity improved in 64 % of the patients on nimesulide and 74.5 % of the patients receiving piroxicam .  Adverse effects were observed in 6 patients on nimesulide and 9 patients receiving piroxicam . No significant difference was found in any of the efficacy and tolerability parameters between the two treatment groups . Magnetic resonance imaging evaluation of the knee joint of 10 patients showed no significant change in the articular cartilage and associated joint structures after 6 months of therapy with both the treatments . The results show that nimesulide and piroxicam are comparable in efficacy and tolerability in patients suffering from osteoarthritis Abstract : Objective : This double-blind , r and omised trial compared the efficacy and safety of meloxicam vs piroxicam in patients with soft-tissue rheumatism of the shoulder.¶Subjects : 599 out patients at 88 centres in 9 countries.¶Treatment and Methods : Oral meloxic 
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In the RCTs that included direct COX-2 comparisons , the drugs were equally tolerated and of equal efficacy .
Using the simpler AGM , with ibuprofen or diclofenac alone as the comparator , all of the COX-2 products are associated with higher costs ( i.e. positive incremental costs ) and small increases in effectiveness ( i.e. positive incremental effectiveness ) , measured in terms of QALYs .
The magnitude of the incremental costs and the incremental effects , and therefore the incremental cost-effectiveness ratios , vary considerably across all COX-2 selective NSAIDs .
When the simpler AGM was run using ibuprofen or diclofenac combined with proton pump inhibitor ( PPI ) as the comparator , the results change substantially , with the COX-2 selective NSAIDs looking generally unattractive from a cost-effectiveness point of view ( COX-2 selective NSAIDs were dominated by ibuprofen or diclofenac combined with PPI in most cases ) .
This applies both to ' st and ard ' and ' high-risk ' arthritis patients defined in terms of previous GI ulcers .
The full AGM produced results broadly in line with the simpler model .
The COX-2 selective NSAIDs examined were found to be similar to non-selective NSAIDs for the symptomatic relief of RA and OA and to provide superior GI tolerability ( the majority of evidence is in patients with OA ) .
Although COX-2 selective NSAIDs offer protection against serious GI events , the amount of evidence for this protective effect varied considerably across individual drugs .
The volume of trial evidence with regard to cardiovascular safety also varied substantially between COX-2 selective NSAIDs .
Increased risk of MI compared to non-selective NSAIDs was observed among those drugs with greater volume of evidence in terms of exposure in patient-years .
Economic modelling shows a wide range of possible costs per QALY gained in patients with OA and RA .
Costs per QALY also varied if individual drugs were used in ' st and ard ' or ' high'-risk patients , the choice of non-selective NSAID comparator and whether that NSAID was combined with a PPI .