***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 Glucosamine and chondroitin sulfate are used to treat osteoarthritis . The multicenter , double-blind , placebo- and celecoxib-controlled Glucosamine/chondroitin Arthritis Intervention Trial ( GAIT ) evaluated their efficacy and safety as a treatment for knee pain from osteoarthritis . METHODS We r and omly assigned 1583 patients with symptomatic knee osteoarthritis to receive 1500 mg of glucosamine daily , 1200 mg of chondroitin sulfate daily , both glucosamine and chondroitin sulfate , 200 mg of celecoxib daily , or placebo for 24 weeks . Up to 4000 mg of acetaminophen daily was allowed as rescue analgesia . Assignment was stratified according to the severity of knee pain ( mild [ N=1229 ] vs. moderate to severe [ N=354 ] ) . The primary outcome measure was a 20 percent decrease in knee pain from baseline to week 24 . RESULTS The mean age of the patients was 59 years , and 64 percent were women . Overall , glucosamine and chondroitin sulfate were not significantly better than placebo in reducing knee pain by 20 percent . As compared with the rate of response to placebo ( 60.1 percent ) , the rate of response to glucosamine was 3.9 percentage points higher ( P=0.30 ) , the rate of response to chondroitin sulfate was 5.3 percentage points higher ( P=0.17 ) , and the rate of response to combined treatment was 6.5 percentage points higher ( P=0.09 ) . The rate of response in the celecoxib control group was 10.0 percentage points higher than that in the placebo control group ( P=0.008 ) . For patients with moderate-to-severe pain at baseline , the rate of response was significantly higher with combined therapy than with placebo ( 79.2 percent vs. 54.3 percent , P=0.002 ) . Adverse events were mild , infrequent , and evenly distributed among the groups . CONCLUSIONS Glucosamine and chondroitin sulfate alone or in combination did not reduce pain effectively in the overall group of patients with osteoarthritis of the knee . Exploratory analyses suggest that the combination of glucosamine and chondroitin sulfate may be effective in the subgroup of patients with moderate-to-severe knee pain . ( Clinical Trials.gov number , NCT00032890 . ) Background The heterogeneity statistic I2 , interpreted as the percentage of variability due to heterogeneity between studies rather than sampling error , depends on precision , that is , the size of the studies included . Methods Based on a real meta- analysis , we simulate artificially ' inflating ' the sample size under the r and om effects model . For a given inflation factor M = 1 , 2 , 3 , ... and for each trial i , we create a M-inflated trial by drawing a treatment effect estimate from the r and om effects model , using si2MathType@MTEF@5@5@+=feaagaart1ev2aaatCvAUfKttLearuWrP9MDH5MBPbIqV92AaeXatLxBI9gBaebbnrfifHhDYfgasaacPC6xNi = xH8viVGI8Gi = hEeeu0xXdbba9frFj0xb9qqpG0dXdb9aspeI8k8fiI+fsY = rqGqVepae9pg0db9vqaiVgFr0xfr = xfr = xc9adbaqaaeGaciGaaiaabeqaaeqabiWaaaGcbaGaem4Cam3aa0baaSqaaiabdMgaPbqaaiabikdaYaaaaaa@2FBE@/M as within-trial sampling variance . Results As precision increases , while estimates of the heterogeneity variance τ2 remain unchanged on average , estimates of I2 increase rapidly to nearly 100 % . A similar phenomenon is apparent in a sample of 157 meta-analyses . Conclusion When deciding whether or not to pool treatment estimates in a meta- analysis , the yard-stick should be the clinical relevance of any heterogeneity present . τ2 , rather than I2 , is the appropriate measure for this purpose OBJECTIVE This study compared the efficacy and tolerability of a once-daily controlled-release formulation of hydromorphone ( OROS ) hydromorphone , Janssen-Cilag , Beerse , Belgium ) and twice-daily extended-release ( ER ) oxycodone in patients with chronic , moderate to severe osteoarthritis ( OA ) pain .  OROS hydromorphone is currently available only in Europe . METHODS Adults who met American College of Rheumatology clinical criteria for OA of the knee or hip with moderate to severe mean daily pain intensity despite chronic use of stable doses of NSAIDs or other nonsteroidal , nonopioid therapies were eligible for participation in this r and omized , open-label study . The study consisted of a 14-day dose-titration and stabilization phase and a 28-day maintenance phase . OROS hydromorphone and ER oxycodone were initiated at dosages of 8 mg QD and 10 mg BID , respectively . Patients maintained diaries in which they rated their pain ( from 0 = none to 3 = severe ) and pain relief ( from 0 = no relief to 4 = complete relief ) . Other assessment s completed every 14 days included patient and investigator global evaluations of treatment effectiveness ( scale from 1 = poor to 5 = excellent ) , the Western Ontario and McMaster Universities ( WOMAC ) Osteoarthritis Index , and the Medical Outcomes Study ( MOS ) Sleep Scale . Adverse events ( whether observed by study personnel , identified in response to question ing , or spontaneously reported ) and vital signs were monitored throughout the study . The primary efficacy measures were the mean pain relief score at end point and the time from initiation of treatment to the third day of moderate to complete pain relief , as reported in the patient diary . Noninferiority analyses were conducted on all primary and secondary efficacy variables . RESULTS One hundred thirty-eight patients ( 71 OROS hydromorphone , 67 ER oxycodone ) received treatment ( safety population ) , and 83 ( 60.1 % ) completed the study . Data from 124 patients were included in the efficacy analyses ; the majority of these patients were white ( 85.5 % ) and female ( 69.4 % ) , with a mean age of 63.6 years . The most commonly affected joint was the knee ( 79.8 % ) . At end point , the OROS hydromorphone group had a mean pain relief score of 2.3 ( median , 2.0 ) and the ER oxycodone group had a mean pain relief score of 2.3 ( median , 2.3 ) ( 95 % CI , -0.30 to infinity ) . The mean time to the third day of moderate to complete pain relief was 6.2 days ( median , 4.0 ) in the OROS hydromorphone group and 5.5 days ( median , 5.0 ) in the ER oxycodone group ( 95 % CI , -0.31 to infinity ) . Mean pain intensity decreased from baseline to end point by 0.6 point in the OROS hydromorphone group and by 0.4 point in the ER oxycodone group . Mean scores on the patient global evaluation improved by a respective 1.2 and 1.0 points ( median , 1 in both groups ) . Approximately two thirds of patients in each group ( 67.2 % and 66.7 % ) rated the overall effectiveness of treatment as good to excellent at end point . There were no statistically significant differences between groups in total WOMAC scores at end point , and similar improvements from baseline in the WOMAC physical function , stiffness , and pain scales were observed in both groups . Whereas MOS sleep outcomes scores improved from baseline in both groups , OROS hydromorphone was associated with a significantly greater improvement on the MOS Sleep Problems Index I compared with ER oxycodone ( P < 0.045 ) . Adverse events were comparable in both groups ; the most frequently reported adverse events were nausea ( 35.2 % and 29.9 % ) , constipation ( 29.6 % and 25.4 % ) , somnolence ( 25.4 % and 17.9 % ) , vomiting ( 16.9 % and 11.9 % ) , and dizziness ( 14.1 % and 22.4 % ) . Adverse events led to study discontinuation in 35.2 % ( 25/71 ) of patients in the OROS hydromorphone group and 32.8 % ( 22/67 ) in the ER oxycodone group . Discontinuations due to adverse events during the titration phase were numerically greater in the OROS hydromorphone group ( 29.6 % [ 21/71 ] ) than in the ER oxycodone group ( 19.4 % [ 13/67 ] ) . Only 1 serious adverse event ( diarrhea in a patient receiving OROS hydromorphone ) was considered possibly related to study drug . CONCLUSIONS Once-daily OROS hydromorphone and twice-daily ER oxycodone provided similar pain relief in these patients with OA of the knee or hip . The tolerability profiles of the 2 agents were similar We aim ed to evaluate the efficacy and safety of oxycodone/acetaminophen ( O/A ) and codeine/acetaminophen ( C/A ) vs. conventional therapy ( CT ) without opioids in older women suffering from osteoarthritis (OA)-related pain , sub-optimally responsive to prior conventional treatments . We performed a 6 week , r and omized , single blind , controlled study in three nursing homes . We enrolled 154 women with painful OA . They were assigned to treatment with O/A ( n=52 ) and C/A ( n=52 ) vs. CT ( n=50 ) . We evaluated at baseline and at week 6 : average pain in the last week ( mean pain , MeP ) , pain at rest ( RP ) , pain in movement ( MP ) ( numeric rating scale , NRS ) ; depressive symptoms ( Beck Depression Inventory-II , BDI-II ) ; functional status ( activities of daily living , ADL ) and cognitive status ( mini mental state evaluation , MMSE ) . We considered the adverse events ( AEs ) in the study period . At week 6 , MeP , RP and MP were significantly reduced in all three groups ( p<0.001 ) ; compared to CT , O/A and C/A were associated with greater reductions in MeP ( p<0.001 and p=0.004 , respectively ) , in RP ( p=0.028 and p=0.032 , respectively ) in MP ( p<0.001 and p=0.002 , respectively ) and with significant improvement in BDI-II score ( p=0.05 and p=0.04 , respectively ) and ADL value ( p=0.04 and p=0.05 , respectively ) . AE rates did not differ between groups OBJECTIVE Evaluate the long-term safety , tolerability , and efficacy of Remoxy ® ( extended-release oxycodone ) in patients with chronic pain related to osteoarthritis of the hip and /or knee or chronic low back pain . DESIGN Open-label , 12-month , phase 3 trial . SETTING Fifty-nine US sites . PATIENTS Men and women with moderate to severe hip and /or knee pain caused by osteoarthritis or persistent moderate to severe low back pain . INTERVENTION Remoxy 5 mg twice daily , which could be increased in fixed increments up to 80 mg twice daily . OUTCOME MEASURES Safety and tolerability assessment s included adverse events ( AEs ) , laboratory tests , vital signs , physical examinations , and electrocardiograms . Efficacy was assessed through ratings of pain intensity , quality of analgesia , and global assessment of study drug . RESULTS Of the 828 patients enrolled , 823 received ≥1 dose of Remoxy , with 469 exposed for ≥180 days and 381 for ≥358 days . At least one AE was experienced by 678 patients ( 82 % ) , the most common of which were opioid related , including constipation , nausea , and somnolence ; 173 patients ( 21 % ) discontinued treatment because of AEs . No clinical ly relevant changes were seen in other safety assessment s. Mean pain intensity scores decreased significantly from baseline at all time points ( P < 0.001 ) . At month 12 , quality of analgesia and global assessment of study drug were rated positively ( good , very good , or excellent ) by 64 % and 61 % of patients ( last observation carried forward ) , respectively . CONCLUSIONS Long-term treatment with Remoxy was safe , well tolerated , and efficacious in patients with chronic pain related to osteoarthritis of the hip and /or knee or chronic low back pain UNLABELLED ALO-01 ( EMBEDA [ morphine sulfate and naltrexone hydrochloride ] extended-release capsules [ King Pharmaceuticals , Inc , Bridgewater , NJ ] ) , indicated for chronic moderate-to-severe pain , is design ed to release naltrexone upon tampering ( eg , by crushing ) , reducing morphine-induced subjective effects . This multicenter , r and omized , double-blind , crossover study assessed pharmacokinetics , efficacy , and safety of ALO-01 and compared them with extended-release morphine sulfate ( ERMS , KADIAN [ morphine sulfate extended-release ] 
    Output:
    
Adverse events were more frequent in participants receiving opioids compared with control .
The small mean benefit of non-tramadol opioids are contrasted by significant increases in the risk of adverse events .