***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 a single intra-articular injection of triamcinolone hexacetonide ( THA ) in knee osteoarthritis ( OA ) and examine factors which may relate to treatment efficacy . METHODS --Eighty four patients with clinical and radiographic evidence of knee OA were recruited and r and omly allocated to receive either THA ( 20 mg in 1 ml ) or placebo ( 0.9 % normal saline , 1 ml ) . Follow up assessment s evaluated the following outcome variables : patient opinion of overall change in the treated knee , visual analogue pain score ( VAS ) , distance walked in one minute ( WD ) , and Health Assessment Question naire modified for lower limb function ( HAQ ) . RESULTS --Seventy eight percent of THA and 49 % of placebo treated patients reported overall improvement at week 1 ( p < 0.05 ) . At week 6 , improvement was reported in 57 % and 55 % of patient groups , respectively . VAS improved in both groups at week 1 ( THA , p < 0.001 ; placebo , p < 0.05 ) and week 6 ( both p < 0.01 ) . Improvement in VAS was significantly greater among THA treated patients at week 1 only ( p < 0.01 ) . Subgroup analysis of THA treated patients revealed greater improvement in VAS among patients with clinical evidence of an effusion ( p < 0.05 ) , and those who had synovial fluid successfully aspirated at the time of injection ( p < 0.01 ) . WD improved in THA treated patients at week 1 ( p < 0.001 ) , and in both groups at week 6 ( THA , p < 0.001 ; placebo , p < 0.01 ) . Improvements in HAQ were seen in THA patients only at weeks 1 and 6 ( p < 0.05 ) . Regression analysis did not identify any additional clinical , radiographic , or synovial fluid characteristics which influenced the response . CONCLUSIONS --THA provided short term pain relief in knee OA . Increased benefit was associated with both clinical evidence of joint effusion and successful aspiration of synovial fluid at the time of injection We report the results of a double-blind three-centre study , employing a cross-over design , set up to compare the efficacy of intra-articular injections of Myc 2095 ( 20 mg ) , triamcinolone hexacetonide ( Lederspan ) ( 20 mg ) and placebo in 40 patients with synovitis of the knee joint . Each patient included in the study contributed data on 2 of the 3 treatment variables being compared . Seven clinical parameters were assessed every 6 weeks , while the doctor 's and the patient 's assessment s were scored . Intra articular treatment both with Myc 2095 and triamcinolone hexacetonide proved to be effective .  Placebo response was also very high . After the first Myc 2095 injection , improvement in " tenderness " , " pain under load " and " swelling and hydrops " was significantly superior to that following placebo treatment . The evaluation of the second injections indicated a marked carry-over effect from the first course . This was also evident from the doctor 's and patient 's assessment s. The importance of including a placebo in the evaluation of anti-phlogistic drugs in clinical trials , emerged from this study 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 . ) IMPORTANCE Osteoarthritis ( OA ) of the knee is the most frequent form of arthritis and a cause of pain and disability . Combined nonpharmacologic and pharmacologic treatments are recommended as the optimal treatment approach , but no evidence supports the recommendation . OBJECTIVE To assess the clinical benefits of an intra-articular corticosteroid injection given before exercise therapy in patients with OA of the knee . DESIGN , SETTING , AND PARTICIPANTS We performed a r and omized , blinded , placebo-controlled clinical trial evaluating the benefit of intra-articular corticosteroid injection vs placebo injection given before exercise therapy at an OA outpatient clinic from October 1 , 2012 , through April 2 , 2014 . The participants had radiographic confirmation of clinical OA of the knee , clinical signs of localized inflammation in the knee , and knee pain during walking ( score > 4 on a scale of 0 to 10 ) . INTERVENTIONS Participants were r and omly allocated ( 1:1 ) to an intra-articular 1-mL injection of the knee with methylprednisolone acetate ( Depo-Medrol ) , 40 mg/mL , dissolved in 4 mL of lidocaine hydrochloride ( 10 mg/mL ) ( corticosteroid group ) or a 1-mL isotonic saline injection mixed with 4 mL of lidocaine hydrochloride ( 10 mg/mL ) ( placebo group ) . Two weeks after the injections , all participants started a 12-week supervised exercise program . MAIN OUTCOMES AND MEASURES The primary outcome was change in the Pain subscale of the Knee Injury and Osteoarthritis Outcome Score ( KOOS ) question naire ( range , 0 - 100 ; higher scores indicate greater improvement ) at week 14 . Secondary outcomes included the remaining KOOS subscales and objective measures of physical function and inflammation . Outcomes were measured at baseline , week 2 ( exercise start ) , week 14 ( exercise stop ) , and week 26 ( follow-up ) . RESULTS One hundred patients were r and omized to the corticosteroid group ( n = 50 ) or the placebo group ( n = 50 ) ; 45 and 44 patients , respectively , completed the trial . The mean ( SE ) changes in the KOOS Pain subscale score at week 14 were 13.6 ( 1.8 ) and 14.8 ( 1.8 ) points in the corticosteroid and placebo groups , respectively , corresponding to a statistically insignificant mean difference of 1.2 points ( 95 % CI , -3.8 to 6.2 ; P = .64 ) . We found no statistically significant group differences in any of the secondary outcomes at any time point . CONCLUSIONS AND RELEVANCE No additional benefit results from adding an intra-articular injection of 40 mg of corticosteroid before exercise in patients with painful OA of the knee . Further research is needed to establish optimal and potentially synergistic combinations of conservative treatments . TRIAL REGISTRATION clinical trialsregister.eu Identifier : 2012 - 002607 - 18 ; clinical trials.gov Identifier : NCT01945749 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 OBJECTIVES : To show whether intra-articular steroid injections are effective in osteoarthritis ; to determine factors that predict response ; and to determine whether injection has a beneficial effect on muscle strength . METHODS : Double blind , placebo controlled , crossover study in 59 patients with symptomatic osteoarthritis of the knee . Outcome measure- Primary outcome measure : change in visual analogue score for pain at three weeks . Predictors of response analysed using logistic regression with a 15 % decrease in pain score at three weeks defining response . RESULTS : Intra-articular methyl prednisolone acetate produced a significant reduction in visual analogue pain score at three weeks compared to both baseline ( median change -2.0 mm , interquartile range -16.25 to 4.0 ) and placebo ( median 0.0 mm , interquartile range -9.0 to 6.25 ) . No clinical predictors of response could be identified . Muscle strength was not significantly improved in the short term by intra-articular injection . CONCLUSIONS : Intra-articular corticosteroids are effective for short term relief of pain in osteoarthritis but predicting responders is not possible . There may be a place for their more widespread use Background Studies have evaluated the concomitant use of hyaluronan ( HA ) with steroids , anti-inflammatory drugs and analgesic agents in an attempt to magnify the extent and duration of pain relief due to knee osteoarthritis . To date there has not been an intra-articular combination therapy available for relief of knee osteoarthritis symptoms – one that combines the fast acting onset of symptom relief provided by a corticosteroid with the long-lasting symptom relief provided by HA in a single injection . The objective of this study was to evaluate the safety and preliminary performance of two new HA formulations , Hydros ( hyaluronan-based hydrogel suspended in hyaluronan solution ) and Hydros-TA ( HA plus 10 mg of triamcinolone acetonide [ TA ] ) in subjects with knee osteoarthritis . Methods We conducted a Phase 2 prospect i ve , multicenter , r and omized , double-blind feasibility trial . Participants ( n = 98 ; mean age 60 years ) with knee osteoarthritis ( Kellgren-Lawrence grade 2 or 3 ) were r and omized to three treatment groups : Hydros , Hydros-TA , and Synvisc-One ® ( hylan G-F 20 ) . Participants received one 6 ml intra-articular injection in the treatment knee and were evaluated at 2 , 6 , 13 , and 26 weeks post-treatment . Safety was assessed from adverse events at all study visits . The primary efficacy outcome was the change from baseline on the Western Ontario and McMaster Universities 
    Output:
    
An analysis of multiple time points suggested that effects decrease over time , and our analysis provided no evidence that an effect remains six months after a corticosteroid injection