***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 
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    ***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 Pharmacological treatment for osteoarthritis ( OA ) can be divided into two groups : symptom-modifying drugs and disease-modifying drugs . Symptom-modifying drugs are currently the prescription of choice for patients with OA , as disease-modifying drugs are not yet available in usual care . However , there has recently been a lot of debate about glucosamine sulphate ( GS ) , a biological agent that is thought to have both symptom-modifying and disease-modifying properties . This assumption has yet to be proved . The objective of this article is to present the design of a blind r and omised clinical trial that examines the long-term symptom-modifying and disease-modifying effectiveness of GS in patients with hip OA . This trial is ongoing and will finish in March 2006 . Methods / design Patients with hip OA meeting the ACR- criteria are r and omly allocated to either 1500 mg of oral GS or placebo for the duration of two years . The primary outcome measures , which are joint space narrowing ( JSN ) , and change in the pain and function score of the Western Ontario McMaster Universities Osteoarthritis index ( WOMAC ) , are determined at baseline and after two years of follow-up during the final assessment . Intermediate measures at three-month intervals throughout the trial are used to study secondary outcome measures . Secondary outcome measures are changes in WOMAC stiffness score , quality of life , medical consumption , side effects and differences in biomarker CTX-II Summary A new preparation of pure glucosamine sulphate , in injectable and oral form , was investigated in a controlled clinical trial in patients with osteoarthrosis . Two groups of 15 in- patients received either 400 mg glucosamine sulphate daily ( 12by the intramuscular and 3 by the intra-articular route ) for 7 days , followed by 2 weeks at 1.5 g daily of oral glucosamine sulphate in 3 divided doses , or an intramuscular injection daily of a piperazine/chlorbutanol combination for 7 days , followed by oral placebo during the following 2 weeks . Semi-quantitative scoring of pain at rest and during active and passive movements , of restricted function and , where possible , of walking time over 20 metres , were taken as therapeutic activity indices , and tested before and after 1 and 3 weeks of treatment . Patients were positively question ed daily for possible intolerance symptoms . Laboratory tests were recorded before and after treatment . With both initial parenteral treatments , each symptom significantly improved , wit BACKGROUND Treatment of osteoarthritis is usually limited to short-term symptom control . We assessed the effects of the specific drug glucosamine sulphate on the long-term progression of osteoarthritis joint structure changes and symptoms . METHODS We did a r and omised , double-blind placebo controlled trial , in which 212 patients with knee osteoarthritis were r and omly assigned 1500 mg sulphate oral glucosamine or placebo once daily for 3 years . Weightbearing , anteroposterior radiographs of each knee in full extension were taken at enrolment and after 1 and 3 years . Mean joint-space width of the medial compartment of the tibiofemoral joint was assessed by digital image analysis , whereas minimum joint-space width -- ie , at the narrowest point -- was measured by visual inspection with a magnifying lens . Symptoms were scored by the Western Ontario and McMaster Universities ( WOMAC ) osteoarthritis index . FINDINGS The 106 patients on placebo  had a progressive joint-space narrowing , with a mean joint-space loss after 3 years of -0.31 mm ( 95 % CI -0.48 to -0.13 ) . There was no significant joint-space loss in the 106 patients on glucosamine sulphate : -0.06 mm ( -0.22 to 0.09 ) . Similar results were reported with minimum joint-space narrowing . As assessed by WOMAC scores , symptoms worsened slightly in patients on placebo compared with the improvement observed after treatment with glucosamine sulphate . There were no differences in safety or reasons for early withdrawal between the treatment and placebo groups . INTERPRETATION The long-term combined structure-modifying and symptom-modifying effects of gluosamine sulphate suggest that it could be a disease modifying agent in osteoarthritis BACKGROUND Conventional symptomatic treatments for osteoarthritis do not favorably affect disease progression . The aim of this r and omized , placebo-controlled trial was to determine whether long-term ( 3-year ) treatment with glucosamine sulfate can modify the progression of joint structure and symptom changes in knee osteoarthritis , as previously suggested . METHODS Two hundred two patients with knee osteoarthritis ( using American College of Rheumatology criteria ) were r and omized to receive oral glucosamine sulfate , 1500 mg once a day , or placebo . Changes in radiographic minimum joint space width were measured in the medial compartment of the tibiofemoral joint , and symptoms were assessed using the algo-functional indexes of Lequesne and WOMAC ( Western Ontario and McMaster Universities ) . RESULTS  Osteoarthritis was of mild to moderate severity at enrollment , with average joint space widths of slightly less than 4 mm and a Lequesne index score of less than 9 points . Progressive joint space narrowing with placebo use was -0.19 mm ( 95 % confidence interval , -0.29 to -0.09 mm ) after 3 years . Conversely , there was no average change with glucosamine sulfate use ( 0.04 mm ; 95 % confidence interval , -0.06 to 0.14 mm ) , with a significant difference between groups ( P = .001 ) . Fewer patients treated with glucosamine sulfate experienced predefined severe narrowings ( > 0.5 mm ) : 5 % vs 14 % ( P = .05 ) . Symptoms improved modestly with placebo use but as much as 20 % to 25 % with glucosamine sulfate use , with significant final differences on the Lequesne index and the WOMAC total index and pain , function , and stiffness subscales . Safety was good and without differences between groups . CONCLUSION Long-term treatment with glucosamine sulfate retarded the progression of knee osteoarthritis , possibly determining disease modification OBJECTIVE To assess whether improvement in knee pain biased the determination of the structure-modifying effect reported for glucosamine sulfate in two recent 3-year , r and omised , placebo-controlled clinical trials , in which conventional st and ing antero-posterior full extension knee radiographs were used for the measurement of joint space narrowing , and in which pain relief might have improved knee full extension . DESIGN Patients completing the 3-year treatment course were selected based on a WOMAC pain decrease at least equal to the mean improvement in the glucosamine sulfate arms in either of the original studies , irrespective of treatment with glucosamine sulfate or placebo ( drug responders or placebo responders ) . In a second approach , 3-year completers were selected if their baseline st and ing knee pain ( item # 5 of the WOMAC pain scale ) was ' severe ' or ' extreme ' and improved by any degree at the end of the trials . In both cases , changes in minimum joint space width were compared between treatment groups . RESULTS Global knee pain was mild-to-moderate in the two study population s and in all patient subsets identified . There were obviously more pain improvers in the glucosamine sulfate subsets ( N=76 in the two studies combined ) than in the placebo subsets ( N=57 ) , but WOMAC pain scores improved to the same extent , which was as large as over 50 % relative to baseline . Nevertheless , the placebo subsets in both studies underwent an evident mean ( SD ) joint space narrowing , which in the pooled analysis of both studies was -0.22 ( 0.80 ) mm , and was not observed with glucosamine sulfate : + 0.15 ( 0.60 ) mm ( P=0.003 vs placebo ) . Similar results were found in the smaller subsets with > or = severe baseline st and ing knee pain that improved after 3 years , with a joint space narrowing nevertheless of -0.28 ( 0.76 ) mm with placebo ( N=26 ) , not observed with glucosamine sulfate : + 0.21 ( 0.68 ) mm ( N=31 ; P=0.014 vs placebo ) . CONCLUSIONS Knee pain relief did not bias the report of a structure-modifying effect of glucosamine sulfate in two recent long-term trials using conventional st and ing antero-posterior radiographs , possibly due to the mild-to-moderate patient characteristics OBJECTIVE To assess the effects of the prescription formulation of glucosamine sulfate ( 1,500 mg administered once daily ) on the symptoms of knee osteoarthritis ( OA ) during a 6-month treatment course . METHODS Three hundred eighteen patients were enrolled in this r and omized , placebo-controlled , double-blind trial in which acetaminophen , the currently preferred medication for symptomatic treatment of OA , was used as a side comparator . Patients were r and omly assigned to receive oral glucosamine sulfate 1,500 mg once daily ( n = 106 ) , acetaminophen 3 gm/day ( n = 108 ) , or placebo ( n = 104 ) . The primary efficacy outcome measure was the change in the Lequesne index after 6 months . Secondary parameters included the Western Ontario and McMaster Universities Osteoarthritis Index ( WOMAC ) and response according to the Osteoarthritis Research Society International criteria . These outcome measures were assessed using an intent-to-treat analysis . RESULTS At baseline , the study patients had moderately severe OA symptoms ( mean Lequesne index approximately 11 points ) . Glucosamine sulfate was more effective than placebo in improving the Lequesne score , with a final decrease of 3.1 points , versus 1.9 with placebo ( difference between glucosamine sulfate and placebo -1.2 [ 95 % confidence interval -2.3 , -0.8 ] ) ( P = 0.032 ) . The 2.7-point decrease with acetaminophen was not significantly different from that with placebo ( difference -0.8 [ 95 % confidence interval -1.9 , 0.3 ] ) ( P = 0.18 ) . Similar results were observed for the WOMAC . There were more responders to glucosamine sulfate ( 39.6 % ) and acetaminophen ( 33.3 % ) than to placebo ( 21.2 % ) ( P = 0.004 and P = 0.047 , respectively , versus placebo ) . Safety was good , and was comparable among groups . CONCLUSION The findings of this study indicate that glucosamine sulfate at the oral once-daily dosage of 1,500 mg is more effective than placebo in treating 
    Output:
    
Some studies suggest that glucosamine may provide greater benefit to patients with less severe radiographic osteoarthritis than to patients with more severe disease ( 5 , 6 ) .