***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: Introduction : Some argued that clinical efficacy of Chondroitin Sulfate ( CS ) could vary upon the product origin . The objective of this trial is to compare the effect of 2 CS medicinal products from different origin : Structum ® ( avian , 1000mg/day ) and Chondrosulf ® ( bovine , 1200mg/day ) . Methods : This was a r and omized , double-blind , double placebo , active-controlled , parallel-group study using a non-inferiority design . Symptomatic osteoarthritis of the knee patients , according to American College of Rheumatology criteria , aged 50 - 80 years received either Structum ® ( 500 mg BID ) or Chondrosulf ® ( 400 mg TID ) during 24 weeks . Inclusion criteria were : global pain in the target knee ≥ 40 mm on a Visual Analog Scale ( VAS 0 - 100 ) , a Lequesne ’s Algofunctional Index ( LFI ) score ≥ 7 ( range : 0 - 24 ) and a radiological Kellgren-Lawrence grade 2 or 3 . Primary outcome was the mean change over 24 weeks of pain VAS and LFI score . Secondary outcomes were patient ’s and physician ’s global assessment s , Outcome Measures in Rheumatology Clinical Trials and Osteoarthritis Research Society International responders rate , analgesics intake and Medical Outcomes Survey Short-Form 12 ( SF-12 ) . Safety was assessed by recording adverse events . A non-inferiority test was performed on the Structum ® -Chondrosulf ® difference for VAS and LFI score changes . Predefined non inferiority limit was settled as the lower limit of the 95 % CI above -5 mm and -1pt for pain VAS and LFI score respectively . Results : 837 patients were r and omized : 817 available for the full analysis data set ( FAS ) , 692 for the per protocol ( PP ) analysis . No statistical and clinical differences were observed for demographics and disease characteristics between the 2 groups . PP analysis showed no difference between groups on mean variations of pain VAS or LFI scores over 24 weeks . Mean Pain VAS decreased by 23.9 mm ( 17.5 ) in Structum ® group and 23.8 mm ( 17.2 ) in Chondrosulf ® group ( difference : 0.012 [ CI95 % : -2.6 ; 2.6 ] ) . Mean LFI score decreased by 3.2 ( 2.4 ) and 3.1 ( 2.4 ) respectively ( difference : 0.139 [ CI95 % : -0.2 ; 0.5 ] ) . The lower limits of the 2 CI were above predefined non inferiority margin , which demonstrated the non inferiority of Structum ® in comparison with Chondrosulf ® . FAS analysis gave similar results . Secondary efficacy outcomes analysis showed the same trends . Responders rate were 76.3 % and 73.8 % respectively ( PP , W24 ) . Treatments were well tolerated : 2.4 % in Structum ® group and 4.5 % in Chondrosulf ® group withdrew from the study for safety reasons . Conclusion : Structum ® and Chondrosulf ® were equally effective in reducing functional impairment and relieving pain over 6 months in knee osteoarthritis patients , without any safety concerns . Trial Registration : http://www.controlled-trials.com Number : IS RCT N04305346 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 . ) OBJECTIVE To evaluate the symptomatic effects of highly purified chondroitin 4 and chondroitin 6 sulfate ( CS ) therapy in patients with osteoarthritis ( OA ) of the h and . METHODS This investigator-initiated , single-center , r and omized , double-blind , placebo-controlled clinical trial included 162 symptomatic patients with radiographic evidence of h and OA ( American College of Rheumatology criteria ) . Inclusion criteria included patient 's assessment of global spontaneous h and pain of at least 40 mm on a 0 - 100-mm visual analog scale ( VAS ) and functional impairment of at least 6 ( 0 - 30 scale ) on the Functional Index for H and OA ( FIHOA ) in the most symptomatic h and . Patients received either 800 mg of CS ( n = 80 patients ) or placebo ( n = 82 patients ) once daily for 6 months and were analyzed in an intent-to-treat approach . The two primary outcomes were the change in the patient 's assessment of global spontaneous h and pain and in h and function ( by FIHOA score ) from baseline to month 6 . Secondary outcomes were improvement in grip strength , duration of morning stiffness , acetaminophen consumption , and the investigator 's global impression of treatment efficacy . RESULTS There was a significantly more pronounced decrease in the patient 's global assessment of h and pain in the CS group than in the placebo group ( difference VAS scores -8.7 mm ; P = 0.016 ) . H and function improved significantly more in the CS group than in the placebo group ( difference in FIHOA scores -2.14 ; P = 0.008 ) . There was a statistically significant between-group difference in favor of CS for the duration of morning stiffness and for the investigator 's global impression of treatment efficacy . Changes in grip strength , acetaminophen consumption , and safety end points were not significantly different between the two groups . CONCLUSION This study demonstrates that CS improves h and pain and function in patients with symptomatic OA of the h and and shows a good safety profile AIM To determine the minimum clinical ly important difference ( MCID ) in joint space width ( JSW ) progression in patients with hip osteoarthritis ( OA ) , based upon evaluation by a panel of clinical experts as a gold st and ard . METHODS A sample of 298 patients with hip OA was selected from a multicentre , prospect i ve , longitudinal , 3-yr follow-up study . A pelvic radiograph was obtained at entry and after 3 yr . For each film , the narrowest JSW was measured using a 0.1-mm graduated magnifying glass . The difference between baseline and 3-yr follow-up JSW was calculated . Two senior rheumatologists , who were experts in osteoarthritis , evaluated each pair of films and noted whether a clinical ly relevant deterioration in osteoarthritis stage occurred at 3 yr compared with baseline . Interobserver reliabilities were evaluated using the kappa coefficient and proportions of agreements . Then , for each measured difference in JSW ( 0.1 mm per 0.1 mm ) , the sensitivity and specificity for MCID , defined as the assessment of expert 1 , expert 2 or a combination of both , were calculated . This allowed us to obtain , from graphic representations of the correct classification probabilities , the best measured JSW threshold , with the maximal true positive and the minimal false positive results . RESULTS The mean measured change in JSW was -0.63 + /- 0.74 mm . Experts 1 and 2 considered the decrease in JSW to be clinical ly relevant in 122 ( 40.9 % ) and 100 pairs ( 33.6 % ) respectively . The proportion of agreements between the experts was 79.9 % , with a kappa coefficient of 0.572 . The best measured JSW threshold was -0.4 mm for expert 1 , expert 2 and the combination of both ; sensitivity and specificity were 0.75 and 0.8 , 0.71 and 0.72 , and 0.75 and 0.7 respectively . CONCLUSION This study suggests that a change of at least 0.4 mm in the radiological JSW could be considered clinical ly relevant . Other studies using other sets of patients and other methods are needed for validation Objective To determine the effect of chondroitin sulphate ( CS ) treatment on cartilage volume loss , subchondral bone marrow lesions ( BML ) , synovitis and disease symptoms in patients with knee osteoarthritis ( OA ) . Methods In this pilot multicentre , r and omised , double-blind , controlled trial in primary knee OA , 69 patients with clinical signs of synovitis were r and omised to receive CS 800 mg or placebo once daily for 6 months followed by an open-label phase of 6 months in which patients in both groups received CS 800 mg once daily . Cartilage volume and BML were assessed by MRI at baseline and at 6 and 12 months ; synovial membrane thickness was assessed at baseline and at 6 months . Results The CS group showed significantly less cartilage volume loss than the placebo group as early as 6 months for the global knee ( p=0.030 ) , lateral compartment ( p=0.015 ) and tibial plateaus ( p=0.002 ) , with significance persisting at 12 months . Significantly lower BML scores were found for the CS group at 12 months in the lateral compartment ( p=0.035 ) and the lateral femoral condyle ( p=0.044 ) . Disease symptoms were similar between the two groups . Conclusion CS treatment significantly reduced the cartilage volume loss in knee OA starting at 6 months of treatment , and BML at 12 months . These findings suggest a joint structure protective effect of CS and provide new in vivo information on its mode of action in knee OA BACKGROUND Osteoarthritis ( OA ) is the most common joint disease encountered throughout Europe . A task force for the EULAR St and ing Committee for Clinical Trials met in 1998 to determine the method ological and logistical approach required for the development of evidence based guidelines for treatment of knee OA . The guidelines were restricted to cover all currently available treatments for knee OA diagnosed either clinical ly and /or radiographically affecting any compartment of the knee . METHODS The first stage was the selection of treatment modalities to be considered . The second stage comprised a search of the electronic data bases Medline and Embase using a combination of subject headings and keywords . All European language publications in the form of systematic review s , meta-analyses , r and omised controlled trials , controlled trials , and observational studies were included . During stage three all the relevant studies were quality scored . The summary statistics for vali date d outcome measures , when available , were recorded and , where practical , the numbers needed to treat and the effect size for each treatment were calculated . In the fourth stage key clinical propositions were determined by expert consensus employing a Delphi approach . The final stage ranked these propositions according to the available evidence . A second set of propositions relating to a future research agenda was determined by expert consensus using a Delphi approach . RESULTS Over 2400 English language publications and 400 non-English language publications were identified . Seven hundred and forty four studies presented outcome data of the effects of specific treatments on knee OA . Quantitative analysis of treatment effect was possible in only 61 studies . Recommendations for the management of knee OA based on currently available data and expert opinion are presented . Proposals for a future research agenda are highlighted . CONCLUSIONS These are the first clinical guidelines on knee OA to combine an evidence based approach and a consensus approach across a wide range of treatment modalities . It is apparent that certain clinical propositions are supported by substantial research based evidence , while others are not . There is thus an urgent need for 
    Output:
    
Chondroitin did not result in statistically significant numbers of adverse events or withdrawals due to adverse events compared with placebo or another drug .
The beneficial effects of chondroitin in pain and Lequesne 's index persisted when evidence was limited to studies with adequate blinding or studies that used appropriate intention to treat ( ITT ) analyses .
These beneficial effects were uncertain when we limited data to studies with appropriate allocation concealment or a large study sample ( > 200 ) or to studies without pharmaceutical funding .
A review of r and omized trials of mostly low quality reveals that chondroitin ( alone or in combination with glucosamine ) was better than placebo in improving pain in participants with osteoarthritis in short-term studies .
Chondroitin had a lower risk of serious adverse events compared with control .
The combination of some efficacy and low risk associated with chondroitin may explain its popularity among patients as an over-the-counter supplement