***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: The aim of the study was to evaluate the safety and efficacy of viscosupplementation with hylan G-F 20 in patients with mild to moderate osteoarthritis ( OA ) presenting with persistent knee pain 4–12 weeks after arthroscopic meniscectomy .  A prospect i ve , multi-centre , open study was carried out in patients with pain due to OA of the knee , not resolved by simple analgesics , 4–12 weeks after undergoing arthroscopic meniscectomy .  To be eligible , patients had to score ≥50 mm and ≤90 mm on both walking pain and patient global assessment visual analogue scales ( VAS ; 0–100 mm ) at baseline and be radiologically diagnosed pre-operatively with OA grade I or II on the Kellgren-Lawrence scale , with < 50 % joint space narrowing . Patients received three intra-articular , 2 ml injections of hylan G-F 20 in the target knee with an interval of 1 week between injections , and were followed for 52 weeks . The primary efficacy endpoint was the change from baseline in the walking pain VAS score at 26 weeks . Secondary outcome measures were the walking pain VAS scores at all other time points , the WOMAC Index at all time points , and patient and physician global assessment at all time points . The safety of the treatment was assessed using adverse event ( AE ) reports . A total of 62 patients ( mean age 55.4 years , 52 % male ) were enrolled . The mean walking pain VAS score decreased by 36.8 mm from baseline at 26 weeks ( P < 0.0001 ) , and also showed statistically significant decreases ( P < 0.0001 ) at all other time points . The change in WOMAC total and subscale scores from baseline were statistically significant ( P < 0.0001 ) at all time points , as were the decreases in the physician and patient global assessment VAS scores . There were 18 target knee AEs ( mostly pain and /or swelling and /or effusion ) in 12 patients ( 19 % ) considered to be at least possibly related to treatment . The majority of these ( 78 % ) were mild or moderate in intensity . One patient ( 1.6 % ) experienced a serious adverse event ( synovitis ) in the target knee that was considered possibly related to study treatment . Hylan G-F 20 provides effective pain relief and improves stiffness and physical function in patients with mild to moderate OA presenting with persistent osteoarthritic pain 4–12 weeks after arthroscopic meniscectomy . Symptomatic efficacy was maximised at 12 weeks and maintained at 26 and 52 weeks . The type ( pain and /or swelling and /or effusion ) and the intensity ( mostly mild/moderate ) of AEs reported in this study are similar to those reported in other trials in different patient population s , but the incidence was higher ( 19 % ) . The risk/benefit of hylan G-F 20 in this particular population of patients is favourable Background Osteoarthritis is the most prevalent joint disease and a frequent cause of joint pain , functional loss , and disability . Osteoarthritis often becomes chronic , and conventional treatments have demonstrated only modest clinical benefits without lesion reversal . Cell-based therapies have shown encouraging results in both animal studies and a few human case reports . We design ed a pilot study to assess the feasibility and safety of osteoarthritis treatment with mesenchymal stromal cells ( MSCs ) in humans and to obtain early efficacy information for this treatment . Methods Twelve patients with chronic knee pain unresponsive to conservative treatments and radiologic evidence of osteoarthritis were treated with autologous exp and ed bone marrow MSCs by intra-articular injection ( 40 × 106 cells ) . Clinical outcomes were followed for 1 year and included evaluations of pain , disability , and quality of life . Articular cartilage quality was assessed by quantitative magnetic resonance imaging T2 mapping . Results Feasibility and safety were confirmed , and strong indications of clinical efficacy were identified . Patients exhibited rapid and progressive improvement of algofunctional indices that approached 65 % to 78 % by 1 year . This outcome compares favorably with the results of conventional treatments . Additionally , quantification of cartilage quality by T2 relaxation measurements demonstrated a highly significant decrease of poor cartilage areas ( on average , 27 % ) , with improvement of cartilage quality in 11 of the 12 patients . Conclusions MSC therapy may be a valid alternative treatment for  chronic knee osteoarthritis . The intervention is simple , does not require hospitalization or surgery , provides pain relief , and significantly improves cartilage quality Systematic review s ( SRs ) are an increasingly popular evidence -based tool and are often used to answer complex research questions across many different research domains . Early SR methodology was advanced by social scientists , and the term meta- analysis was coined by a social scientist who also conducted research in psychology . SRs have recently become popular in healthcare and are likely to be beneficial in any field . The aim of this report is to highlight issues in SR conduct with a focus on the field of nutrition and to make recommendations on improving SR conduct in this area . Development of the research question is probably the most important step in conducting an SR . The 4 main components of an answerable question are 1 ) the patient , population , or problem ; 2 ) the intervention , independent variable , or exposure ; 3 ) the comparators ; and 4 ) the dependent variables or outcomes of interest . The question will be used to determine the optimal methods for conducting the SR . SRs often include study design s beyond r and omized trials and do not always include a meta- analysis of the results . Other topics explored include underst and ing and interpreting discordant review s and the importance of reporting tools [ eg , QUality Of Reporting Of Meta-analyses ( QUOROM Statement ) or CONsoli date d St and ards Of Reporting of Trials ( CONSORT Statement ) ] . Recommendations are then provided , such as developing a capacity-building program , search ing the primary literature for research gaps , and extending reporting tools such as the QUOROM Statement to the field of nutrition Objective To examine the long-term efficacy and safety of five intra-articular injections with hyaluronan in knee osteoarthritis . Methods A multicentre , r and omised , placebo-controlled double-blind study of 337 patients fulfilling the American College of Rheumatology ( ACR ) criteria for knee osteoarthritis ( clinical and laboratory ) and with a Lequesne algofunctional index score ( LFI ) of 10 or greater . Patients received a hyaluronan product ( sodium hyaluronate ; Hyalgan ) ( n=167 ) or saline ( n=170 ) intra-articularly weekly for 5 weeks and were followed up to 1 year . Time to recurrence was the primary efficacy parameter . LFI , pain on walking 50 m based on visual analogue scale ( VAS pain 50 m ) , paracetamol consumption , patients ' global assessment , Nottingham health profile , joint effusion and number of responders were secondary efficacy parameters . The efficacy parameters were analysed by intention to treat ( ITT ) and per protocol ( PP ) . All adverse events ( AE ) were recorded as safety parameters . Results Time to recurrence showed no significant treatment effect ( ITT analysis , p=0.26 ) . Change from baseline in LFI and VAS pain 50 m for the ITT population showed no treatment effect . Paracetamol consumption , patients ' global assessment , responder rates and AE displayed no significant difference between treatment groups , analysed by both ITT and PP . Treatment compliance was 95 % in the hyaluronan group and 99 % in the placebo group . No safety problems were registered . Conclusion In patients fulfilling the ACR criteria for osteoarthritis of the knee with moderate to severe disease activity ( LFI ≥10 ) , five intra-articular injections of hyaluronan did not improve pain , function , paracetamol consumption or other efficacy parameters 3 , 6 , 9 and 12 months after the treatment OBJECTIVE The Arthritis , Diet , and Activity Promotion Trial ( ADAPT ) was a r and omized , single-blind clinical trial lasting 18 months that was design ed to determine whether long-term exercise and dietary weight loss are more effective , either separately or in combination , than usual care in improving physical function , pain , and mobility in older overweight and obese adults with knee osteoarthritis ( OA ) . METHODS Three hundred sixteen community-dwelling overweight and obese adults ages 60 years and older , with a body mass index of > or = 28 kg/m(2 ) , knee pain , radiographic evidence of knee OA , and self-reported physical disability , were r and omized into healthy lifestyle ( control ) , diet only , exercise only , and diet plus exercise groups . The primary outcome was self-reported physical function as measured with the Western Ontario and McMaster Universities Osteoarthritis Index ( WOMAC ) . Secondary outcomes included weight loss , 6-minute walk distance , stair-climb time , WOMAC pain and stiffness scores , and joint space width . RESULTS Of the 316 r and omized participants , 252 ( 80 % ) completed the study .  Adherence was as follows : for healthy lifestyle , 73 % ; for diet only , 72 % ; for exercise only , 60 % ; and for diet plus exercise , 64 % . In the diet plus exercise group , significant improvements in self-reported physical function ( P < 0.05 ) , 6-minute walk distance ( P < 0.05 ) , stair-climb time ( P < 0.05 ) , and knee pain ( P < 0.05 ) relative to the healthy lifestyle group were observed . In the exercise group , a significant improvement in the 6-minute walk distance ( P < 0.05 ) was observed . The diet-only group was not significantly different from the healthy lifestyle group for any of the functional or mobility measures . The weight-loss groups lost significantly ( P < 0.05 ) more body weight ( for diet , 4.9 % ; for diet plus exercise , 5.7 % ) than did the healthy lifestyle group ( 1.2 % ) . Finally , changes in joint space width were not different between the groups . CONCLUSION The combination of modest weight loss plus moderate exercise provides better overall improvements in self-reported measures of function and pain and in performance measures of mobility in older overweight and obese adults with knee OA compared with either intervention alone Background Osteoarthritis is the most prevalent joint disease and a common cause of joint pain , functional loss , and disability . Conventional treatments demonstrate only modest clinical benefits without lesion reversal . Autologous mesenchymal stromal cell ( MSC ) treatments have shown feasibility , safety , and strong indications for clinical efficacy . We performed a r and omized , active control trial to assess the feasibility and safety of treating osteoarthritis with allogeneic MSCs , and we obtain information regarding the efficacy of this treatment . Methods We r and omized 30 patients with chronic knee pain unresponsive to conservative treatments and showing radiological evidence of osteoarthritis into 2 groups of 15 patients . The test group was treated with allogeneic bone marrow MSCs by intra-articular injection of 40 × 106 cells . The control group received intra-articular hyaluronic acid ( 60 mg , single dose ) . Clinical outcomes were followed for 1 year and included evaluations of pain , disability , and quality of life . Articular cartilage quality was assessed by quantitative magnetic resonance imaging T2 mapping . Results Feasibility and safety were confirmed and indications of clinical efficacy were identified . The MSC-treated patients displayed significant improvement in algofunctional indices versus the active controls treated with hyaluronic acid . Quantification of cartilage quality by T2 relaxation measurements showed a significant decrease in poor cartilage areas , with cartilage quality improvements in MSC-treated patients . Conclusions Allogeneic MSC therapy may be a valid alternative for the treatment of  chronic knee osteoarthritis  that is more logistically convenient than autologous MSC treatment . The intervention is simple , does not require surgery , provides pain relief , and significantly improves cartilage quality 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 
    Output:
    
Lifestyle modifications ( moderate exercise and weight loss ) , paracetamol , glucosamine , Intraarticular Hyaluronic Acid ( IAHA ) and platelet-rich-plasma ( PRP ) injections have a low risk of harm and beneficial ≥12 month outcomes .
Although Nonsteroidal Anti-inflammatory Drugs ( NSAIDs ) provide pain relief , they are associated with increased risk of medical complications .
Cortisone injections are associated with radiological cartilage degeneration at > 12 months .
Arthroscopy for degenerative meniscal tears in KOA leads to a 3-fold increase in total knee arthroplasty ( TKA ) .
TKA improves primary outcomes of KOA but has a low rate of significant medical complications .
Treatment with opioids has a lack of evidence for use and a high risk of long-term harm .
The use of IAHA and PRP may provide additional symptomatic benefit without the risk of harm .
TKA is associated with significant medical complications but is justified by the efficacy of joint replacement in late-stage disease .