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      Exercise for lower limb osteoarthritis: systematic review incorporating trial sequential analysis and network meta-analysis

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          Abstract

          Objective To determine whether there is sufficient evidence to conclude that exercise interventions are more effective than no exercise control and to compare the effectiveness of different exercise interventions in relieving pain and improving function in patients with lower limb osteoarthritis.

          Data sources Nine electronic databases searched from inception to March 2012.

          Study selection Randomised controlled trials comparing exercise interventions with each other or with no exercise control for adults with knee or hip osteoarthritis.

          Data extraction Two reviewers evaluated eligibility and methodological quality. Main outcomes extracted were pain intensity and limitation of function. Trial sequential analysis was used to investigate reliability and conclusiveness of available evidence for exercise interventions. Bayesian network meta-analysis was used to combine both direct (within trial) and indirect (between trial) evidence on treatment effectiveness.

          Results 60 trials (44 knee, two hip, 14 mixed) covering 12 exercise interventions and with 8218 patients met inclusion criteria. Sequential analysis showed that as of 2002 sufficient evidence had been accrued to show significant benefit of exercise interventions over no exercise control. For pain relief, strengthening, flexibility plus strengthening, flexibility plus strengthening plus aerobic, aquatic strengthening, and aquatic strengthening plus flexibility, exercises were significantly more effective than no exercise control. A combined intervention of strengthening, flexibility, and aerobic exercise was also significantly more effective than no exercise control for improving limitation in function (standardised mean difference −0.63, 95% credible interval −1.16 to −0.10).

          Conclusions As of 2002 sufficient evidence had accumulated to show significant benefit of exercise over no exercise in patients with osteoarthritis, and further trials are unlikely to overturn this result. An approach combining exercises to increase strength, flexibility, and aerobic capacity is likely to be most effective in the management of lower limb osteoarthritis. The evidence is largely from trials in patients with knee osteoarthritis.

          Protocol registration PROSPERO ( www.crd.york.ac.uk/prospero/) No CRD42012002267.

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          Most cited references 76

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          OARSI recommendations for the management of hip and knee osteoarthritis, Part II: OARSI evidence-based, expert consensus guidelines.

          To develop concise, patient-focussed, up to date, evidence-based, expert consensus recommendations for the management of hip and knee osteoarthritis (OA), which are adaptable and designed to assist physicians and allied health care professionals in general and specialist practise throughout the world. Sixteen experts from four medical disciplines (primary care, rheumatology, orthopaedics and evidence-based medicine), two continents and six countries (USA, UK, France, Netherlands, Sweden and Canada) formed the guidelines development team. A systematic review of existing guidelines for the management of hip and knee OA published between 1945 and January 2006 was undertaken using the validated appraisal of guidelines research and evaluation (AGREE) instrument. A core set of management modalities was generated based on the agreement between guidelines. Evidence before 2002 was based on a systematic review conducted by European League Against Rheumatism and evidence after 2002 was updated using MEDLINE, EMBASE, CINAHL, AMED, the Cochrane Library and HTA reports. The quality of evidence was evaluated, and where possible, effect size (ES), number needed to treat, relative risk or odds ratio and cost per quality-adjusted life years gained were estimated. Consensus recommendations were produced following a Delphi exercise and the strength of recommendation (SOR) for propositions relating to each modality was determined using a visual analogue scale. Twenty-three treatment guidelines for the management of hip and knee OA were identified from the literature search, including six opinion-based, five evidence-based and 12 based on both expert opinion and research evidence. Twenty out of 51 treatment modalities addressed by these guidelines were universally recommended. ES for pain relief varied from treatment to treatment. Overall there was no statistically significant difference between non-pharmacological therapies [0.25, 95% confidence interval (CI) 0.16, 0.34] and pharmacological therapies (ES=0.39, 95% CI 0.31, 0.47). Following feedback from Osteoarthritis Research International members on the draft guidelines and six Delphi rounds consensus was reached on 25 carefully worded recommendations. Optimal management of patients with OA hip or knee requires a combination of non-pharmacological and pharmacological modalities of therapy. Recommendations cover the use of 12 non-pharmacological modalities: education and self-management, regular telephone contact, referral to a physical therapist, aerobic, muscle strengthening and water-based exercises, weight reduction, walking aids, knee braces, footwear and insoles, thermal modalities, transcutaneous electrical nerve stimulation and acupuncture. Eight recommendations cover pharmacological modalities of treatment including acetaminophen, cyclooxygenase-2 (COX-2) non-selective and selective oral non-steroidal anti-inflammatory drugs (NSAIDs), topical NSAIDs and capsaicin, intra-articular injections of corticosteroids and hyaluronates, glucosamine and/or chondroitin sulphate for symptom relief; glucosamine sulphate, chondroitin sulphate and diacerein for possible structure-modifying effects and the use of opioid analgesics for the treatment of refractory pain. There are recommendations covering five surgical modalities: total joint replacements, unicompartmental knee replacement, osteotomy and joint preserving surgical procedures; joint lavage and arthroscopic debridement in knee OA, and joint fusion as a salvage procedure when joint replacement had failed. Strengths of recommendation and 95% CIs are provided. Twenty-five carefully worded recommendations have been generated based on a critical appraisal of existing guidelines, a systematic review of research evidence and the consensus opinions of an international, multidisciplinary group of experts. The recommendations may be adapted for use in different countries or regions according to the availability of treatment modalities and SOR for each modality of therapy. These recommendations will be revised regularly following systematic review of new research evidence as this becomes available.
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            Lifetime risk of symptomatic knee osteoarthritis.

            To estimate the lifetime risk of symptomatic knee osteoarthritis (OA), overall and stratified by sex, race, education, history of knee injury, and body mass index (BMI). The lifetime risk of symptomatic OA in at least 1 knee was estimated from logistic regression models with generalized estimating equations among 3,068 participants of the Johnston County Osteoarthritis Project, a longitudinal study of black and white women and men age >or=45 years living in rural North Carolina. Radiographic, sociodemographic, and symptomatic knee data measured at baseline (1990-1997) and first followup (1999-2003) were analyzed. The lifetime risk of symptomatic knee OA was 44.7% (95% confidence interval [95% CI] 40.0-49.3%). Cohort members with history of a knee injury had a lifetime risk of 56.8% (95% CI 48.4-65.2%). Lifetime risk rose with increasing BMI, with a risk of 2 in 3 among those who were obese. Nearly half of the adults in Johnston County will develop symptomatic knee OA by age 85 years, with lifetime risk highest among obese persons. These current high risks in Johnston County may suggest similar risks in the general US population, especially given the increase in 2 major risk factors for knee OA, aging, and obesity. This underscores the immediate need for greater use of clinical and public health interventions, especially those that address weight loss and self-management, to reduce the impact of having knee OA.
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              EULAR evidence based recommendations for the management of hip osteoarthritis: report of a task force of the EULAR Standing Committee for International Clinical Studies Including Therapeutics (ESCISIT).

              To develop evidence based recommendations for the management of hip osteoarthritis (OA). The multidisciplinary guideline development group comprised 18 rheumatologists, 4 orthopaedic surgeons, and 1 epidemiologist, representing 14 European countries. Each participant contributed up to 10 propositions describing key clinical aspects of hip OA management. Ten final recommendations were agreed using a Delphi consensus approach. Medline, Embase, CINAHL, Cochrane Library, and HTA reports were searched systematically to obtain research evidence for each proposition. Where possible, outcome data for efficacy, adverse effects, and cost effectiveness were abstracted. Effect size, rate ratio, number needed to treat, and incremental cost effectiveness ratio were calculated. The quality of evidence was categorised according to the evidence hierarchy. The strength of recommendation was assessed using the traditional A-D grading scale and a visual analogue scale. Ten key treatment propositions were generated through three Delphi rounds. They included 21 interventions, such as paracetamol, NSAIDs, symptomatic slow acting disease modifying drugs, opioids, intra-articular steroids, non-pharmacological treatment, total hip replacement, osteotomy, and two general propositions. 461 studies were identified from the literature search for the proposed interventions of efficacy, side effects, and cost effectiveness. Research evidence supported 15 interventions in the treatment of hip OA. Evidence specific for the hip was strikingly lacking. Strength of recommendation varied according to category of research evidence and expert opinion. Ten key recommendations for the treatment of hip OA were developed based on research evidence and expert consensus. The effectiveness and cost effectiveness of these recommendations were evaluated and the strength of recommendation was scored.
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                Author and article information

                Contributors
                Role: assistant professor in applied research, systematic reviewer
                Role: professor of primary care epidemiology
                Role: research information manager
                Role: Arthritis Research UK professor of musculoskeletal therapies
                Role: research fellow
                Role: professor of clinical epidemiology
                Role: NIHR professor of musculoskeletal health in primary care
                Journal
                BMJ
                BMJ
                bmj
                BMJ : British Medical Journal
                BMJ Publishing Group Ltd.
                0959-8138
                1756-1833
                2013
                2013
                20 September 2013
                : 347
                Affiliations
                [1 ]Arthritis Research UK Primary Care Centre, Keele University, Keele, Staffordshire ST5 5BG, UK
                [2 ]Warwick-Centre for Applied Health Research and Delivery (WCAHRD), Division of Health Sciences, Warwick Medical School, University of Warwick, Coventry CV4 7AL UK
                Author notes
                Correspondence to: D van der Windt d.van.der.windt@ 123456keele.ac.uk
                Article
                utho011070
                10.1136/bmj.f5555
                3779121
                24055922
                © Uthman et al 2013

                This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 3.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/3.0/.

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