The Cochrane Musculoskeletal Group (CMSG), one of 53 groups of the not-for-profit, international Cochrane Collaboration, prepares, maintains, and disseminates systematic reviews of treatments for ...musculoskeletal diseases. It is important that authors conducting CMSG reviews and the readers of our reviews be aware of and use updated, state-of-the-art systematic review methodology. One hundred sixty reviews have been published. Previous method guidelines for systematic reviews of interventions in the musculoskeletal field published in 2006 have been substantially updated to incorporate methodological advances that are mandatory or highly desirable in Cochrane reviews and knowledge translation advances. The methodological advances include new guidance on searching, new risk-of-bias assessment, grading the quality of the evidence, the new Summary of Findings table, and comparative effectiveness using network metaanalysis. Method guidelines specific to musculoskeletal disorders are provided by CMSG editors for various aspects of undertaking a systematic review. These method guidelines will help improve the quality of reporting and ensure high standards of conduct as well as consistency across CMSG reviews.
Visceral adipose tissue is harmful to metabolic health. Exercise training reduces visceral adipose tissue mass, but the underlying mechanisms are not known. Interleukin-6 (IL-6) stimulates lipolysis ...and is released from skeletal muscle during exercise. We hypothesized that exercise-induced reductions in visceral adipose tissue mass are mediated by IL-6. In this randomized placebo-controlled trial, we assigned abdominally obese adults to tocilizumab (IL-6 receptor antibody) or placebo during a 12-week intervention with either bicycle exercise or no exercise. While exercise reduced visceral adipose tissue mass, this effect of exercise was abolished in the presence of IL-6 blockade. Changes in body weight and total adipose tissue mass showed similar tendencies, whereas lean body mass did not differ between groups. Also, IL-6 blockade increased cholesterol levels, an effect not reversed by exercise. Thus, IL-6 is required for exercise to reduce visceral adipose tissue mass and emphasizes a potentially important metabolic consequence of IL-6 blockade.
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•Exercise reduces visceral adipose tissue mass•Loss of visceral adipose tissue mass following exercise is dependent on IL-6•IL-6 receptor blockade increases total cholesterol and is not influenced by exercise•Improvements in cardiorespiratory fitness following exercise are not IL-6 dependent
Wedell-Neergaard et al. show that in abdominally obese people, exercise-mediated loss of visceral adipose tissue mass requires IL-6 receptor signaling. Given that abdominal fat is metabolically harmful to health, this study raises a potentially important side effect of IL-6 receptor antibodies, such as tocilizumab, used to treat some forms of arthritis.
Abstract Objectives To analyze if exercise interventions for patients with knee osteoarthritis (OA) following the American College of Sports Medicine (ACSM) definition of muscle strength training ...differs from other types of exercise, and to analyze associations between changes in muscle strength, pain, and disability. Methods A systematic search in 5 electronic databases was performed to identify randomized controlled trials comparing exercise interventions with no intervention in knee OA, and reporting changes in muscle strength and in pain or disability assessed as standardized mean differences (SMD) with 95% confidence intervals (95%CI). Interventions were categorized as ACSM interventions or not-ACSM interventions and compared using stratified random effects meta-analysis models. Associations between knee extensor strength gain and changes in pain/disability were assessed using meta-regression analyses. Results The 45 eligible trials with 4,699 participants and 56 comparisons (22 ACSM interventions) were included in this analysis. A statistically significant difference favoring the ACSM interventions with respect to knee extensor strength was found (SMD difference: 0.448 95%CI 0.091 to 0.805). No differences were observed regarding effects on pain and disability. The meta-regressions indicated that increases in knee extensor strength of 30 and 40% would be necessary for a likely concomitant beneficial effect on pain and disability, respectively. Conclusion Exercise interventions following the ACSM criteria for strength training provide superior outcomes in knee extensor strength but not in pain or disability. An increase of less than 30% in knee extensor strength is not likely to be clinically beneficial in terms of changes in pain and disability. PROSPERO: CRD42014015344
Several new treatment modalities with different mechanisms of action have been studied in patients with Behçet's syndrome (BS). The aim of the current effort was to update the recommendations in the ...light of these new data under the auspices of the European League Against Rheumatism (EULAR) Standing Committee for Clinical Affairs. A task force was formed that included BS experts from different specialties including internal medicine, rheumatology, ophthalmology, dermatology, neurology, gastroenterology, oral health medicine and vascular surgery, along with a methodologist, a health professional, two patients and two fellows in charge of the systematic literature search. Research questions were determined using a Delphi approach. EULAR standardised operating procedures was used as the framework. Results of the systematic literature review were presented to the task force during a meeting. The former recommendations were modified or new recommendations were formed after thorough discussions followed by voting. The recommendations on the medical management of mucocutaneous, joint, eye, vascular, neurological and gastrointestinal involvement of BS were modified; five overarching principles and a new recommendation about the surgical management of vascular involvement were added. These updated, evidence-based recommendations are intended to help physicians caring for patients with BS. They also attempt to highlight the shortcomings of the available clinical research with the aim of proposing an agenda for further research priorities.
Summary Background Serious infections are a major concern for patients considering treatments for rheumatoid arthritis. Evidence is inconsistent as to whether biological drugs are associated with an ...increased risk of serious infection compared with traditional disease-modifying antirheumatic drugs (DMARDs). We did a systematic review and meta-analysis of serious infections in patients treated with biological drugs compared with those treated with traditional DMARDs. Methods We did a systematic literature search with Medline, Embase, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov from their inception to Feb 11, 2014. Search terms included “biologics”, “rheumatoid arthritis” and their synonyms. Trials were eligible for inclusion if they included any of the approved biological drugs and reported serious infections. We assessed the risk of bias with the Cochrane Risk of Bias Tool. We did a Bayesian network meta-analysis of published trials using a binomial likelihood model to assess the risk of serious infections in patients with rheumatoid arthritis who were treated with biological drugs, compared with those treated with traditional DMARDs. The odds ratio (OR) of serious infection was the primary measure of treatment effect and calculated 95% credible intervals using Markov Chain Monte Carlo methods. Findings The systematic review identified 106 trials that reported serious infections and included patients with rheumatoid arthritis who received biological drugs. Compared with traditional DMARDs, standard-dose biological drugs (OR 1·31, 95% credible interval CrI 1·09–1·58) and high-dose biological drugs (1·90, 1·50–2·39) were associated with an increased risk of serious infections, although low-dose biological drugs (0·93, 0·65–1·33) were not. The risk was lower in patients who were methotrexate naive compared with traditional DMARD-experienced or anti-tumour necrosis factor biological drug-experienced patients. The absolute increase in the number of serious infections per 1000 patients treated each year ranged from six for standard-dose biological drugs to 55 for combination biological therapy, compared with traditional DMARDs. Interpretation Standard-dose and high-dose biological drugs (with or without traditional DMARDs) are associated with an increase in serious infections in rheumatoid arthritis compared with traditional DMARDs, although low-dose biological drugs are not. Clinicians should discuss the balance between benefit and harm with the individual patient before starting biological treatment for rheumatoid arthritis. Funding Rheumatology Division at the University of Alabama at Birmingham.
Abstract Objective To clarify the GRADE (grading of recommendations assessment, development and evaluation) definition of certainty of evidence and suggest possible approaches to rating certainty of ...the evidence for systematic reviews, health technology assessments and guidelines. Study Design and Setting This work was carried out by a project group within the GRADE Working Group, through brainstorming and iterative refinement of ideas, using input from workshops, presentations, and discussions at GRADE Working Group meetings to produce this document, which constitutes official GRADE guidance. Results Certainty of evidence is best considered as the certainty that a true effect lies on one side of a specified threshold, or within a chosen range. We define possible approaches for choosing threshold or range. For guidelines, what we call a fully contextualized approach requires simultaneously considering all critical outcomes and their relative value. Less contextualized approaches, more appropriate for systematic reviews and health technology assessments, include using specified ranges of magnitude of effect, e.g. ranges of what we might consider no effect, trivial, small, moderate, or large effects. Conclusion It is desirable for systematic review authors, guideline panelists, and health technology assessors to specify the threshold or ranges they are using when rating the certainty in evidence.
Pain is the predominant symptom for people with inflammatory arthritis (IA) and osteoarthritis (OA) mandating the development of evidence-based recommendations for the health professional's approach ...to pain management. A multidisciplinary task force including professionals and patient representatives conducted a systematic literature review of systematic reviews to evaluate evidence regarding effects on pain of multiple treatment modalities. Overarching principles and recommendations regarding assessment and pain treatment were specified on the basis of reviewed evidence and expert opinion. From 2914 review studies initially identified, 186 met inclusion criteria. The task force emphasised the importance for the health professional to adopt a patient-centred framework within a biopsychosocial perspective, to have sufficient knowledge of IA and OA pathogenesis, and to be able to differentiate localised and generalised pain. Treatment is guided by scientific evidence and the assessment of patient needs, preferences and priorities; pain characteristics; previous and ongoing pain treatments; inflammation and joint damage; and psychological and other pain-related factors. Pain treatment options typically include education complemented by physical activity and exercise, orthotics, psychological and social interventions, sleep hygiene education, weight management, pharmacological and joint-specific treatment options, or interdisciplinary pain management. Effects on pain were most uniformly positive for physical activity and exercise interventions, and for psychological interventions. Effects on pain for educational interventions, orthotics, weight management and multidisciplinary treatment were shown for particular disease groups. Underpinned by available systematic reviews and meta-analyses, these recommendations enable health professionals to provide knowledgeable pain-management support for people with IA and OA.
Summary Background Since the prevalence of obesity continues to increase, there is a demand for effective and safe anti-obesity agents that can produce and maintain weight loss and improve ...comorbidity. We did a meta-analysis of all published randomised controlled trials to assess the efficacy and safety of the newly approved anti-obesity agent rimonabant. Methods We searched The Cochrane database and Controlled Trials Register, Medline via Pubmed, Embase via WebSpirs, Web of Science, Scopus, and reference lists up to July, 2007. We collected data from four double-blind, randomised controlled trials (including 4105 participants) that compared 20 mg per day rimonabant with placebo. Findings Patients given rimonabant had a 4·7 kg (95% CI 4·1–5·3 kg; p<0·0001) greater weight reduction after 1 year than did those given placebo. Rimonabant caused significantly more adverse events than did placebo (OR=1·4; p=0·0007; number needed to harm=25 individuals 95% CI 17–58), and 1·4 times more serious adverse events (OR=1·4; p=0·03; number needed to harm=59 27–830). Patients given rimonabant were 2·5 times more likely to discontinue the treatment because of depressive mood disorders than were those given placebo (OR=2·5; p=0·01; number needed to harm=49 19–316). Furthermore, anxiety caused more patients to discontinue treatment in rimonabant groups than in placebo groups (OR=3·0; p=0·03; number needed to harm=166 47–3716). Interpretation Our findings suggest that 20 mg per day rimonabant increases the risk of psychiatric adverse events—ie, depressed mood disorders and anxiety—despite depressed mood being an exclusion criterion in these trials. Taken together with the recent US Food and Drug Administration finding of increased risk of suicide during treatment with rimonabant, we recommend increased alertness by physicians to these potentially severe psychiatric adverse reactions.
OMERACT uses an evidence-based framework known as the ‘OMERACT Filter Instrument Selection Algorithm’ (OFISA) to guide decisions in the assessment of outcome measurement instruments for inclusion in ...a core outcome set for interventional and observational clinical trials.
A group of OMERACT imaging and patient-centered outcome methodologists worked with imaging outcome groups to facilitate the selection of imaging outcome measurement instruments using the OFISA approach. The lessons learned from this work influenced the evolution to Filter 2.2 and necessitated changes to OMERACT's documentation and processes.
OMERACT has revised documentation and processes to incorporate the evolution of instrument selection to Filter 2.2. These revisions include creation of a template for detailed definitions of the target domain which is a necessary first step for instrument selection, modifications to the Summary of Measurement Properties (SOMP) table to account for sources of variability, and development of standardized reporting tables for each measurement property.
OMERACT Filter 2.2 represents additional modifications of the OMERACT guide for working groups in their rigorous assessment of measurement properties of instruments of various types, including imaging outcome measurement instruments. Enhanced reporting aims to increase the transparency of the evidence base leading to judgements for the endorsement of instruments in core outcome sets.
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