Vivian Welch

Calcium-channel blockers for Raynaud's phenomenon in systemic sclerosis

OBJECTIVEnMost patients with systemic sclerosis (SSc) have Raynauds phenomenon (RP), which is often more severe than idiopathic RP. This study was a meta-analysis to determine the efficacy of calcium-channel blockers for the treatment of RP in SSc. The primary outcome measures were frequency and severity of ischemic attacks, digital skin temperature, patient and physician global assessments, and digital ulcers.nnnMETHODSnThe Cochrane search strategy was used to ascertain all trials in all languages. Primary data sources included Medline, Current Contents, and the Cochrane Controlled Trials Register. Studies that met the inclusion criteria were randomized controlled trials of >2 days duration with a dropout rate of <35%. Twenty-nine studies were found, of which 8 randomized controlled trials were eligible for inclusion. The total number of patients included was small (n = 109). Most trials included primary and secondary RP, and the main reasons for trial exclusion were inability to extract subset data on SSc patients (18 trials), data published previously (2 trials), and lack of a control group (1 trial). Data were abstracted independently by 2 reviewers, and either a weighted mean difference (WMD) or a standardized mean difference (SMD) was calculated for all continuous outcomes; however, information was not available for all outcomes within trials.nnnRESULTSnThe WMD of all calcium-channel blockers versus placebo (6 trials) and of nifedipine alone versus placebo (5 trials) for the reduction in the frequency of ischemic attacks over a 2-week period was -8.31 (95% confidence interval [95% CI] -15.71, -0.91) and -10.21 (95% CI -20.09, -0.34), respectively. The SMD of all calcium-channel blockers versus placebo (3 trials) and of nifedipine alone versus placebo (2 trials) for the reduction in the severity of ischemic attacks was -0.69 (95% CI -1.21, -0.17) and -0.99 (95% CI -1.74, -0.24), respectively.nnnCONCLUSIONnCalcium-channel blockers for RP in SSc have been tested in several small clinical trials and appear to lead to significant clinical improvement in both the frequency and the severity of ischemic attacks. Most trials were crossover trials in which order effect was not studied. This could have introduced bias. The results of this study suggest that the efficacy of calcium-channel blockers in reducing the severity and frequency of ischemic attacks in RP secondary to SSc is moderate at best (mean reduction of 8.3 attacks in 2 weeks and 35% less severity), and a further large, randomized controlled trial needs to be conducted.

PRISMA-Equity 2012 Extension: reporting guidelines for systematic reviews with a focus on health equity

Vivian Welch and colleagues present consensus-based guidelines for reporting equity-focused systematic reviews, the PRISMA-Equity extension.

Assessing equity in systematic reviews: realising the recommendations of the Commission on Social Determinants of Health

A group from the Cochrane Collaboration, Campbell Collaboration, and the World Health Organization Measurement and Evidence Knowledge Network has developed guidance on assessing health equity effects in systematic reviews of healthcare interventions. This guidance is also relevant to primary research

Do silicone breast implants cause rheumatologic disorders? A systematic review for a court-appointed national science panel.

OBJECTIVEnTo assist in evaluating expert testimony and scientific evidence presented in law suits brought against silicone breast implant manufacturers, a US District Court Order established a National Science Panel to assess whether existing studies provide scientific evidence of an association between silicone breast implants and systemic classic/accepted connective disease, atypical connective disease, and certain signs and symptoms identified by plaintiffs in the law suits. Local disorders potentially associated with these implants were not addressed in this review. Therefore, we performed a systematic review of published studies on the association between silicone breast implants and systemic connective tissue disorders.nnnMETHODSnData from relevant studies (human cohort, case-control, or cross-sectional studies with > or = 10 participants and appropriate controls) were identified through literature searches of Medline, Current Contents, HealthStar, Biological Abstracts, EMBase, Toxline, and Dissertation Abstracts. Two independent reviewers, using standard collection forms, extracted data from the included studies. Adjusted relative risks (RRs) in cohort studies and odds ratios (ORs) in case-control and cross-sectional studies were reported if provided; otherwise, unadjusted RRs and ORs were calculated.nnnRESULTSnTwenty-four studies meeting inclusion criteria were identified. No association was evident between breast implants and any established or atypical connective tissue disorder. There was discordance among studies in reports of arthralgias, lymphadenopathy, myalgias, sicca symptoms, skin changes, and stiffness.nnnCONCLUSIONnThe panel found no evidence to support expert testimony suggesting an association between silicone breast implants and connective diseases. Discordance for symptoms may reflect differences in symptoms included in various categories, the small number of cases, and the effect of having single subjects with > 1 symptom represented in analyses of each symptom reported. The process presented here is an early example of the use of independent scientific panels to help courts clarify scientific evidence in legal proceedings.

Calcitonin for preventing and treating corticosteroid‐induced osteoporosis

BACKGROUND Corticosteroid-induced osteoporosis is a cause of morbidity in patients with chronic obstructive lung disease, asthma, and rheumatologic disorders. Corticosteroid treatment causes bone loss by a variety of complex mechanisms. It has been shown that bone mineral loss at the hip averages 14% in the first year after starting corticosteroid therapy. OBJECTIVES To review the efficacy of calcitonin (subcutaneous or nasal) for the treatment and prevention of corticosteroid-induced osteoporosis. SEARCH STRATEGY We conducted a search of Medline, the Cochrane Controlled Trials Register and Embase using the Cochrane Musculoskeletal Group search strategy for randomized controlled trials (RCTs) up to May 1998. We also searched bibliographic references and consulted content experts. SELECTION CRITERIA Two independent reviewers selected RCTs which met predetermined inclusion criteria. DATA COLLECTION AND ANALYSIS Two reviewers independently extracted data using predetermined forms and assessed methodological quality of randomization, blinding and dropouts. For dichotomous outcomes, relative risks (RR) were calculated. For continuous data, weighted mean differences (WMD) of the percent change from baseline were calculated. We decided a priori to use random effects models for all outcomes, because of uncertainty about whether a consistent true effect exists in such different populations. MAIN RESULTS Nine trials met the inclusion criteria, including 221 patients randomized to calcitonin and 220 to placebo. The median methodologic quality was two out of a maximum of five points. Calcitonin was more effective than placebo at preserving bone mass at the lumbar spine after six and 12 months of therapy with a WMD of 2.8% (95% CI: 1.4 to 4.3) and 3.2% (95% CI: 0.3 to 6.1). At 24 months, lumbar spine BMD was not statistically different between groups: WMD 4.5% (95% CI: -0.6 to 9.5)]. Bone density at the distal radius was also higher with calcitonin after six months of therapy, but bone density at the femoral neck was not different between placebo and calcitonin treated groups. The relative risk of fractures was not significantly different between calcitonin and placebo with a relative risk (RR) of 0.71 (95% CI: 0.26 to 1.89) for vertebral and 0.52 (95% CI: 0.14 to 1.96) for nonvertebral fractures. The subgroup analyses of methodological quality and duration of corticosteroid therapy were confounded. Trials of patients who had been taking steroids for greater than three months (which were of low methodologic quality) demonstrated a larger effect of calcitonin on spine bone density (about 6%) than prevention trials (about 1%). There was no consistent effect of different dosages (50-100 IU compared to 200-400 IU). However, subcutaneous calcitonin showed substantially greater prevention of bone loss. Withdrawals due to side effects were higher in the calcitonin-treated groups: RR 3.19 (95%CI: 0.66 to 15.47). Important side effects included nausea and facial flushing. REVIEWERS CONCLUSIONS Calcitonin appears to preserve bone mass in the first year of glucocorticoid therapy at the lumbar spine by about 3% compared to placebo, but not at the femoral neck. Our analysis suggests that the protective effect on bone mass may be greater for the treatment of patients who have been taking corticosteroids for more than three months. Efficacy of calcitonin for fracture prevention in steroid-induced osteoporosis remains to be established.

Cost effectiveness of nasal calcitonin in postmenopausal women: use of Cochrane Collaboration methods for meta-analysis within economic evaluation.

AbstractObjective: To assess the cost effectiveness of nasal calcitonin (Miacalcin®) compared with no therapy, alendronate or etidronate in the treatment of postmenopausal women with previous osteoporotic fracture.n Design and setting: Meta-analysis followed by economic analysis.n Perspective: A Canadian provincial Ministry of Health.n Methods: The meta-analysis of randomised controlled clinical trials was based on the recommendations of the Cochrane Collaboration. Economic analysis was conducted within a Markov model using probabilities and costs derived from Canadian sources.n Results: The meta-analysis found evidence of the positive effect of both nasal calcitonin and alendronate in reducing the risks of hip, wrist and vertebral fractures in postmenopausal women. However, there was a lack of evidence of the effect of etidronate on hip and wrist fractures. For a 65-year-old woman, with 5 years’ therapy, the incremental cost per quality-adjusted life-year (QALY) gained for nasal calcitonin was 46 500 Canadian dollars (

A review of economic evaluation in osteoporosis

Can) compared with no therapy and

Reliability and Validity of a New Survey to Assess Global Health Competencies of Health Professionals

Can32 600 compared with etidronate (1998 values). Comparison with alendronate was highly sensitive to the inclusion of one specific trial.n Conclusions: Given the results of the analysis, based on current evidence, nasal calcitonin can be considered at themargins of being cost effectiv ewhen compared with no therapy. Compared with active therapy, nasal calcitonin can be considered more cost effective than etidronate, but its cost effectiveness versus alendronate is inconclusive.

Evidence in agenda setting: new directions for the Cochrane Collaboration

Economic evaluation of therapeutic agents in rheumatology is receiving increased attention. A recent overview by Bosi Ferraz et al outlined the economic evaluations conducted in rheumatology (1). The authors identified 36 full economic evaluations, 8 (22%) of which evaluated drugs or screening methods for osteoporosis. The main intervention studied was hormone replacement therapy (HRT). Osteoporosis is a chronic metabolic bone disease manifested by fragility fractures that represent a significant economic burden to society. In the United States the cost of treating osteoporosis-related fractures each year is estimated to be

Including Health Equity Considerations in Development of Instruments for Rheumatology Research: An Introduction to a Novel OMERACT Paradigm

13.8 billion (2). It has been predicted that the number of hip fractures will triple by 2040 (3). The goal of this review is to provide an overview of the existing economic evaluations of therapies for osteoporosis and a framework with which to interpret them. There are now many therapeutic options available to treat osteoporosis, and even more agents are under investigation. The potential costs of drug therapy for the prevention and treatment of osteoporosis represent a considerable burden to those who are paying for them—consumers, third-party payers, governments. Approaches to limit increasing costs of medications have been developed in many countries; these include drug pricing, refusal to add drugs to the formulary that are not cheaper than existing drugs, or limiting the amount of money available for a given drug. Economic evaluation has been recommended as a means to assist in the efficient allocation of health care resources. Economic evaluation differs from a simple costing exercise in that it is concerned not only with the costs associated with a drug, but with the health benefits obtained. An evaluation will involve the purchase price of the drug, the costs of monitoring treatment, and the treatment of adverse effects (direct costs). An economic evaluation should also incorporate the relative benefits of medication such as reduction in fractures, decreased hospitalization costs, and improved quality of life. In this review we will describe the key elements of economic evaluations in the field of osteoporosis by reviewing published economic evaluations.