Objective: To develop evidence based recommendations for the management of ankylosing spondylitis (AS) as a combined effort of the 'ASsessment in AS' international working group and the European League Against Rheumatism. Methods: Each of the 22 participants was asked to contribute up to 15 propositions describing key clinical aspects of AS management. A Delphi process was used to select 10 final propositions. A systematic literature search was then performed to obtain scientific evidence for each proposition. Outcome data for efficacy, adverse effects, and cost effectiveness were abstracted. The effect size, relative risk, number needed to treat, and incremental cost effectiveness ratio were calculated. On the basis of the search results, 10 major recommendations for the management of AS were constructed. The strength of recommendation was assessed based on the strength of the literature evidence, risk-benefit trade-off, and clinical expertise. Results: The final recommendations considered the use of non-steroidal anti-inflammatory drugs (NSAIDs) (conventional NSAIDs, coxibs, and co-prescription of gastroprotective agents), disease modifying antirheumatic drugs, treatments with biological agents, simple analgesics, local and systemic steroids, non-pharmacological treatment (including education, exercise, and physiotherapy), and surgical interventions. Three general recommendations were also included. Research evidence (categories I-IV) supported 11 interventions in the treatment of AS. Strength of recommendation varied, depending on the category of evidence and expert opinion. Conclusion: Ten key recommendations for the treatment of AS were developed and assessed using a combination of research based evidence and expert consensus. Regular updating will be carried out to keep abreast of new developments in the management of AS.A nkylosing spondylitis (AS) is a chronic, inflammatory rheumatic disease characterised by inflammatory back pain due to sacroiliitis and spondylitis, the formation of syndesmophytes leading to ankylosis, and frequently associated with peripheral arthritis, enthesitis, and acute anterior uveitis. Symptoms commonly begin in late adolescence and early adulthood.1 2 With an estimated prevalence of 0.9% in northern European white populations 3 AS is a significant health burden to the community.AS has long been a therapeutic challenge for the clinician. Exercise and non-steroidal anti-inflammatory drugs (NSAIDs) have been the mainstay of symptom control for decades, but there has until recently been a dearth of disease modifying treatments. The advent of biological treatment is currently revolutionising the management of AS, but too little is known yet about the long term benefits and risks of such treatment. Clearly, these treatments necessitate socioeconomic cost calculations. Moreover, there is a need for rational, evidence based recommendations to guide the physician in the management of AS. The ASsessment in AS (ASAS) international working group has made important contributions to the eval...
Objectives:To develop evidence-based recommendations for the use of methotrexate in daily clinical practice in rheumatic disorders.Methods:751 rheumatologists from 17 countries participated in the 3E (Evidence, Expertise, Exchange) Initiative of 2007–8 consisting of three separate rounds of discussions and Delphi votes. Ten clinical questions concerning the use of methotrexate in rheumatic disorders were formulated. A systematic literature search in Medline, Embase, Cochrane Library and 2005–7 American College of Rheumatology/European League Against Rheumatism meeting abstracts was conducted. Selected articles were systematically reviewed and the evidence was appraised according to the Oxford levels of evidence. Each country elaborated a set of national recommendations. Finally, multinational recommendations were formulated and agreement among the participants and the potential impact on their clinical practice was assessed.Results:A total of 16 979 references was identified, of which 304 articles were included in the systematic reviews. Ten multinational key recommendations on the use of methotrexate were formulated. Nine recommendations were specific for rheumatoid arthritis (RA), including the work-up before initiating methotrexate, optimal dosage and route, use of folic acid, monitoring, management of hepatotoxicity, long-term safety, mono versus combination therapy and management in the perioperative period and before/during pregnancy. One recommendation concerned methotrexate as a steroid-sparing agent in other rheumatic diseases.Conclusions:Ten recommendations for the use of methotrexate in daily clinical practice focussed on RA were developed, which are evidence based and supported by a large panel of rheumatologists, enhancing their validity and practical use.
We aimed to develop evidence-based multinational recommendations for the diagnosis and management of gout. Using a formal voting process, a panel of 78 international rheumatologists developed 10 key clinical questions pertinent to the diagnosis and management of gout. Each question was investigated with a systematic literature review. Medline, Embase, Cochrane CENTRAL and abstracts from 2010–2011 European League Against Rheumatism and American College of Rheumatology meetings were searched in each review. Relevant studies were independently reviewed by two individuals for data extraction and synthesis and risk of bias assessment. Using this evidence, rheumatologists from 14 countries (Europe, South America and Australasia) developed national recommendations. After rounds of discussion and voting, multinational recommendations were formulated. Each recommendation was graded according to the level of evidence. Agreement and potential impact on clinical practice were assessed. Combining evidence and clinical expertise, 10 recommendations were produced. One recommendation referred to the diagnosis of gout, two referred to cardiovascular and renal comorbidities, six focused on different aspects of the management of gout (including drug treatment and monitoring), and the last recommendation referred to the management of asymptomatic hyperuricaemia. The level of agreement with the recommendations ranged from 8.1 to 9.2 (mean 8.7) on a 1–10 scale, with 10 representing full agreement. Ten recommendations on the diagnosis and management of gout were established. They are evidence-based and supported by a large panel of rheumatologists from 14 countries, enhancing their utility in clinical practice.
Systemic sclerosis (SSc) is an autoimmune disease that shows one of the highest mortality rates among rheumatic diseases. We perform a large genome-wide association study (GWAS), and meta-analysis with previous GWASs, in 26,679 individuals and identify 27 independent genome-wide associated signals, including 13 new risk loci. The novel associations nearly double the number of genome-wide hits reported for SSc thus far. We define 95% credible sets of less than 5 likely causal variants in 12 loci. Additionally, we identify specific SSc subtype-associated signals. Functional analysis of high-priority variants shows the potential function of SSc signals, with the identification of 43 robust target genes through HiChIP. Our results point towards molecular pathways potentially involved in vasculopathy and fibrosis, two main hallmarks in SSc, and highlight the spectrum of critical cell types for the disease. This work supports a better understanding of the genetic basis of SSc and provides directions for future functional experiments.
Early mortality in SSc is substantial, and prevalent cohorts underestimate mortality in SSc by failing to capture early deaths, particularly in men and those with diffuse disease.
Extensive disease (>20%) on HRCT at baseline, reported using a semi-quantitative grading system, is associated with a three-fold increased risk of deterioration or death in SSc-ILD, compared with limited disease. Serial PFTs are informative in follow-up of patients.
The findings indicate that there are different risk factors for falls for people living in residential aged care facilities who can and cannot stand unaided. These findings provide important information for developing fall-prevention strategies and suggest that those who can stand unaided but have multiple falls risk factors constitute the highest priority group for such interventions.
Objective: To assess available management strategies in ankylosing spondylitis (AS) using a systematic approach, as a part of the development of evidence based recommendations for the management of AS. Methods: A systematic search of Medline, Embase, CINAHL, PEDro, and the Cochrane Library was performed to identify relevant interventions for the management of AS. Evidence for each intervention was categorised by study type, and outcome data for efficacy, adverse effects, and cost effectiveness were abstracted. The effect size, rate ratio, number needed to treat, and incremental cost effectiveness ratio were calculated for each intervention where possible. Results from randomised controlled trials were pooled where appropriate. Results: Both pharmacological and non-pharmacological interventions considered to be of interest to clinicians involved in the management of AS were identified. Good evidence (level Ib) exists supporting the use of non-steroidal anti-inflammatory drugs (NSAIDs) and coxibs for symptomatic treatment. Nonpharmacological treatments are also supported for maintaining function in AS. The use of conventional antirheumatoid arthritis drugs is not well supported by high level research evidence. Tumour necrosis factor inhibitors (infliximab and etanercept) have level Ib evidence supporting large treatment effects for spinal pain and function in AS over at least 6 months. Level IV evidence supports surgical interventions in specific patients. Conclusion: This extensive literature review forms the evidence base considered in the development of the new ASAS/EULAR recommendations for the management of AS.A nkylosing spondylitis (AS) is a chronic inflammatory rheumatic disease most commonly affecting the axial skeleton, which historically has been difficult to treat. Recent years have seen the introduction of exciting new therapeutic strategies, particularly the tumour necrosis factor inhibitors. Therefore it is important that clinicians are aware of the relative benefits and risks of the different treatments available to them, and have evidence based information about which strategies are the most efficacious in particular patient settings.The ASsessment in AS (ASAS) International Working Group, in collaboration with the European League Against Rheumatism (EULAR), recently developed evidence based recommendations for the management of AS 1 to assist all health professionals involved in the care of patients with AS.The recommendations were developed using information from two major sources: a systematic review of the literature, and expert opinion based on the research evidence and clinical expertise.1 This review details the literature search performed and the results presented to the expert committee for the purpose of developing recommendations for the management of AS. METHODSA systematic search of the literature published between January 1966 and December 2004 was undertaken using Medline, Embase, CINHAL, PEDro, and Cochrane Library databases. The search included both a general search and an interve...
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