Do anti-TNF agents have equal efficacy in patients with rheumatoid arthritis?

Tumor necrosis factor (TNF) antagonists have dramatically improved the outcomes of rheumatoid arthritis (RA). Three agents currently available in the USA – infliximab, etanercept, and adalimumab – have been designed to modify the biologic effects of TNF. Infliximab and adalimumab are monoclonal antibodies, and etanercept is a soluble protein. The pharmacokinetic and pharmacodynamic properties of each differs significantly from those of the others. All three agents are effective and safe, and can improve the quality of life in patients with RA. Although no direct comparisons are available, clinical trials provide evidence that can be used to evaluate the comparative efficacy of these agents. Infliximab, in combination with methotrexate, has been shown to relieve the signs and symptoms of RA, decrease total joint score progression, prevent joint erosions and joint-space narrowing, and improve physical function for up to 2 years. Etanercept has been shown to relieve the signs and symptoms of RA, decrease total joint score progression, and slow the rate of joint destruction, and might improve physical function. Etanercept is approved with and without methotrexate for patients who have demonstrated an incomplete response to therapy with methotrexate and other disease-modifying anti-rheumatic drugs (DMARDs), as well as for first-line therapy in early RA, psoriatic arthritis, and juvenile RA. Adalimumab relieves the signs and symptoms of RA with and without methotrexate and other DMARDs, decreases total joint score progression, prevents joint erosions and joint-space narrowing in combination with methotrexate, and might improve physical function. When selecting a TNF antagonist, rheumatologists should weigh evidence and experience with specific agents before a decision is made for use in therapy

Risk factors for incident falls in older men and women:The English longitudinal study of ageing

Background: falls are a major cause of disability and death in older people, particularly women. Cross-sectional surveys suggest that some risk factors associated with a history of falls may be sex-specific, but whether risk factors for incident falls differ between the sexes is unclear. We investigated whether risk factors for incident falls differ between men and women.Methods: participants were 3298 people aged ≥60 who took part in the Waves 4-6 surveys of the English Longitudinal Study of Ageing. At Wave 4, they provided information about sociodemographic, lifestyle, behavioural and medical factors and had their physical and cognitive function assessed. Data on incident falls during the four-year follow-up period was collected from them at Waves 5 and 6. Poisson regression with robust variance estimation was used to derive relative risks (RR) for the association between baseline characteristics and incident falls.Results: in multivariable-adjusted models that also controlled for history of falls, older age was the only factor associated with increased risk of incident falls in both sexes. Some factors were only predictive of falls in one sex, namely more depressive symptoms (RR (95% CI) 1.03 (1.01,1.06)), incontinence (1.12 (1.00,1.24)) and never having married in women (1.26 (1.03,1.53)), and greater comorbidity (1.04 (1.00,1.08)), higher levels of pain (1.10 (1.04,1.17) and poorer balance, as indicated by inability to attempt a full-tandem stand, (1.23 (1.04,1.47)) in men. Of these, only the relationships between pain, balance and comorbidity and falls risk differed significantly by sex.Conclusions: there were some differences between the sexes in risk factors for incident falls. Our observation that associations between pain, balance and comorbidity and incident falls risk varied by sex needs further investigation in other cohorts. <br/

Mechanisms of Vasorelaxation

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72633/1/j.1527-3466.1992.tb00249.x.pd

Efficacy of a multifaceted podiatry intervention to improve balance and prevent falls in older people: study protocol for a randomised trial

<p>Abstract</p> <p>Background</p> <p>Falls in older people are a major public health problem, with at least one in three people aged over 65 years falling each year. There is increasing evidence that foot problems and inappropriate footwear increase the risk of falls, however no studies have been undertaken to determine whether modifying these risk factors decreases the risk of falling. This article describes the design of a randomised trial to evaluate the efficacy of a multifaceted podiatry intervention to reduce foot pain, improve balance, and reduce falls in older people.</p> <p>Methods</p> <p>Three hundred community-dwelling men and women aged 65 years and over with current foot pain and an increased risk of falling will be randomly allocated to a control or intervention group. The "usual cae" control group will receive routine podiatry (i.e. nail care and callus debridement). The intervention group will receive usual care plus a multifaceted podiatry intervention consisting of: (i) prefabricated insoles customised to accommodate plantar lesions; (ii) footwear advice and assistance with the purchase of new footwear if current footwear is inappropriate; (iii) a home-based exercise program to strengthen foot and ankle muscles; and (iv) a falls prevention education booklet. Primary outcome measures will be the number of fallers, number of multiple fallers and the falls rate recorded by a falls diary over a 12 month period. Secondary outcome measures assessed six months after baseline will include the Medical Outcomes Study Short Form 12 (SF-12), the Manchester Foot Pain and Disability Index, the Falls Efficacy Scale International, and a series of balance and functional tests. Data will be analysed using the intention to treat principle.</p> <p>Discussion</p> <p>This study is the first randomised trial to evaluate the efficacy of podiatry in improving balance and preventing falls. The trial has been pragmatically designed to ensure that the findings can be generalised to clinical practice. If found to be effective, the multifaceted podiatry intervention will be a unique addition to common falls prevention strategies already in use.</p> <p>Trial registration</p> <p>Australian New Zealand Clinical Trials Registry: ACTRN12608000065392</p

Biomechanical spinal growth modulation and progressive adolescent scoliosis – a test of the 'vicious cycle' pathogenetic hypothesis: Summary of an electronic focus group debate of the IBSE

There is no generally accepted scientific theory for the causes of adolescent idiopathic scoliosis (AIS). As part of its mission to widen understanding of scoliosis etiology, the International Federated Body on Scoliosis Etiology (IBSE) introduced the electronic focus group (EFG) as a means of increasing debate on knowledge of important topics. This has been designated as an on-line Delphi discussion. The text for this debate was written by Dr Ian A Stokes. It evaluates the hypothesis that in progressive scoliosis vertebral body wedging during adolescent growth results from asymmetric muscular loading in a "vicious cycle" (vicious cycle hypothesis of pathogenesis) by affecting vertebral body growth plates (endplate physes). A frontal plane mathematical simulation tested whether the calculated loading asymmetry created by muscles in a scoliotic spine could explain the observed rate of scoliosis increase by measuring the vertebral growth modulation by altered compression. The model deals only with vertebral (not disc) wedging. It assumes that a pre-existing scoliosis curve initiates the mechanically-modulated alteration of vertebral body growth that in turn causes worsening of the scoliosis, while everything else is anatomically and physiologically 'normal' The results provide quantitative data consistent with the vicious cycle hypothesis. Dr Stokes' biomechanical research engenders controversy. A new speculative concept is proposed of vertebral symphyseal dysplasia with implications for Dr Stokes' research and the etiology of AIS. What is not controversial is the need to test this hypothesis using additional factors in his current model and in three-dimensional quantitative models that incorporate intervertebral discs and simulate thoracic as well as lumbar scoliosis. The growth modulation process in the vertebral body can be viewed as one type of the biologic phenomenon of mechanotransduction. In certain connective tissues this involves the effects of mechanical strain on chondrocytic metabolism a possible target for novel therapeutic intervention

Recent insights into targeting the IL-6 cytokine family in inflammatory diseases and cancer

The IL-6 family of cytokines consists of IL-6, IL-11, IL-27, IL-31, oncostatin M (OSM), leukaemia inhibitory factor (LIF), ciliary neurotrophic factor (CNTF), cardiotrophin 1 (CT-1) and cardiotrophin-like cytokine factor 1 (CLCF1). Membership of this cytokine family is defined by usage of common β-receptor signalling subunits, which activate various intracellular signalling pathways. Each IL-6 family member elicits responses essential to the physiological control of immune homeostasis, haematopoiesis, inflammation, development and metabolism. Accordingly, distortion of these cytokine activities often promotes chronic disease and cancer; the pathological importance of this is exemplified by the successful treatment of certain autoimmune conditions with drugs that target the IL-6 pathway. Here, we discuss the emerging roles for IL-6 family members in infection, chronic inflammation, autoimmunity and cancer and review therapeutic strategies designed to manipulate these cytokines in disease