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Permanent Rheumatology Job in 45 minutes from Raleigh North Carolina with Enterprise Medical Services
Seeking BC/BE Rheumatologist to join one other in practice. There will be no medical call. Every other month call for Rheumatology. Competitive 1st year income guarantee. Production base from two
Permanent Rheumatology Job in Mayfield., MA Position Massachusetts with Enterprise Medical Services
Hospital system is seeking a Rheumatologist to cover the Mansfield, MA area. Physician will share office space with several Internal Medicine, Family Medicine and Mid-Level providers. Work 35 hours
Permanent Rheumatology Job in Northeast Wisconsin with Horton Smith Associates
Seeking a BC/BE Rheumatologist to join a state-of-the-art musculoskeletal center. The organization has developed a three-tier system, known as Orthopedics Plus. This program provides comprehensive,

Arthritis Research & Therapy - Latest articles

Trends towards improved disease state in Rheumatoid Arthritis over time: the influence of new therapies and changes in management approach: analysis of the EMECAR cohort
Isidoro Gonzalez-Alvaro, Miguel A Descalzo, Loreto Carmona and The EMECAR Study group Wed, 26 Nov 2008 00:00:00 -0000
IntroductionThe disease activity in patients with rheumatoid arthritis has improved during the past decade. The availability of new drugs and also a better assessment of the disease have been proposed to be responsible for this improvement. In the present work we estimate the effect of these factors on disease activity and function in patients with rheumatoid arthritis at the beginning of the new century. Methods: The Estudio de la Morbilidad y Expresion Clinica de la Artritis Reumatoide (EMECAR) cohort was assembled in 2000 from the random sampling of rheumatoid arthritis patients registered in 34 centers. The cohort was composed of 789 patients who underwent a baseline assessment plus four annual follow-up visits in which functional ability (Health Assessment Questionnaire score), the disease activity score obtained from 28-joint count with three parameters (DAS28-3) and radiological progression (Larsen score) were recorded. The effect of the calendar year on the DAS28-3, the Health Assessment Questionnaire score, and the Larsen score was obtained from adjusted models in which all treatments were included as dummy variables. Results: The effect of time as the b coefficient (95% confidence interval) for 2004, taking 2000 as a reference year, was -0.43 (-0.58 to -0.28) for the DAS28-3, 0.15 (0.07 to 0.22) for the Health Assessment Questionnaire score, and 4.4 (2.68 to 6.12) for the Larsen score. Treatment with new therapies, either leflunomide or TNF antagonists, increased in frequency from 1.1% (n = 8) in 2000 to 30.9% (n = 144) in 2004. Treatment with TNF antagonists (-0.28 (-0.5 to -0.05)) and with gold salts (-0.21 (-0.38 to -0.04)) was independently associated with a decrease in the DAS28-3 over time, whereas cyclosporin A treatment (0.45 (0.13 to 0.76)) was associated with an increase in disease activity. Conclusions: The mean disease activity of rheumatoid arthritis has improved from 2000 to 2004. An explanation is the introduction of new therapies, but not solely. Other factors related to the calendar year, plausibly a better management of available drugs, show a greater effect on improvement than the drugs used.
Identification of possible candidate genes regulating Sjogren's syndrome-associated autoimmunity: a potential role for TNFSF4 in autoimmune exocrinopathy
Cuong Q Nguyen, Janet G Cornelius, Lauren Cooper, Jonathan Neff, Joann Tao, Byung Ha Lee and Ammon B Peck Tue, 25 Nov 2008 00:00:00 -0000
IntroductionSjogren's syndrome is a systemic autoimmune disease in which an immunological attack primarily against the salivary and lacrimal glands results in loss of acinar cell tissue and function leading to stomatitis sicca and keratoconjunctivitis sicca. In recent years, two genetic regions, one on chromosome 1 (designated autoimmune exocrinopathy 2 or Aec2) and the second on chromosome 3 (designated autoimmune exocrinopathy 1 or Aec1) derived from non-obese diabetic mice, have been shown to be necessary and sufficient to replicate Sjogren's syndrome-like disease in non-susceptible C57BL/6 mice. Methods: Starting with the Sjogren's syndrome-susceptible C57BL/6-derived mouse, referred to as C57BL/6.NOD-Aec1Aec2, we generated a large set of recombinant inbred lines containing portions of autoimmune exocrinopathy 2 as a means of identifying more precisely the genetic elements of chromosome 1 responsible for disease development. Results: Disease profiling of these recombinant inbred lines has revealed that the Sjogren's syndrome-susceptibility genes of autoimmune exocrinopathy 2 lie within a region located at approximately 79 +/- 5 centimorgan distal to the centromere, as defined by microsatellite markers. This chromosomal region contains several sets of genes known to correlate with various immuno-pathological features of SjS, as well as disease susceptibility genes for both type 1 diabetes and systemic lupus erythematosus in mice. One gene in particular, tumor necrosis factor (ligand) superfamily, member 4 (or Ox40 ligand), encoding a product whose biological functions correlate with both physiological homeostasis and immune regulations, could be a potential candidate Sjogren's syndrome-susceptibility gene. Conclusions: These new recombinant inbred lines not only represent the first step in fine mapping a Sjogren's syndrome-susceptibility locus, but also in identifying potential candidate Sjogren's syndrome-susceptibility genes. Identification of possible candidate genes permits construction of models describing underlying molecular pathogenic mechanisms in this model of Sjogren's syndrome and establishes a basis for construction of specific gene knockout mice.
Fibromyalgia and sleep-disordered breathing: the missing link – author's response
Jean Eisinger Tue, 25 Nov 2008 00:00:00 -0000
Fibromyalgia: the labyrinth
Fibromyalgia and sleep-disordered breathing: the missing link
Denis Martinez and Cristiane Maria Cassol Tue, 25 Nov 2008 00:00:00 -0000
none
NOD-like receptors and inflammation
Rebeccah J Mathews, Michael B Sprakes and Michael F McDermott Tue, 25 Nov 2008 00:00:00 -0000
The nucleotide-binding and oligomerisation domain, leucine rich repeat (also known as NOD-like receptors, both of which are abbreviated to the symbol NLR) family of intracellular pathogen recognition receptors (PRRs) are increasingly being recognised to play a pivotal role in the pathogenesis of a number of rare monogenic diseases, as well as some more common polygenic conditions. Bacterial wall constituents and other cellular stressor molecules are recognised by a range of different NLRs, which leads to activation of the innate immune response and upregulation of key proinflammatory pathways, such as IL-1beta production and translocation of NF-kB to the nucleus. These signalling pathways are increasingly being targeted as potential sites for new therapies. This review discusses the role of NLRs in a variety of inflammatory diseases and describes the remarkable success to date of these therapeutic agents in treating some of the disorders associated with aberrant NLR function.
Epitope spreading in animal models: array of hope in rheumatoid arthritis and multiple sclerosis
Karin Lundberg and Patrick J Venables Tue, 25 Nov 2008 00:00:00 -0000
The paradigm for pathogenic autoimmunity is the generation of high-titre, affinity-matured autoantibodies to a restricted family of autoantigens, in the appropriate genetic context. Genetic determinants of autoimmunity are largely found within the major histocompatibility complex (MHC) and the "genotype to serotype to phenotype" concept is supported in a number of autoimmune diseases, where both genotype and serotype are well established. The serotype is autoantigen-driven, with evidence of epitope spreading as the disease evolves from asymptomatic to pathogenic autoimmunity. In rheumatoid arthritis and multiple sclerosis, where the autoantigens are poorly characterised, the use of an array in animal models may produce a hint of what happens in human disease. A more complete picture will be obtained from animals transgenic for human MCH, immunised with known human autoantigens.

Annals of the Rheumatic Diseases current issue

[Editorials] The art of medicine in treating osteoarthritis: I will please
Bijlsma, J W J, Welsing, P M J Wed, 12 Nov 2008 00:00:00 -0000

[Recommendation] EULAR recommendations for the management of Behcet disease
Hatemi, G, Silman, A, Bang, D, Bodaghi, B, Chamberlain, A M, Gul, A, Houman, M H, Kotter, I, Olivieri, I, Salvarani, C, Sfikakis, P P, Siva, A, Stanford, M R, Stubiger, N, Yurdakul, S, Yazici, H Wed, 12 Nov 2008 00:00:00 -0000
Objectives: To develop evidence-based European League Against Rheumatism (EULAR) recommendations for the management of Behçet disease (BD) supplemented where necessary by expert opinion. Methods: The multidisciplinary expert committee, a task force of the EULAR Standing Committee for Clinical Affairs (ESCCA), consisted of nine rheumatologists (one who was also a clinical epidemiologist and one also a Rehabilitation Medicine doctor), three ophthalmologists, one internist, one dermatologist and one neurologist, representing six European countries plus Tunisia and Korea. A patient representative was also present. Problem areas and related keywords for systematic literature research were identified. Systematic literature research was performed using Medline and the Cochrane Library databases from 1966 through to December 2006. A total of 40 initial statements were generated based on the systematic literature research. These yielded the final recommendations developed from two blind Delphi rounds of voting. Results: Nine recommendations were developed for the management of different aspects of BD. The strength of each recommendation was determined by the level of evidence and the experts’ opinions. The level of agreement for each recommendation was determined using a visual analogue scale for the whole committee and for each individual aspect by the subgroups, who consider themselves experts in that field of BD. There was excellent concordance between the level of agreement of the whole group and the "experts in the field". Conclusion: Recommendations related to the eye, skin–mucosa disease and arthritis are mainly evidence based, but recommendations on vascular disease, neurological and gastrointestinal involvement are based largely on expert opinion and uncontrolled evidence from open trials and observational studies. The need for further properly designed controlled clinical trials is apparent.
[Reviews] Gene expression profiling in rheumatoid arthritis: current concepts and future directions
Toonen, E J M, Barrera, P, Radstake, T R D J, van Riel, P L C M, Scheffer, H, Franke, B, Coenen, M J H Wed, 12 Nov 2008 00:00:00 -0000
Over the last years microarray technologies have generated new perspectives for the high-throughput analysis of biological systems. Nowadays, it is possible to monitor thousands of genes in a single experiment. This molecular profiling technology combined with standardised and validated clinical measurements can allow a more precise characterisation of a patient’s phenotype, and may lead to the design of therapeutic protocols and procedures better tailored to an individual patient’s needs. In this report we provide an overview of expression profiling studies in rheumatoid arthritis (RA). RA is a chronic inflammatory disease in which both genetic and environmental factors are involved. The precise molecular mechanisms underlying RA are not fully understood. A systematic literature search revealed nine array-based expression profiling studies in patients with RA. Findings from these studies were compared with those of linkage and genome-wide association (GWA) studies. Although we observed many differences in study design, analysis and interpretation of results between the different studies, we extracted two sets of genes: (1) those differentially expressed in more than one study, and (2) genes differentially expressed in at least one of the reviewed studies and present in RA linkage or GWA loci. We suggest that both sets of genes include interesting candidate genes for further study in RA.
[Clinical and epidemiological research] A high incidence of disease flares in an open pilot study of infliximab in patients with refractory inflammatory myopathies
Dastmalchi, M, Grundtman, C, Alexanderson, H, Mavragani, C P, Einarsdottir, H, Helmers, S B., Elvin, K, Crow, M K, Nennesmo, I, Lundberg, I E Wed, 12 Nov 2008 00:00:00 -0000
Objective: To investigate the effect of the tumour necrosis factor (TNF) blocking agent infliximab in patients with treatment-resistant inflammatory myopathies. Methods: A total of 13 patients with refractory polymyositis (PM), dermatomyositis (DM), or inclusion body myositis (IBM) were treated with 4 infliximab infusions (5 mg/kg body weight) over 14 weeks. Outcome measures included myositis disease activity score with improvement defined according to The International Myositis Assessment and Clinical Studies Group (IMACS), and MRI. Repeated muscles biopsies were investigated for cellular infiltrates, major histocompatibility complex (MHC) class I and II, TNF, interleukin (IL)1, IL6, high mobility group box chromosomal protein 1 (HMGB-1), interferon (IFN), myxovirus resistance protein A (MxA) and membrane attack complex (MAC) expression. Type I IFN activity was analysed in sera. Results: Nine patients completed the study. Three patients discontinued due to adverse events and one due to a discovered malignancy. Three of the completers improved by >=20% in three or more variables of the disease activity core set, four were unchanged and two worsened >=30%. No patient improved in muscle strength by manual muscle test. At baseline, two completers had signs of muscle inflammation by MRI, and five at follow-up. T lymphocytes, macrophages, cytokine expression and MAC deposition in muscle biopsies were still evident after treatment. Type I IFN activity was increased after treatment. Conclusions: Infliximab treatment was not effective in refractory inflammatory myopathies. In view of radiological and clinical worsening, and activation of the type I IFN system in several cases, infliximab is not an alternative treatment in patients with treatment-resistant myositis.
[Clinical and epidemiological research] The optimal assessment of the rheumatoid arthritis hindfoot: a comparative study of clinical examination, ultrasound and high field MRI
Wakefield, R J, Freeston, J E, O'Connor, P, Reay, N, Budgen, A, Hensor, E M A, Helliwell, P S, Emery, P, Woodburn, J Wed, 12 Nov 2008 00:00:00 -0000
Objectives: The aim of this pilot study was to compare clinical examination (CE) and ultrasound (US) with high field MRI (as the reference standard) for the detection of rearfoot and midtarsal joint synovitis and secondly tenosynovitis of the ankle tendons in patients with established rheumatoid arthritis (RA). Methods: Patients with RA (as determined by the modified American College of Rheumatology (ACR) criteria) with symptoms of midfoot and rearfoot disease were recruited. Demographic data were collected. All underwent CE, US and high field MRI (with intravenous gadolinium contrast) of their right foot. Percentage exact agreement (PEA), sensitivity and specificity were calculated for CE and US when compared to MRI. Inter-reader reliability for CE and US was also assessed. Results: Compared to the gold standard of MRI, for CE (joint synovitis) the ranges for sensitivity, specificity and PEA were 55–83%, 23–46% and 46–60%, and for US were 64–89%, 60–80% and 64–78%, respectively. Compared to the gold standard of MRI, for CE (tenosynovitis) the ranges for sensitivity, specificity and PEA were 0–100%, 20–91% and 55–91%, and for US were 0–67%, 86–100% and 59–86%, respectively. Conclusion: CE was sensitive but US more specific in identifying hindfoot pathology in RA when compared to the reference standard of MRI. There was poor interobserver variability between ultrasonographers suggesting a need for standardisation of acquisition and interpretation of US images of the hindfoot.
[Clinical and epidemiological research] Precision of 3.0 Tesla quantitative magnetic resonance imaging of cartilage morphology in a multicentre clinical trial
Eckstein, F, Buck, R J, Burstein, D, Charles, H C, Crim, J, Hudelmaier, M, Hunter, D J, Hutchins, G, Jackson, C, Kraus, V B., Lane, N E, Link, T M, Majumdar, L S, Mazzuca, S, Prasad, P V, Schnitzer, T J, Taljanovic, M S, Vaz, A, Wyman, B, Le Graverand, M-P H., on behalf of the A9001140 Study Group Wed, 12 Nov 2008 00:00:00 -0000
Objective: Quantitative MRI (qMRI) of cartilage morphology is a promising tool for disease-modifying osteoarthritis drug (DMOAD) development. Recent studies at single sites have indicated that measurements at 3.0 Tesla (T) are more reproducible (precise) than those at 1.5 T. Precision errors and stability in multicentre studies with imaging equipment from various vendors have, however, not yet been evaluated. Methods: A total of 158 female participants (97 Kellgren and Lawrence grade (KLG) 0, 31 KLG 2 and 30 KLG 3) were imaged at 7 clinical centres using Siemens Magnetom Trio and GE Signa Excite magnets. Double oblique coronal acquisitions were obtained at baseline and at 3 months, using water excitation spoiled gradient echo sequences (1.0x0.31x0.31 mm3 resolution). Segmentation of femorotibial cartilage morphology was performed using proprietary software (Chondrometrics GmbH, Ainring, Germany). Results: The precision error (root mean square coefficient of variation (RMS CV)%) for cartilage thickness/volume measurements ranged from 2.1%/2.4% (medial tibia) to 2.9%/3.3% (lateral weight-bearing femoral condyle) across all participants. No significant differences in precision errors were observed between KLGs, imaging sites, or scanner manufacturers/types. Mean differences between baseline and 3 months ranged from <0.1% (non-significant) in the medial to 0.94% (p<0.01) in the lateral femorotibial compartment, and were 0.33% (p<0.02) for the total femorotibial subchondral bone area. Conclusions: qMRI performed at 3.0 T provides highly reproducible measurements of cartilage morphology in multicentre clinical trials with equipment from different vendors. The technology thus appears sufficiently robust to be recommended for large-scale multicentre trials.

Arthritis Care & Research

Interpreting studies of cardiovascular mortality in rheumatoid arthritis: The importance of timing
Michael M. Ward Wed, 26 Nov 2008 07:02:00 -0000
No abstract.
Risk of cardiovascular mortality in patients with rheumatoid arthritis: A meta-analysis of observational studies
J. Antonio Aviña-Zubieta, Hyon K. Choi, Mohsen Sadatsafavi, Mahyar Etminan, John M. Esdaile, Diane Lacaille Wed, 26 Nov 2008 07:02:00 -0000
To determine the magnitude of risk of cardiovascular mortality in patients with rheumatoid arthritis (RA) compared with the general population through a meta-analysis of observational studies.We searched Medline, EMBase, and Lilacs databases from their inception to July 2005. Observational studies that met the following criteria were assessed by 2 researchers: 1) prespecified RA definition, 2) clearly defined cardiovascular disease (CVD) outcome, including ischemic heart disease (IHD) and cerebrovascular accidents (CVAs), and 3) reported standardized mortality ratios (SMRs) and 95% confidence intervals (95% CIs). We calculated weighted-pooled summary estimates of SMRs (meta-SMRs) for CVD, IHD, and CVAs using the random-effects model, and tested for heterogeneity using the I2 statistic.Twenty-four studies met the inclusion criteria, comprising 111,758 patients with 22,927 cardiovascular events. Overall, there was a 50% increased risk of CVD death in patients with RA (meta-SMR 1.50, 95% CI 1.39-1.61). Mortality risks for IHD and CVA were increased by 59% and 52%, respectively (meta-SMR 1.59, 95% CI 1.46-1.73 and meta-SMR 1.52, 95% CI 1.40-1.67, respectively). We identified asymmetry in the funnel plot (Egger's test P = 0.002), as well as significant heterogeneity in all main analyses (P < 0.0001). Subgroup analyses showed that inception cohort studies (n = 4, comprising 2,175 RA cases) were the only group that did not show a significantly increased risk for CVD (meta-SMR 1.19, 95% CI 0.86-1.68).Published data indicate that CVD mortality is increased by [sim]50% in RA patients compared with the general population. However, we found that study characteristics may influence the estimate.
Efficacy of wrist working splints in patients with rheumatoid arthritis: A randomized controlled study
M. M. Veehof, E. Taal, L. M. Heijnsdijk-Rouwenhorst, M. A. F. J. van de Laar Wed, 26 Nov 2008 07:02:00 -0000
To investigate the efficacy of wrist working splints after a period of splinting in patients with rheumatoid arthritis (RA).We performed a 4-week randomized controlled trial among 33 RA patients with wrist arthritis. Patients were randomly allocated to the splinting group (n = 17) or the control group (n = 16). Patients in the splinting group received a prefabricated wrist working splint and were instructed to use this splint as much as possible during the day. The primary outcome measure was average wrist pain during the past week, measured using a visual analog scale (VAS). Secondary outcome measures were grip strength and functional ability. The latter was measured using the Disabilities of the Arm, Shoulder, and Hand questionnaire and the short version of the Sequential Occupational Dexterity Assessment. Measurements were performed at baseline and after 4 weeks. Performance tests were performed without splint. Differences in change scores between the splinting and the control group were analyzed using analysis of covariance. To indicate the magnitude of the treatment effects, effect sizes were calculated.A large and highly significant treatment effect on wrist pain was found. VAS pain scores decreased by 32% in the splinting group and increased by 17% in the control group. Small and nonsignificant treatment effects were found with regard to nonsplinted grip strength and functional ability.Prefabricated wrist working splints are highly effective in reducing wrist pain after 4 weeks of splint wearing in RA patients with wrist arthritis.

Arthritis & Rheumatism

In this issue
Wed, 26 Nov 2008 07:00:00 -0000
No abstract.
Signaling in response to hypoxia and normoxia in the intervertebral disc
Adele L. Boskey Wed, 26 Nov 2008 07:00:00 -0000
No abstract.
Behçet's syndrome is not so rare: Why do we need to know?
Hasan Yazici, Emire Seyahi, Sebahattin Yurdakul Wed, 26 Nov 2008 07:00:00 -0000
No abstract.

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