Rheumatoid Arthritis: Davis J

Dall'Era M, Davis J. · Division of Rheumatology, University of California San Francisco, San Francisco, USA. · Lupus. · Pubmed #15230295 No free full text.

Abstract: T cell costimulatory pathways are believed to play important roles in the pathogenesis of various autoimmune diseases including systemic lupus erythematosus (SLE). Animal models of SLE support the role of T cell costimulation in B cell activation and the production of autoantibodies. CTLA4Ig is a novel fusion protein that interferes with T cell costimulation by inhibiting the CD28-B7 interaction. A pivotal study demonstrated the ability of CTLA4Ig to suppress the production of anti-dsDNA antibodies and decrease nephritis in lupus prone mice. In an additional study, the combination of CTLA4Ig and cyclophosphamide significantly reduced proteinuria and prolonged survival in mice with advanced nephritis. In small human studies of psoriasis and rheumatoid arthritis, CTLA4Ig improved clinical outcomes and was well tolerated. These promising experiences with CTLA4Ig have paved the way for future studies in human SLE.

Keller C, Webb A, Davis J. · University of California San Francisco, San Francisco, California, USA. · Ann Rheum Dis. · Pubmed #14644847 links to  free full text

Abstract: Rheumatoid arthritis (RA) is a disease well characterised by proinflammatory cytokine secretion (particularly tumour necrosis factor, interferon gamma, interleukin (IL) 1, and IL6). Less has been reported about the cytokine profiling in the spondyloarthropathies (SpA). Several trials suggest that, similar to RA, proinflammatory cytokines are globally expressed in the SpA. However, other studies report a down regulation of these cytokines in the SpA, with a relative anti-inflammatory polarisation (featuring increases in IL4, IL5, and IL10). This review summarises current published reports and the variation in cytokine data in the SpA. Additionally, results of cytokine profiles in patients with ankylosing spondylitis before and after treatment with etanercept are reported.

Milne S, Brosseau L, Robinson V, Noel MJ, Davis J, Drouin H, Wells G, Tugwell P. · School of Rehabilitation Sciences, University of Ottawa, 451 Smyth Road, Ottawa, Ontario, Canada, K1H 8M5. · Cochrane Database Syst Rev. · Pubmed #12804511 No free full text.

Abstract: BACKGROUND: Knee arthroplasty (KA) is a common intervention that can enhance the quality of life for patients with osteoarthritis (OA) and rheumatoid arthritis (RA). Post-surgery rehabilitation protocols often include continuous passive motion (CPM). However, CPM protocols vary considerably amongst institutions. OBJECTIVES: The purpose of the current meta-analysis is to evaluate the effectiveness of continuous passive motion following total knee arthroplasty. SEARCH STRATEGY: An electronic search of MEDLINE (1966 to 2002), EMBASE (1988 to 2002), CINAHL (1982 to 2002), HEALTH STAR (1991 to 1994) and CURRENT CONTENTS (1997 to 2002) was conducted to identify randomized controlled trials. SELECTION CRITERIA: Following an a priori protocol, only randomized controlled trials of CPM for the treatment of participants post KA were eligible. Subjects were 18 years of age or older and had a pre-surgery diagnosis of degenerative joint disease. Both the experimental and control groups received physiotherapy. In addition to the physiotherapy intervention, the experimental group received CPM. DATA COLLECTION AND ANALYSIS: Two reviewers independently selected trials for inclusion. Data were then extracted and the quality of the trial assessed using predetermined forms. Outcome measures of interest were: active and passive knee range of motion (ROM) length of hospital stay, pain, swelling and quadriceps strength. A fixed effects model was used throughout for continuous variables, except where heterogeneity existed; in which case, a random effects model was used. Results were analyzed as weighted mean differences (WMD) with 95% confidence intervals (CI). Standardized mean differences (SMD) were used when different scales were used to measure the same concept (e.g. pain). Dichotomous outcomes were presented as a relative risk. MAIN RESULTS: Fourteen trials were retained for analysis. Results favouring CPM were found for the main comparison of CPM combined with physiotherapy (PT) versus PT alone at end of treatment. For the primary outcomes of interest, CPM combined with PT was found to statistically significantly increase active knee flexion (WMD 4.30 degrees, 95% CI: 1.96, 6.63) and decrease length of stay (WMD -0.69 days, 95% CI: -1.35, -0.03). CPM was also found to decrease the need for post-operative manipulation (RR 0.12, 95% CI: 0.03, 0.53). CPM did not significantly improve passive knee flexion and passive or active knee extension. REVIEWER'S CONCLUSIONS: CPM combined with PT, may offer beneficial results compared to PT alone in the short term rehabilitation following total knee arthroplasty.

Braun J, Sieper J, Breban M, Collantes-Estevez E, Davis J, Inman R, Marzo-Ortega H, Mielants H. · Rheumazentrum Ruhrgebiet, Landgrafenstrasse 15, 44652 Herne, Germany. · Ann Rheum Dis. · Pubmed #12381511 links to  free full text

Abstract: The conventional approach to treatment of patients with spondyloarthritis (SpA), particularly ankylosing spondylitis (AS), has serious limitations, adding a sense of urgency to the evaluation of new treatments for these rheumatic disorders. Tumour necrosis factor alpha (TNFalpha) is a cytokine that has been shown to mediate inflammatory and regulatory activities in SpA and other immune mediated diseases, including other arthritides and inflammatory bowel disease. Positive results have been reported in several international open label and randomised controlled trials of infliximab and etanercept, the two main biological agents targeting TNFalpha, which have included approximately 300 patients with SpA. Specifically, TNFalpha-directed therapy resulted in significant improvements in disease activity, function, and quality of life in these patients, most of whom had AS and received infliximab. Preliminary evidence from open label, long term extension trials suggests clinical benefit with continued use. Serious side effects were rare and consistent with experience from patient groups receiving infliximab or etanercept treatment for inflammatory bowel disease or rheumatoid arthritis. Together, these findings herald an age of more effective treatment of patients with AS with anti-TNFalpha and other emerging biological agents.

Brosseau L, Milne S, Wells G, Tugwell P, Robinson V, Casimiro L, Pelland L, Noel MJ, Davis J, Drouin H. · School of Rehabilitation Sciences, University of Ottawa, Ottawa, Ontario, Canada. · J Rheumatol. · Pubmed #15517640 No free full text.

Abstract: OBJECTIVE: The objective of this metaanalysis is to examine the effectiveness of continuous passive motion (CPM) following total knee arthroplasty (TKA). METHODS: This metaanalysis used the methodology proposed by the Cochrane Collaboration. RESULTS: This review of 14 studies (952 patients) found significant improvements in active knee flexion and analgesic use 2 weeks postoperatively with the use of CPM and physiotherapy (PT) compared to PT alone. In addition, length of hospital stay and need for knee manipulations were significantly decreased in the CPM group. Not enough data were available to compare the degree of knee flexion applied or number of hours of application of CPM. However, significant results were not found for other comparisons such as short term CPM application versus longterm CPM application and wide treatment range versus small treatment range for the outcomes of active knee flexion, passive knee flexion and extension, presence of a fixed flexion deformity, use of analgesic, or total knee range of motion. CONCLUSION: CPM combined with PT may offer beneficial results for patients post-TKA. However, the potential benefits will need to be carefully weighed against the inconvenience and expense of CPM. More research is necessary to assess the differences in effectiveness with different characteristics of application such as total duration of treatment and intensity of CPM interventions.

Peersman G, Laskin R, Davis J, Peterson MG, Richart T. · Department of Orthopaedic Surgery, ZNA Stuivenberg, Lange Beeldekensstraat 267, 2060 Antwerpen, Belgium. · Acta Orthop Belg. · Pubmed #18686462 No free full text.

Abstract: The American Society of Anesthesiologists Physical Status Classification System (ASA) ranks patients for risk of adverse events during a surgical procedure. The ASA classification is used as a surrogate for the patient's underlying severity of illness and has been recommended for use in Surgical Site Infection (SSI) and risk stratification. We assessed the predictive power of the ASA score for total knee replacement surgery infection, and compared it to a comorbidity score. All patients who had TKA (total knee arthroplasty) surgery performed during the period of 1993 to 1999 at one institution were identified. One hundred and thirteen infected cases were matched with 236 controls and nominal variables were statistically processed. A total co-morbidity score (TCOMORBID) was created to help the analysis. All possible predictors of infection were tested against infection in bivariate analysis. The association of the ASA score with infection was examined in detail. An ASA score beyond 2 showed an increased risk of infection. The average ASA score for the infected TKA group was 2.3 +/- 0.6, and the non-infected TKA average score was 2.6 +/- 0.7 (cohort effect). The relationship between the ASA score and TCOMORBID score was poor; Spearman rank correlation rho = 0.2, (p < 0.0001). In fact, the ASA score predicted only 6% of the occurrences of infection, but since it predicts 98% of the cases where there is no infection correctly, it is 70% accurate over all. Infection in TKA surgery was associated with an increased ASA score, but only when the high ASA score was due to a combination of specific co-morbidities. We propose that the ASA score should be cross-checked with the current co-morbidities, like rheumatoid arthritis or active infections in order to assess TKA infection risk.

Lukas C, Landewé R, Sieper J, Dougados M, Davis J, Braun J, van der Linden S, van der Heijde D, Anonymous00034. · University Hospital and CAPHRI Research Institute, Maastricht 6202 AZ, The Netherlands. · Ann Rheum Dis. · Pubmed #18625618 No free full text.

Abstract: OBJECTIVES: To develop a new index for disease activity in ankylosing spondylitis (ASDAS) that is truthful, discriminative and feasible, and includes domains/items that are considered relevant by patients and doctors. METHODS: Eleven candidate variables covering six domains of disease activity, selected by ASAS experts in a Delphi exercise, were tested in a three-step approach, similar to the methodology used for the disease activity score in rheumatoid arthritis. Data on 708 patients included in ISSAS (International Study on Starting tumour necrosis factor blocking agents in Ankylosing Spondylitis) were used. Cross validation was carried out in the OASIS cohort (Outcome in Ankylosing Spondylitis International Study). RESULTS: Principal component analysis disclosed three factors with eigenvalues >0.75: patient assessments, peripheral joint assessments and acute phase reactants. Discriminant function analysis resulted in a correct classification in approximately 72% of the cases (prior probability approximately 50%). Regression analysis resulted in an index with five variables (total back pain, patient global assessment, duration of morning stiffness, C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR)). Three additional candidate indices were designed using similar methodology while omitting either ESR or CRP or patient global assessment. All four scores correlated with the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI; r = 0.67-0.80), patient (0.58-0.75) and physician's global assessment (0.41-0.48) of disease activity. All four candidate ASDAS indices performed better than BASDAI or single-item variables in discriminating between high and low disease activity state, according to doctors as well as patients in the OASIS cohort. CONCLUSION: The first steps in the development of a new assessment tool of disease activity in AS derived four candidate indices with good face and construct validity, and high discriminant capacity.