Entity

Time filter

Source Type

Seattle, WA, United States

Mease P.J.,Swedish Medical Center | Mease P.J.,University of Washington
Annals of the Rheumatic Diseases | Year: 2011

Psoriatic arthritis (PsA) is classified as a spondyloarthropathy and characterised by synovitis, enthesitis, dactylitis and spondylitis usually manifesting as skin and nail psoriasis. Our understanding about the PsA disease state, its genetics, pathophysiology and comorbidities, as well as the ability to assess and treat the disease, has advanced as a result of significant collaborative efforts by rheumatologists and dermatologists in the development of classification criteria, outcome measures to assess the various clinical domains, and treatment trials with agents also used for diseases such as rheumatoid arthritis (RA) and psoriasis. Biological agents, especially the antitumour necrosis factors, have demonstrated significant efficacy and reasonable safety in all clinical domains of the disease, resulting in amelioration of clinical symptoms, inhibition of structural damage and improvement of function and quality of life. Although there is considerable overlap with RA, there are some differences in pathophysiology and approach to assessment and management that are important to consider. This paper reviews these subjects, with an emphasis on recent data. Source


Mease P.,Swedish Medical Center
Bulletin of the Hospital for Joint Diseases | Year: 2013

Psoriatic arthritis (PsA) is a form of inflammatory arthritis that occurs in patients with psoriasis and is distinct from rheumatoid arthritis (RA). Methotrexate (MTX) is one of the most commonly used drugs for the treatment of PsA, yet there is scant controlled trial data to document its efficacy. Controlled trials have not demonstrated significant separation from placebo, but the studies have significant limitations which inhibit our ability to draw firm conclusions about the efficacy of MTX. A number of observational studies have described benefit for joint and skin disease. As yet unstudied, are the effects on enthesitis, dactylitis, and spondylitis of PsA. Psoriasis studies have shown modest benefit for psoriatic skin lesions. It is not yet known if MTX contributes an additive or synergistic benefit when used in combination with TNF inhibitors in PsA. The potential value of low dose MTX to suppress antibody formation against biologic therapies should be considered in a patient failing benefit from such therapy. Although adverse effects are similar to those seen in RA treatment with MTX, awareness of the tendency for PsA and psoriasis patients to be obese and have non-alcoholic steato-hepatosis, which may amplify transaminitis potential, should be borne in mind. © 2013, J. Michael Ryan Publishing Inc.All right reserved. Source


Mease P.J.,Swedish Medical Center | Armstrong A.W.,University of California at Davis
Drugs | Year: 2014

Psoriatic arthritis (PsA) is a chronic, systemic inflammatory disease. Up to 40 % of patients with psoriasis will go on to develop PsA, usually within 5-10 years of cutaneous disease onset. Both conditions share common pathogenic mechanisms involving genetic and environmental factors. Because psoriasis is typically present for years before PsA-related joint symptoms emerge, dermatologists are in a unique position to detect PsA earlier in the disease process through regular, routine screening of psoriasis patients. Distinguishing clinical features of PsA include co-occurrence of psoriatic skin lesions and nail dystrophy, as well as dactylitis and enthesitis. Patients with PsA are usually seronegative for rheumatoid factor, and radiographs may reveal unique features such as juxta-articular new bone formation and pencil-in-cup deformity. Early treatment of PsA with disease-modifying anti-rheumatic drugs has the potential to slow disease progression and maintain patient quality of life. Optimally, a single therapeutic agent will control both the skin and joint psoriatic symptoms. A number of traditional treatments used to manage psoriasis, such as methotrexate and cyclosporine, are also effective for PsA, but these agents are often inadequately effective, temporary in benefit and associated with significant safety concerns. Biologic anti-tumour necrosis factor agents, such as etanercept, infliximab and adalimumab, are effective for treating patients who have both psoriasis and PsA. However, a substantial number of patients may lose efficacy, have adverse effects or find intravenous or subcutaneous administration inconvenient. Emerging oral treatments, including phosphodiesterase 4 inhibitors, such as apremilast, and new biologics targeting interleukin-17, such as secukinumab, brodalumab and ixekizumab, have shown encouraging clinical results in the treatment of psoriasis and/or PsA. Active and regular collaboration of dermatologists with rheumatologists in managing patients who have psoriasis and PsA is likely to yield more optimal control of psoriatic dermal and joint symptoms, and improve long-term patient outcomes. © 2014 The Author(s). Source


Carroll J.D.,University of Colorado at Denver | Saver J.L.,University of California at Los Angeles | Thaler D.E.,Tufts University | Smalling R.W.,Texas Heart Institute | And 4 more authors.
New England Journal of Medicine | Year: 2013

BACKGROUND: Whether closure of a patent foramen ovale is effective in the prevention of recurrent ischemic stroke in patients who have had a cryptogenic stroke is unknown. We conducted a trial to evaluate whether closure is superior to medical therapy alone in preventing recurrent ischemic stroke or early death in patients 18 to 60 years of age. METHODS: In this prospective, multicenter, randomized, event-driven trial, we randomly assigned patients, in a 1:1 ratio, to medical therapy alone or closure of the patent foramen ovale. The primary results of the trial were analyzed when the target of 25 primary end-point events had been observed and adjudicated. RESULTS: We enrolled 980 patients (mean age, 45.9 years) at 69 sites. The medical-therapy group received one or more antiplatelet medications (74.8%) or warfarin (25.2%). Treatment exposure between the two groups was unequal (1375 patient-years in the closure group vs. 1184 patient-years in the medical-therapy group, P=0.009) owing to a higher dropout rate in the medical-therapy group. In the intention-to-treat cohort, 9 patients in the closure group and 16 in the medical-therapy group had a recurrence of stroke (hazard ratio with closure, 0.49; 95% confidence interval [CI], 0.22 to 1.11; P=0.08). The between-group difference in the rate of recurrent stroke was significant in the prespecified per-protocol cohort (6 events in the closure group vs. 14 events in the medical-therapy group; hazard ratio, 0.37; 95% CI, 0.14 to 0.96; P=0.03) and in the as-treated cohort (5 events vs. 16 events; hazard ratio, 0.27; 95% CI, 0.10 to 0.75; P=0.007). Serious adverse events occurred in 23.0% of the patients in the closure group and in 21.6% in the medical-therapy group (P=0.65). Procedure-related or device-related serious adverse events occurred in 21 of 499 patients in the closure group (4.2%), but the rate of atrial fibrillation or device thrombus was not increased. CONCLUSIONS: In the primary intention-to-treat analysis, there was no significant benefit associated with closure of a patent foramen ovale in adults who had had a cryptogenic ischemic stroke. However, closure was superior to medical therapy alone in the pre-specified per-protocol and as-treated analyses, with a low rate of associated risks. Copyright © 2013 Massachusetts Medical Society. Source


Heme oxygenase-1 (HO-1) concentrations have been recently reported to be elevated in impaired glucose tolerance and type 2 diabetes mellitus (T2DM). However, no study has examined the association between HO-1 concentrations and gestational diabetes mellitus (GDM). In a case-control study, nested within a prospective cohort of pregnant women (186 GDM cases and 191 women who remained eu-glycemic through pregnancy), we assessed the association of maternal serum HO-1 concentrations, measured in samples collected at 16 weeks gestation, on average, with subsequent risk of GDM. Maternal serum HO-1 concentrations were determined using ELISA. We fitted multivariate logistic regression models to derive estimates of odds ratios (ORs) and 95% confidence intervals (CIs). Median serum HO-1 concentrations in early pregnancy were lower in women who subsequently developed GDM compared with those who did not (1.60 vs. 1.80 ng/mL, p-value=0.002). After adjusting for maternal age, race, family history of T2DM and pre-pregnancy body mass index, women with HO-1 ≥ 3.05 ng/mL (highest decile) experienced a 74% reduction of GDM risk (95% CI; 0.09-0.77) compared with women whose concentrations were<1.23 ng/mL (lowest quartile). Serum HO-1 concentrations were inversely associated with subsequent GDM risk. These findings underscore the role of oxidative stress in the pathogenesis of GDM. Additional studies are warranted to confirm the clinical utility of serum HO-1 in diagnosis of GDM, particularly in the early pregnancy. Source

Discover hidden collaborations