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OBJECTIVES:: We sought to determine occurrence, predictors, and prognosis of alcohol withdrawal syndrome and delirium tremens in patients with traumatic injury. DESIGN:: Retrospective multicenter cohort study. SETTING:: Three U.S. trauma centers. PATIENTS:: Twenty-eight thousand one hundred one trauma patients admitted from 2010-2014. INTERVENTIONS:: None. MEASUREMENTS AND MAIN RESULTS:: Measures included occurrence of alcohol withdrawal syndrome and delirium tremens, injury characteristics, risk factors for alcohol withdrawal syndrome, clinical outcomes, pharmacologic treatment for alcohol withdrawal syndrome, and Clinical Institute Withdrawal Assessment for Alcohol, Revised (CIWA-Ar) scores. Alcohol withdrawal syndrome severity was defined by CIWA-Ar score as minimal (< 10), moderate (10–20), and severe (> 20). Alcohol withdrawal syndrome developed in 0.88% (n = 246), including 12% minimal, 36% moderate, and 53% severe. Alcohol withdrawal syndrome progressed to delirium tremens in 11%. Before adjustment, alcohol withdrawal syndrome severity was associated with injury severity, hypokalemia, baseline CIWA-Ar score, and established alcohol withdrawal syndrome risk factors. Logistic regression identified the following predictors of delirium tremens: baseline CIWA-Ar score greater than or equal to 10 (odds ratio, 6.05; p = 0.02) and age greater than or equal to 55 (odds ratio, 3.24; p = 0.03). In patients with severe alcohol withdrawal syndrome, severe head injury also predicted progression to delirium tremens (odds ratio, 6.08; p = 0.01), and hypokalemia was borderline significant (odds ratio, 3.23; p = 0.07). Clinical outcomes of hospital length of stay, ICU length of stay, and alcohol withdrawal syndrome complications differed significantly by alcohol withdrawal syndrome severity and were worse with more severe manifestations of alcohol withdrawal syndrome. Mortality also significantly differed by alcohol withdrawal syndrome severity but was only greater in patients who progressed to delirium tremens (11.1%; p = 0.02); otherwise, there were no differences in mortality by severity (4%, 4%, and 0% by minimal, moderate, and severe alcohol withdrawal syndrome). CONCLUSIONS:: Trauma patients with alcohol withdrawal syndrome experience a high occurrence of delirium tremens that is associated with significant mortality. These data demonstrate the predictive ability of baseline CIWA-Ar score, age, and severe head injury for developing delirium tremens. Copyright © by 2017 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.


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).


The International Association of HealthCare Professionals is pleased to welcome Gale A. Sisney, MD, FACR, Diagnostic Radiologist, to their prestigious organization with her upcoming publication in The Leading Physicians of the World. Dr. Gale A. Sisney is a highly trained and qualified radiologist with an extensive expertise in all facets of her work, especially breast imaging. Dr. Sisney has been in practice for more than 23 years and is currently serving patients within Global Radiology Outreach in Madison, Wisconsin. She is also serving patients within Radiology Mammography International. Dr. Sisney attended the University of Illinois at Chicago, graduating with her Medical Degree in 1988. Following her graduation, she subsequently completed her Diagnostic Radiology residency at Northwestern University Medical School, before undertaking her fellowship training in Breast Imaging and Intervention at the Swedish Medical Center: Radiology Imaging Associates. She has earned the coveted title of Fellow of the American College of Radiology. In addition to her clinical practice, Dr. Sisney is a lecturer for Herzing University, providing education and training for medical imaging and radiation therapy professionals. To keep up to date with the latest advances in her field, Dr. Sisney maintains professional memberships with the American College of Radiology, the Radiological Society of North America, the Association for American Women Radiologists, the Society of Breast Imaging, the American Roentgen Ray Society, and the Wisconsin Radiological Society. With her wealth of experience and knowledge, Dr. Sisney has been published extensively, and has appeared on several media, radio, and television broadcasts. Dr. Sisney attributes her success to her persistence. Learn more about Dr. Sisney by reading her upcoming publication in The Leading Physicians of the World. FindaTopDoc.com is a hub for all things medicine, featuring detailed descriptions of medical professionals across all areas of expertise, and information on thousands of healthcare topics.  Each month, millions of patients use FindaTopDoc to find a doctor nearby and instantly book an appointment online or create a review.  FindaTopDoc.com features each doctor’s full professional biography highlighting their achievements, experience, patient reviews and areas of expertise.  A leading provider of valuable health information that helps empower patient and doctor alike, FindaTopDoc enables readers to live a happier and healthier life.  For more information about FindaTopDoc, visit http://www.findatopdoc.com


Mease P.,Swedish Medical Center
Bulletin of the NYU Hospital for Joint Diseases | Year: 2012

Some of this past year's key papers or abstracts on psoriatic arthritis (PsA) assessment and treatment are reviewed in this paper. Treatment begins with identification of the PsA patient. Several screening questionnaires have been developed to be used in dermatology and primary care settings to identify which patients with psoriasis have developed PsA as opposed to other common musculoskeletal problems, such as osteoarthritis and fibromyalgia, thus increasing case-finding and targeting referral. PsA can present in a heterogeneous manner, involving arthritis, enthesitis, dactylitis, spondylitis, and skin and nail disease. Measures of these individual domains have been developed for use in clinical trials and improved PsA-specific composite measures of these domains are being evaluated as well. A quantitative therapy target, Minimal Disease Activity criteria, has been developed by the GRAPPA group. Treatment recommendations have been published by EULAR and GRAPPA. Obesity is a risk factor for the development of PsA and may adversely influence treatment outcomes. Although pharmacologic treatment often begins with methotrexate, a recent study does not provide clear evidence of its effectiveness. Anti-TNF therapies remain the gold standard of effectiveness. New therapeutic options are potentially emerging including ustekinumab, abatacept, several IL-17 inhibitors, apremilast, JAK inhibitors, and possibly IL-6 inhibitors.


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.


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.


Morrison M.,Swedish Medical Center
Advances in Experimental Medicine and Biology | Year: 2013

Diabetes studies have increasingly been associated with several types of cancer. Diabetes and pancreatic cancer have a unique relationship. Genetic mutations, such as activation of the KRAS2 oncogene, inactivation of the tumor-suppressor gene CDKN2A, inactivation of the tumor-suppressor gene TP53 and deleted in pancreatic cancer 4 (DPC4) gene defects are seen in those with pancreatic cancer. Approximately 80% of those patients, diagnosed with pancreatic cancer, are identified as having concomitant diabetes with a poor prognostic factor. Damaged pancreatic tissue, secondary to pancreatic cancer, leads to diabetes as islet cells and β cells are taken over by malignancy. Additionally, those on certain anti-diabetic regimens are shown to be at a higher risk of developing pancreatic cancer due to the effect of stimulation on the pancreatic β and islet cells. Therefore, diabetes is thought to be both a potential cause and effect of pancreatic cancer. Diabetes has become a pandemic, and pancreatic cancer is one of the most lethal forms of malignancy known. In order to better understand these diseases and how they are associated, more research needs to be done. Particularly, research focusing on different types of diabetes in the setting of pancreatic cancer will be an important issue for further understanding of the link between diabetes and pancreatic cancer. © 2012 Landes Bioscience and Springer Science+Business Media.


Biological agents, including TNF inhibitors, have revolutionized the treatment of RA in recent years. Certolizumab pegol (CZP) is a novel pegylated anti-TNF approved for the treatment of adult patients with moderately to severely active RA. This article provides an overview of three published clinical trials of CZP in RA in patients with active disease who have shown an inadequate response to DMARDs, including MTX: RA prevention of structural damage (RAPID) 1 and 2, which evaluated the efficacy and safety of CZP added to MTX when dosed every 2 weeks, and efficacy and safety of CZP - 4 weekly dosage in rheumatoid arthritis (FAST4WARD), which evaluated CZP monotherapy when dosed every 4 weeks. In the trials, CZP plus MTX or as monotherapy significantly improved the signs and symptoms of RA and RA disease activity, and CZP plus MTX significantly inhibited the progression of radiographic joint damage as early as Week 16 of the treatment. In addition, CZP treatment significantly improved patient-reported outcome measures, providing significant reductions in pain and fatigue and improvements in physical function as early as Week 1 of treatment; improvements in health-related quality of life were evident at the first assessment at Week 12. CZP treatment improved productivity at work, significantly reducing the number of days of missed work as well as the number of days with reduced productivity, and also increased productivity within the home and improved participation in family, social and leisure activities. CZP was generally well tolerated when used either as monotherapy or added to MTX; most adverse events were mild or moderate. Taken together, the results of these trials suggest that CZP is an effective new option for the treatment of RA. © The Author(s) 2010. Published by Oxford University Press on behalf of The British Society for Rheumatology.


PURPOSE OF REVIEW: In recent years, there has been an increasing understanding of the importance of the TH17 lineage of T cells and related cytokines, including interleukin (IL)17 and IL23, not only in the biology of innate host defense but also in the pathogenesis of inflammatory/autoimmune diseases. These diseases include psoriasis, psoriatic arthritis, the broader category of spondyloarthritides including ankylosing spondylitis and rheumatoid arthritis. It is postulated that in genetically predisposed individuals, external or internal stimuli such as microbial antigens, alterations in the intestinal microbiome, biomechanical stress and/or immunologic dysregulation may lead to an increased expression of cytokines such as IL23, which in turn stimulate the differentiation and activation of TH17 and other immune cells, which are a part of the innate immune system that trigger adaptive immune processes and chronic inflammatory diseases. Herein, we explore the effect of targeting this pathway therapeutically. RECENT FINDINGS: New drugs that are designed to inhibit steps in this pathway, the IL12/IL23 inhibitor, ustekinumab, the IL17A inhibitors secukinumab and ixekizumab, the IL17A receptor inhibitor, brodalumab, and the IL23 inhibitors guselkumab and tildrakizumab, have demonstrated significant effectiveness in treating these diseases, particularly psoriasis, psoriatic arthritis and ankylosing spondylitis. SUMMARY: This article reviews the relevant biology, efficacy and safety of new medications targeting the TH17 pathway, including inhibition of IL17 and IL23, particularly in psoriasis and psoriatic arthritis. Especially for patients who have not gained benefit from, lost effectiveness to or could not use antitumour necrosis factor (TNF) medications for safety or tolerability reasons, having effective medicines with an alternative mechanism of action will improve our ability to diminish disease activity impact on patient lives. Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.


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.

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