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Coyle P.K.,Comprehensive Care
Neurologic Clinics | Year: 2012

Pregnancy is a major concern in multiple sclerosis (MS), because the typical patient is a young woman of childbearing age. This article reviews the impact of pregnancy on MS. Disease activity decreases, particularly during the last trimester. There is a temporary rebound of disease activity in the 3 months postpartum. Pregnancy and the postpartum period have many implications for counseling and for therapeutic decision making in MS. © 2012 Elsevier Inc.

Dimick J.,University of Michigan | Ruhter J.,ArborMetrix | Sarrazin M.V.,Comprehensive Care | Birkmeyer J.D.,University of Michigan
Health Affairs | Year: 2013

Research has shown that black patients more frequently undergo surgery at low-quality hospitals than do white patients. We assessed the extent to which living in racially segregated areas and living in geographic proximity to low-quality hospitals contribute to this disparity. Using national Medicare data for all patients who underwent one of three high-risk surgical procedures in 2005-08, we found that black patients actually tended tolive closer to higher-quality hospitals than white patients did but were 25-58 percent more likely than whites to receive surgery at low-quality hospitals. Racial segregation wasalso a factor, with black patients in the most segregrated areas 41-96 percent more likely than white patients to undergo surgery at low-quality hospitals. To address these disparities, care navigators and public reporting of comparative quality could steer patients and their referring physicians to higher-quality hospitals, while quality improvement efforts could focus on improving outcomes for high-risk surgery at hospitals that disproportionately serve black patients. Unfortunately, existing policies such as pay-for-performance, bundled payments, and nonpayment for adverse events may divert resources and exacerbate these disparities. © 2013 Project HOPE-The People-to-People Health Foundation, Inc.

Berkovich R.,Comprehensive Care | Agius M.A.,University of California at Davis
Therapeutic Advances in Neurological Disorders | Year: 2014

Acute and subacute inflammation, the mechanisms by which demyelination and axonal loss occur in multiple sclerosis (MS), result from the migration of activated immune cells into the central nervous system parenchyma. The triggering antigen is unknown, but the process involves deregulated immune response of T and B lymphocytes, macrophages, and mediators with expansion of autoreactive T cells creating a shift in the balance of pro- and anti-inflammatory cytokines favoring inflammation. Ongoing disease activity and exacerbations early in the course of relapsing-remitting MS may prevent full remission and propagate future progressive disability. A key strategy of immune therapy is timely initiation of treatment to achieve remission, followed by maintenance of remission. In this context, treatment with high-dose methylprednisolone (MP) is currently recommended to induce a faster recovery from a clinical exacerbation that results from an acute inflammatory attack. Adrenocorticotropic hormone (ACTH or corticotropin) gel is an alternative for patients who do not respond to or do not tolerate corticosteroids. ACTH is a universal agonist in the melanocortin (MC) system and, as such, among other functions, stimulates the adrenal cortex to produce cortisol. MCs are a family of peptides that includes ACTH and other MC peptides. This system has five classes of receptors, all of which show a strong affinity for ACTH, suggesting a more complex and dynamic mechanism than only inducing endogenous corticosteroid production. ACTH and MCs regulate processes relevant to MS, including anti-inflammatory and immunomodulatory functions involving lymphocytes, macrophages, the sympathetic nervous system involved in inflammatory processes, and reduction of pro-inflammatory cytokines. The clinical implications of the mechanistic differences between corticosteroid and ACTH gel treatment remain to be elucidated. Recent data show that patients experiencing an acute exacerbation, who previously had suboptimal response to or were unable to tolerate MP treatment, showed positive clinical outcomes with fewer adverse events with ACTH gel. © The Author(s), 2013.

Coyle P.K.,Comprehensive Care
Expert Opinion on Drug Safety | Year: 2014

Multiple sclerosis (MS) is a major neurologic disorder which preferentially affects young women of childbearing age. In the last two decades, a number of disease-modifying therapies have become available to treat relapsing forms of MS. None of these agents is approved for use in pregnancy. The timing of treatment versus conception, and risk of drug pregnancy exposures, are frequent discussion topics when caring for MS patients. This editorial will try to put into context available data, approaches, controversies and future needs. © 2014 Informa UK, Ltd.

Coyle P.K.,Comprehensive Care
Expert Opinion on Biological Therapy | Year: 2014

Introduction: Alemtuzumab is a humanized IgG1 kappa monoclonal antibody approved for treatment of B-cell chronic lymphocytic leukemia. This cytolytic antibody is directed against CD52 and depletes lymphocytes, with monocytes, macrophages, natural killer cells and a subpopulation of granulocytes being affected to a much lesser degree. Alemtuzumab is currently under review to treat relapsing multiple sclerosis (MS) in the United States, based on positive Phase II and Phase III trials in both treatment-naïve and treated relapsing MS patients. There was excellent efficacy in suppressing both clinical and neuroimaging disease activities. In these trials, the comparator arm was not placebo, but high dose frequently dosed subcutaneous interferon beta 1a. Alemtuzumab has recently been approved by the European authorities for active relapsing MS, in essence as a first-line agent. It produces long-standing effects, consistent with an induction agent. Efficacy will have to be weighed against risk of adverse effects, which include autoimmune disorders and infection. Alemtuzumab joins an increasingly crowded market, and will add to the complexity of treating MS. Areas covered: This review will discuss alemtuzumab as a therapy for MS, reviewing PubMed for clinical trials, publications and presentations at international meetings. It will focus on a United States market perspective. Expert opinion: Alemtuzumab offers induction strategy for very active relapsing MS patients who have failed conventional therapy, and possibly selected treatment-naive patients. Alemtuzumab use is likely to be restricted to specialized MS centers, with long-term monitoring to determine the true risk for adverse effects. © 2014 Informa UK, Ltd.

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