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Tomer Y.,Mount Sinai Medical Center | Tomer Y.,James ters Va Medical Center
Annual Review of Pathology: Mechanisms of Disease | Year: 2014

Recent advances in our understanding of genetic-epigenetic interactions have unraveled new mechanisms underlying the etiology of complex autoimmune diseases. Autoimmune thyroid diseases (AITDs) are highly prevalent, affecting 1% to 5% of the population. The major AITDs include Graves disease (GD) and Hashimoto's thyroiditis (HT); although these diseases contrast clinically, their pathogenesis involves shared immunogenetic mechanisms. Genetic data point to the involvement of both shared and unique genes. Among the shared susceptibility genes, HLA-DRβ1-Arg74 (human leukocyte antigen DR containing an arginine at position β74) confers the strongest risk. Recent genome-wide analyses have revealed new putative candidate genes. Epigenetic modulation is emerging as a major mechanism by which environmental factors interact with AITD susceptibility genes. Dissecting the genetic-epigenetic interactions underlying the pathogenesis of AITD is essential to uncover new therapeutic targets. © 2014 by Annual Reviews. All rights reserved.

Barbesino G.,Massachusetts General Hospital | Tomer Y.,The New School | Tomer Y.,James ters Va Medical Center
Journal of Clinical Endocrinology and Metabolism | Year: 2013

Context: TSH receptor antibodies (TRAb) cause Graves' disease (GD) hyperthyroidism. Widely available TRAb measurement methods have been significantly improved recently. However, the role of TRAb measurement in the differential diagnosis of hyperthyroidism, the prediction of remission of GD hyperthyroidism, the prediction of fetal/neonatal thyrotoxicosis, and the clinical assessment of Graves' ophthalmopathy (GO) are controversial. Evidence Acquisition: We reviewed and analyzed the literature reporting primary data on the clinical use of TRAb. We focused our analyses on clinical studies analyzing third-generation TRAb assays. Evidence Synthesis: The performance of TRAb in the differential diagnosis of overt hyperthyroidism is excellent, with sensitivity and specificity in the upper 90%. TRAb can accurately predict short-term relapses of hyperthyroidism after a course of antithyroid drugs but are less effective in predicting long-term relapses or remissions. Pregnancies in women with GD with negative TRAb are highly unlikely to result in fetal hyperthyroidism, whereas high titers of TRAb in pregnancy require careful fetal monitoring. GD patients with GO frequently have high TRAb levels. However, there are insufficient data to use the test to predict the clinical course of GO and response to treatment. Conclusions: Third-generation TRAb assays are suitable in the differential diagnosis of hyperthyroidism. In GD, TRAb should be tested before deciding whether methimazole can be stopped. TRAb should be used in pregnant women with GD to assess the risk of fetal thyrotoxicosis. The use of TRAb in GO requires further studies. Copyright © 2013 by The Endocrine Society.

Baruch L.,James ters Va Medical Center
The Annals of pharmacotherapy | Year: 2011

To report 2 cases in which point-of-care international normalized ratios (INRs) in dabigatran-treated patients were inaccurate. A 59-year-old woman with paroxysmal atrial fibrillation was started on warfarin. After 3 days, warfarin was discontinued, and the decision was made to switch to dabigatran 150 mg twice a day, which was started 2 days after the warfarin was discontinued. As treatment was being converted from warfarin to dabigatran therapy, the woman's primary care physician referred her to our anticoagulation clinic, where her point-of-care INR was 7.2. A laboratory INR performed approximately 30 minutes later was 1.7. Several repeat point-of-care INRs were elevated and discordant with the laboratory INRs. A second patient, a 52-year-old man, was started on dabigatran after an ablation procedure, as a bridge to warfarin. Approximately 16 hours after a single dose of dabigatran etexilate 150 mg, the point-of-care INR was 1.6. Dabigatran etexilate is an oral direct thrombin inhibitor that is approved for use in thromboprophylaxis of atrial fibrillation and deep vein thrombosis. Dabigatran's predictable pharmacokinetic profile allows for a fixed-dose regimen without the need for coagulation monitoring. In certain clinical situations (eg, switching treatment between dabigatran and warfarin), INR testing is performed as part of routine clinical care. During the development program for dabigatran, laboratory testing of INR was performed, with INRs at therapeutic concentrations of dabigatran ranging from 1.1 to 1.7. Supratherapeutic concentrations of dabigatran elevated the INR to slightly higher levels, between 1.7 and 2.4. Even at extremely high dabigatran concentrations, the INR was generally in the range of 2.3-3.5. We advocate laboratory INR testing with simultaneous assessment of the activated partial thromboplastin time in patients who are receiving or who have recently received dabigatran. A prospective evaluation assessing the accuracy of the commonly used point-of-care INR devices in patients receiving dabigatran would confirm our findings with respect to this device and determine whether our findings extend to other commonly used devices.

Baruch L.,James ters Va Medical Center
Postgraduate Medicine | Year: 2013

Novel oral anticoagulants, direct thrombin inhibitors, and factor Xa inhibitors are being introduced into clinical practice. In contrast to vitamin K antagonists, such as warfarin, these novel agents, because of their relatively wide therapeutic range and predictable pharmacokinetics, have been evaluated in clinical trials and approved for clinical use without the need for routine coagulation monitoring. On occasion, it will be important to assess the anticoagulant status of patients treated with these agents. As a result of their targeted mechanisms of action, they affect standard coagulation assays differently than vitamin K antagonists and heparins, and such assay results may not provide clinically useful information. Thus, less commonly used coagulation assays (eg, chromogenic anti-factor Xa activity assays, diluted thrombin time, and ecarin-based clotting tests) may be introduced into clinical practice. These assays are currently limited by the absence of validated therapeutic targets and lack of standardization across laboratories, vendors, and medication classes. This article provides an overview of the coagulation assays and their potential role in determining the anticoagulant status of patients treated with the emerging anticoagulants. © Postgraduate Medicine.

Aldridge M.D.,Mount Sinai School of Medicine | Aldridge M.D.,James ters Va Medical Center | Canavan M.,The New School | Cherlin E.,The New School | Bradley E.H.,The New School
Medical Care | Year: 2015

Background: Hospice use has increased substantially during the past decade by an increasingly diverse patient population; however, little is known about patterns of hospice use and how these patterns have changed during the past decade. Objective: To characterize Medicare hospice users in 2000 and 2010 and estimate the prevalence of (1) very short (r1 wk) hospice enrollment; (2) very long (< 6 mo) hospice enrollment; and (3) hospice disenrollment and how these utilization patterns have varied over time and by patient and hospice characteristics. Research Design: Cross-sectional analysis of Medicare hospice claims data from 2000 and 2010. Subjects: All US Medicare Hospice Benefit enrollees in 2000 (N = 529,573) and 2010 (N = 1,150,194). Results: As of 2010, more than half (53.4%) of all Medicare decedents who used hospice had either very short (r1 wk, 32.4%) or very long (< 6 mo, 13.9%) hospice enrollment or disenrolled from hospice before death (10.6%). This represents an increase of 4.9 percentage points from 2000. In multivariable analysis, patients with noncancer diagnoses, the fastest growing group of hospice users, were approximately twice as likely as those with cancer to have very short or long enrollment periods and to disenroll from hospice. Conclusion: The substantial proportion of hospice users with very short or long enrollment, or enrollments that end before death, underscores the potential for interventions to improve the timing and appropriateness of hospice referral so that the full benefits of hospice are received by patients and families. Copyright © 2014 by Lippincott Williams &Wilkins.

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