James ters Veterans Administration Medical Center

Borough of Bronx, NY, United States

James ters Veterans Administration Medical Center

Borough of Bronx, NY, United States
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Federman A.D.,Mount Sinai School of Medicine | Keyhani S.,Mount Sinai School of Medicine | Keyhani S.,James ters Veterans Administration Medical Center | Keyhani S.,University of California at San Francisco
Health Policy | Year: 2011

Background: Medicare established the Physicians Quality Reporting Initiative (PQRI, recently renamed the Physicians Quality Reporting System) to increase reporting of quality metrics and promote healthcare quality. Objective: To identify characteristics of PQRI participants and examine their beliefs about its impact. Design: National survey of 4934 U.S. physicians, conducted June through October 2009. Setting: All practice settings. Participants: Randomly selected physicians categorized as primary care, medical specialists, surgeons, other specialists. Measurements: Beliefs about impact of PQRI reporting on quality. Results: The response rate was 49.8%. There were no significant differences between respondents and non-respondents by age, gender, specialty, and region. Thirty-eight percent participated in the PQRI, and were more likely than non-participants to be practice owners (69.0% vs. 57.1%, p< .0001) and to receive performance bonuses through their employer or practice (50.4% vs. 37.0%, p< .0001). Half of PQRI participants believed it had no impact on quality. Medical specialists (57.0%) and surgeons (55.1%) were more likely than primary care (40.4%) and other physicians (45.7%) to say that PQRI has no impact on quality (p= .004). Conclusions: Most PQRI participants believed it had little if any impact on quality. Medicare should identify the reasons behind physicians' negative views while it works to expand the Physicians Quality Reporting System. © 2011 Elsevier Ireland Ltd.


Rice T.R.,Mount Sinai School of Medicine | Sher L.,Mount Sinai School of Medicine | Sher L.,James ters Veterans Administration Medical Center
International Journal of Adolescent Medicine and Health | Year: 2013

Adolescent depression is a highly prevalent disorder with significant morbidity and suicide mortality. It is simultaneously highly responsive to treatment. Adolescents wish to discuss depression with their providers, and providers routinely receive opportunities to do so. These characteristics of prevalence, morbidity, mortality, responsiveness, and accessibility make adolescent depression an excellent target of care. However, most health care trainees and professionals report low confidence in caring for adolescent depression. As a caregiver community, we fare poorly in routine matters of assessment and management of adolescent depression. All health care professionals are trained within a medical model. In this light, the conceptualization of adolescent depression and suicidality within the medical model may increase provider confidence and performance. Epidemiology and neurobiology are presented with emphasis in this review. Legal concerns also affect health care professionals. For example, providers may deviate from evidence-based medicine owing to anxieties that the identification and treatment of depression may induce suicide and consequent legal culpability. A review of the historical context and relevant outcome trials concerning the increased risk of suicidality in depressed adolescents treated with selective-serotonin reuptake inhibitors may increase provider comfort. Furthermore, increased didactic and experiential training improve provider performance. In this work, proven models were discussed, and the testable hypothesis that education incorporating the views of this article can produce the best care for depressed adolescents.


Stefan M.,Mount Sinai School of Medicine | Stefan M.,James ters Veterans Administration Medical Center | Wei C.,Mount Sinai School of Medicine | Lombardi A.,Mount Sinai School of Medicine | And 7 more authors.
Proceedings of the National Academy of Sciences of the United States of America | Year: 2014

Graves disease (GD) is an autoimmune condition caused by interacting genetic and environmental factors. Genetic studies have mapped several single-nucleotide polymorphisms (SNPs) that are strongly associated with GD, but the mechanisms by which they trigger disease are unknown. We hypothesized that epigenetic modifications induced by microenvironmental influences of cytokines can reveal the functionality of GD-associated SNPs. We analyzed genome-wide histone H3 lysine 4 methylation and gene expression in thyroid cells induced by IFNα, a key cytokine secreted during viral infections, and overlapped them with known GD-associated SNPs. We mapped an open chromatin region overlapping two adjacent GD-associated SNPs (rs12101255 and rs12101261) in intron 1 of the thyroid stimulating hormone receptor (TSHR) gene. We then demonstrated that this region functions as a regulatory element through binding of the transcriptional repressor promyelocytic leukemia zinc finger protein (PLZF) at the rs12101261 site. Repression by PLZF depended on the rs12101261 disease susceptibility allele and was increased by IFNα. Intrathymic TSHR expression was decreased in individuals homozygous for the rs12101261 disease-associated genotype compared with carriers of the disease-protective allele. Our studies discovered a genetic-epigenetic interaction involving a noncoding SNP in the TSHR gene that regulates thymic TSHR gene expression and facilitates escape of TSHR-reactive T cells from central tolerance, triggering GD.


Rice T.R.,Mount Sinai School of Medicine | Rice T.R.,James ters Veterans Administration Medical Center | Sher L.,Mount Sinai School of Medicine | Sher L.,James ters Veterans Administration Medical Center
Expert Review of Neurotherapeutics | Year: 2012

Military veterans represent a unique, heterogeneous population with suicide prevalence rates, risk factors and preventative management needs that differ from those of the rest of community. Veterans worldwide receive high proportions of their healthcare from community providers, and sensitivity to these distinct needs is required for optimized care. An overview of the recent prevalence-study literature, with a focus upon statistical design, is presented in order to provide a critical orientation within this field with high levels of popular media attention. Attention to psychiatric comorbidity, subthreshold symptomology, select signature disorders of contemporary conflicts (namely, post-traumatic stress disorder and traumatic brain injury), and veteran life narratives before, within and beyond military service will guide our review of risk factor assessment and management strategies. This critical review of the literature provides an overview of this active field of neuropsychiatric research with a select focus upon these topics of special interest. © 2012 Expert Reviews Ltd.


Stefan M.,Mount Sinai School of Medicine | Stefan M.,James ters Veterans Administration Medical Center | Zhang W.,Mount Sinai School of Medicine | Concepcion E.,Mount Sinai School of Medicine | And 3 more authors.
Journal of Autoimmunity | Year: 2014

Type 1 diabetes (T1D) shows ~40% concordance rate in monozygotic twins (MZ) suggesting a role for environmental factors and/or epigenetic modifications in the etiology of the disease. The aim of our study was to dissect the contribution of epigenetic factors, particularly, DNA methylation (DNAm), to the incomplete penetrance of T1D. We performed DNAm profiling in lymphocyte cell lines from 3 monozygotic (MZ) twin pairs discordant for T1D and 6 MZ twin pairs concordant for the disease using HumanMethylation27 BeadChip. This assay assesses the methylation state of 27,578 CpG sites, mostly located within proximal promoter regions. We identified 88 CpG sites displaying significant methylation changes in all T1D-discordant MZ twin pairs. Functional annotation of the genes with distinct CpG methylation profiles in T1D samples showed differential DNAm of immune response and defense response pathways between affected and unaffected twins. Integration of DNAm data with GWAS data mapped several known T1D associated genes, HLA, INS, IL-2RB, CD226, which showed significant differences in DNAm between affected and unaffected of twins. Our findings suggest that abnormalities of DNA methylation patterns, known to regulate gene transcription, may be involved in the pathogenesis of T1D. © 2013.


O'Brien B.S.,Mount Sinai School of Medicine | Sher L.,Mount Sinai School of Medicine | Sher L.,James ters Veterans Administration Medical Center
International Journal of Adolescent Medicine and Health | Year: 2013

Background: Child sexual abuse (CSA) is widespread and is associated with various psychopathologies, including Axis I and II disorders, maladaptive and impulsive behaviors, and suicidal behavior in adolescence and adults. The pathophysiology of this association is not well understood; however, it is clear that suicidal behavior in individuals with a history of CSA is a significant social and medical problem that warrants further investigation. Methods: An electronic search of the major behavioral science databases (limited to the most recent studies in the last 20 years) was conducted to retrieve studies detailing the social, epidemiological, and clinical characteristics of child sexual trauma and their relation to suicidal behavior in adolescents and adults. Results: Studies indicate that CSA is related to an increase in Axis I and II diagnoses, including depression, post-traumatic stress disorder, conduct disorders, eating disorders, alcohol and drug abuse, panic disorders, and borderline personality disorder. CSA not just related to an increase in impulsivity and risky behaviors, it has also been linked to an increase in suicidality as well. Conclusion: CSA makes both direct and indirect contributions to suicidal behavior. It is a complex process involving multiple variables, which include psychopathology, maladaptive personality features and the direct contribution of CSA itself. Psychopathologies, such as impulsivity and mood and personality disorders, may modulate the relationship between CSA and suicidal behavior. Some preventive measures for decreasing the prevalence of CSA and suicidality may include education as well as increased access to mental health services.


Sher L.,Mount Sinai School of Medicine | Sher L.,James ters Veterans Administration Medical Center
QJM | Year: 2011

Studies of the neurobiology of suicidal behavior have become an important and integral part of psychiatric research. Over the past several years, studies of the role of brain-derived neurotrophic factor (BDNF) in the pathophysiology of suicidality have attracted significant interest of researchers. Multiple lines of evidence including studies of levels of BDNF in blood cells and plasma of suicidal patients, postmortem brain studies in suicidal subjects with or without depression, and genetic association studies linking BDNF to suicide suggest that suicidal behavior may be associated with a decrease in BDNF functioning. Studies of the BDNF function are important for suicide research and prevention because of the multiple reasons including the following: (i) BDNF plays a role in the pathophysiology of depression, post-traumatic stress disorder, substance use disorders and other conditions associated with suicidal behavior. Treatment-induced enhancements of BDNF can facilitate neural integrity and recovery of function in psychiatric disorders, and consequently prevent suicidal behavior; (ii) abnormal BDNF function may be associated with elevated suicidality independently of psychiatric diagnoses. It is possible that treatment-induced improvement in the BDNF function prevents suicidal behavior independently of improvement in psychiatric disorders; (iii) BDNF may be a biological marker of suicidal behavior in certain patient populations. It is to be hoped that the studies of the neurobiology of suicidal behavior will lead to the development of new methods of suicide prevention. © The Author 2010. Published by Oxford University Press on behalf of the Association of Physicians. All rights reserved.


Menconi F.,Mount Sinai School of Medicine | Osman R.,Mount Sinai School of Medicine | Monti M.C.,University of Pavia | Greenberg D.A.,Columbia University | And 3 more authors.
Proceedings of the National Academy of Sciences of the United States of America | Year: 2010

There is strong genetic association between type 1A diabetes (T1D) and autoimmune thyroid disease (AITD). T1D and AITD frequently occur together in the same individual, a condition classified as a variant of the autoimmune polyglandular syndrome type 3 (APS3). Because T1D and AITD are individually strongly associated with different HLA class II sequences, we asked which HLA class II pocket sequence and structure confer joint susceptibility to both T1D and AITD in the same individual (APS3v). We sequenced the HLA-DR gene in 105 APS3v patients and 153 controls, and identified a pocket amino acid signature, DRβ-Tyr-26, DRβ-Leu-67, DRβ-Lys-71, and DRβ-Arg-74, that was strongly associated with APS3v (P = 5.4 ± 10-14, odds ratio = 8.38). Logistic regression analysis demonstrated that DRβ-Leu-67 (P = 9.4 ± 10-13) and DRβ-Arg-74 (P = 1.21 ± 10 -13) gave strong independent effects on disease susceptibility. Structural modeling studies demonstrated that pocket 4 was critical for the development of T1D+AITD; all disease-associated amino acids were linked to areas of the pocket that interact directly with the peptide and, therefore, influence peptide binding. The disease-susceptible HLA-DR pocket was more positively charged (Lys-71, Arg-74) compared with the protective pocket (Ala-71, Gln-74). We conclude that a specific pocket amino acid signature confers joint susceptibility to T1D+AITD in the same individual by causing significant structural changes in the MHC II peptide binding pocket and influencing peptide binding and presentation. Moreover, Arg-74 is a major amino acid position for the development of several autoimmune diseases. Thesefindings suggest that blocking the critical Arg-74 pocket might offer a method for treating certain autoimmune conditions.


Sher L.,Mount Sinai School of Medicine | Sher L.,James ters Veterans Administration Medical Center
International Journal of Adolescent Medicine and Health | Year: 2013

Several lines of evidence suggest that there is an association between testosterone and suicidal behavior. A link between testosterone and the neurobiology of suicidal behavior may be related to: a) a direct effect of testosterone on suicidality via certain brain mechanisms; and/or b) a testosterone influence on aggression and, consequently, suicidality; and/or c) a testosterone effect on mood and, consequently, suicidality; and/or d) a testosterone effect on cognition and, consequently, suicidality. At least one study has demonstrated a relation between high levels of testosterone and suicide in young people. A significant number of studies suggest that high testosterone levels are associated with aggression in adolescents and adults. Multiple lines of evidence indicate that aggression is associated with suicidal behavior. The effect of high testosterone levels on suicidality in adolescents and young adults may be mediated by testosterone- related elevated aggression. It is also possible that, in young people, high testosterone levels are directly linked to suicidality via certain brain mechanisms. In older men, decreased testosterone levels are associated with depressive symptoms and reduced cognitive function, whereas higher blood levels of testosterone are associated with better mood and cognitive functioning. Depression and reduced cognition are associated with suicidal behavior and may mediate the effect of decreased testosterone levels on suicidality. Therefore, it is reasonable to propose that suicidal behavior in adolescents and young adults is associated with high testosterone levels, whereas suicidality in older men is associated with decreased testosterone secretion.


Sher L.,Mount Sinai School of Medicine | Sher L.,James ters Veterans Administration Medical Center | Rice T.,Mount Sinai School of Medicine
World Journal of Biological Psychiatry | Year: 2015

Objectives. Homicide is overwhelmingly committed by men compared to women. Conservative estimates suggest that more than a third of these individuals have a treatable psychiatric disorder. These data present an opportunity to mental health clinicians to assist in the prevention of homicide by improving men's mental health. Methods. We review the current literature on men's mental health with a focus on assessing and reducing homicide risk in men with psychiatric conditions. Results. Bipolar disorder and schizophrenia appear to share a neural endophenotype that is a risk factor for homicide. Dual disorders, or the presence of a substance use disorder with other major mental illness, are a major risk factor for homicide in males. Dual diagnosis disorders, personality disorders and pathological traits and male depression share emotion dysregulation, irritability, and reactive aggression. Promoting physician education, addressing firearm safety, reducing the reluctance of men relative to women to engage in help-seeking behaviour, and using targeted risk interviews which integrate these data are all currently recommended. Conclusions. The main focus in prevention of homicidal behaviour in males with psychiatric disorders should be to identify high risk groups, to provide adequate treatment, and to facilitate compliance with long-term treatment while considering male specific problems and needs. © 2015 Informa Healthcare.

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