Insomnia as an Independent Predictor of Incident Cardiovascular Disease in HIV: Data from the Veterans Aging Cohort Study

Background: Insomnia is associated with increased cardiovascular disease (CVD) risk in the general population and is highly prevalent in people with HIV. The CVD risk conferred by insomnia in the HIV population is unknown. Methods: Using the Veterans Aging Cohort Study-Survey Cohort, insomnia symptoms were measured and dummy coded with the item, “Difficulty falling or staying asleep?” (5-point scale from no difficulty to bothers a lot). Incident CVD event ICD-9 codes (acute myocardial infarction, stroke, or coronary artery revascularization) were identified with VA and Medicare administrative data and VA fee-for-service data. Those with baseline CVD were excluded. Results: HIV-infected (N=3,108) veterans had a median follow-up time of 10.8 years, during which 267 CVD events occurred. Compared to HIV-infected veterans with no difficulty falling or staying asleep, HIV-infected veterans bothered a lot by insomnia symptoms had an increased risk of incident CVD after adjusting for demographics (HR=1.64, 95%CI=1.16-2.31, p=.005), CVD risk factors (HR=1.62, 95%CI=1.14-2.30, p=.007), additional potential confounders (hepatitis C infection, renal disease, anemia, alcohol use, cocaine use; HR=1.70, 95%CI=1.19-2.43, p=.003), and HIV-specific factors (HIV-1 RNA, CD4+ T-cell count, ART; HR=1.66, 95%CI=1.16-2.37, p=.005). Additional adjustment for non-benzodiazepine sleep medication (HR=1.62, 95%CI=1.13-2.32, p=.009) did not attenuate the association; however, it fell short of significance at p < .01 after adjustment for depressive symptoms (HR=1.51, 95%CI=0.98-2.32, p=.060) or antidepressant medication (HR=1.51, 95%CI=1.04-2.19, p=.031). Conclusion: Highly bothersome insomnia symptoms were significantly associated with incident CVD in HIV-infected veterans, suggesting that insomnia may be a novel, modifiable risk factor for CVD in HIV

Zinc deficiency and advanced liver fibrosis among HIV and hepatitis C co-infected anti-retroviral naïve persons with alcohol use in Russia

Background and aims Liver disease in people living with HIV co-infected with hepatitis C virus is a source of morbidity and mortality in Russia. HIV accelerates liver fibrosis in the setting of HCV co-infection and alcohol use. Zinc deficiency is common among people living with HIV and may be a factor that facilitates the underlying mechanisms of liver fibrosis. We investigated the association between zinc deficiency and advanced liver fibrosis in a cohort of HIV/HCV co-infected persons reporting heavy drinking in Russia. Methods This is a secondary data analysis of baseline data from 204 anti-retroviral treatment naïve HIV/HCV co-infected Russians with heavy drinking that were recruited into a clinical trial of zinc supplementation. The primary outcome of interest in this cross-sectional study was advanced liver fibrosis. Zinc deficiency, the main independent variable, was defined as plasma zinc \u3c0.75 mg/L. Exploratory analyses were performed examining continuous zinc levels and fibrosis scores. Analyses were conducted using multivariable regression models adjusted for potential confounders. Results The prevalence of advanced liver fibrosis was similar for those with zinc deficiency compared to those with normal zinc levels, (27.7% vs. 23.0%, respectively). We did not detect an association between zinc deficiency and advanced liver fibrosis in the adjusted regression model (aOR: 1.28, 95% CI: 0.62–2.61, p = 0.51) nor in exploratory analyses. Conclusions In this cohort of Russians with HIV/HCV co-infection, who are anti-retroviral treatment naïve and have heavy alcohol use, we did not detect an association between zinc deficiency or zinc levels and advanced liver fibrosis

Inclusive School Community: Why is it so Complex?

This paper addresses the question: why is it so hard for school communities to respond to diversity in learners, staff and parents in inclusive ways? The authors draw on theory and recent professional experience in Queensland, Australia, to offer four guiding principles that address traditional assumptions about learning that result in inequality of opportunity and outcomes for students. The authors suggest these principles to support the development of a more inclusive school community: (1) develop a learning community incorporating a critical friend; (2) value and collaborate with parents and the broader community; (3) engage students as citizens in school review and develop¬ment; and (4) support teachers’ critical engagement with inclusive ideals and practices. The authors describe how the principles can work in concert in a school community

Association Between Depressive Disorders and Incident Acute Myocardial Infarction in Human Immunodeficiency Virus–Infected Adults

IMPORTANCE With the advent of highly effective antiretroviral therapy and improved survival, human immunodeficiency virus (HIV)–infected people are living longer and are now at an increased risk for cardiovascular disease (CVD). There is an urgent need to identify novel risk factors and primary prevention approaches for CVD in HIV. Although depression is prevalent in HIV-infected adults and is associated with future CVD in the general population, its association with CVD events has not been examined in the HIV-infected population. OBJECTIVE To examine whether depressive disorders are prospectively associated with incident acute myocardial infarction (AMI) in a large cohort of adults with HIV. DESIGN, SETTING, AND PARTICIPANTS Included in this cohort study were 26 144 HIV-infected veterans without CVD at baseline (1998–2003) participating in the US Department of Veterans Affairs Veterans Aging Cohort Study from April 1, 2003, through December 31, 2009. At baseline, 4853 veterans (19%) with major depressive disorder (MDD; International Classification of Diseases, Ninth Revision [ICD-9] codes 296.2 and 296.3) and 2296 (9%) with dysthymic disorder (ICD-9 code 300.4) were identified. The current analysis was conducted from January 2015 to November 2015. MAIN OUTCOMES AND MEASURES Incident AMI (defined by discharge summary documentation, enzyme/electrocardiography evidence of AMI, inpatient ICD-9 code for AMI (410), or AMI as underlying cause of death [International Statistical Classification of Diseases and Related Health Problems, Tenth Revision code 121]) between the enrollment date and December 31, 2009. RESULTS The mean (SD) age of those with MDD was 47.3 (7.9) years and for those without MDD was 48.2 (9.7) years. During 5.8 years of follow-up, 490 AMI events (1.9%) occurred. Baseline MDD was associated with incident AMI after adjusting for demographics (hazard ratio [HR], 1.31; 95% CI, 1.05–1.62), CVD risk factors (HR, 1.29; 95% CI, 1.04–1.60), and HIV-specific factors (HR, 1.30; 95% CI, 1.05–1.62). Further adjustment for hepatitis C, renal disease, substance abuse, and hemoglobin level (HR, 1.25; 95% CI, 1.00–1.56) and antidepressant use (HR, 1.12; 95% CI, 0.87–1.42) attenuated associations. Baseline dysthymic disorder was not associated with incident AMI. CONCLUSIONS AND RELEVANCE We report novel evidence that HIV-infected adults with MDD have a 30% increased risk for AMI than HIV-infected adults without MDD after adjustment for many potential confounders. Our findings raise the possibility that MDD may be independently associated with incident atherosclerotic CVD in the HIV-infected population

Mental health diversion courts : some directions for further development

Recent years have seen a growth in the number of specialist courts operating in Australia, including those which aim to address the needs of mentally disordered offenders. This article describes some of the key characteristics of mental health courts, using case studies from the most established court in Australia, the South Australian Magistrates Court Diversion Program (MCDP). This is followed by a consideration of some factors that may affect the future development of this type of program. It is concluded that there is a need to pay careful attention to issues of risk assessment and risk management if the dual goals of improving both the health of individual and the safety of the community are to be realised.<br /

CD8+ T-cells count in acute myocardial infarction in HIV disease in a predominantly male cohort.

Human Immunodeficiency Virus- (HIV-) infected persons have a higher risk for acute myocardial infarction (AMI) than HIV-uninfected persons. Earlier studies suggest that HIV viral load, CD4+ T-cell count, and antiretroviral therapy are associated with cardiovascular disease (CVD) risk. Whether CD8+ T-cell count is associated with CVD risk is not clear. We investigated the association between CD8+ T-cell count and incident AMI in a cohort of 73,398 people (of which 97.3% were men) enrolled in the U.S. Veterans Aging Cohort Study-Virtual Cohort (VACS-VC). Compared to uninfected people, HIV-infected people with high baseline CD8+ T-cell counts (\u3e1065 cells/mm3) had increased AMI risk (adjusted HR=1.82,

Design and testing of hydrophobic core/hydrophilic shell nano/micro particles for drug-eluting stent coating

In this study, we designed a novel drug-eluting coating for vascular implants consisting of a core coating of the anti-proliferative drug docetaxel (DTX) and a shell coating of the platelet glycoprotein IIb/IIIa receptor monoclonal antibody SZ-21. The core/shell structure was sprayed onto the surface of 316L stainless steel stents using a coaxial electrospray process with the aim of creating a coating that exhibited a differential release of the two drugs. The prepared stents displayed a uniform coating consisting of nano/micro particles. In vitro drug release experiments were performed, and we demonstrated that a biphasic mathematical model was capable of capturing the data, indicating that the release of the two drugs conformed to a diffusion-controlled release system. We demonstrated that our coating was capable of inhibiting the adhesion and activation of platelets, as well as the proliferation and migration of smooth muscle cells (SMCs), indicating its good biocompatibility and anti-proliferation qualities. In an in vivo porcine coronary artery model, the SZ-21/DTX drug-loaded hydrophobic core/hydrophilic shell particle coating stents were observed to promote re-endothelialization and inhibit neointimal hyperplasia. This core/shell particle-coated stent may serve as part of a new strategy for the differential release of different functional drugs to sequentially target thrombosis and in-stent restenosis during the vascular repair process and ensure rapid re-endothelialization in the field of cardiovascular disease

Don't Stop Thinking About Leptoquarks: Constructing New Models

We discuss the general framework for the construction of new models containing a single, fermion number zero scalar leptoquark of mass $\simeq 200-220$ GeV which can both satisfy the D0/CDF search constraints as well as low energy data, and can lead to both neutral and charged current-like final states at HERA. The class of models of this kind necessarily contain new vector-like fermions with masses at the TeV scale which mix with those of the Standard Model after symmetry breaking. In this paper we classify all models of this type and examine their phenomenological implications as well as their potential embedding into SUSY and non-SUSY GUT scenarios. The general coupling parameter space allowed by low energy as well as collider data for these models is described and requires no fine-tuning of the parameters.Comment: Modified text, added table, and updated reference

Human immunodeficiency virus, hepatitis C, and inflammatory biomarkers in individuals with alcohol problems: a cross-sectional study

BACKGROUND: Assessing whether hepatitis C (HCV) co-infection with human immunodeficiency virus (HIV) is associated with increased inflammation is complex. The liver, integral to inflammatory biomarker synthesis, is compromised by HCV and alcohol abuse. Using single liver-synthesized biomarkers (e.g. C-reactive protein) to represent inflammation may not be appropriate in HIV/HCV co-infection. We hypothesized that 1) detectable HIV/HCV RNA was independently associated with increased inflammation; 2) a composite inflammation measure describes inflammation differently from single inflammatory biomarkers. METHODS: We compared inflammation by HIV/HCV group in a cohort of 361 HIV infected participants from the HIV-Longitudinal Interrelationships of Viruses and Ethanol study. Inflammatory biomarkers >75th percentile were considered elevated. Associations between HIV/HCV group and elevated biomarkers were analyzed as a composite measure (inflammatory burden) or individually. We defined inflammatory burden as number of concurrently elevated biomarkers. Biomarkers included interleukin-6 (IL-6), C-reactive protein (CRP), cystatin C, serum amyloid-A (SAA), tumor necrosis factor-alpha (TNF-α), interleukin-10 (IL-10). Covariates: alcohol, liver fibrosis, comorbidities, CD4 count, antiretroviral therapy, substance use. RESULTS: Detectable HIV and HCV RNA (OR = 2.49; 95% CI = 1.05–5.89) and detectable HCV RNA alone (2.95; 1.08–8.01) were independently associated with increased odds of having a greater inflammatory burden compared to undetectable viremia. Elevated IL-10 (7.79; 1.90–31.97) and TNF-α (7.70; 1.42–41.83) were independently associated with detectable HIV and HCV RNA. Elevated IL-10 was also associated with detectable HCV RNA alone (5.51; 1.17, 25.84). CONCLUSIONS: Detectable HIV and HCV replication versus undetectable replication was associated with inflammatory burden and certain inflammatory biomarkers independently of alcohol consumption, liver fibrosis and other comorbidities

Depression and All-Cause Mortality Risk in HIV-infected and HIV-uninfected U.S. Veterans: A cohort study

Objectives: The contribution of depression to mortality in adults with and without HIV infection is unclear. We hypothesized that depression increases mortality risk and that this association is stronger among those with HIV infection. Methods: Veterans Aging Cohort Study (VACS) data were analysed from the first clinic visit on or after 1 April 2003 (baseline) to 30 September 2015. Depression definitions were: (1) major depressive disorder defined using International Classification of Diseases, Ninth Revision (ICD-9) codes; (2) depressive symptoms defined as Patient Health Questionnaire (PHQ)-9 scores ≥ 10. The outcome was all-cause mortality. Covariates were demographics, comorbid conditions and health behaviours. Results: Among 129 140 eligible participants, 30% had HIV infection, 16% had a major depressive disorder diagnosis, and 24% died over a median follow-up time of 11 years. The death rate was 25.3 [95% confidence interval (CI) 25.0-25.6] deaths per 1000 person-years. Major depressive disorder was associated with mortality [hazard ratio (HR) 1.04; 95% CI 1.01, 1.07]. This association was modified by HIV status (interaction P-value = 0.02). In HIV-stratified analyses, depression was significantly associated with mortality among HIV-uninfected veterans but not among those with HIV infection. Among those with PHQ-9 data (n = 7372), 50% had HIV infection, 22% had PHQ-9 scores ≥ 10, and 28% died over a median follow-up time of 12 years. The death rate was 27.3 (95% CI 26.1-28.5) per 1000 person-years. Depressive symptoms were associated with mortality (HR 1.16; 95% CI 1.04, 1.28). This association was modified by HIV status (interaction P-value = 0.05). In HIV-stratified analyses, depressive symptoms were significantly associated with mortality among veterans with HIV infection but not among those without HIV infection. Conclusions: Depression was associated with all-cause mortality. This association was modified by HIV status and method of depression ascertainment