INTRODUCTION With effective highly active antiretroviral therapy (HAART), individuals with human immunodeficiency virus (HIV) infection now enjoy life expectancies approaching those of uninfected individuals. Prolonged longevity has increased the prevalence of non-communicable comorbidities within the HIV patient population. HIV is a known independent risk factor for atherosclerotic cardiovascular disease (ASCVD), imparting a 1.5-2 -fold higher incidence of major adverse cardiovascular events (MACE) on infected patients. Deaths from ASCVD have increased as a result, despite a decline in total mortality. The Center of Excellence for HIV/AIDS care established a Cardiovirology Clinic (CvC) focused on providing primary and secondary preventative cardiovascular care to its patients. To date, there are no known data on the efficacy of such an intervention. We sought to define the performance of this care model for primary prevention. METHODS Unique CvC patients (n=68) with a treatment delivery window between September 1, 2017 to August 31, 2018 were identified through billing records. All patients were receiving HAART as prescribed by their infectious disease provider. Those with established ASCVD (n=10) were excluded from analysis to limit the study to primary prevention patients. We collected data on ASCVD risk factors (family history of premature ASCVD and personal histories of smoking, diabetes, hypertension [with degree of control], dyslipidemia, drug and alcohol use, and exercise) from the electronic health record. Body-mass index and systolic (SBP) and diastolic (DBP) blood pressures were also collected. Laboratory values including CD4 cell count, HIV-1 viral load, proteinuria, glomerular filtration rate, total cholesterol (TC), triglycerides (TG), and high (HDL) and low density (LDL) lipoprotein were included in the data collection. Estimates of 5-year risk of cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, or need for major revascularization was calculated using the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) equations. Patient data were de-identified. Two-tailed, paired T-testing was performed for each factor comparing the initial and most recent follow-up values. Significance was defined as p value <0.05. RESULTS Using univariate analysis, reductions in D:A:D risk (relative 32.01%, absolute 1.49%, p CONCLUSION In this initial assessment, treated HIV patients appeared to enjoy meaningful reductions in MACE risk through the preventive care they received in this clinic, suggesting that CvCs could be a partial solution to the growing ASCVD morbidity and mortality among HIV-infected individuals. Limitations of this study include a small patient population (n=58) (limiting us to univariate analyses) and short duration of follow up (≤ 1 year). Data collection will continue annually for 4 additional years. With increasing subject numbers, multivariate analyses to determine if components of ASCVD risk reduction show interactions, and which factors, interactions and interventions impart the greatest risk reduction, will be performed in improve the quality of care.

The global prevalence of peripheral artery disease (PAD) is estimated to be about 120 million, making up about 25.6% of the worldwide burden of cardiovascular diseases (CVD). In the United States (U.S.), the prevalence of PAD is about 7%, representing nearly 8 million adults. There is a higher prevalence of disease in Blacks and non-Hispanic Whites, with approximately 30% of Blacks and 20% of non-Hispanic Whites developing PAD in their lifetime. The strong risk factors associated with PAD include smoking, diabetes, hypertension, age, and male sex. Our study aimed to estimate the effects of obesity, alcohol abuse, renal failure, and hypertension on patients’ length of stay (LOS) among patients admitted with a diagnosis of PAD. Using the 2012 U.S. National Inpatient Sample database, we included 336,790 patients with PAD as a separate comorbidity during their index admission. Our main outcome variable was patients’ total length of stay (LOS) during the index admission. We categorized LOS < 1 into next day discharge (NDD) and LOS > 1 into non-NDD. Our predictor variables were hypertension, obesity, alcohol abuse and renal failure. We ran descriptive statistics to delineate the baseline characteristics of our sample population, and bivariate analysis with t-test and chi-square analysis. Multivariable logistic regression was used to estimate odds of non-NDD given our comorbidities; obesity, hypertension, alcohol abuse, renal failure while adjusting for age, race, and sex. We reported frequencies, p-values, and odd ratios (ORs) at a 95% significance level with alpha at 0.05. Of our final sample, 54.8% were males while 45.2% were females and the mean age of patients was 71.7 + 12.8. Hypertension, obesity, alcohol abuse and renal failure were present in 75%, 12%, 3.4%, and 30.9% of patients, respectively. Majority (75%) of the patients were white, while Black and Hispanic patients made up 13.3% and 7.1%, respectively. In our adjusted model, we found that patients with hypertension had 12% lower odds of non-NDD (OR = 0.88, CI= 0.86-0.90, P<0.0001) compared to those without hypertension, females had 20% increase in the odds of non-NDD compared to males (OR = 1.20, CI= 1.18-1.23, P<0.0001), patients with obesity, alcohol abuse and renal failure had 39%, 43% and 45% increase in odds of non-NDD compared to those without these comorbidities. (OR = 1.39, CI= 1.34-1.44, P<0.0001), (OR = 1.43, CI= 1.35-1.52, P<0.0001), (OR = 1.45, CI= 1.42-1.49, P<0.0001). Given the significant association between obesity, alcohol abuse, and renal failure with prolonged hospital stay in patients admitted to hospital with PAD, our study highlights the importance of adequate management of pre-existing patients' comorbidities. This is expected to improve overall length of stay and total healthcare utilization and costs, among patients with PAD.

Chapter One justified the need for research into methodology which can examine the upper limb stroke patients and older adults using portable kinematic recording software on the basis of the prevalence of stroke and aging and the potential importance of upper limb impairment as a predictor of recovery from stroke. Chapter Two reviewed the literature on methodologies which measured tracking in stroke patients and found that a wide range of methodologies were available but measurement metrics tended to focus on a small number of indices, mostly root mean square error, suggesting that measuring tracking using other indices might be informative. Chapter Three examined differences in tracking performance between stroke patients and older adults at a range of tracking speeds using a novel kinematic recording technology. The equipment appeared to be feasible for use in a community setting and found that older adults were less accurate, consistent and smooth compared to younger adults, and that accuracy was particularly affected by speed of trial. It was suggested that this interaction between speed and age may have been due to poorer feedback control mechanisms in older adults. Chapter Four looked at stroke patients compared to age-matched controls in tracking performance and found, contrary to the hypothesis, that stroke patients were more accurate, consistent and smooth with both the contralesional and ipsilesional hand; while there was no difference between the hands within stroke patients. Stroke patients may have outperformed controls due to qualitative differences in neural strategies for tracking control or the differences found may have related to methodological differences in collecting data. Chapter Five used the same stroke data to examine the relationship between tracking impairment, activity limitations and participation restrictions within the framework of the International Classification of Functioning, Disability and Health (ICF) (WHO, 2001). It was found that impairment of tracking consistency in the ipsilesional limb predicted participation restriction partially mediated by activity - 5 - limitation. It was argued that tracking in the “unimpaired limb” may be important for predicting participation restriction due to a potential mediating relationship with cognition. The study also suggested that the ipsilesional limb might have potential for rehabilitation of the contralesional limb. Chapter Six discussed the main findings of the thesis. Despite lack of sensitivity of tracking task to stroke impairment, the results of the thesis showed that measuring tracking in older adults and stroke patients provided important information about contralesional and ipsilesional hand function compared to age-matched controls and in relation to activity and participation after stroke. The methodology used may have the potential to examine other research questions which involve the measurement of upper limb kinematics after stroke.

Background: Endothelial dysfunction is a major factor in the development of atherosclerosis, thrombosis and heart disease. Evidence suggests dietary fat composition may modify cardiovascular risk, as well as surrogate markers of cardiovascular risk such as blood pressure, arterial stiffness and endothelium-dependent vasodilation. Aim: To investigate the impact of dietary fat composition on endothelial function and associated markers of vascular health. Methods: The effects of oils rich in eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) were separately investigated in a parallel-design, placebo-controlled randomised controlled trial (n=48, 6 weeks, 2.9 g/d), carried out in free-living healthy young men. Following a 2 week run-in period taking placebo capsules (olive oil), participants underwent baseline measurements of finger capillary density, endothelial progenitor cell numbers (EPC), platelet-monocyte aggregate numbers (PMA), ambulatory blood pressure (ABP), pulse wave analysis (PWA), digital volume pulse analysis (DVP), and gave blood samples for plasma lipid, glucose, insulin, nitric oxide metabolites (NOx) and isoprostanes. The same measurements were made at the study endpoint, 6 weeks. An in vitro investigation of the effects of physiologically-relevant fatty acid profiles on microvascular endothelial cell nitric oxide and prostacyclin production was also performed. Results: Neither EPA nor DHA supplementation influenced EPCs, capillary density, PMA, ABP, PWA, DVP or plasma cholesterol, triacylglycerol, glucose, insulin, NOx or isoprostanes compared to placebo. However, ambulatory night-time heart rate was increased following EPA supplementation compared to DHA. Furthermore, both EPA and DHA decreased plasma non-esterified fatty acids (NEFA) compared to placebo. The in vitro investigations suggested that the composition of circulating NEFA may differentially affect endothelial function in the microvasculature. Conclusion: Dietary EPA and DHA at relatively high doses do not improve a number of novel markers of vascular function, including microvascular function and a marker of endothelial repair in young healthy men. EPA and DHA have differing effects on heart rate during sleep, suggesting that further research is required into the possible adverse effects of higher doses of individual marine fatty acids in at-risk individuals. Further work is required to elucidate the role of physiological fatty acid profiles on endothelial function.

The main purpose of this study was to determine the impact of depression and anxiety on mortality, CHD incidence, and quality-of-life in patients hospitalised for an acute myocardial infarction (MI). Questionnaires, including the Beck Depression Inventory (BDI) and the State-Trait Anxiety Inventory were completed during hospitalisation by 288 MI patients, and four months and 12 months after discharge among survivors. Quality-of-life was assessed at both follow-up points using the Dartmouth COOP charts. Twenty-five (8.7%) patients died, 22 of cardiac causes, during the four month follow-up. Six further fatalities occurred between four and 12 months following MI. Symptoms of depression and anxiety did not predict either cardiac or all-cause mortality, or CHD incidence at either follow-up point. Indices of disease severity predicted both four month and 12 month mortality and CHD incidence. In a subset of seven patients who died prior to discharge, depressive symptoms did predict mortality, but the association did not withstand correction for severity of infarction. Multiple regression analyses revealed that baseline depression and state anxiety, as well as severity of infarction, predicted both four and 12 month quality-of-life. In addition, partner status and living alone also predicted four and 12 month quality-of-life, respectively. Attendance at rehabilitation was positively associated with quality-of-life at both four and 12 months, and negatively associated with 12 month CHD morbidity. In conclusion, depression and anxiety were not significant predictors of mortality, or CHD incidence, during the first year following MI but they were predictive of four and 12 month quality-of-life among survivors.

The purpose of this study was to investigate the impact of Medicare Part D coverage on medication adherence and health outcomes in dialysis patients. A retrospective analysis (2006-2010) using the United States Renal Data System was conducted for Medicare-eligible dialysis patients. Cardiovascular disease morbidity, healthcare utilization and expenditures, medication adherence, and mortality rates were compared, categorized based on patients’ Part D coverage in 2007 for those who: 1) did not reach the coverage gap (cohort 1); 2) reached the coverage gap but not catastrophic coverage (cohort 2); 3) reached catastrophic coverage (cohort 3); and 4) did not reach the coverage gap but received a low-income subsidy (cohort 4). Cox proportional hazards models, Kaplan-Meier methods, logistic regressions, generalized linear models, and generalized estimating equations were used. A total of 11,732 patients were included as meeting inclusion criteria: 1) cohort 1: 3,678 patients had out-of-pocket drug costs <$799; 2) cohort 2: 4,349 patients had out-of-pocket drug costs between $799 and $3,850; 3) cohort 3: 1,310 patients had out-of-pocket drug costs > $3,850; and 4) cohort 4: the remaining 2,395 patients had out-of-pocket drug costs <$799 but received a low-income subsidy. After adjusting for demographic and clinical factors, patients in cohort 2 and cohort 3 had 42 percent and 36 percent increased risk of cardiovascular disease (odds ratio (OR)=1.42, 95% confidence interval (CI):1.20-1.67; OR=1.38, 95% CI:1.10-1.72); and had 36 percent and 37 percent higher death rates compared to those in cohort 4, respectively (hazard ratio (HR)=1.36, 95% CI:1.27-1.44; HR=1.37, 95% CI:1.27-1.48). Patients in cohort 2 were more likely to be nonadherent to medications for diabetes (OR=1.72, 95% CI:1.48-1.99), hypertension (OR=1.69, 95% CI:1.54-1.85), hyperlipidemia (OR=2.01, 95% CI:1.76-2.29), hyperphosphatemia (OR=1.74, 95% CI:1.55-1.95), and hyperparathyroidism (OR=2.08, 95% CI:1.66-2.60) after reaching the coverage gap. These patients had total health care costs that were $2,644 higher due to increased rates of hospitalization and outpatient visits, despite $2,419 lower pharmacy costs compared to patients in cohort 4 after controlling for covariates (p<0.0001). Reaching the Part D coverage gap was associated with decreased medication adherence and unfavorable clinical and economic outcomes in dialysis patients. / text

Homocysteine, an independent risk factor for cardiovascular disease, is methylated in the liver via the zinc metalloenzyme betaine-homocysteine methyltransferase (BHMT). Established assays for BHMT include a radiochemical assay, a colorometric assay, an HPLC assay and an in vivo microbiological assay. These techniques are either unsuitable for substrate specificity studies, or are unable to give kinetic measurements. BHMT was purified from liver and measured directly and kinetically by a novel ¹H-NMR spectroscopic assay. The disappearance of substrates and the formation of products are monitored simultaneously. Using 2 mM glycine betaine and homocysteine as substrates in 20 mM phosphate buffer (pH = 7.5) and measuring the production of N,N-dimethylglycine the CV is 6.3% (n = 6) and the detection limit is 6 nkatal. An endpoint assay for BHMT activity was also developed and had CV = 5.3%, n = 6, with a detection limit of 2 nkatal. The NMR spectroscopic assay was used to determine the substrate specificity with a library of alternative substrates. Analysis of betaine analogues with different chain length, α-substitution, substitution of the nitrogen and carboxyl moieties demonstrated that BHMT is inactive if there is any steric crowding of the nitrogen or α-carbon positions. BHMT is capable of using group VI heteroatom betaines as methyl donors, with much faster rates than glycine betaine. For glycine betaine the Km was 0.19 ± 0.03 mM with a Vmax of 17 ± 0.7 nMol min-1 mg-1. The same assay was used to detect and partially characterise a BHMT activity from hagfish liver that is similar to that of the mammalian enzyme. NMR spectroscopy was adapted for measurements of glycine betaine in urine, along with other medically significant methylamines. These were shown to be valid for clinical use and in animal studies. A novel metabolite of the sulfonium analogue of glycine betaine (methylsulfinylmethanoate) was identified in rats.

No description available.

Objectives: Research literature points to a range of “factors” that are associated with return to work outcomes but little understanding of the experience of workers, the strategies used to adapt, how work shapes and influences adjustment, and the trajectories that describe their return to work experience. The aim of this qualitative, workplace-based study was to characterize workers readaptation to the workplace and develop a substantive framework for return to work following disabling cardiac illness. Methods: The study used a concurrent, nested, mixed methods approach, using grounded theory to inform the sampling and analysis framework. Participant workers were 12 males having suffered occupational disability owing to cardiac illness and returning to work at a large auto manufacturing plant. Participants were purposefully sampled for a range of disease and disability experiences as well as a range of work roles in the plant. Data were derived from semi-structured in-depth interviews, standardized questionnaire measures of health-related quality of life and work limitations, observations within the plant, and extensive field notes and memos. Longitudinal information was obtained through follow-up interviews over a two to ten month period. Results: Participants had a range of illness impacts and representations and fulfilled diverse roles in the plant including assembly jobs and trade work. Thematic analysis revealed that participants used adaptive strategies including changing mindset in relation to work, building physical capacity and efficiency, managing relationships and work schedules, and using supports in the plant. Thematic analysis highlighted the importance of the nature of work, the quality of work relationships, organizational practices around accommodation and supports in the workplace including occupational health support. Conclusions: Worker adaptation following disabling cardiac illness involved a process of self-regulation including elements of illness and work representations, deployment of adaptive strategies to compensate for ongoing impairments, self-monitoring, goal setting and adaptive selection of work activities. Work demands, relationships and structures provide a range of possibility for self-regulation and quality of life. Implications for practice for work and health researchers and professionals as well as potential linkages to theory are discussed.

With the increased marketing and popularity of a range of dairy products in recent years, research has become widespread concerning the influence of dairy on human health. It is also becoming evident that an individual’s genetic make-up contributes to shaping their health responses to dietary intakes. This research was primarily designed to investigate the impact of genetic variability on responsiveness of cholesterol metabolism, a classic biomarker of cardiovascular health, to the recommended level of dairy consumption in Canada. A secondary objective was to assess the influence of dairy intake on systemic inflammation as an emerging risk factor for cardiovascular disease. In a multicentre, randomized, free-living crossover design, 124 healthy individuals consumed 3 servings/day of conventional low-fat and regular milk, yogurt, and cheese (DAIRY diet) or dairy-free control products (CONTROL diet), each for 28 days as part of a prudent background dietary protocol. At the end of the study, DAIRY was associated with increased plasma concentrations of two established fatty acid biomarkers of dairy fat, pentadecanoic acid (C15:0) and heptadecanoic acid (C17:0), as well as with small increases in serum total cholesterol (TC) and LDL-cholesterol (LDL-C) concentrations. Inter-individual variability in the cholesterol transport gene ABCG5, bile acid synthesis gene CYP7A1, and cholesterol synthesis gene DHCR7 contributed to shaping the degree of TC and LDL-C responsiveness to DAIRY; with higher cholesterol concentrations observed among ABCG5 rs6720173-G/G homozygotes, CYP7A1 rs3808607-G allele carriers, and DHCR7 rs760241-A allele carriers, relative to the C allele, T/T, and G/G carriers of these genes, respectively. Also, after DAIRY, the major allele T homozygosity of CYP7A1 rs3808607 and the minor allele A of DHCR7 rs760241 were associated with reduced plasma [3,4]13C cholesterol enrichment and deuterium incorporation, respectively, suggesting reduced cholesterol absorption and synthesis rates. DAIRY intake did not influence the inflammatory status. Overall, this research has provided evidence of a potential impact of the genomic architecture on responsiveness of cholesterol metabolism to dairy consumption. The novel findings are expected to advance knowledge of the inherited basis by which health biomarkers may be modified in response to whole foods, hence launching an important step towards an era of personalized nutrition. / February 2016