Quality of initial HIV care in Canada: extension of a composite programmatic assessment tool for HIV therapy.

OBJECTIVES: To document the quality of initial HIV care in Canada using the Programmatic Compliance Score (PCS), to explore the association of the PCS with mortality, and to identify factors associated with higher quality of care. METHODS: We analysed data from the Canadian Observational Cohort Collaboration (CANOC), a multisite Canadian cohort of HIV-positive adults initiating combination antiretroviral therapy (ART) from 2000 to 2011. PCS indicators of noncompliance with HIV treatment guidelines include: fewer than three CD4 count tests in the first year of ART; fewer than three viral load tests in the first year of ART; no drug resistance testing before initiation; baseline CD4 count < 200 cells/mm3 ; starting a nonrecommended ART regimen; and not achieving viral suppression within 6 months of initiation. Indicators are summed for a score from 0 to 6; higher scores indicate poorer care. Cox regression was used to assess the association between PCS and mortality and ordinal logistic regression was used to explore factors associated with higher quality of care. RESULTS: Of the 7460 participants (18% female), the median score was 1.0 (Q1-Q3 1.0-2.0); 21% scored 0 and 8% scored ≥ 4. In multivariable analysis, compared with a score of 0, poorer PCS was associated with mortality for scores > 1 [score = 2: adjusted hazard ratio (AHR) 1.64; 95% confidence interval (CI) 1.13-2.36; score = 3: AHR 2.02; 95% CI 1.38-2.97; score ≥ 4: AHR 2.14; 95% CI 1.43-3.21], after adjustments for age, sex, province, ART start year, hepatitis C virus (HCV) coinfection, and baseline viral load. Women, individuals with HCV coinfection, younger people, and individuals starting ART earlier (2000-2003) had poorer scores. CONCLUSIONS: Our findings further validate the PCS as a predictor of all-cause mortality. Disparities identified suggest that further efforts are needed to ensure that care is equitably accessible.

Evaluating the risk of obstructive sleep apnea in type 2 diabetic patients, and its associations

OBJECTIVE: To assess the prevalence of high risk of Obstructive Sleep Apnoea (OSA) in Type 2 diabetics. To identify risk associations of OSA with obesity, sleep quality, daytime sleepiness and Acanthosis Nigricans. DESIGN AND METHODS: A cross sectional study was done in the diabetic wards of health facilities governed by three Regional Health Authorities in Trinidad. OSA risk was assessed by the Snoring, Tiredness, Observed Apnea, high blood Pressure (STOP) – Body mass index, Age, Neck circumference and Gender (BANG) questionnaire. Sleep quality and daytime sleepiness were also assessed by the Pittsburgh Sleep Quality Index and Epworth Sleepiness Scale respectively. Bioimpedance analysis was also done using a stadiometer and standard bioimpedance scale. RESULTS: A total of 281 diabetic patients and 147 non-diabetic patients were interviewed throughout Trinidad. Females made up the majority of the sample, 67% of the diabetics and 66% of the non diabetics. The prevalence of OSA was found to be 73.2% in type 2 diabetics. Non diabetics had an OSA prevalence of 39.5%. Results from a binary regression showed that having diabetes increased the probability of “High Risk of OSA” by 93.1%. CONCLUSION: The prevalence of high risk of OSA in Trinidad was high in type 2 diabetic patients, and has strong correlations with obesity and Acanthosis Nigricans.

Relationship of chronic hepatitis C infection to rates of AIDS-defining illnesses in a Canadian cohort of HIV seropositive individuals receiving highly active antiretroviral therapy.

BACKGROUND: The influence of chronic hepatitis C virus (HCV) infection on the risk, timing, and type of AIDS-defining illnesses (ADIs) is not well described. To this end, rates of ADIs were evaluated in a Canadian cohort of HIV seropositive individuals receiving highly active antiretroviral therapy (HAART). METHODS: ADIs were classified into 6 Centers for Disease Control and Prevention (CDC)-defined etiological subgroups: non-Hodgkin lymphoma, viral infection, bacterial infection, HIV-related disease, protozoal infection, and mycotic infection. Generalized estimating equation (GEE) Poisson regression models were used to estimate the effect of HCV on rates of ADIs after adjusting for covariates. RESULTS: Among 2,706 HAART recipients, 768 (28%) were HCV coinfected. Rates of all ADIs combined and of bacterial infection, HIV-related disease, and mycotic infection were increased in HCV-coinfected persons and among those with CD4 counts <200 cells/mm3 HCV was associated with an increased risk of ADIs (rate ratio [RR], 1.38; 95% CI, 1.01-1.88) and a 2-fold increased risk of mycotic infections (RR, 2.21; 95% CI, 1.35-3.62) in univariate analyses and after adjusting for age, baseline viral load, baseline CD4 count, and region of Canada. However, after further adjustment for HAART interruptions, HCV was no longer associated with an increased rate of ADIs overall (RR, 1.13; 95% CI, 0.80-1.59), but remained associated with an increased rate of mycotic infections (RR, 1.97, 95% CI, 1.08-3.61). CONCLUSION: Although HCV coin-fected individuals are at increased risk of developing ADIs overall, our analysis suggests that behavioral variables associated with HCV (including rates of retention on HAART), and not biological interactions with HCV itself, are primarily responsible.

An extracellular source of heme can induce a significant heme oxygenase mediated relaxation in the rat aorta.

Carbon monoxide has been under active investigation for a role in controlling vascular tone throughout the last decade because of its ability to induce relaxation in blood vessels. The underlying mechanisms of this response are hypothesized to be mediated by soluble guanylyl cyclase (sGC) and, in some instances, KCa channels. The major source of CO in major blood vessels is the catabolic process of heme degradation, which is catalyzed by heme oxygenase (HO). This heme substrate could be derived from heme sources within vascular smooth muscle cells, such as heme proteins, or by uptake from the extracellular milieu. The current study shows that the isolated rat aorta relaxes upon exposure to pharmacological concentrations of heme in the bathing medium. This response was inhibited by an inhibitor of HO (tin protoporphyrin) and sGC (1-H-[1,2,4]-oxadiazolo[4,3-a]quinoxalin-1-one). These observations were interpreted to mean that vascular smooth muscle cells are capable of taking up and utilizing heme for the production of CO.

Evaluation of Trinidad and Tobago traditional medicine I: effects of traditional folk remedy on diarrhoea

Hot aqueous extract of bark of Anacardium occidentale (Cashew), commonly used in Trinidadian folk medicine for the treatment of diarrhoea was evaluated for antidiarrhoeal activity. The extract inhibited castor oil-induced diarrhoea in rats as judged by a decrease in the number of wet faeces in the extract-treated rats. The extract was also inhibited the propulsive movement of intestinal contents in mice. The extract showed no direct effect on the isolated guinea-pig ileum, however, it inhibited in a dose-related manner the contractile effects of acetylcholine, histamine, and 5-hydroxytryptamine. The inhibitary effects on these agonists were non competitive in nature. Phytochemical tests revealed the main constituents as tannin, steroids, triterpenoid and carbohydrates. The results indicates that action of A. occidentale bark extract could be through a combination of inhibition of elevated transmitter released and reduced propulsive movement of the small intestine. There is merit in the folk medicinal use of the extract (AU)

Chemical transduction with fluorescent lipid membranes using selective interactions of acetylcholine receptor with agonist/antagonist and acetylcholine with substrate.

Alterations in the physical structure of vesicles and monolayers of phospholipids and soybean lecithin were monitored by measurement on the average fluorescence intensity changes from N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)dipalmitoyl-L-a-phosphatidyl ethanolamine (NBD-PE) located in the lipid matrices. This probe was intimately dispersed at a concentration of 1-2 mol-% in lipid membranes and had an emission sensitive to local environmental structure. Alterations in the structure of soybean lecithin vesicles were induced by the selective interaction of acetylcholine receptor with the agonist carbamylcholine and the antagonist alpha-bungarotoxin. Structural changes in vesicles with a 7:3 mole ratio of dipalmitoylphosphatidyl choline to dipalmitoylphosphatidic acid were observed for selective interactions between acetylcholinesterase and acetylcholine. Enhancement of fluorescence emission from the lipid membranes provided transduction of the selective binding events of the receptor and enzyme. A maximum sensitivity of about a 30% enhancement per micromole of carbamylcholine and a detection limit for the toxin of 10 nM were observed for the receptor. Fluorescence microscopy was used to establish that protein could be incorporated in monolayer lipid membranes and to provide information about potential mechanisms of fluorescence enhancement. These studies show that lipid membranes containing NBD-PE can be used as generic transducers of protein-ligand interactions.