Prediction-based classification for longitudinal biomarkers

Assessment of circulating CD4 count change over time in HIV-infected subjects on antiretroviral therapy (ART) is a central component of disease monitoring. The increasing number of HIV-infected subjects starting therapy and the limited capacity to support CD4 count testing within resource-limited settings have fueled interest in identifying correlates of CD4 count change such as total lymphocyte count, among others. The application of modeling techniques will be essential to this endeavor due to the typically nonlinear CD4 trajectory over time and the multiple input variables necessary for capturing CD4 variability. We propose a prediction-based classification approach that involves first stage modeling and subsequent classification based on clinically meaningful thresholds. This approach draws on existing analytical methods described in the receiver operating characteristic curve literature while presenting an extension for handling a continuous outcome. Application of this method to an independent test sample results in greater than 98% positive predictive value for CD4 count change. The prediction algorithm is derived based on a cohort of $n=270$ HIV-1 infected individuals from the Royal Free Hospital, London who were followed for up to three years from initiation of ART. A test sample comprised of $n=72$ individuals from Philadelphia and followed for a similar length of time is used for validation. Results suggest that this approach may be a useful tool for prioritizing limited laboratory resources for CD4 testing after subjects start antiretroviral therapy.Comment: Published in at http://dx.doi.org/10.1214/10-AOAS326 the Annals of Applied Statistics (http://www.imstat.org/aoas/) by the Institute of Mathematical Statistics (http://www.imstat.org

Expanding HAART Treatment to All Currently Eligible Individuals under the 2008 IAS-USA Guidelines in British Columbia, Canada

Background In 2008, the IAS-USA published the revised guidelines for the use of HAART in adults substantially increasing the number of individuals eligible for HAART. The epidemic in British Columbia (BC) is mainly among men who have sex with men and those with injection drug use. Here, we explored the potential impact of different HAART coverage scenarios, based on the new guidelines, on the HIV-related incidence, morbidity and mortality in BC, Canada. Methodology We built a mathematical transmission model to investigate different HAART coverage scenarios (50%, 60%, 75% and 100%) of those medically eligible to receive HAART under the 2008 IAS guidelines. All new scenarios were compared to the current coverage in BC under the 2006 IAS guidelines (i.e. baseline scenario). In BC, it is estimated that 25–30% of individuals are unaware of their status. Costs were drug-related and reported in Canadian dollars. HIV-related morbidity and mortality were estimated based on the disability-adjusted life years (DALY) methodology. Principal Findings Currently, there are 4379 individuals on HAART under the IAS 2006 guidelines and 6781 individuals who qualify for treatment based on the new guidelines. Within 5 years, increasing HAART coverage decreased yearly new infections by at least 44.8%. In the 50% scenario, in 5 years, DALY decreased by 53% corresponding to 4155 averted DALYs, and in 25 years it decreased by 66% corresponding to 5837 averted DALYs. The effect was even stronger if the 75% scenario was chosen instead. Compared to the 100% expansion scenario, we observed an excess in annual direct treatment expenditures at the end of 5 years of approximately 1 million dollars in the 75% scenario, and of approximately 2 million dollars in the 50% scenario. Conclusions/Significance The individual and public health benefits of these new guidelines are immense. The results show that by increasing the number of individuals on HAART save lives, it is cost averting, and it positively impacts society by decreasing the number of new HIV infections. Thus, public health community should consider incremental gains when considering guidelines and policy

Effect of CGM in the HbA1c and Coefficient of Variation of glucose in a pediatric sample

Aim of the study: Previous studies have found no significant improvements in glycated hemoglobin (HbA1c), while using Continuous Glucose Monitoring (CGM), with children and adolescents. The aim of this paper is to measure the change in HbA1c, and the Coefficient of Variation in glucose levels, when using CGM, once the effect of other relevant variables, such as gender, actual age, the years the patient has had diabetes, use of an insulin pump, the presence of autoimmune disease, other associated pathologies, and weekly hours of exercise, are controlled for. Methods: This is a retrospective study that uses a linear regression model. Data was collected from Type 1 Diabetes Mellitus (T1DM), children diagnosed between 2003 and 2017 in the Pediatric Unit for Diabetes in Zaragoza, Spain. We used a linear regression and the method of estimation is Ordinary Least Squares. Results: Results show that the use of CGM decreased the HbA1c value by 3.5% and the Coefficient of Variation by 14%. Conclusions: The implication of these results is that this device helped in the management of diabetes, although more research is needed to distinguish between different devices in terms of their efficacy

Disparities in the Burden of HIV/AIDS in Canada

Background We aimed to characterize changes in patterns of new HIV diagnoses, HIV-related mortality, and HAART use in Canada from 1995 to 2008. Methods Data on new HIV diagnoses were obtained from Health Canada, HIV-related mortality statistics were obtained from Statistics Canada, and information on the number of people on HAART was obtained from the single antiretroviral distribution site in British Columbia (BC), and the Intercontinental Marketing Services Health for Ontario and Quebec. Trends of new HIV-positive tests were assessed using Spearman rank correlations and the association between the number of individuals on HAART and new HIV diagnoses were estimated using generalized estimating equations (GEE). Results A total of 34,502 new HIV diagnoses were observed. Rates of death in BC are higher than those in Ontario and Quebec with the rate being 2.03 versus 1.06 and 1.21 per 100,000 population, respectively. The number of HIV infected individuals on HAART increased from 5,091 in 1996 to 20,481 in 2008 in the three provinces (4 fold increase). BC was the only province with a statistically significant decrease (trend test p<0.0001) in the rate of new HIV diagnoses from 18.05 to 7.94 new diagnoses per 100,000 population. Our analysis showed that for each 10% increment in HAART coverage the rate of new HIV diagnoses decreased by 8% (95% CI: 2.4%, 13.3%) Interpretation Except for British Columbia, the number of new HIV diagnoses per year has remained relatively stable across Canada over the study period. The decline in the rate of new HIV diagnoses per year may be in part attributed to the greater expansion of HAART coverage in this province

Does ratification of human-rights treaties have effects on population health?

Human-rights treaties indicate a country's commitment to human rights. Here, we assess whether ratification of human-rights treaties is associated with improved health and social indicators. Data for health (including HIV prevalence, and maternal, infant, and child [<5 years] mortalities) and social indicators (child labour, human development index, sex gap, and corruption index), gathered from 170 countries, showed no consistent associations between ratification of human-rights treaties and health or social outcomes. Established market economy states had consistently improved health compared with less wealthy settings, but this was not associated with treaty ratification. The status of treaty ratification alone is not a good indicator of the realisation of the right to health. We suggest the need for stringent requirements for ratification of treaties, improved accountability mechanisms to monitor compliance of states with treaty obligations, and financial assistance to support the realisation of the right to health

Prescription opioid injection and risk of hepatitis C in relation to traditional drugs of misuse in a prospective cohort of street youth

Objective: Despite dramatic increases in the misuse of prescription opioids, the extent to which their intravenous injection places drug users at risk of acquiring hepatitis C virus (HCV) remains unclear. We sought to compare risk of HCV acquisition from injection of prescription opioids to that from other street drugs among high-risk street youth. Design: Prospective cohort study. Setting: Vancouver, British Columbia, Canada from September 2005 to November 2011. Participants: The At-Risk Youth Study (ARYS) is a prospective cohort of drug-using adolescents and young adults aged 14–26 years. Participants were recruited through street-based outreach and snowball sampling. Primary outcome measure HCV antibody seroconversion, measured every 6 months during follow-up. Risk for seroconversion from injection of prescription opioids was compared with injection of other street drugs of misuse, including heroin, cocaine or crystal methamphetamine, using Cox proportional hazards regression controlling for age, gender and syringe sharing. Results: Baseline HCV seropositivity was 10.6%. Among 512 HCV-seronegative youth contributing 860.2 person-years of follow-up, 56 (10.9%) seroconverted, resulting in an incidence density of 6.5/100 person-years. In bivariate analyses, prescription opioid injection (HR=3.48; 95% CI 1.57 to 7.70) predicted HCV seroconversion. However, in multivariate modelling, only injection of heroin (adjusted HR=4.56; 95% CI 2.39 to 8.70), cocaine (adjusted HR=1.88; 95% CI 1.00 to 3.54) and crystal methamphetamine (adjusted HR=2.91; 95% CI 1.57 to 5.38) remained independently associated with HCV seroconversion, whereas injection of prescription opioids did not (adjusted HR=0.94; 95% CI 0.40 to 2.21). Conclusions: Although misuse of prescription opioids is on the rise, traditional street drugs still posed the greatest threat of HCV transmission in this setting. Nonetheless, the high prevalence and incidence of HCV among Canadian street youth underscore the need for evidence-based drug prevention, treatment and harm reduction interventions targeting this vulnerable population