Q-learning: flexible learning about useful utilities

Dynamic treatment regimes are fast becoming an important part of medicine, with the corresponding change in emphasis from treatment of the disease to treatment of the individual patient. Because of the limited number of trials to evaluate personally tailored treatment sequences, inferring optimal treatment regimes from observational data has increased importance. Q-learning is a popular method for estimating the optimal treatment regime, originally in randomized trials but more recently also in observational data. Previous applications of Q-learning have largely been restricted to continuous utility end-points with linear relationships. This paper is the first attempt at both extending the framework to discrete utilities and implementing the modelling of covariates from linear to more flexible modelling using the generalized additive model (GAM) framework. Simulated data results show that the GAM adapted Q-learning typically outperforms Q-learning with linear models and other frequently-used methods based on propensity scores in terms of coverage and bias/MSE. This represents a promising step toward a more fully general Q-learning approach to estimating optimal dynamic treatment regimes

Prenatal exposure to insecticides and weight trajectories among South African children in the VHEMBE birth cohort

DATA AVAILABLITY STATEMENT : Access to data and computing may be discussed by contacting the corresponding author.BACKGROUND : Dichlorodiphenyltrichloroethane (DDT) or pyrethroid insecticides are sprayed inside dwellings for malaria vector control, resulting in high exposure to millions of people, including pregnant women. These chemicals disrupt endocrine function and may affect child growth. To our knowledge, few studies have investigated the potential impact of prenatal exposure to DDT or pyrethroids on growth trajectories. METHODS : We investigated associations between gestational insecticide exposure and child growth trajectories in the Venda Health Examination of Mothers, Babies and their Environment, a birth cohort of 751 children born between 2012 and 2013 in South Africa. Based on child weight measured at follow-up and abstracted from medical records, we modeled weight trajectories from birth to 5 years using SuperImposition, Translation and Rotation, which estimated two child-specific parameters: size (average weight) and tempo (age at peak weight velocity). We estimated associations between peripartum maternal concentrations of serum DDT, dichlorodiphenyldichloroethylene, or urinary pyrethroid metabolites and SuperImposition, Translation and Rotation parameters using marginal structural models. RESULTS : We observed that a 10-fold increase in maternal concentrations of the pyrethroid metabolite trans-3-(2,2,-dicholorvinyl)-2,2-dimethyl-cyclopropane carboxylic acid was associated with a 21g (95% confidence interval = −40, −1.6) smaller size among boys but found no association among girls (Pinteraction = 0.07). Estimates suggested that pyrethroids may be associated with earlier tempo but were imprecise. We observed no association with serum DDT or dichlorodiphenyldichloroethylene. CONCLUSIONS : Inverse associations between pyrethroids and weight trajectory parameters among boys are consistent with hypothesized disruption of androgen pathways and with our previous research in this population, and support the endocrine-disrupting potential of pyrethroids in humans.The VHEMBE study was funded by the Canadian Institutes of Health Research and the US National Institute of Environmental Health Sciences; a Canada Research Chair in Global Environmental Health and Epidemiology; a Doctoral Award from the Fonds de recherche du Québec—Santé, with prior fund- ing from McGill University’s Faculty of Medicine.hj2023School of Health Systems and Public Health (SHSPH)UP Centre for Sustainable Malaria Control (UP CSMC

Risk of End-Stage Liver Disease in HIV-Viral Hepatitis Coinfected Persons in North America From the Early to Modern Antiretroviral Therapy Eras

Background. Human immunodeficiency virus (HIV)–infected patients coinfected with hepatitis B (HBV) and C (HCV) viruses are at increased risk of end-stage liver disease (ESLD). Whether modern antiretroviral therapy has reduced ESLD risk is unknown

Missing Confounding Data in Marginal Structural Models: A Comparison of Inverse Probability Weighting and Multiple Imputation

Standard statistical analyses of observational data often exclude valuable information from individuals with incomplete measurements. This may lead to biased estimates of the treatment effect and loss of precision. The issue of missing data for inverse probability of treatment weighted estimation of marginal structural models (MSMs) has often been addressed, though little has been done to compare different missing data techniques in this relatively new method of analysis. We propose a method for systematically dealing with missingness in MSMs by treating missingness as a cause for censoring and weighting subjects by the inverse probability of missingness. We developed a series of simulations to systematically compare the effect of using case deletion, our inverse weighting approach, and multiple imputation in a MSM when there is missing information on an important confounder. We found that multiple imputation was slightly less biased and considerably less variable than the inverse probability approach. Thus, the lower variability achieved through multiple imputation makes it desirable in most practical cases where the missing data are strongly predicted by the available data. Inverse probability weighting is, however, a superior alternative to naive approaches such as complete-case analysis.NSER

Hepatitis C co-infection is associated with an increased risk of incident chronic kidney disease in HIV-infected patients initiating combination antiretroviral therapy

Background: Combination antiretroviral therapy (cART) has reduced mortality from AIDS-related illnesses and chronic comorbidities have become prevalent among HIV-infected patients. We examined the association between hepatitis C virus (HCV) co-infection and chronic kidney disease (CKD) among patients initiating modern antiretroviral therapy. Methods: Data were obtained from the Canadian HIV Observational Cohort for individuals initiating cART from 2000 to 2012. Incident CKD was defined as two consecutive serum creatinine-based estimated glomerular filtration (eGFR) measurements <60 mL/min/1.73m2 obtained ≥3 months apart. CKD incidence rates after cART initiation were compared between HCV co-infected and HIV mono-infected patients. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using multivariable Cox regression. Results: We included 2595 HIV-infected patients with eGFR >60 mL/min/1.73m2 at cART initiation, of which 19% were HCV co-infected. One hundred and fifty patients developed CKD during 10,903 person-years of follow-up (PYFU). The CKD incidence rate was higher among co-infected than HIV mono-infected patients (26.0 per 1000 PYFU vs. 10.7 per 1000 PYFU). After adjusting for demographics, virologic parameters and traditional CKD risk factors, HCV co-infection was associated with a significantly shorter time to incident CKD (HR 1.97; 95% CI: 1.33, 2.90). Additional factors associated with incident CKD were female sex, increasing age after 40 years, lower baseline eGFR below 100 mL/min/1.73m2, increasing HIV viral load and cumulative exposure to tenofovir and lopinavir. Conclusions: HCV co-infection was associated with an increased risk of incident CKD among HIV-infected patients initiating cART. HCV-HIV co-infected patients should be monitored for kidney disease and may benefit from available HCV treatments.Medicine, Faculty ofOther UBCNon UBCReviewedFacult

Risk of End-Stage Liver Disease in HIV-Viral Hepatitis Coinfected Persons in North America From the Early to Modern Antiretroviral Therapy Eras

Background. Human immunodeficiency virus (HIV)–infected patients coinfected with hepatitis B (HBV) and C (HCV) viruses are at increased risk of end-stage liver disease (ESLD). Whether modern antiretroviral therapy has reduced ESLD risk is unknown. Methods. Twelve clinical cohorts in the United States and Canada participating in the North American AIDS Cohort Collaboration on Research and Design validated ESLD events from 1996 to 2010. ESLD incidence rates and rate ratios according to hepatitis status adjusted for age, sex, race, cohort, time-updated CD4 cell count and HIV RNA were estimated in calendar periods corresponding to major changes in antiretroviral therapy: early (1996–2000), middle (2001–2005), and modern (2006–2010) eras. Results. Among 34 119 HIV-infected adults followed for 129 818 person-years, 380 incident ESLD outcomes occurred. ESLD incidence (per 1000 person-years) was highest in triply infected (11.57) followed by HBV- (8.72) and HCV- (6.10) coinfected vs 1.27 in HIV-monoinfected patients. Adjusted incidence rate ratios (95% confidence intervals) comparing the modern to the early antiretroviral era were 0.95 (.61–1.47) for HCV, 0.95 (.40–2.26) for HBV, and 1.52 (.46–5.02) for triply infected patients. Use of antiretrovirals dually activity against HBV increased over time. However, in the modern era, 35% of HBV-coinfected patients were not receiving tenofovir. There was little use of HCV therapy. Conclusions. Despite increasing use of antiretrovirals, no clear reduction in ESLD risk was observed over 15 years. Treatment with direct-acting antivirals for HCV and wider use of tenofovir-based regimens for HBV should be prioritized for coinfected patients