Physicians' patient base composition and mortality among people living with HIV who initiated antiretroviral therapy in a universal care setting.

OBJECTIVES: To assess the impact of physicians' patient base composition on all-cause mortality among people living with HIV (PLHIV) who initiated highly active antiretroviral therapy (HAART) in British Columbia (BC), Canada. DESIGN: Observational cohort study from 1 January 2000 to 31 December 2013. SETTING: BC Centre for Excellence in HIV/AIDS' (BC-CfE) Drug Treatment Program, where HAART is available at no cost. PARTICIPANTS: PLHIV aged ≥ 19 who initiated HAART in BC in the HAART Observational Medical Evaluation and Research (HOMER) Study. OUTCOME MEASURES: All-cause mortality as determined through monthly linkages to the BC Vital Statistics Agency. STATISTICAL ANALYSIS: We examined the relationships between patient characteristics, physicians' patient base composition, the location of the practice, and physicians' experience with PLHIV and all-cause mortality using unadjusted and adjusted Cox proportional hazards models. RESULTS: A total of 4 445 PLHIV (median age = 42, Q1, Q3 = 34-49; 80% male) were eligible for our study. Patients were seen by 683 prescribing physicians with a median experience of 77 previously treated PLHIV in the past 2 years (Q1, Q3 = 23-170). A multivariable Cox model indicated that the following factors were associated with all-cause mortality: age (aHR = 1.05 per 1-year increase, 95% CI = 1.04 to 1.06), year of HAART initiation (2004-2007: aHR = 0.65, 95% CI = 0.53 to 0.81, 2008-2011: aHR = 0.46, 95% CI = 0.35 to 0.61, Ref: 2000-2003), CD4 cell count at baseline (aHR = 0.88 per 100-unit increase in cells/mm3, 95% CI = 0.82 to 0.94), and < 95% adherence in first year on HAART (aHR = 2.28, 95% CI = 1.88 to 2.76). In addition, physicians' patient base composition, specifically, the proportion of patients who have a history of injection drug use (aHR = 1.11 per 10% increase in the proportion of patients, 95% CI = 1.07 to 1.15) or Indigenous ancestry (aHR = 1.07 per 10% increase , 95% CI = 1.03-1.11) and being a patient of a physician who primarily serves individuals outside of the Vancouver Coastal Health Authority region (aHR = 1.22, 95% CI = 1.01 to 1.47) were associated with mortality. CONCLUSIONS: Our findings suggest that physicians with a higher proportion of individuals who face potential barriers to care may need additional supports to decrease mortality among their patients. Future research is required to examine these relationships in other settings and to determine strategies that may mitigate the associations between the composition of physicians' patient bases and survival.

In Utero Exposure to Benzo[a]Pyrene Increases Mutation Burden in the Soma and Sperm of Adult Mice.

BACKGROUND: Mosaicism, the presence of genetically distinct cell populations within an organism, has emerged as an important contributor to disease. Mutational events occurring during embryonic development can cause mosaicism in any tissue, but the influence of environmental factors on levels of mosaicism is unclear. OBJECTIVES: We investigated whether in utero exposure to the widespread environmental mutagen benzo[a]pyrene (BaP) has an impact on the burden and distribution of mutations in adult mice. METHODS: We used the Muta™Mouse transgenic rodent model to quantify and characterize mutations in the offspring of pregnant mice exposed to BaP during postconception days 7 through 16, covering the major period of organogenesis in mice. Next-generation DNA sequencing was then used to determine the spectrum of mutations induced in adult mice that were exposed to BaP during fetal development. RESULTS: Mutation frequency was significantly increased in the bone marrow, liver, brain, and sperm of first filial generation (F1) males. Developing embryos accumulated more mutations and exhibited higher proportions of mosaicism than exposed adults, particularly in the brain. Decreased sperm count and motility revealed additional negative impacts on the reproductive function of F1 males. CONCLUSION: In utero exposure to environmental mutagens contributes to somatic and germline mosaicism, permanently affecting both the genetic health of the F1 and the population gene pool. Citation: Meier MJ, O'Brien JM, Beal MA, Allan B, Yauk CL, Marchetti F. 2017. In utero exposure to benzo[a]pyrene increases mutation burden in the soma and sperm of adult mice. Environ Health Perspect 125:82-88; http://dx.doi.org/10.1289/EHP211.