Faculty Bibliography

As people age with HIV, their needs increase beyond solely managing HIV care. Ageing people with HIV, defined as people with HIV who are 50 years or older, face increased risk of both age-regulated comorbidities and ageing-related issues. Globally, health-care systems have struggled to meet these changing needs of ageing people with HIV. We argue that health systems need to rethink care strategies to meet the growing needs of this population and propose models of care that meet these needs using the WHO health system building blocks. We focus on care provision for ageing people with HIV in the three different funding mechanisms: President's Emergency Plan for AIDS Relief and Global Fund funded nations, the USA, and single-payer government health-care systems. Although our categorisation is necessarily incomplete, our efforts provide a valuable contribution to the debate on health systems strengthening as the need for integrated, people-centred, health services increase.

BACKGROUND:Fetal exposure to endocrine-disrupting chemicals such as phthalates and bisphenols might lead to fetal cardiovascular developmental adaptations and predispose individuals to cardiovascular disease in later life. OBJECTIVES/OBJECTIVE:We examined the associations of maternal urinary bisphenol and phthalate concentrations in pregnancy with offspring carotid intima-media thickness and distensibility at the age of 10 y. METHODS:In a population-based, prospective cohort study of 935 mother-child pairs, we measured maternal urinary phthalate and bisphenol concentrations at each trimester. Later, we measured child carotid intima-media thickness and distensibility in the children at age 10 y using ultrasound. RESULTS: DISCUSSION/CONCLUSIONS:In this large prospective cohort, higher maternal urinary bisphenols concentrations were associated with smaller childhood carotid intima-media thickness. Further studies are needed to replicate this association and to identify potential underlying mechanisms. https://doi.org/10.1289/EHP10293.

BACKGROUND:The quality of prostate cancer (PCa) content on Instagram is unknown. METHODS:We examined 62 still-images and 64 video Instagram posts using #prostatecancer on 5/18/20. Results were assessed with validated tools. RESULTS:Most content focused on raising awareness or sharing patient stories (46%); only 9% was created by physicians. 90% of content was low-to-moderate quality and most was understandable, but actionability was 0%. Of the 30% of content including objective information, 40% contained significant misinformation. Most posts had comments offering social support. CONCLUSIONS:Instagram is a source of understandable PCa content and social support; however, information was poorly actionable and had some misinformation.

Survival modeling with time-varying coefficients has proven useful in analyzing time-to-event data with one or more distinct failure types. When studying the cause-specific etiology of breast and prostate cancers using the large-scale data from the Surveillance, Epidemiology, and End Results (SEER) Program, we encountered two major challenges that existing methods for estimating time-varying coefficients cannot tackle. First, these methods, dependent on expanding the original data in a repeated measurement format, result in formidable time and memory consumption as the sample size escalates to over one million. In this case, even a well-configured workstation cannot accommodate their implementations. Second, when the large-scale data under analysis include binary predictors with near-zero variance (e.g., only 0.6% of patients in our SEER prostate cancer data had tumors regional to the lymph nodes), existing methods suffer from numerical instability due to ill-conditioned second-order information. The estimation accuracy deteriorates further with multiple competing risks. To address these issues, we propose a proximal Newton algorithm with a shared-memory parallelization scheme and tests of significance and nonproportionality for the time-varying effects. A simulation study shows that our scalable approach reduces the time and memory costs by orders of magnitude and enjoys improved estimation accuracy compared with alternative approaches. Applications to the SEER cancer data demonstrate the real-world performance of the proximal Newton algorithm.

To identify biomarkers of exposure present in Heated Tobacco Products (HTPs) users' urine which are associated with bladder cancer and to compare quantitative biomarker levels to those seen in combustible cigarette users. A systematic literature review was conducted in December 2020 with no date limits. Relevant studies that reported quantitative urinary biomarker of exposure in HTP users were included. Biomarkers and their parent compounds were classified by carcinogenicity according to the International Agency for Research on Cancer Monographs and were cross-referenced with the Collaborative on Health and the Environment Toxicant and Disease Database to determine associations with bladder cancer. Our literature search identified 561 articles and 30 clinical trial reports. 11 studies met inclusion criteria. These studies identified 29 biomarkers of exposure present in HTP users' urine, which reflect exposure to 21 unique parent compounds. Of these parent compounds, 14 are carcinogens and 10 have a known link to bladder cancer. HTP users' biomarkers of exposure were present at lower levels than combustible cigarette users but higher than never-smokers. Biomarkers of exposure to bladder carcinogens are present in the urine of HTP users. While levels of these biomarkers appear to be lower than combustible cigarette users, chronic urothelial exposure to bladder carcinogens is concerning and degree of bladder cancer risk remains unknown. Further long-term study is needed to elucidate the bladder cancer risk of HTP use.

Metabolomics genome wide association study (GWAS) help outline the genetic contribution to human metabolism. However, studies to date have focused on relatively healthy, population-based samples of White individuals. Here, we conducted a GWAS of 537 blood metabolites measured in the Chronic Renal Insufficiency Cohort (CRIC) Study, with separate analyses in 822 White and 687 Black study participants. Trans-ethnic meta-analysis was then applied to improve fine-mapping of potential causal variants. Mean estimated glomerular filtration rate was 44.4 and 41.5 mL/min/1.73m² in the White and Black participants, respectively. There were 45 significant metabolite associations at 19 loci, including novel associations at PYROXD2, PHYHD1, FADS1-3, ACOT2, MYRF, FAAH, and LIPC. The strength of associations was unchanged in models additionally adjusted for estimated glomerular filtration rate and proteinuria, consistent with a direct biochemical effect of gene products on associated metabolites. At several loci, trans-ethnic meta-analysis, which leverages differences in linkage disequilibrium across populations, reduced the number and/or genomic interval spanned by potentially causal single nucleotide polymorphisms compared to fine-mapping in the White participant cohort alone. Across all validated associations, we found strong concordance in effect sizes of the potentially causal single nucleotide polymorphisms between White and Black study participants. Thus, our study identifies novel genetic determinants of blood metabolites in chronic kidney disease, demonstrates the value of diverse cohorts to improve causal inference in metabolomics GWAS, and underscores the shared genetic basis of metabolism across race.

Peritonitis, as a major consequence of hollow visceral perforation, anastomotic disruption, ischemic necrosis, or other injuries of the gastrointestinal tract, often drives acute care in the emergency department, operating room, and the ICU. Chronic critical illness (CCI) represents a devastating challenge in modern surgical critical care where successful interventions have fostered a growing cohort of patients with prolonged dependence on mechanical ventilation and other organ supportive therapies who would previously have succumbed much earlier in the acute phase of critical illness. An important subset of CCI patients are those who have survived an emergency abdominal operation, but who subsequently require prolonged open abdomen management complicated by persistent peritoneal space infection or colonization, fistula formation, and gastrointestinal (GI) tract dysfunction; these patients are described as having tertiary peritonitis (TP).The organ dysfunction cascade in TP terminates in death in between 30 and 64% of patients. This narrative review describes key-but not all-elements in a framework for the coordinate multiprofessional team-based management of a patient with tertiary peritonitis to mitigate this risk of death and promote recovery. Given the prolonged critical illness course of this unique patient population, early and recurrent Palliative Care Medicine consultation helps establish goals of care, support adjustment to changes in life circumstance, and enable patient and family centered care.