Faculty Bibliography

Maternal immune activity during pregnancy has been associated with risk for psychiatric disorders in offspring, but less is known about its implications for children's emotional and behavioral development. This study examined whether concentrations of five cytokines assayed from prenatal serum were associated with socioeconomic status (SES) and racial disparities in their offspring's self-regulation abilities. Participants included 1,628 women in the Collaborative Perinatal Project (CPP). Seven behavioral items conceptually related to self-regulation were rated by CPP psychologists when children were 4 years old. Concentrations of interleukin (IL)-1β, IL-6, IL-8, tumor necrosis factor (TNF)-α, and IL-10 were assessed. Covariates included child sex and mother's age, psychiatric disorders, and medical conditions during pregnancy. There were significant SES differences in child self-regulation, with higher SES children scoring higher on self-regulation (β = .18, 95% CI [.11, .25]), but no racial differences. The concentration of IL-8 in maternal serum was associated with higher child self-regulation, β = .09, 95% CI [.02, .16]. In mediation analyses, variation in maternal IL-8 contributed to the association between family SES and child self-regulation (β = .02, 95% CI [.003, .030]), explaining about one-tenth of the SES disparities. This study suggests pregnancy as an early sensitive period and maternal immune activity as an important context for child development.

Global disparities in breast cancer care become particularly evident when patients seek definitive care in the United States (USA) after receiving a breast cancer diagnosis and initiating care in low- and middle-income countries (LMICs). We performed a retrospective review of 26 patients with breast cancer who immigrated from LMICs and received care at Bellevue Hospital. Fifteen (58%) presented with advanced disease (stage III or IV), including 7 (27%). All 26 patients required diagnostic work-up in the USA, and all 19 (73.1%) patients with stage 0-III disease underwent surgical excision. Patients from LMICs frequently present with advanced disease and in varying stages of breast cancer treatment. Improving communication with previous providers and fostering a collaborative approach with the international community are essential to developing efficacious treatment plans and improving oncologic outcomes.

OBJECTIVE:To quantify the risk of hyperkalemia and acute kidney injury (AKI) when spironolactone use is added on to loop diuretic use among patients with heart failure, and to evaluate whether the risk is modified by level of kidney function. METHODS:We identified 17,110 patients with heart failure treated with loop diuretics between January 1, 2004, and December 31, 2016 within the Geisinger Health System. We estimated the incidence of hyperkalemia and AKI associated with spironolactone initiation, and used target trial emulation methods to minimize confounding by indication. RESULTS:During a mean follow-up of 134 mo, 3229 of 17,110 patients (18.9%) initiated spironolactone. Incidence rates of hyperkalemia and AKI in patients using spironolactone with a loop diuretic were 2.9 and 10.1 events per 1000 person-months, respectively. In propensity score-matched analyses, spironolactone initiation was associated with higher hyperkalemia and AKI risk compared with loop alone (hazard ratio, 1.69; 95% CI, 1.35 to 2.10; P<.001, and hazard ratio, 1.12; 95% CI, 1.00 to 1.26; P=.04, respectively). There were no differences in the relative risk of either outcome associated with spironolactone by level of kidney function. CONCLUSION:The addition of spironolactone to loop diuretics in patients with heart failure was associated with higher risk of hyperkalemia and AKI; these risks must be weighed against the potential benefits of spironolactone.

Availability of medicines for treatment of cardiovascular disease (CVD) is low in low-income and middle-income countries (LMIC). Supply chain models to improve the availability of quality CVD medicines in LMIC communities are urgently required. Our team established contextualised revolving fund pharmacies (RFPs) in rural western Kenya, whereby an initial stock of essential medicines was obtained through donations or purchase and then sold at a small mark-up price sufficient to replenish drug stock and ensure sustainability. In response to different contexts and levels of the public health system in Kenya (eg, primary versus tertiary), we developed and implemented three contextualised models of RFPs over the past decade, creating a network of 72 RFPs across western Kenya, that supplied 22 categories of CVD medicines and increased availability of essential CVD medications from <30% to 90% or higher. In one representative year, we were able to successfully supply 5 793 981 units of CVD and diabetes medicines to patients in western Kenya. The estimated programme running cost was US$6.5-25 per patient, serving as a useful benchmark for public governments to invest in medication supply chain systems in LMICs going forward. One important lesson that we have learnt from implementing three different RFP models over the past 10 years has been that each model has its own advantages and disadvantages, and we must continue to stay nimble and modify as needed to determine the optimal supply chain model while ensuring consistent access to essential CVD medications for patients living in these settings.

BACKGROUND AND PURPOSE:Data on the significance of combined white matter hyperintensities (WMH)/lacunar brain infarcts, and their progression over time for the prediction of stroke are scarce. We studied associations between the progression in combined measures of microvascular brain disease and risk of stroke in the ARIC study (Atherosclerosis Risk in Communities). METHODS:Prospective analysis of 907 stroke-free ARIC participants who underwent a brain magnetic resonance imaging (MRI) in 1993 to 1995, a second brain MRI in 2004 to 2006, and were subsequently followed for stroke incidence through December 31, 2017 (median [25%-75%] follow-up 12.6 [8.9-13.4] years). A combined measure of microvascular brain disease was defined at each visit and categorized by progression from first to second brain MRI as no progression; mild progression (increase of ≥1 unit in WMH grade or new lacune), and moderate progression (increase of ≥1 unit in WMH grade and new lacune). All definite/probable ischemic or hemorrhagic incident strokes occurring after this second MRI, and through 2017, were included. Associations between microvascular brain disease, progression in the combined measures, and stroke incidence were studied with Cox proportional hazard models, adjusting for age, sex, race, education level, time from first to second MRI, body mass index, smoking, hypertension, diabetes mellitus, and coronary heart disease. RESULTS:At the second brain MRI (mean age 72), the distribution of the combined measure was 37% WMH grade <2 and no lacune; 57% WMH grade ≥2 or lacune; and 6% WMH grade ≥2 and lacune. No progression in the combined measures was observed in 38% of participants, 57% showed mild progression and 5% showed moderate progression. Sixty-four incident strokes occurred during the follow-up period. Compared with no change in the combined measure, moderate progression of microvascular brain disease was significantly associated with higher risk of stroke (adjusted hazard ratio, 3.00 [95% CI, 1.30-6.94]). CONCLUSIONS:Progression of microvascular brain disease, manifesting as both new lacunes and increase in WMHs grade, is related to substantial increase in long-term risk of stroke.

The COVID-19 pandemic is challenging health systems across the world. The potential for devastating consequences in resource-limited low- and middle-income countries (LMICs) is just beginning to be understood. In the majority of LMICs, maternal healthcare is focused outside a health center through the use of community health workers and birth attendants. These essential workers provide the majority of maternal health care around the globe and are ill prepared for the highly transmissible nature of this novel virus and its consequences for their communities. Little attention has been focused on their training and responsiveness during this pandemic.

The purpose of this study was to examine and quantify spatial mobility among HIV-negative young men who have sex with men (YMSM) within and across high prevalence HIV neighborhoods in New York City (NYC). We completed an analysis with global positioning system (GPS) and survey data to quantify spatial mobility for participants enrolled in the P18 Neighborhood Study (analytic n = 211; 83.4%). Spatial mobility was documented with self-reported survey data and objective GPS data, which was uncorrelated. Nearly one-quarter of participants (26.1%) said that they consider the neighborhood in which they currently live to differ from the neighborhood in which they had sex most frequently. In addition, 62.9% of participants' GPS points were recorded in NYC ZIP Code Tabulation Areas within the highest quartile of HIV prevalence. Future studies of YMSM populations should be conducted to examine how environments beyond the residential neighborhood can influence sexual health, which may guide HIV prevention services.

INTRODUCTION/BACKGROUND:The population and spatial characteristics of COVID-19 infections are poorly understood, but there is increasing evidence that in addition to individual clinical factors, demographic, socioeconomic and racial characteristics play an important role. METHODS:We analyzed positive COVID-19 testing results counts within New York City ZIP Code Tabulation Areas (ZCTA) with Bayesian hierarchical Poisson spatial models using integrated nested Laplace approximations. RESULTS:Spatial clustering accounted for approximately 32% of the variation in the data. There was a nearly five-fold increase in the risk of a positive COVID-19 test. (IDR = 4.8, 95% Cr I 2.4, 9.7) associated with the proportion of Black / African American residents. Increases in the proportion of residents older than 65 years, housing density and the proportion of residents with heart disease were each associated with an approximate doubling of risk. In a multivariable model including estimates for age, COPD, heart disease, housing density and Black/African American race, the only variables that remained associated with positive COVID-19 testing with a probability greater than chance were the proportion of Black/African American residents and proportion of older persons. CONCLUSIONS:Areas with large proportions of Black/African American residents are at markedly higher risk that is not fully explained by characteristics of the environment and pre-existing conditions in the population.