Faculty Bibliography

Rationale & Objective/UNASSIGNED:Evaluation of glomerular filtration rate (GFR) is challenging in adults undergoing bariatric surgery because creatinine and cystatin C levels are influenced by changes in muscle and fat mass. Additionally, indexing of GFR by body surface area (BSA) may by affected by decreases in BSA. Study Design/UNASSIGNED:Prospective observational study. Setting & Participants/UNASSIGNED:who underwent measurement of GFR before and after bariatric surgery. Outcomes/UNASSIGNED:Indexed and nonindexed GFRs measured (mGFRs) using plasma iohexol clearance, indexed and nonindexed estimated GFR (eGFR) based on levels of creatinine, cystatin C, or both from Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations. Analytic Approach/UNASSIGNED:) for estimating equations were examined. Results/UNASSIGNED:was unbiased before (median bias, -6.0 [95% CI, -11.0 to 1.0] mL/min) and after surgery (-2.0 [95% CI, -8.8 to 4.9] mL/min). Findings were similar for indexed eGFR compared with indexed mGFR. Limitations/UNASSIGNED:Small, mostly white sample. Conclusions/UNASSIGNED:because of opposite biases in estimating mGFR.

OBJECTIVE:This study examined the extent to which maternal immune activity during pregnancy is associated with childhood adiposity, and if so, whether associations at birth differ from those in infancy and childhood. Sex-specific associations were also examined. METHODS:Participants were 1,366 singleton pregnancies from the Collaborative Perinatal Project (1959-1966). Interleukin-1β (IL-1β), IL-6, TNF-α, IL-8, and IL-10 in maternal sera were assayed repeatedly during pregnancy. Children's BMI was calculated repeatedly from birth through age 8 and derived age- and sex-normalized BMI z scores (BMIz). Linear mixed models were used to estimate the cumulative concentration of each cytokine in the second and third trimesters and then related this concentration to child BMIz. RESULTS:Children exposed to higher IL-1β, IL-6, IL-8, and IL-10 concentrations had lower BMIz at birth but higher BMIz during childhood. Higher concentrations of IL-8 and IL-1β were also associated with higher BMIz during infancy (B per log increase in IL-8 = 0.04; 95% CI: 0.02 to 0.07; B per log increase in IL-1β = 0.03; 95% CI: 0.001 to 0.06). The associations between TNF-α and BMIz were in opposing directions in boys (B = -0.13; 95% CI: -0.31 to 0.04) and girls (B = 0.14; 95% CI: 0.02 to 0.26) during childhood. CONCLUSIONS:Maternal prenatal inflammation contributes to the age- and sex-specific programming of obesity risk in childhood.

OBJECTIVE:To understand how to potentially improve inappropriate prostate cancer imaging rates we used National Comprehensive Cancer Network's (NCCN) guidelines to design and implement a Clinical Reminder Order Check (CROC) that alerts ordering providers of potentially inappropriate imaging orders in real-time based on patient features of men diagnosed with low-risk prostate cancer. METHODS:We implemented the CROC at VA New York Harbor Healthcare System (VANYHHS) from April 2, 2015 to November 15, 2017. We then used VA administrative claims from the VA's Corporate Data Warehouse to analyze imaging rates among men with low-risk prostate cancer at VHANYHHS before and after CROC implementation. We also collected and cataloged provider responses in response to overriding the CROC in qualitative analysis. RESULTS:57% (117/205) of Veterans before CROC installation and 73% (61/83) of Veterans post-intervention with low-risk prostate cancer received guideline-concordant care. CONCLUSION/CONCLUSIONS:While the decrease in inappropriate imaging during our study window was almost certainly due to many factors, a CPRS-based CROC intervention is likely associated with at least moderate improvement in guideline-concordant imaging practices for Veterans with low-risk prostate cancer.

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.

OBJECTIVES/OBJECTIVE:We examined associations between household food insecurity status and parental feeding behavior, weight perception, and child weight status in a diverse sample of young children. METHODS:Cross-sectional analysis of 2-year old children in Greenlight, a cluster randomized trial to prevent childhood obesity. The exposure was food insecurity, defined as a positive response to a validated screen. Outcomes were parent feeding behaviors/beliefs measured by the Child Feeding Questionnaire and child weight status. T-tests and linear regression were used to assess associations between food insecurity and each outcome. We adjusted for child sex, race/ethnicity, parent education, employment, site, number of children in the home, and WIC status. RESULTS:503 households (37%) were food insecure. After adjusting for covariates, parents from insecure households reported more pressuring feeding behaviors (mean factor score 3.2 compared to food secure parents mean factor score 2.9, p=0.01) and were more worried about their child becoming overweight (mean factor score 2.3 vs 2.0; p=0.02). No differences were observed in monitoring or restrictive feeding behaviors. After adjusting for covariates, there was no difference in weight status or prevalence of overweight/obesity of children or parents based on household food insecurity status. CONCLUSIONS:Parents from food insecure households reported more pressuring feeding behaviors. This finding underscores the need to address food insecurity and potentially prevent harmful effects on child feeding. Parents in food insecure households might benefit from linkage with resources and education to develop healthier feeding behaviors.

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.

OBJECTIVES/OBJECTIVE:The Nigerian Urban Reproductive Health Initiative (NURHI) was implemented in six urban sites in Nigeria from 2009 to early 2015. Under a second phase (NURHI-2), activities ceased operations in four of the original six sites in 2015 (Ilorin, Abuja, Benin City and Zaria), and continued in two sites (Kaduna and Ibadan). This paper examines the sustainability of facility-based intervention activities implemented under NURHI-1 in Ilorin and Kaduna. METHODS:A qualitative study that used in-depth interviews was conducted with 31 service providers purposively selected from 10 of the NURHI-1 intervention facilities in Ilorin and six in Kaduna. Interviews were digitally recorded and transcripts uploaded into ATLAS.ti for analysis. Structured observations to document renovations implemented during the NURHI-1 interventions were also conducted in the health facilities. RESULTS:Family planning (FP) awareness creation within the facilities and integration of FP into existing maternal and child health and HIV services, were sustained in both cities. The majority of the equipment supplied as part of the NURHI 72-hour clinic makeover were still functional in both cities. Respondents in both cities reported that FP awareness and demand were sustained. On the whole, challenges with sustaining activities were reported more among respondents in Ilorin than Kaduna. In Ilorin, NURHI outreach activities and trainings, had discontinued while in Kaduna, they were no longer being implemented to the same degree as occurred during NURHI-1. Inadequate funds was a major reason for discontinued activities in both cities while integration of FP into existing services enhanced sustainability. CONCLUSIONS:Many activities were not sustained in Ilorin compared with Kaduna although FP awareness and demand remained high in both cities. Integration of FP into existing services promoted sustainability in Ilorin and Kaduna. A gradual closeout of donor projects with concomitant input from government and indigenous institutions could be useful in sustaining donor activities.

Elevated blood pressure in childhood is an important risk factor for hypertension in adulthood. Environmental exposures have been associated with elevated blood pressure over the life course and exposure to mercury (Hg) has been linked to cardiovascular effects in adults. As subclinical vascular changes begin early in life, Hg may play a role in altered blood pressure in children. However, the evidence linking early life Hg exposure to altered blood pressure in childhood has been largely inconsistent. In the ongoing New Hampshire Birth Cohort Study, we investigated prenatal and childhood Hg exposure at multiple time points and associations with blood pressure measurements in 395 young children (mean age 5.5 years, SD 0.4). Hg exposure was measured in children's toenail clippings at age 3 and in urine at age 5-6 years, as well as in maternal toenail samples collected at ∼28 weeks gestation and 6 weeks postpartum, the latter two samples reflecting early prenatal and mid-gestation exposures, respectively. Five measurements of systolic blood pressure (SBP), diastolic blood pressure (DBP) and mean arterial pressure (MAP) were averaged for each child using a standardized technique. In covariate-adjusted linear regression analyses, we observed that a 0.1 μg/g increase in child toenail Hg at age 3 or a 0.1 μg/L urine Hg at age 5-6 were individually associated with greater DBP (toenail β: 0.53 mmHg; 95% CI: -0.02, 1.07; urine β: 0.48 mmHg; 95% CI: 0.10, 0.86) and MAP (toenail β: 0.67 mmHg; 95% CI: 0.002, 1.33; urine β: 0.55 mmHg; 95% CI: 0.10, 1.01). Neither early prenatal nor mid-gestation Hg exposure, as measured by maternal toenails, were related to any changes to child BP. Simultaneous inclusion of both child urine Hg and child toenail Hg in models suggested a potentially stronger relationship of urine Hg at age 5-6 with DBP and MAP, as compared to toenail Hg at age 3. Our findings suggest that Hg exposure during childhood is associated with alterations in BP. Childhood may be an important window of opportunity to reduce the impacts of Hg exposure on children's blood pressure, and in turn, long-term health.

BACKGROUND:Fetal growth is predictive of health later in life. Both toxic and essential metals influence fetal growth, but most studies have focused on these elements individually and used birth weight as an indicator of fetal growth. The objective of the current study was to investigate the impact of a mixture of metals on fetal size in mid-pregnancy in a predominately lower income Hispanic pregnancy cohort in Los Angeles. METHODS:For our primary analysis, we focused on six elements that have previously been associated individually with fetal size, including arsenic (As), barium (Ba), cadmium (Cd), mercury (Hg), molybdenum (Mo), and tin (Sn), measured in maternal urine samples collected in early pregnancy (median: 12.4 weeks gestation). In an exploratory analysis, we additionally included cobalt (Co), nickel (Ni), antimony (Sb), and thallium (Tl). Using covariate-adjusted Bayesian Kernel Machine Regression (BKMR) as our main mixture modeling approach, we examined the impact of these metals on fetal biometry measures obtained between 18 and 22 weeks gestation, with a focus on estimated fetal weight (EFW). RESULTS: = 0.03). In an exploratory analysis accounting for a larger mixture of metals, Mo and Ba consistently contributed most to associations with EFW. An inverse association was also identified between Sb and EFW. CONCLUSIONS:Our results suggest that Mo may promote fetal growth, while Ba and Sb may reduce fetal growth, in this population.