Faculty Bibliography

OBJECTIVE:The objective of this study is to use a machine learning approach to identify predictors of BMI percentile among Hispanic/Latino youth in the United States. METHODS:Participants were Hispanic/Latino 8- to 16-year-olds from the cross-sectional Study of Latino Youth (SOL Youth; n = 1466). A supervised machine learning approach, LASSO regression, was used with BMI percentile as the outcome. A total of 102 predictor variables were examined spanning parent and child demographics; health behaviors; and psychological, sociocultural, and environmental measures. RESULTS: = 0.42), but a 10-variable solution was selected for parsimony. Six associations were significant. Dieting 1-4 or ≥ 5 times/year (β = 8.69 [95% CI: 10.25 to 14.52] or 10.86 [95% CI: 13.14 to 18.33], respectively) and having a parent of Dominican heritage (β = 3.48 [95% CI: 4.05 to 9.90]) or with obesity (β = 2.96 [95% CI: 2.99 to 6.85]) were associated with a higher BMI percentile. Perception of being smaller than the "ideal" body size (β = -1.65 [95% CI: -6.84 to -1.35]) and use of the food/activity parenting practice Control (β = -1.17 [95% CI: -3.63 to -1.69]) were associated with a lower BMI percentile. CONCLUSIONS:Family-based approaches and focusing on dieting and body image satisfaction may be important for weight management in Hispanic/Latino youth.

BACKGROUND:Building a learning health system (LHS) at a federally qualified health center (FQHC) can generate research with diverse communities. However, FQHCs face challenges in integrating research with their mission to deliver high-quality primary care to vulnerable populations. OBJECTIVE:Our FQHC serves over 110,000 patients annually and partners with an academic medical center. We have implemented LHS strategies to align research with health care service priorities, enable clinician involvement in research, support data analysis, disseminate findings, and seek research funding. Drawing on the Consolidated Framework for Implementation Research, we identify contextual factors that impeded or facilitated our LHS implementation. Lessons can inform LHS practice in safety-net primary care. DESIGN/METHODS:Case study of LHS development at an FQHC. STAKEHOLDERS/UNASSIGNED:FQHC leaders, clinicians, staff, and academic partners.  APPROACH: Descriptive analysis of 168 research proposals and 13 grant-funded studies. Review of procedures to approve, implement, and disseminate research. RESULTS:Supportive leadership, preexisting culture of continuous QI, academic partners who understand the FQHC mission, and investment in research infrastructure (e.g., structured research review and access to data) facilitated the implementation of our strategies to integrate research with health care delivery as part of building an LHS. Inherent characteristics of research can pose challenges for research-practice integration, e.g., research often runs on longer timelines than quality improvement initiatives. Importantly, our approach is modular and iterative: we selectively and progressively launched strategies for LHS development, beginning with essential processes to review research, administer grants, provide data, and share findings. Alongside continually enhancing these processes, our work ahead includes building clinician and staff competencies for research, extending data analyst capacity, and establishing an organizational policy on equitable patient and community engagement in research. CONCLUSIONS:Taking a modular approach and iterating LHS activities can enable FQHCs to integrate research with health care service delivery in safety-net primary care.

BACKGROUND AND OBJECTIVES/OBJECTIVE:Despite longstanding efforts to design, implement, and study parenting interventions early in life to address disparities in school readiness, gaps remain related to understanding their long-term effects and pathways of influence on child development. Here we describe sustained impacts at child age 6 of the innovative, tiered birth to age 3 Smart Beginnings (SB) model. METHODS:We performed a single-blind, 2-site randomized clinical trial of the SB model. SB integrates PlayReadVIP, a universal, pediatric primary care-based program, and Family Check-Up, a targeted secondary home-based parenting intervention. Mother-infant dyads (N = 403) were randomized at birth to standard pediatric care or the SB model. In line with SB's theory of change that supporting parents will promote their children's development, single and serial mediation pathways evaluated intervention effects of SB on age 6 child academic skills through parental cognitive stimulation at age 2 and child academic functioning at age 4. RESULTS:We found significant single and serially mediated indirect effects of SB on academic outcomes through parental cognitive stimulation in toddlerhood and preacademic skills in preschool. The total indirect pathways were positive and statistically significant for all academic outcomes at age 6, including receptive vocabulary (effect size [ES] = 0.04, P = .04), oral comprehension (ES = 0.05, P = .04), letter-word recognition (ES = 0.04, P = .04), phonemic decoding (ES = 0.04, P = .04), and applied problems (ES = 0.05, P = .04). CONCLUSIONS:Findings build on the demonstrated scalability of the SB model, support the cumulative process of academic functioning in childhood, and offer a promising model to address disparities early in life.

BACKGROUND:Prostate cancer survivors often experience reduced health-related quality of life (QOL). Diet is related to QOL in the general population and prostate cancer survivors, with benefits observed from greater consumption of a plant-based diet post-treatment. We examined whether post-diagnostic Western and prudent dietary patterns were associated with cancer-specific QOL. METHODS:We studied 1,032 participants in the Health Professionals Follow-up Study diagnosed with non-metastatic prostate cancer (2005-2014). Diet scores were cumulatively averaged from validated food frequency questionnaires post-diagnosis. QOL was assessed with the Expanded Prostate Cancer Index Composite Short Form (EPIC-26) 2-5 years after diagnosis/treatment (2010-2016). We assessed associations between the two diet patterns and cancer-specific QOL domains (sexual function, urinary irritation/obstruction, urinary incontinence, bowel function, hormonal/vitality function), adjusting for patient, tumor, and lifestyle characteristics. RESULTS:Median age at diagnosis was 75 years; 93% had clinically localized cancer. Higher Western diet scores were associated with worse bowel function by 3 points (p-trend=0.02), below the 4-6 point threshold for clinical relevance, with suggestive trends among radiation-treated patients (p-trend=0.07). Higher prudent diet scores tended to be associated with better bowel function (p-trend=0.09). Neither diet score was associated with bowel function among patients receiving radical prostatectomy or active surveillance. There were no associations with sexual, urinary, or hormonal/vitality function. CONCLUSIONS:Among survivors of non-metastatic prostate cancer, dietary patterns were largely unrelated to cancer-specific QOL across domains and treatment subgroups. IMPACT/CONCLUSIONS:In the 2-5-year window, QOL was largely unaffected by post-diagnostic dietary patterns, warranting further research with longer follow-up to assess potential latency.

The locus coeruleus (LC) plays important roles in sleep/wake regulation and cognitive functions. LC neurons may be particularly sensitive to neural injury and serve as an early site of accumulation pathological tau in Alzheimer's disease. Obstructive sleep apnea (OSA) creates both chronic intermittent hypoxia and sleep fragmentation as potential insults to differentially sensitive neural populations including the locus coeruleus (LC). Using high field 7T imaging in cognitively normal older adults, we demonstrate that time spent with an oxygen saturation below 90% (T90), a measure of OSA's hypoxic burden, inversely correlates with LC structural integrity and explains significant variance in LC structural integrity after controlling for age, sex, and BMI. In contrast, other sleep variables such as the apnea-hypopnea index (AHI), total sleep time, and sleep efficiency did not contribute significant variance in LC structural integrity in this model. Thus, in the diagnosis of OSA, attention to hypoxic burden variables may be important in risk stratification for LC neural injury. This observation may inform future work determining whether mitigation of the hypoxemic burden from OSA can slow deterioration in LC integrity.

OBJECTIVE:To investigate associations between prepregnancy cardiometabolic risk factors and early childhood weight status, independent of genetic susceptibility. METHODS:The ancillary study of the HCHS/SOL (Hispanic Community Health Study/Study of Latinos) included 227 dyads consisting of Hispanic/Latina mothers who had singleton live births between baseline and visit 2 and their children, aged 3-9 years. Child outcomes included body mass index (BMI) z-scores, and weight status categories. Maternal prepregnancy biomarkers included fasting triglycerides, high-density lipoprotein cholesterol (HDL-C), glucose, insulin, blood pressure, BMI, and waist circumference. Child DNA was used to calculate a polygenic risk score for obesity. Linear and logistic regression models adjusted for confounders and child genetic risk. RESULTS:On average, 10.9 years elapsed between maternal baseline assessment and child anthropometry. At baseline, 4.8% of women reported having diabetes or hypertension, one-third had obesity (BMI 30 or higher), and more than half had elevated waist circumference or low HDL-C. Among children (mean age 7.5 years), 17.2% were categorized as having overweight and 27.8% were categorized as having obesity. Higher maternal BMI, larger waist circumference, and higher fasting insulin and diastolic blood pressure were significantly associated with higher child BMI z-scores. A 1-SD increase in maternal BMI (6.1 units) or waist circumference (13.3 cm) was linked to greater odds of child overweight or obesity. Elevated maternal insulin was associated with having a child with overweight status, and higher diastolic blood pressure with having a child in the obesity category in minimally adjusted models. CONCLUSION/CONCLUSIONS:Prepregnancy cardiometabolic risk factors in Hispanic/Latina women are associated with higher BMI and obesity risk in their children, independent of genetic predisposition. These findings highlight the prepregnancy period as a critical window for interventions to improve intergenerational health outcomes.

BACKGROUND:Sepsis is a life-threatening complication of infection with high mortality. A high-throughput analysis of circulating blood proteins may provide mechanistic insight and potent therapeutic targets for the prevention of sepsis. METHODS:We used multivariable Cox regression analysis to examine the association of 4955 plasma proteins, measured by SomaScan, with the risk of incident sepsis among 11 065 participants of the Atherosclerosis Risk in Communities (ARIC) Study (visit 3 in 1993 to 1995; mean age, 60.1 years, 54.4% female, 21.0% Black). Proteins (false discovery rate [FDR] of P < 0.05) discovered at visit 3 were replicated using data at visit 5 (n = 4869 in 2011 to 2013: mean age, 75.5 years) and in the Cardiovascular Health Study (CHS) (n = 3512 in 1992 to 1993; mean age, 74.5 years). Canonical pathways were identified by enrichment analyses. RESULTS:At ARIC visit three, 669 proteins were associated with the risk of sepsis; 175 were replicated at visit 5. Of these, 90 were validated in the CHS. The top 20 proteins ranked by P value were relevant to acute inflammatory signaling in innate immunity. Pathway analyses implicated activation of pro-inflammatory pathways (e.g., cytokine storm signaling) as well as inhibition of anti-inflammatory pathways (e.g., liver X receptor/retinoid X receptor [LXR/RXR] activation), which also play relevant roles in lipid metabolism. CONCLUSIONS:In this analysis, levels of acute inflammatory proteins measured during routine visits were associated with the subsequent incidence of sepsis. An increased risk of sepsis associated with the inhibition of anti-inflammatory pathways, such as LXR/RXR warrants further mechanistic investigation.