Faculty Bibliography

BACKGROUND/UNASSIGNED:The American Heart Association Predicting Risk of Cardiovascular Disease EVENT (PREVENT) equations were developed from observational research cohorts and electronic health record data and provide sex-specific risk estimates for cardiovascular disease (CVD), atherosclerotic CVD (ASCVD), and heart failure (HF). External validation in large contemporary samples across multiple health systems in the United States is needed. METHODS/UNASSIGNED:We assembled a national electronic health record-based cohort of US adults with individual-level patient data pooled from a collective of 30 health systems (Truveta) to externally validate the outcome-specific 10-year PREVENT equations (PREVENT-CVD, PREVENT-ASCVD, and PREVENT-HF). We included patients aged 30 to 79 years without a history of prior CVD and with an ambulatory encounter in the electronic health record between 2013 and 2018. The outcomes were defined as total CVD (composite of ASCVD and HF), ASCVD, and HF through December 2024 using diagnosis codes. Model performance of the outcome-specific PREVENT base equations was assessed with the Harrell C statistic and calibration slope, stratified by sex. RESULTS/UNASSIGNED:Of the 680 864 adults included, the mean (SD) age was 55 (13) years, and 56% were female. Over a mean (SD) follow-up of 6.8 (2.3) years, there were 29 535 incident CVD events, 19 280 incident ASCVD events, and 16 824 incident HF events. The median (interquartile range) 10-year predicted risk of PREVENT-CVD among women was 3.6% (1.3%-8.8%), and among men was 5.8% (2.5%-11.7%). The C statistic (95% CI) was 0.788 (0.786-0.790), and the calibration slope (95% CI) was 0.98 (0.95-1.01) for PREVENT-CVD. PREVENT-ASCVD and PREVENT-HF demonstrated similar C statistics (0.774 [0.771-0.777] and 0.824 [0.820-0.828]) and calibration slopes (1.07 [1.04-1.10] and 1.01 [0.97-1.04]) for prediction of the 10-year risk of ASCVD and HF, respectively. CONCLUSIONS/UNASSIGNED:The PREVENT equations accurately and precisely estimate the 10-year risk of CVD, ASCVD, and HF in a large sample of US adults. These findings support the generalizability of the PREVENT equations to inform guideline-recommended risk assessment and preventive efforts.

BACKGROUND:Care coordination between primary care providers and nephrologists is crucial for preemptive kidney transplantation (KT), which confers health advantages over KT after dialysis. Residence in areas with limited primary care (Medically Underserved Areas [MUAs]/Health Professional Shortage Areas [HPSAs]) and nephrology access may differentially affect preemptive listing/KT. OBJECTIVE:To quantify access to preemptive KT by residence in limited primary care/nephrology access areas. DESIGN/METHODS:Retrospective cohort study from the US national registry. PARTICIPANTS/METHODS:A total of 353,636 adult KT candidates (age ≥ 18) listed between 2005-2020. EXPOSURES/METHODS:ZIP-code level MUA and HPSA information (HRSA), and distance to nearest nephrologist (CMS; urbanicity-specific thresholds for "far" from nephrologists: suburban, > 5.8 km; urban, > 2.3 km; small town, > 19.4 km; rural, > 25.2 km). MAIN MEASURES/METHODS:Poisson regression with robust variance estimator quantified adjusted prevalence ratios (aPRs) of preemptive listing, and cause-specific hazards models quantified adjusted hazard ratios (aHRs) of preemptive KT by MUAs/HPSAs/distance to nephrologists. Interaction terms quantified differences in the aforementioned associations by race and ethnicity/neighborhood urbanicity/socioeconomic determinants. KEY RESULTS/RESULTS: < 0.05). Lastly, there were no associations between distance to nephrologists and preemptive listing/KT. CONCLUSIONS:Limited primary care access may impede KT access. Greater investment in primary care within MUAs/HPSAs, addressing geographic/linguistic barriers, and improved nephrology care coordination may increase transplant equity. CLINICAL TRIAL NUMBER/BACKGROUND:Not applicable.

BACKGROUND:We investigated whether OPE urinary concentrations during pregnancy were associated with child's autism-related outcomes. METHODS:We included 4159 mother-child pairs from 15 cohorts in the NIH Environmental influences on Child Health Outcomes (ECHO) Consortium, with children born from 2006-2020 (median age [interquartile range]: 6 [4,10] years). Nine OPE biomarkers were measured in urine samples collected mid- to late pregnancy. Dilution-adjusted biomarkers were modeled continuously, categorically (high [>median], moderate [≤median], nondetect), or as detect/nondetect depending on their detection frequency. We assessed child autism-related traits via a) parent report on the Social Responsiveness Scale (SRS) and b) clinical autism diagnosis. We examined associations of OPEs with child outcomes, including modification by child sex, using generalized estimating equations to account for clustering by ECHO cohort. RESULTS:Compared with nondetectable concentrations, high exposure to bis-(butoxyethyl) phosphate (BBOEP) was associated with higher autistic trait scores (adj-β 0.97, 95% confidence interval [CI]: 0.42, 1.52) and greater odds of autism diagnosis (adjusted odds ratio [adj-OR]: 1.27, 95% CI: 1.07, 1.50). Bis-(1-chloro-2-propyl) phosphate (BCPP) showed associations with autistic trait scores (BCPP adj-β for high exposure vs nondetect: 0.34, 95% CI: -0.46, 1.13; BCPP adj-β for moderate exposure vs nondetect: 0.72, 95% CI: 0.24, 1.20). High exposure to bis-(2-chloroethyl) phosphate (BCETP) was associated with lower odds of autism diagnosis (adj-OR: 0.76, 95% CI: 0.60, 0.95). Other OPEs showed no associations in adjusted models. Associations between BBOEP and higher autistic trait scores were stronger in males than females. DISCUSSION:Prenatal exposure to OPEs, specifically BCPP and BBOEP, may be associated with a higher risk of autism diagnosis and related traits in childhood.

OBJECTIVE:The quality of discharge processes impacts adverse outcomes post hospitalization for children with medical complexity (CMC). Perspectives of caregivers at risk for communication challenges (eg, non-English speakers, those with limited health literacy, immigrants) on understandability and feasibility of discharge instructions for CMC are understudied. Our objective was to explore their perspectives on barriers and facilitators to comprehension and implementation of discharge instructions for CMC. PATIENTS AND METHODS/METHODS:In this qualitative, descriptive study, we used maximum variation sampling to enroll caregivers of CMC (N = 40) discharged from acute or intensive care units of 2 urban hospitals. English- and Spanish-speaking caregivers of CMC (Pediatric Medical Complexity Algorithm) aged 18 years or older and discharged on 1 or more daily medications were eligible. We conducted semistructured interviews, audio-recorded and transcribed interviews, and performed content analysis. Two team members applied codes from a codebook (developed based on prior literature and preliminary analyses) and identified emerging themes. RESULTS:Equal numbers of participants spoke English and Spanish (n = 20 per language) and were recruited from each hospital (n = 20 per hospital). Half (47.5%) had low health literacy; 85% were of non-US birth. Themes emerged across 4 categories: (1) clinician and medication access; (2) patient- and family-centered approaches to discharge planning and education; (3) caregiver prior experience; and (4) resources and support systems. CONCLUSIONS:Caregivers identified barriers and facilitators affecting discharge plan comprehension and implementation. Optimizing postdischarge care for CMC is complex and requires family-centered, language-concordant, and health literacy-informed processes. Future interventions should focus on systems-level changes that enhance access and account for caregiver perspectives.

INTRODUCTION/BACKGROUND:Skeletal muscle loss is associated with cognitive decline, but whether neuroimaging-derived muscle characteristics predict incident dementia remains unclear. METHODS:We evaluated associations of deep learning-derived temporalis muscle (TM) cross-sectional area (CSA) and radiomic texture features from baseline T1-weighted magnetic resonance imaging (MRI) with incident dementia in dementia-free participants from the Alzheimer's Disease Neuroimaging Initiative (ADNI) (n = 750) and the Atherosclerosis Risk in Communities (ARIC) study (n = 532). TM was segmented using a convolutional neural network trained in ADNI and externally validated in ARIC. Radiomic features were reduced using least absolute shrinkage and selection operator-penalized Cox models to generate a composite score. Multivariable Cox regression adjusted for demographics, apolipoprotein E ε4, baseline cognition, body mass index, and physical performance. RESULTS:Higher TM radiomic scores were associated with increased dementia risk in ADNI (hazard ratio per SD, 1.32) and ARIC (1.64). Smaller TM CSA predicted dementia in ADNI but not ARIC. DISCUSSION/CONCLUSIONS:TM texture patterns from routine brain MRI are associated with dementia risk, supporting TM phenotyping as a scalable marker of systemic biological vulnerability.

BACKGROUND/UNASSIGNED:Multilevel interventions targeting patients, providers, and health systems improve hypertension outcomes, but little is known about how well they are implemented in resource-limited settings. This study evaluated the implementation fidelity of ALTA, a multilevel approach for hypertension management, supported by practice facilitation, across six primary care practices in a Federally Qualified Health Center (FQHC). METHODS/UNASSIGNED:patients' BP and goals. We used a multi-method approach to assess implementation fidelity (adherence, dose, quality, responsiveness, differentiation) guided by Proctor's Implementation Outcome's Framework. Data sources included a structured EHR-embedded tool, narrative reports, and interviews over 12 months. ALTA adaptations were tracked using the Framework for Reporting Adaptations and Modifications-Expanded. RESULTS/UNASSIGNED: = 46) highlighted the need for team support, ongoing practice facilitation, and feedback on patients' progress as factors affecting fidelity. CONCLUSIONS/UNASSIGNED:Implementation fidelity varied across the ALTA components and participating sites, with the greatest variability observed in delivery of the site-level components of identify and refer. Centralized components delivered by the nurse-led team (coach, document, monitor) were delivered consistently with high fidelity. Contextual factors like staffing and patient engagement shaped implementation success. CLINICAL TRIAL REGISTRATION/UNASSIGNED:ClinicalTrials.gov, NCT03713515.

PURPOSE/OBJECTIVE:Young adults with cancer (YAs) are rarely provided the necessary resources to make informed decisions about fertility preservation (FP) prior to beginning treatment. Digital decision aids are a promising strategy to ensure YAs receive timely, guideline-concordant information. We developed an alpha version Fertilit-e, a digital FP navigator, and conducted usability testing to obtain feedback from YAs. METHODS:We designed an alpha version of Fertilit-e that drew from existing evidence-based FP resources. Feedback was obtained from two waves of participants using a think-aloud framework, and modifications were made to the decision aid. RESULTS:Across waves, participants (n = 12) understood the purpose of Fertilit-e and thought modules were comprehensive and easy to understand. The usability of Fertilit-e was rated as excellent across waves and devices (iPad and computer). Participants suggested reducing the use of and better defining medical terminology and adding text to videos to enhance comprehensibility. CONCLUSIONS:YAs reported that Fertilit-e provided important information regarding FP in an understandable manner. Participants made suggestions for how to improve comprehensibility and usability that will guide future iterations of Fertilit-e. For example, tailoring algorithms and reorganization may direct users to the most relevant information. IMPLICATIONS FOR CANCER SURVIVORS/CONCLUSIONS:Digital decision aids may be a feasible and useful strategy for helping YAs navigate decisions regarding whether to pursue FP at the time of diagnosis. Additional research is needed to refine and evaluate such tools before integration into routine care.

PURPOSE/OBJECTIVE:This study aimed to examine associations of bisphenol and phthalate exposure with arterial stiffness among women of reproductive age. METHODS:Participants include 637 adult women enrolled in the New York University Children's Health and Environment Study (NYU CHES), a prospective pregnancy cohort. The concentrations of eight bisphenols and 22 phthalate metabolites were quantified in up to three spot urine samples. Primary outcomes included brachial artery distensibility (BrachD) and carotid-femoral pulse wave velocity (cfPWV) as measures of peripheral and central arterial stiffness, respectively, along with blood pressure assessed at repeated study visits up to seven years from exposure measures. Associations between averaged, log2-transformed, creatinine-standardized chemical concentrations and subclinical vascular outcomes of interest were examined using linear mixed-effects models. RESULTS:In covariate-adjusted models, a doubling of bisphenol A was positively associated with BrachD (0.09%/mmHg, 95% confidence interval [CI] = 0.02, 0.16), a doubling of bisphenol S was negatively associated with mean arterial pressure (MAP) (-0.52 mmHg, 95% CI = -0.98, -0.05), a doubling of di(2-ethylhexyl) phthalate (DEHP) metabolites was negatively associated with diastolic blood pressure (DBP) (-0.81 mmHg, 95% CI = -1.38, -0.23) and MAP (-0.83 mmHg, 95% CI = -1.45, -0.21), and a doubling of antiandrogenic phthalate metabolites was associated with 0.62 mmHg lower DBP (95% CI = -1.22, -0.03) and 0.66 mmHg lower MAP (95% CI = -1.30, -0.02). CONCLUSION/CONCLUSIONS:These findings suggest that routine exposure to bisphenols and DEHP may be associated with vasorelaxation, potentially related to these chemicals' estrogenic and/or antiandrogenic effects.