Faculty Bibliography

Lead exposure remains a significant public health problem, and even within current standards, most individuals have limited means to avoid it. Regulating or removing toxic exposures remains a priority, but complementary nearer-term protections are needed. We previously observed that health insurance coverage attenuated associations of blood lead levels with two DNA methylation-based biomarkers of morbidity and mortality: GrimAge2 and DunedinPoAm. In this study, we evaluated whether healthcare access could account for or modify these relationships. We conducted a cross-sectional analysis of 2,312 adults aged 50-84 years from the 1999-2002 National Health and Nutrition Examination Survey (NHANES). Survey-weighted generalized linear models were used to test effect modification of the lead-epigenetic aging relationship by health insurance and by healthcare access, defined as having a routine place of healthcare. In models adjusted for demographic, socioeconomic, lifestyle, and health factors, insurance significantly modified associations of lead with epigenetic age. Although model estimates remained comparable, interactions were no longer statistically significant after healthcare access was added as a covariate for GrimAge2 (β_insured = 0.08, 95%CI_insured: -0.08, 0.23, β_uninsured = 0.60, 95%CI_uninsured: -0.10, 1.28, P_interaction = 0.09) and DunedinPoAm (β_insured = 0.001, 95%CI_insured: -0.002, 0.003, β_uninsured = 0.01, 95%CI_uninsured: -0.003, 0.02, P_interaction = 0.09). Healthcare access alone did not significantly modify the associations of lead with either biomarker in models with or without insurance as a covariate. These findings suggest that healthcare access may partially contribute to the attenuation of lead-related epigenetic aging observed among insured adults and a need for further research to better understand these complex relationships.

INTRODUCTION/BACKGROUND:Puberty is a key transition point in adolescents' lives that plays a foundational role in shaping health behaviors and outcomes across one's life course. This period holds significant potential to empower adolescents and support autonomy in health and well-being, but limited puberty education curricula exist for early adolescents (age 8-14), and those that do exist vary in content. There is a paucity of evaluations of puberty competencies and limited consensus on what competencies should be measured to assess effectiveness or even how to measure these competencies. OBJECTIVE:The objective of this scoping review is to systematically map and characterize the outcomes, domains, and instruments used to evaluate puberty education curricula for early adolescents aged 8-14 years. In accordance with PRISMA-ScR and JBI scoping review guidance, this review does not synthesize effect sizes or assess intervention efficacy, but maps the breadth of evidence to identify conceptual gaps and inform future framework development. METHODS:The review protocol is registered with the Open Science Framework (OSF). We will search PubMed, CINAHL, PsycInfo, ERIC, Education Source, Scopus, Web of Science Core Collection, ProQuest Dissertations and Theses Global, and OpenAlex for relevant sources. Two reviewers will independently screen and extract studies that meet inclusion criteria using our data extraction tool. EXPECTED OUTPUTS/UNASSIGNED:Findings from the scoping review will be synthesized to create an overarching framework that can guide approaches to the development and evaluation of puberty curricula targeted to early adolescents. Focus group discussions with adolescents, parents, and school representatives will be conducted to assess the applicability and appropriateness of identified competencies and evaluation measures prior to broader dissemination. Insights from this scoping review will ultimately be used to inform the implementation and evaluation of puberty education.

BACKGROUND:Ketamine is increasingly prescribed in an off-label manner to treat psychiatric disorders, raising concerns about direct-to-consumer advertising and the proliferation of clinics offering ketamine for at-home use without direct medical supervision. OBJECTIVES/OBJECTIVE:We aimed to identify and characterize clinics advertising ketamine for psychiatric conditions online in the New York metropolitan area (New York, New Jersey, and Connecticut), with attention to advertising suggesting ketamine is prescribed for at-home use. METHODS:In 2025, systematic web searches were conducted to identify clinics advertising prescription ketamine for psychiatric indications. Public-facing website content was reviewed to describe clinic characteristics: service delivery modality, clinician credentials, routes of administration, disorders treated, and advertising practices. A generalized linear model was used to delineate correlates of clinics advertising ketamine for at-home use. RESULTS:233 clinics were located; 36.5% prescribed ketamine for at-home use. 51.5% listed a medical doctor as part of their team and 42.9% advertised oral ketamine. Depression was the most commonly listed disorder treated (94.0%) and 21.9% advertised ketamine to treat substance use disorder. In the multivariable model, advertising ketamine for at-home use was more common among clinics advertising oral ketamine (aPR = 4.10, 95% CI: 2.20-7.60) and less common among clinics listing a medical doctor (aPR = 0.54, 95% CI: 0.30-0.99). CONCLUSIONS:Over a third of clinics advertised ketamine for at-home use. A limitation is that we only focused on public-facing websites. Advertising practices and clinician representation suggest clinics may be advertising in a more consumer-oriented manner, underscoring the need for monitoring and clearer guidance to mitigate potential safety risks.

Tobacco smoking is critical risk factor for cardiovascular disease (CVD) and mortality, with epigenetics implicated as a key biological mechanism. Smoking disproportionately impacts CVD risk in women; however, limited research has examined smoking-associated DNA methylation (DNAm) changes in women. We measure whole blood DNAm (EPICv2) and self-reported smoking (three-category, pack-years, and years since cessation) via questionnaires in 6,005 Women's Health Initiative Memory Study participants. We perform epigenome-wide association studies and develop epigenetic predictors of each smoking phenotype, and compare DNAm and self-reported pack-years for CVD-related and all-cause mortality prediction. Here we find 20,388 FDR-significant sites related to current smoking, 2149 for former smoking, 14,709 for pack-years, and 753 for smoking cessation. The epigenetic predictors of smoking activity are highly correlated with their respective phenotypes and DNAm pack-years outperforms self-reported pack-years in mortality prediction. We report robust validation of previous findings, novel smoking associations in women, and introduce epigenetic predictors of smoking activity.

Patient and stakeholder engagement is increasingly emphasized in clinical research, yet practical guidance on how to operationalize engagement in high-acuity, multicenter surgical trials remains limited. We describe the design and early implementation of a structured engagement strategy within the IMPROVE-AD (Improving Outcomes in Vascular Disease-Aortic Dissection) trial. IMPROVE-AD is a pragmatic, multicenter randomized trial comparing optimal medical therapy alone with optimal medical therapy plus thoracic endovascular aortic repair for uncomplicated type B aortic dissection. A formal patient engagement committee, supported by a stakeholder engagement core, was established to integrate patient perspectives into trial design and conduct. Engagement activities included inputs on trial design, recruitment strategies, participant-facing materials, and communication approaches. Observations were derived from the early implementation of these activities. Stakeholder engagement informed several aspects of trial development and implementation. Early engagement contributed to the refinement of trial design elements, including the prioritization of clinical endpoints over surrogate measures. During trial implementation, patient engagement committee input supported the revision of informed consent language, development of public-facing materials, and refinement of recruitment messaging, with an emphasis on clarity, transparency, and clinical equipoise. Access to aggregated screening and enrollment data enabled the identification of potential barriers to recruitment and underrepresentation. These observations are descriptive. A formal evaluation of the impact of engagement on enrollment, retention, or other trial outcomes has not yet been conducted. Structured stakeholder engagement can be incorporated into the design and conduct of a high-acuity, multicenter randomized trial and may inform communication, recruitment, and implementation strategies. Although the full model described here is resource intensive, selected elements may be adaptable across diverse research settings. Further work is needed to evaluate the impact of engagement and to identify scalable approaches.

BACKGROUND AND OBJECTIVES/OBJECTIVE:The contribution of late-life vascular risk factors to dementia risk remains controversial. Because low blood pressure (BP) has been associated with worse clinical outcomes in frail individuals, we hypothesized hypertension, but not diabetes or smoking, is associated with higher dementia risk in robust than in frail older adults. METHODS:We performed a prospective cohort analysis of the Atherosclerosis Risk in Communities Neurocognitive Study (ARIC-NCS) over 11 years (2011-2022). We included all community-living White and Black participants aged 67-89 years without dementia at baseline visit 5 (2011-2013) from ARIC-NCS field centers (Jackson, Mississippi; Forsyth County, North Carolina; Washington County, Maryland; Minneapolis suburbs, Minnesota). The primary vascular risk factors measured at baseline included elevated BP (systolic BP 120-129 mm Hg and diastolic BP < 80 mm Hg), hypertension (systolic BP ≥ 130 mm Hg, diastolic BP ≥ 80 mm Hg, or use of medication for BP), diabetes (fasting glucose ≥126 mg/dL, nonfasting glucose ≥200 mg/dL, self-reported physician's diagnosis, or use of diabetes medication), and former and current smoking (self-reported). We defined frailty status using the Fried criteria (5 components that include low energy, low physical activity, slowness, weakness, and weight loss). We estimated cause-specific hazard ratios (HRs) of incident dementia (ascertained from in-person neuropsychological assessments, semiannual participant or informant report, or surveillance of claims from hospitalizations and death certificates) with Cox proportional hazards models including a multiplicative interaction between vascular factors and frailty. HRs of dementia were then stratified by frailty (robust [no frailty components present] vs prefrail/frail [at least 1 frailty component present]). RESULTS:= 0.026). For robust participants, HRs were 1.03 (95% CI 0.65-1.64) for elevated BP and 1.39 (95% CI 1.00-1.94) for hypertension relative to normal BP. For prefrail/frail participants, HRs were 0.68 (95% CI 0.49-0.95) and 0.82 (95% CI 0.66-1.01), respectively. Diabetes and current smoking were associated with higher dementia risk in both robust and prefrail/frail individuals. DISCUSSION/CONCLUSIONS:Late-life hypertension was associated with a lower relative risk of dementia in prefrail/frail participants, but the association was positive in robust participants. BP interpretation and management to support brain health in older adults could consider age-related functional status.

Individuals are exposed to chemicals in daily life. Yet, few studies have examined the long-lasting joint effect of prenatal and childhood exposure to endocrine-disrupting chemical (EDC) on cognitive performance. We analyzed data from mother-child pairs from the Generation R birth cohort (The Netherlands, 2002-2006) with urinary levels of ten phthalate metabolites, bisphenol A, and five nonspecific organophosphate pesticides metabolites three times during pregnancy (n = 565) and at 5 years of age (n = 539). Child cognitive performance was assessed using the vocabulary, matrix reasoning, digit span, and coding subtests of the Wechsler Intelligence Scale at 13 years. Using hierarchical Bayesian kernel machine regression, we found that prenatal EDC mixture level at 75th percentile versus the median was associated with 0.33 decrease (95% credible interval: -0.60, -0.06) in verbal comprehension and with 0.26 decrease (-0.51, -0.02) in matrix reasoning scores, with di(2-ethyhexyl) phthalate and dibutyl phthalates as primary contributing chemicals to the mixture effect for matrix reasoning. Higher childhood levels of EDC mixture were associated with higher verbal scores, in contrast to the inverse associations observed for prenatal exposure, although this finding should be interpreted with caution due to potential exposure misclassification, selection bias, and residual confounding. Overall, our findings suggest that prenatal exposure to a mixture of plasticizers and pesticides may have a long-lasting adverse effect on offspring's cognition.

Uncomplicated Type B aortic dissection (uTBAD) treatment is changing, and the evidence driving this change is scarce. The decision to offer upfront thoracic endovascular aortic repair (TEVAR) or medical therapy varies significantly among providers, driven more by individual preference than scientific evidence. The IMPROVE-AD trial is a randomized, multidisciplinary, prospective, controlled, superiority trial designed to compare treatment efficacy; functional outcomes; quality of life; and costs in patients with uTBAD undergoing upfront TEVAR or medical therapy with selective TEVAR for deterioration during follow-up. In all, 60 clinical sites in the United States and Canada will enroll 1,100 patients with uTBAD, who are candidates for both treatment options and randomized in a 1:1 ratio. The primary efficacy endpoint of the trial is all-cause mortality and major aortic complications at 4 years. The IMPROVE-AD trial is the only ongoing North America-based large pragmatic trial comparing upfront TEVAR to medical therapy with selective TEVAR in patients with uTBAD. This landmark comparative effectiveness trial aims to provide Level I data to clarify the appropriate role for both treatment strategies and inform clinical practice.

BACKGROUND:Patients with frequent emergency department (ED) use often have poor connection to primary care, limiting access to preventive screening. Screening patients at risk for diabetes is essential to ensure early treatment via medication and lifestyle changes. While ED screening programs have shown success in diagnosing diabetes, it is unknown the impact on follow-up with subsequent care, and thus downstream patient outcomes. This study aimed to evaluate the efficacy of an emergency department (ED)-based diabetes screening program, assessing follow-up for subsequent management, if patients changed health behaviors or initiated medications, and barriers reported to follow-up if patients did not establish care. METHODS:Screening results and patient data from four ED sites of a health system were retrospectively collected; we then performed a phone-based survey of all patients diagnosed with diabetes via ED screening over one year. Patients were queried about diagnosis awareness, connection to follow-up or barriers to establishing care, and health behavior changes (diet, exercise, medications). RESULTS:Of 9,897 screened ED patients, 615 (6.2%) had diabetes. We surveyed 307 patients (50% response rate). Among newly diagnosed patients; 79% reported obtaining outpatient care, but only 46% recalled ED diagnosis. Health behavior changes included 65% reporting diet improvement, 35% increasing exercise, and 52% starting diabetes medication. Patients who failed to follow-up reported barriers including awareness of screening result, time/scheduling issues, and financial considerations. CONCLUSION/CONCLUSIONS:This study assesses the reported rate of outpatient care following diabetes diagnosis via an ED screening program and identifies barriers experienced by patients who did not obtain follow-up. Improved connections between screening programs and subsequent care are needed to improve outcomes.

Methadone is a highly effective treatment for opioid use disorder. However, its public health impact in the U.S. has long been constrained by strict regulations requiring dispensing through specialty opioid treatment programs (OTPs). In 2021, the U.S. Drug Enforcement Administration authorized mobile medication units (MMUs) to dispense methadone in community settings, raising hopes that mobile delivery could expand access for underserved populations. This commentary examines New York State's early experience implementing MMUs as a case study of both the opportunities and persistent challenges associated with this care delivery model in the U.S. We discuss how burdensome methadone requirements, high start-up and operating costs, complex staffing and logistical burdens, community opposition, and a continued emphasis on diversion control over patient access have limited the ability to effectively scale MMUs as a low-threshold treatment option. Although MMUs have and will continue to improve convenience and access for some patients, their potential to substantially improve geographic access, provide lower-threshold care, and deliver comprehensive OUD services is inhibited by the broader U.S. "methadone exceptionalism" framework, which silos methadone as a separate and more restrictive treatment modality requiring excessive vigilance and oversight . We argue that without greater regulatory clarity, flexibility, and alignment with patient-centered care goals, MMUs may likely remain a welcomed but modest, rather than transformative, innovation in addressing methadone gaps in the United States.