Faculty Bibliography

Type 2 diabetes is a risk factor for cardiac arrhythmias, but it is unknown how specific aberrations in glucose (e.g., episodes of high or low glucose) might contribute to the occurrence of heart rhythm abnormalities. The overarching goal of this study is to address research questions regarding how glucose patterns might contribute to the occurrence of arrhythmias, primarily atrial fibrillation, in adults with diabetes. To fulfill this goal, the Atherosclerosis Risk in Communities (ARIC) Gen2 study recruited 507 community-dwelling adults aged 50-80 years with type 2 diabetes to wear continuous glucose monitoring (CGM) and electrocardiogram (ECG) "patch" monitoring sensors simultaneously for up to 14 days. Gen2 study had high CGM and ECG completeness: the median wear time for sensors was 14 days and approximately 80% of participants wore both sensors for ≥10 days. By combining Gen2 and data from the original ongoing ARIC cohort (aged 80+), we have the capacity to conduct a comprehensive evaluation of the impact of CGM-defined glucose patterns on arrhythmias across a wide age spectrum from middle-aged to very old adults (aged 50-100) with type 2 diabetes. The findings from this study may help inform clinical strategies for the prevention and management of arrhythmias among adults with type 2 diabetes.

Several decades of converging research in the fields of pediatrics, child development, and neuroscience demonstrate that the first years of life set the stage for children's school readiness and have lasting impacts on health, learning, and well-being across the lifespan. Early childhood is therefore an ideal time to deliver preventive interventions to reduce disparities in child development that emerge due to poverty, toxic stress, and other adversities. Early Relational Health (ERH), which includes parent-child interactions and relationships supports child development and can serve as a protective factor in the pathway between poverty/early stress and child outcomes. It is also the focus of recent policy statements and recommendations from key experts and leaders within the early childhood landscape. In the current paper, we describe interventions and strategies that use primary care alone or as a point of entry to other programs to promote ERH in order to enhance early child development. Primary care offers early contact and relationship building with families, provides near universal reach, and is low cost compared to other platforms, and layering and linking programs helps to address diverse family needs and preferences. We highlight challenges and bright spots in these endeavors and note the need for additional advocacy for the promotion of ERH that leverages a strong evidence base and converging policy recommendations.

BACKGROUND/UNASSIGNED:Individuals with opioid use disorder (OUD) who return to the community from incarceration face a high risk of fatal drug overdose. This mortality risk is related to significant barriers to accessing health care, social support, and resources needed to transition to and thrive within the community safely. Digital health tools have effectively supported substance use treatment and recovery, but their potential to support OUD during the high-risk period of reentry is underexplored. OBJECTIVE/UNASSIGNED:This study aimed to examine how adults with OUD returning from incarceration perceive and engage with digital health tools, and identify barriers and facilitators to their use. METHODS/UNASSIGNED:Semistructured interviews were conducted with a purposive sample of 39 adults recently released from New Hampshire prisons and jails. Participants were recruited from a randomized clinical trial (EXIT-CJS) comparing the effectiveness of extended-release buprenorphine, naltrexone, and enhanced treatment as usual on treatment retention. Interviews were audio recorded, transcribed, and analyzed using a deductive-inductive approach to content analysis. The COREQ (Consolidated Criteria for Reporting Qualitative Research) criteria were used to guide the study reporting. RESULTS/UNASSIGNED:Most participants preferred digital health over in-person care for both OUD treatment and other health care, mainly due to its convenience and resilience against reentry challenges. Yet, most participants also underscored the irreplaceable role of in-person therapeutic human connection in recovery and recognized this as a trade-off of stand-alone digital health. Participants described using digital health tools to overcome barriers that otherwise would have prevented them from receiving in-person care, such as transportation shortages, limited provider availability, and work scheduling conflicts. Accessing digital health was acknowledged as contingent on access to internet-capable devices, affordable connectivity, and digital literacy. CONCLUSIONS/UNASSIGNED:The findings suggest that maximizing digital health's impact in reentry will require a multipronged approach: investing in infrastructure to close the digital divide, addressing upstream structural barriers to accessing care, and partnering with impacted persons to co-design hybrid care models that enhance the feasibility of engaging in care during reentry while enhancing therapeutic human connection and respecting patient preferences.

For a more comprehensive understanding of health disparities, consideration must be given not only to morbidity and mortality outcomes but also to more holistic health-related constructs, such as well-being. We assessed differences in well-being across sociodemographic subgroups in the United States (US). We used data from the Gallup National Health and Well-being Index (2014-2016, n = 530,920) to assess independent cross-sectional associations of self-reported race, ethnicity, educational attainment, and rural residence with measures of well-being for non-institutionalized residents from 50 US states and the District of Columbia. Our outcome measures are thriving, calculated from self-reported current and future life evaluation, and the composite Well-Being Index (WBI), calculated from 38 self-reported metrics spanning 5 domains of well-being (Career, Community, Physical, Financial, Social). We summarized these measures for race-education-urban subgroups and tested for interactions among these three factors, before and after adjustment for year of survey completion, age, sex, marital status, household size, and income. Among our sample, 55% were thriving. After adjustment, higher levels of education were associated with increased odds of thriving: compared with those with no high school degree, we found higher odds of thriving for respondents reporting completion of high school/technical school/some college (OR=1.61(1.57,1.66)), college (OR=2.77(2.69,2.85)), and postgraduate (OR=3.38 (3.29,3.49)) education. Compared with White respondents, Black (OR (95% CI)=1.15 (1.12,1.17)) and Hispanic (OR=1.26 (1.23,1.29)) respondents had higher odds of thriving; results were similar for WBI, except Asian respondents had also higher WBI after adjustment for all covariates (OR=2.54 (2.28,2.80)). Across race-education-urban subgroups, non-White respondents with a college degree living in urban and rural areas had the highest odds of thriving; White respondents with no college degree living in urban areas had the lowest odds of thriving (p < 0.001 for each), after adjustment. These findings raise questions about how well-being is mediated given the known worse clinical health measures among minoritized groups.

INTRODUCTION/UNASSIGNED:Adolescents in low- and middle-income countries experience high rates of common mental disorders (CMDs) but have limited access to adolescent-friendly, evidence-based care. While Interpersonal Psychotherapy for Adolescents (IPT-A) is effective, brief group IPT-A delivered through task-shifted, stepped-care has not been rigorously evaluated in Kenyan primary care. METHODS/UNASSIGNED: = 32) were randomized to the Ushirikiano Model or enhanced treatment as usual (eTAU). Quantitative and qualitative data were collected at baseline, post-treatment, and at follow-up at months 1 and 2. The COM-B framework informed the assessment of behavior change. RESULTS/UNASSIGNED:All adolescents in the intervention arm were retained compared with 69% in eTAU. Intervention fidelity ranged from moderate to high and showed improvement with supervision. Participants found the intervention acceptable, relevant, and supportive, and reported applying IPT-G-A skills to handle interpersonal and school-related stressors. Community health promoters reported increased confidence with blended training and ongoing supervision. Preliminary outcomes trends suggested potential reductions in depressive symptoms and modest functional improvement in the Ushirikiano arm, with most participants achieving symptomatic remission at the month 2 follow-up. As a pilot study, these findings provide preliminary evidence of potential benefit and support further evaluation of the intervention in a fully powered trial. CONCLUSION/UNASSIGNED:The Ushirikiano treatment model appears acceptable and feasible for addressing adolescent depression in Kenyan primary care. While preliminary findings suggest the potential for improvements in depressive symptoms and functioning, the study was not designed to establish effectiveness and did not assess for anxiety and somatic symptom disorder. These findings support further evaluation in fully powered trials to determine clinical effectiveness for CMDs, cost-effectiveness, and optimal implementation strategies. CLINICAL TRIAL REGISTRATION/UNASSIGNED:https://pactr.samrc.ac.za/TrialDisplay.aspx?TrialID=33227, Pan African Clinical Trial Registry, PACTR202503728947243.

Prenatal inflammation is a recognized risk factor for autism spectrum disorder (ASD), but the neural pathways linking in utero immune exposure to later outcomes remain unclear. We examined whether chronic placental inflammation (CPI), a sustained immune response within the placenta, is associated with fetal brain functional connectivity differences and later ASD traits. A cohort of 105 pregnant individuals (85.7% African American/Black, 1.0% Asian American, 4.8% Bi-racial, 4.8% White, 1.0% Other, 2.9% Missing) underwent fetal resting-state fMRI between 24 and 38 weeks' gestation. After delivery, placental tissues were evaluated by expert pathologists for CPI lesions. Fetuses exposed to CPI (n = 44) showed significant differences in resting-state functional connectivity (RSFC) compared to non-exposed fetuses (n = 61) across ten network pairs, with the greatest effects in prefrontal, cerebellar, visual, and motor regions. These connectivity differences were associated with behavioral outcomes: cerebellar-medial visual RSFC was the strongest prenatal predictor of ASD traits at age 3. An exploratory structural equation modeling indicated that CPI was associated with reduced cerebellum-medial visual RSFC, which was associated with higher ASD trait scores, though the indirect pathway did not reach statistical significance. This study provides the first human evidence that chronic placental inflammation is associated with large-scale fetal brain network differences that are also associated with autism traits, suggesting that prenatal immune activity may be relevant to neurodevelopmental trajectories.

PURPOSE/UNASSIGNED:Microhematuria may be a sign of underlying genitourinary pathology, but diagnoses of bladder cancer are rare among those who complete evaluations. This study determines the incidence of bladder cancer in a large cohort of patients with microhematuria, assesses the diagnostic potential of current guideline recommendations, and characterizes the relative risks of clinicodemographic factors to inform the need for microhematuria evaluation. MATERIALS AND METHODS/UNASSIGNED:microhematuria. The main outcome was a new bladder cancer diagnosis within 2 years of index urinalysis with microhematuria. Patients were stratified by American Urologic Association risk categories to compare guideline-based risk classification with model-based estimation. The Fine-Gray method was used to estimate adjusted associations between clinicodemographic characteristics and incident bladder cancer, accounting for the competing risk of death. RESULTS/UNASSIGNED:Among 267,133 patients with microhematuria, the two-year cumulative incidences of cystoscopy completion and a new bladder cancer diagnosis were 11.9% (95% CI 11.7, 12.0) and 1.5% (95% CI 1.4, 1.5), respectively. Older age, male sex, smoking history, and ≥25 RBC/hpf were associated with a new bladder cancer diagnosis when adjusted for competing risk of death. Performance of our bladder cancer prediction model was better (ROC AUC=0.63) than that of the current AUA guidelines (AUC=0.52, p<0.001) and allowed for further risk-estimation of patients designated "high risk" by AUA criteria. CONCLUSIONS/UNASSIGNED:Estimation of patient-level microhematuria-related bladder cancer risk is possible with readily available clinicodemographic factors. Current approaches lack nuance, particularly among "high risk" patients. Precision approaches that use relative risk-factor weights and/or novel diagnostic tools may improve individualized decision-making for evaluation.

BACKGROUND/UNASSIGNED:Research suggests that hearing loss in older adults is associated with elevated neuroinflammation and neurodegeneration, both of which are risk factors for dementia. In a secondary analysis of the Aging and Cognitive Health Evaluation in Elders (ACHIEVE) randomised controlled trial (ClinicalTrials.gov identifier: NCT03243422), we examined if hearing intervention slowed 3-year change in blood-based biomarkers of neuroinflammation (glial fibrillary acidic protein [GFAP]) and neurodegeneration (neurofilament light chain [NfL]). METHODS/UNASSIGNED:ACHIEVE, a clinical trial in the United States conducted between January 4, 2018 and November 30, 2022, tested the effects of hearing intervention (audiological counselling, provision of hearing aids) versus health education control (counselling on chronic disease prevention) on 3-year cognitive decline among older adults without substantial cognitive impairment and with untreated hearing loss. Plasma was collected at baseline and three years later among ACHIEVE participants recruited from the Atherosclerosis Risk in Communities cohort. Covariate-adjusted linear mixed effects models estimated intention-to-treat effects on 3-year change in inverse-normal transformed values of GFAP and NfL. FINDINGS/UNASSIGNED:Participants in the analytic sample (n = 164) were mean (SD) age 78.1 (2.9) years, 64.0% female, and 73.2% White. Over three years, hearing intervention was associated with a slower rise in GFAP (intervention: -0.026; 95% CI: -0.144, 0.093, control: 0.149; 95% CI: 0.039, 0.260; difference: -0.175; 95% CI: -0.322, -0.028; p-difference: 0.019) and NfL (intervention: 0.171; 95% CI: 0.022, 0.319, control: 0.330; 95 %CI: 0.185, 0.475, difference: -0.159; 95 %CI: -0.348, 0.029; p-difference: 0.098). INTERPRETATION/UNASSIGNED:Randomisation to hearing intervention was associated with a slower three-year rise in a blood-based biomarker of neuroinflammation. Comparable estimates were observed for neurodegeneration, although the effect was not statistically significant. Findings suggest that hearing intervention may reduce the rate of change in non-specific blood-based biomarkers associated with brain health and dementia progression. FUNDING/UNASSIGNED:US National Institutes of Health.