Faculty Bibliography

Physical frailty is a syndrome that typically manifests in later life, although the pathogenic process causing physical frailty likely begins decades earlier. To date, few studies have examined the biological signatures in mid-life associated with physical frailty later in life. Among 4,189 middle-aged participants (57.8 ± 5.0 years, 55.8% women) from the Atherosclerosis Risk in Community (ARIC) study, we evaluated the associations of 4,955 plasma proteins (log 2-transformed and standardized) measured using the SomaScan platform with their frailty status approximately 20 years later. Using multinomial logistic regression models adjusting for demographics, health behaviors, kidney function, total cholesterol, and comorbidities, 12 and 221 proteins were associated with prefrailty and frailty in later life, respectively (FDR p < 0.05). Top frailty-associated proteins included neurocan core protein (NCAN, OR = 0.66), fatty acid-binding protein heart (FABP3, OR = 1.62) and adipocyte (FABP4, OR = 1.65), as well proteins involved in the contactin-1 (CNTN1), toll-like receptor 5 (TLR5), and neurogenic locus notch homolog protein 1 (NOTCH1) signaling pathway relevant to skeletal muscle regeneration, myelination, and inflammation. Pathway analyses suggest midlife dysregulation of inflammation, metabolism, extracellular matrix, angiogenesis, and lysosomal autophagy among those at risk for late-life frailty. After further adjusting for midlife body mass index (BMI) - an established frailty risk factor - only CNTN1 (OR = 0.75) remained significantly associated with frailty. Post-hoc analyses demonstrated that the top 41 midlife frailty-associated proteins mediate 32% of the association between mid-life BMI and late-life frailty. Our findings provide new insights into frailty etiology earlier in the life course, enhancing the potential for prevention.

INTRODUCTION/BACKGROUND:Six hospitals within the New York City public hospital system implemented the Consult for Addiction Treatment and Care in Hospitals (CATCH) program, an interprofessional addiction consult service. A stepped-wedge cluster randomized controlled trial tested the effectiveness of CATCH for increasing initiation and engagement in post-discharge medication for opioid use disorder (MOUD) treatment among hospital patients with opioid use disorder (OUD). The objective of this study was to identify facility characteristics that were associated with stronger performance of CATCH. METHODS:This study used a mixed methods multiple-case study design. The six hospitals in the CATCH evaluation were each assigned a case rating according to intervention reach. Reach was considered high if ≥50 % of hospitalized OUD patients received an MOUD order. Cross-case rating comparison identified attributes of high-performing hospitals and inductive and deductive approaches were used to identify themes. RESULTS:Higher-performing hospitals exhibited attributes that were generally absent in lower-performing hospitals, including (1) complete medical provider staffing; (2) designated office space and resources for CATCH; (3) existing integrated OUD treatment resources; and (4) limited overlap between the implementation period and COVID-19 pandemic. CONCLUSIONS:Hospitals with attributes indicative of awareness and integration of OUD services into general care were generally higher performing than hospitals that had siloed OUD treatment programs. Future implementations of addiction consult services may benefit from an increased focus on hospital- and community-level buy-in and efforts to integrate MOUD treatment into general care.

BACKGROUND:A major challenge in epidemiology is knowing when an exposure effect is large enough to be clinically important, in particular how to interpret a difference in mean outcome in unexposed/exposed groups. Where it can be calculated, the proportion/percentage beyond a suitable cut-point is useful in defining individuals at high risk to give a more meaningful outcome. In this simulation study we compute differences in outcome means and proportions that arise from hypothetical small effects in vulnerable sub-populations. METHODS:Data from over 28,000 mother/child pairs belonging to the Environmental influences on Child Health Outcomes Program were used to examine the impact of hypothetical environmental exposures on mean birthweight, and low birthweight (LBW) (birthweight < 2500g). We computed mean birthweight in unexposed/exposed groups by sociodemographic categories (maternal education, health insurance, race, ethnicity) using a range of hypothetical exposure effect sizes. We compared the difference in mean birthweight and the percentage LBW, calculated using a distributional approach. RESULTS:When the hypothetical mean exposure effect was fixed (at 50, 125, 167 or 250g), the absolute difference in % LBW (risk difference) was not constant but varied by socioeconomic categories. The risk differences were greater in sub-populations with the highest baseline percentages LBW: ranging from 3.1-5.3 percentage points for exposure effect of 125g. Similar patterns were seen for other mean exposure sizes simulated. CONCLUSIONS:Vulnerable sub-populations with greater baseline percentages at high risk fare worse when exposed to a small insult compared to the general population. This illustrates another facet of health disparity in vulnerable individuals.

Child lifestyle behaviors are influenced by their caregivers. Targeting the caregiver-child relationship can establish healthy habits, especially healthful eating patterns, in both the caregiver and child. The purpose of this study was to identify the context for addressing strategies used to establish nutritious eating for the caregiver and child taken together as a unit (e.g., the caregiver-child dyad), through the perspectives of nutrition-promoting professionals. We performed purposive sampling of professionals who address healthful nutrition. Semi-structured qualitative interviews were conducted to elicit perspectives on caregiver-child eating dynamics and techniques to produce dietary behavior change. Data were coded through the constant comparative method, and subthemes and themes were identified by grouping similar codes and excerpts. We identified four themes relevant to dyadic dietary behavior change: (1) factors to consider when approaching nutrition such as family dynamics, (2) dyad-specific strategies for dietary behavior change, (3) patient-centered approaches professionals implement in interactions with the dyad, and (4) time as a barrier to dietary behavior change. In conclusion, study is novel in eliciting the perspectives of professionals across multiple settings to provide a context for dyadic dietary behavior change. Future studies can focus on developing training for lifestyle medicine professionals to approach dyad-specific behavior modification.

BACKGROUND:Black men consistently have higher rates of prostate cancer (PCA)- related mortality. Advances in PCA treatment, screening, and hereditary cancer assessment center around germline testing (GT). Of concern is the significant under-engagement of Black males in PCA GT, limiting the benefit of precision therapy and tailored cancer screening despite longstanding awareness of these disparities. To address these critical disparities, the Socioecological Model (SEM) was employed to develop comprehensive recommendations to overcome barriers and implement equitable strategies to engage Black males in PCA GT. METHODS:Clinical/research experts, national organization leaders, and community stakeholders spanning multiple regions in US and Africa participated in developing a framework for equity in PCA GT grounded in the SEM. A novel mixed-methods approach was employed to generate key areas to be addressed and informed statements for consensus consideration utilizing the modified Delphi model. Statements achieving strong consensus (> =75% agreement) were included in final equity frameworks addressing clinical/community engagement and research engagement. RESULTS:All societal levels of the SEM (interpersonal, institutional, community, and policy/advocacy) must deliver information about PCA GT to Black males that address benefits/limitations, clinical impact, hereditary cancer implications, with acknowledgment of mistrust (mean scores [MS] 4.57-5.00). Interpersonal strategies for information delivery included engagement of family/friends/peers/Black role models to improve education/awareness and overcome mistrust (MS 4.65-5.00). Institutional strategies included diversifying clinical, research, and educational programs and integrating community liaisons into healthcare institutions (MS 4.57-5.00). Community strategies included partnerships with healthcare institutions and visibility of healthcare providers/researchers at community events (MS 4.65-4.91). Policy/advocacy included improving partnerships between advocacy and healthcare/community organizations while protecting patient benefits (MS 4.57-5.00). Media strategies were endorsed for the first time at every level (MS 4.56-5.00). CONCLUSION/CONCLUSIONS:The SEM-based equity frameworks proposed provide the first multidisciplinary strategies dedicated to increase engagement of Black males in PCA GT, which are critical to reduce disparities in PCA-mortality through informing tailored screening, targeted therapy, and cascade testing in families.

BACKGROUND:Incarceration is a social determinant of cardiovascular health but is rarely addressed in clinical settings or public health prevention efforts. People who have been incarcerated are more likely to develop cardiovascular disease (CVD) at younger ages and have worse cardiovascular outcomes compared with the general population, even after controlling for traditional risk factors. This study aims to identify incarceration-specific factors that are associated with uncontrolled CVD risk factors to identify potential targets for prevention. METHODS AND RESULTS/RESULTS:Using data from JUSTICE (Justice-Involved Individuals Cardiovascular Disease Epidemiology), a prospective cohort study of individuals released from incarceration with CVD risk factors, we examine the unique association between incarceration-specific factors and CVD risk factor control. Participants (N=471), with a mean age of 45.0±10.8 (SD) years, were disproportionately from racially minoritized groups (79%), and poor (91%). Over half (54%) had at least 1 uncontrolled CVD risk factor at baseline. People released from jail, compared with prison, had lower Life's Essential 8 scores for blood pressure and smoking. Release from jail, as compared with prison, was associated with an increased odds of having an uncontrolled CVD risk factor, even after adjusting for age, race and ethnicity, gender, perceived stress, and life adversity score (adjusted odds ratio 1.62 [95% CI, 1.02-2.57]). DISCUSSION/CONCLUSIONS:Release from jail is associated with poor CVD risk factor control and requires tailored intervention, which is informative as states design and implement the Centers of Medicare & Medicaid Services Reentry 1115 waiver, which allows Medicaid to cover services before release from correctional facilities.

Previous studies regarding the associations between perfluoroalkyl and polyfluoroalkyl substances (PFAS) and autism spectrum disorder (ASD) have yielded inconsistent results, with the underlying mechanisms remaining unknown. In this study, we quantified 13 PFAS in cord serum samples from 396 neonates and followed the children at age 4 to assess ASD-related symptoms. Our findings revealed associations between certain PFAS and ASD-related symptoms, with a doubling of perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA), and perfluoroundecanoic acid (PFUnDA) concentrations associated with respective increases of 1.79, 1.62, and 1.45 units in language-related symptoms and PFDA exhibiting an association with higher score of sensory stimuli. Nonlinear associations were observed in the associations of 6:2 chlorinated polyfluorinated ether sulfonate (Cl-PFAES) and 8:2 Cl-PFAES with ASD-related symptoms. Employing weighted quantile sum (WQS) regression, we observed significant mixture effects of multiple PFAS on all domains of ASD-related symptoms, with PFNA emerging as the most substantial contributor. Assuming causality, we found that 39-40% of the estimated effect of long-chain PFAS (PFUnDA and PFDoDA) exposure on sensory stimuli was mediated by androstenedione. This study provides novel epidemiological data about prenatal PFAS mixture exposure and ASD-related symptoms.