Faculty Bibliography

BACKGROUND:Children from migrant families with absent parents are more likely to have poorer physical and mental health than children from non-migrant families. The impact of labor migration on left-behind family members in South Asian countries is not well-known. This study aimed to examine the patterns of labor migration and its impact on the health and development of children and their caregivers in rural Nepal. METHODS:Baseline family data collected from a school-based violence prevention program were utilized. Parents/caregivers (N = 346) with school-aged children (aged 3 to 15 years attending nursery to primary grades) from the rural Arghakhanchi district of Nepal were included in the study. A series of descriptive and chi-square analyses were carried out to explore the pattern of labor migration and differences between labor-migrant and non-labor-migrant families. Multivariate linear and logistic regression analyses were applied to explore the correlates and moderators involved. RESULTS:Labor migration has been a common practice in rural Nepal, with an estimated 49% of families having parents working overseas, mostly in India (57%) and Gulf countries (39%) on low-skill labor jobs. Labor migration was significantly associated with left-behind caregivers' and children's mental health. Left-behind caregivers in father-only labor-migrant families reported higher levels of depression than did parents in non-labor migrant families and left-behind children from labor-migrant families reported greater anger than did children from non-labor migrant families. The impact of labor migration on families was moderated by social class. For low social-class father migrant families, left-behind children were at greater risk for developmental delay and behavioral problems, but there seems to be a protective effect for high social-class father migrant families (with lower risk of developmental delay and problem behaviors compared to all other groups). CONCLUSIONS:Labor migration has a substantial impact on the mental health of left-behind families and children. The impact of labor migration may vary by living social-cultural context. Understanding the complex dynamics of labor migration has important implications for local and global migration-related health service planning.

Experimental evidence shows that organophosphate esters (OPEs), common flame retardants and plasticizers, can cause developmental neurotoxicity. We investigated the extent to which prenatal OPE exposure was associated with child cognition. Participants were 831 mother-child pairs from 3 sites in the Environmental influences on Child Health Outcomes (ECHO) Cohort with data on urinary levels of 9 OPE analytes during gestation (2009-2019) and child cognition. Based on detection frequencies, analytes were modeled continuously (adjusted for urinary dilution and log2-transformed), categorically (high/low/non-detect), or dichotomously (detect/non-detect). Children's cognition was measured using the Wechsler Preschool and Primary Scale of Intelligence or Wechsler Intelligence Scale for Children at mean age 5.7 years (SD=0.7). We examined associations of OPE analyte with age- and sex-standardized cognition scores using linear regression with generalized estimating equations to account for clustering within sites. We also tested for effect measure modification by sex. The analyte with the highest detection frequency (96.4%) was diphenyl phosphate (DPHP), a primary metabolite of triphenyl phosphate (TPHP). Higher concentrations of DPHP were associated with lower cognition scores ( per doubling of concentrations=-0.46, 95%CI: -0.90, -0.02). Bis(butoxyethyl) phosphate (BBOEP), bis(1-chloro-2-propyl) phosphate (BCPP), and bis(2-methylphenyl) phosphate (BMPP) above the detection limit (vs. below) were associated with higher cognition scores mainly in boys; but, sex interaction with BMPP was not significant. Prenatal exposure to DPHP, a widely detected OPE, was associated with lower cognitive functioning, though the effect size was small. Given widespread exposure, findings related to this and other OPEs should be further examined in mechanistic studies.

Transgender women of color (TWOC) are disproportionately impacted by psychological distress. Though gender-affirming care (GAC) has been recommended to alleviate this distress, research examining associations between perceived access to GAC, specific gender-affirming medical interventions (GAMIs), and mental health among TWOC in the United States remains limited. In this study, we examine cross-sectional and longitudinal associations between perceived access to GAC, completion of specific GAMIs, and psychological distress among TWOC, using modified Poisson regression and multilevel linear modeling. Data came from the Trying to Understand Relationships, Networks and Neighborhoods Among Transgender Women of Color (TURNNT) Cohort Study. In multivariable analyses, increased access to GAC was associated with reduced psychological distress risk. All assessed GAMIs suggested protective effects against psychological distress (aRR < 1), with statistical significance found for breast augmentation and facial feminization surgery. On average, those with unmet GAMI needs experienced higher distress risk than those without. Longitudinally, those experiencing reduced access to GAC over 6 months faced the highest distress risk among all trajectory groups (aRR: 1.40, 95% CI, 1.08-1.82). Our findings support the need for further inquiry in this area and suggest that policies protecting and increasing access to GAC may improve mental health among TWOC. This article is part of a Special Collection on Methods in Social Epidemiology.

BACKGROUND:Permanent supportive housing (PSH) is an evidence-based intervention for people experiencing homelessness which integrates permanent housing with voluntary support services. PSH tenants are at high risk for overdose death, yet little research to date has examined overdose in PSH. We sought to examine overdose risk and existing responses in PSH, which can shed light on opportunities for future overdose prevention efforts. METHODS:We conducted focus groups with PSH tenants, staff, and leaders in New York City and New York's Capital Region. Focus groups were recorded and professionally transcribed. Two investigators independently completed rapid turnaround qualitative analysis, completing templated summaries of each focus group and compiling key content in an analysis matrix, which a third investigator reviewed; discrepancies were resolved by consensus. RESULTS:From October to December 2022, we held 8 focus group sessions with PSH tenants (3 focus groups, n = 10 total participants), staff (3 focus groups, n = 13), and leaders (2 focus groups, n = 11) grouped by role and region. Participants were diverse in age (26-67 years), gender (18 women, 16 men), race (3 Asian, 12 Black, 11 White, 5 multiracial, 3 other), and ethnicity (5 Latinx, 29 not Latinx). Analysis revealed four main themes: (1) Overdose was a large concern in PSH and created significant trauma for tenants and staff; (2) Environmental factors in PSH contributed to overdose risk; (3) There was heterogeneity in PSH buildings' current overdose prevention efforts and adoption of harm reduction principles; and (4) Multifactorial barriers resulted in limited tenant use of opioid agonist treatment. CONCLUSIONS:Overdose is a major concern for PSH tenants, staff, and leaders. Our findings shed new light on overdose in PSH settings, providing insight into risk factors, existing responses, and barriers and facilitators to future overdose prevention efforts. These findings can inform future overdose prevention interventions within PSH. TRIAL REGISTRATION/BACKGROUND:ClinicalTrials.gov, NCT05786222, registered 27 March 2023.

BACKGROUND/UNASSIGNED:Traditional Chinese medicine (TCM) has guided generations of practice on disease treatment and health maintenance. The TCM principles include the framework of body constitution. However, no study has assessed the body constitution in US population. METHODS/UNASSIGNED:This is an ancillary study of the Personalized Prevention of Colorectal Cancer Trial which conducted in US in 2012-2016. 191 white participants were evaluated for body constitution type using a self-administered Traditional Chinese Medicine Questionnaire (English version). The body constitution subtypes and cardiovascular disease (CVD) risk were assessed. RESULTS/UNASSIGNED:Fifty-seven (29.8%) were identified as balanced constitution (BC), while Blood-stasis (17.3%), Qi-deficient (13.6%), and inherited-special constitutions (10.5%) were the pre-eminent pathologic subtypes. Additional analyses investigated the relationship between CVD risk and body constitution subtypes. No major types of TCM body constitution were associated with the GCRS and other CVD biomarkers. CONCLUSIONS/UNASSIGNED:It is important to understand the underlying mechanisms contributing to these differences, which may not only help to understand the underlying mechanism for TCM, but also help to identify novel factors or mechanisms for CVD risk, prevention and treatment.

Epigenetic clocks are valuable tools for assessing biological age. Exposure to secondhand smoke (SHS) and polycyclic aromatic hydrocarbons (PAHs) has been linked with epigenetic age deviation (EAD) in adults. However, associations in children remain largely unexplored. We investigated relationships between exposure-spanning prenatal, early postnatal, current (36-60 months, time of sample collection) periods-and EAD in preschool-aged children. DNA methylation was measured in buccal cells from 43 children (mean age: 4.1 years) in the CAries Risk from exposure to Environmental tobacco Smoke-Household Air Pollution Intervention Network cohort. SHS exposure was assessed using urinary cotinine and 3-hydroxycotinine (3-HC), while PAHs exposure was assessed via urinary 2-naphthol (2-NAP) and 1-hydroxypyrene (1-PYR). Nicotine equivalents were calculated as molar sum of cotinine + 3-HC. EAD was estimated using Horvath, Skin&Blood, Pediatric Buccal Epigenetic (PedBE), and DNA methylation-based telomere length (DNAmTL) clocks. Associations between exposures and EAD were evaluated using linear regression, adjusting for study site, mother's education, child's body mass index z-score, age, and sex. Chronological age significantly correlated with all epigenetic clocks (r = 0.37-0.78) and with DNAmTL estimator (r = -0.38). Current SHS exposure, as measured by urinary cotinine, was associated with Horvath EAD (B = 0.23 years, P = .05). Similarly, current 3-HC and nicotine equivalents were positively associated with PedBE EAD (B = 0.08 years, P = .04; B = 0.11 years, P = .05, respectively). Among PAH metabolites, current 2-NAP levels were associated with principal component-based Skin&Blood EAD (B = 0.21 years, P = .02) and PedBE EAD (B = 0.13 years, P = .05). Findings suggest early-life SHS and PAHs exposure may contribute to accelerated epigenetic aging in children.

INTRODUCTION/BACKGROUND:Process evaluation provides insight into how interventions are delivered across varying contexts and why interventions work in some contexts and not in others. This manuscript outlines the protocol for a process evaluation embedded in a hybrid type 1 effectiveness-implementation randomised clinical trial of incremental-start haemodialysis (HD) versus conventional HD delivered to patients starting chronic dialysis (the TwoPlus Study). The trial will simultaneously assess the effectiveness of incremental-start HD in real-world settings and the implementation strategies needed to successfully integrate this intervention into routine practice. This manuscript describes the rationale and methods used to capture how incremental-start HD is implemented across settings and the factors influencing its implementation success or failure within this trial. METHODS AND ANALYSIS/METHODS:We will use the Consolidated Framework for Implementation Research (CFIR) and the Reach, Effectiveness, Adoption, Implementation and Maintenance (RE-AIM) frameworks to inform process evaluation. Mixed methods include surveys conducted with treating providers (physicians) and dialysis personnel (nurses and dialysis administrators); semi-structured interviews with patient participants, caregivers of patient participants, treating providers (physicians and advanced practice practitioners), dialysis personnel (nurses, dieticians and social workers); and focus group meetings with study investigators and stakeholder partners. Data will be collected on the following implementation determinants: (a) organisational readiness to change, intervention acceptability and appropriateness; (b) inner setting characteristics underlying barriers and facilitators to the adoption of HD intervention at the enrollment centres; (c) external factors that mediate implementation; (d) adoption; (e) reach; (f) fidelity, to assess adherence to serial timed urine collection and HD treatment schedule; and (g) sustainability, to assess barriers and facilitators to maintaining intervention. Qualitative and quantitative data will be analysed iteratively and triangulated following a convergent parallel and pragmatic approach. Mixed methods analysis will use qualitative data to lend insight to quantitative findings. Process evaluation is important to understand factors influencing trial outcomes and identify potential contextual barriers and facilitators for the potential implementation of incremental-start HD into usual workflows in varied outpatient dialysis clinics and clinical practices. The process evaluation will help interpret and contextualise the trial clinical outcomes' findings. ETHICS AND DISSEMINATION/BACKGROUND:The study protocol was approved by the Wake Forest University School of Medicine Institutional Review Board (IRB). Findings from this study will be disseminated through peer-reviewed journals and scientific conferences. TRIAL REGISTRATION NUMBER/BACKGROUND:NCT05828823.

Repetitive head impacts are common in contact and collision sports and are linked to structural brain changes and an elevated risk of neurodegenerative diseases such as Chronic Traumatic Encephalopathy. Identifying early in vivo structural markers remains challenging. Although diagnosis currently requires post-mortem confirmation, clinical symptoms, including cognitive impairment and behavioural changes, are reflected in the diagnosis of Traumatic Encephalopathy Syndrome. These symptoms align with dysfunction in key brain regions-amygdala, hippocampus and thalamus-which support memory, emotion and behaviour and commonly show tau pathology in Chronic Traumatic Encephalopathy. This study uses shape analysis to examine structural differences in these regions between former American football players and unexposed asymptomatic controls and evaluates the influence of age, head impact exposure and clinical diagnosis on brain structure. We analyzed brain morphology in former American football players (n = 163) and unexposed, asymptomatic controls (n = 53). Structural segmentation was performed with FreeSurfer 7.1, and the shape analysis pipeline was used to generate subregional reconstructions. Vertex-level morphometry, based on the logarithm of the Jacobian determinant and radial distance, quantified local surface area dilation and thickness. Group differences were examined with covariate-adjusted linear regression models contrasting football players and controls, as well as participants with and without a Traumatic Encephalopathy Syndrome diagnosis. Partial correlations examined the influence of age, age of first football exposure and cumulative head impact index metrics, including frequency, linear acceleration and rotational force. Models were adjusted accordingly for age, body mass index, education, race, imaging site, apolipoprotein