Faculty Bibliography

BACKGROUND:In vivo biomarkers that can detect long-term neuropathologies from repetitive head impact (RHI) exposure are needed, especially for the neurodegenerative tauopathy chronic traumatic encephalopathy (CTE). Here, we evaluated plasma p-tau217 as a potential biomarker for CTE p-tau pathology, and examined the concordance between plasma p-tau217 and Aβ pathology in an at-risk for CTE sample. METHOD/METHODS:The sample included 180 male former football players (120 professional, 60 college), and 56 asymptomatic men without RHI (i.e., controls). Participants completed blood draws, 18F-florbetapir (Aβ+=SUVR≥1.10), and 18F-flortaucipir PET. Traumatic encephalopathy syndrome (TES) diagnoses were made. Single molecule array for plasma p-tau217 (ALZpath) was performed (≥0.6 cutoff used to maximize sensitivity). Nine participants had post-mortem tissue. ANCOVA examined group differences in p-tau217 (football vs controls; TES-CTE no, TES-CTE suggestive, TES-CTE possible/probable). Multivariable regression models tested associations between p-tau217 and florbetapir/flortaucipir PET. Covariates included age, race and APOE e4. RESULT/RESULTS:Sample characteristics are in Table 1. p-tau217 concentrations were higher in former football players compared to controls (est. marginal mean difference=-0.217, p = 0.005). There were no group differences in Aβ-PET SUVR. No differences were found across TES-CTE certainty levels. In football players, higher p-tau217 was associated with higher Aβ-PET SUVR (B=1.380, 95%CI[0.597-2.155], p = 0.001) but not when Aβ+ (n = 17) participants and those with kidney/liver disease (n = 5) were excluded. Aβ+ participants had the highest p-tau217 (Figure 1). When compared against Aβ-PET, several false Aβ-positives (high p-tau217, Aβ-) were identified, including one extreme outlier (assay related) and a cluster of Aβ- participants with p-tau217 between 0.60-1.0. There were no associations with flortaucipir SUVR (frontal, mesial temporal, left parietal). Two extreme p-tau217 outliers had autopsy-confirmed CTE stage III (AD-, Table 2). Of the remaining donors, all were AD- and four had CTE (stages II-IV) with ptau217 between 0.125-0.449. CONCLUSION/CONCLUSIONS:Plasma p-tau217 has usefulness in quantifying Aβ pathology but restricted utility for detection of CTE. In this at-risk for CTE sample, p-tau217 and Aβ-PET were associated at the group level. At the individual level, false Aβ-positives (and negatives) existed, including Aβ- participants with high p-tau217. We will explore whether this discrepancy is due to disease or peripheral interference with the N-terminal binding in p-tau assays.

Wearables yield a wide array of sleep-related measures that are relevant to Long COVID. We leveraged wearables-derived sleep measures (WDSM) to identify differences between individuals with Long COVID (LC) versus individuals with possible or no LC in the RECOVER adult cohort. We found significant associations between LC and reduced heart rate variability measured during sleep and increased nightly variability in sleep duration after adjusting for confounders. Moreover, LC was independently associated with lower sleep efficiency, greater variability of nighttime sleep timing, higher resting heart rate, lower respiratory rate during rapid eye movement (REM) sleep, prolonged REM sleep onset latency, worse global physical and mental health. Cluster analysis identified distinct multidimensional patterns of WDSM that are associated with LC and quality of life. Together, the strong association between WDSM, or WDSM clusters, with LC provides a potential biomarker for future validation efforts to detect LC and monitor treatment effectiveness.

BACKGROUND/UNASSIGNED:Evidence-based interventions (EBI) for cardiovascular disease (CVD) in low- and middle-income countries (LMIC) may face feasibility challenges due to the inadequacy of existing instruments. To address this, researchers developed the Contextual Index of Feasibility on Early-Stage Implementation in LMIC (CATALYTIC) tool, which integrates contextual factors into the assessment of feasibility. METHODS/UNASSIGNED:The tool's items were developed through a systematic review and key informant interviews, and were later assessed for relevance and importance by 13 LMIC researchers and implementers employing a Delphi technique. The survey was then tested for usability by five individuals with CVD experience in LMIC. The CATALYTIC tool consists of 17 items that measure contextual factors that directly influence early-stage LMIC implementation. Descriptive analysis, logistic regression, item reliability using Cronbach's alpha, and exploratory factor analysis (EFA) were performed on survey data. RESULTS/UNASSIGNED:In a survey of 216 respondents from 46 countries, 63.4 to 81.5% of respondents noted a significant impact of contextual factors on implementation feasibility, with high reliability (Cronbach's alpha 0.88) for 12 items. The majority of interventions focused on patient-level care in rural settings. The survey items align primarily with constructs related to implementation climate and readiness for implementation, as well as inductive themes addressing existing needs and barriers to inform intervention design. The survey found diversity in geographic and experiential backgrounds, with significant representation from South Africa, Mexico, and India. Over a third identified as researchers, and 15% held multiple roles. The survey identified three distinct factors influencing how researchers and implementers assess CVD intervention feasibility in LMIC. A 6% increase in odds for moderately feasible interventions was linked to each point increase in the composite score of perceived contextual influence. CONCLUSION/UNASSIGNED:Overall, the CATALYTIC tool with 12 reliable survey items can help researchers and implementers elucidate perceptions of contextual factors influencing the feasibility of CVD-related EBI in LMIC. The survey items reflect respondents' practical focus in resource-limited settings and can inform intervention design by addressing existing needs and barriers. The tool's integration of contextual factors into the assessment of feasibility can help overcome the inadequacy of existing instruments by providing more tailored and conceptually clear assessments of feasibility.

Research suggests lower-level supervisors may suffer greater burdens of mental illness and substance use than workers and upper management, a pattern that may arise from their contradictory class location. For example, lower-level supervisors may be compelled to discipline subordinates and enforce policies over which they have little say, and contend with antagonism from workers, exposing them to stressors like job strain. However, to our knowledge, no U.S. studies have investigated whether job strain is elevated among lower-level supervisors. We addressed this gap using 2002-2022 General Social Survey data (n = 9261). We classified respondents as workers, lower-level supervisors, higher-level supervisors, top executives, petit bourgeoisie, or capitalists using self-employment and supervisory-authority items, and created a continuous job-strain score using five job-control and six job-demands items. Age- and gender-adjusted Poisson models suggested job strain decreased approximately linearly across classes, as mean scores were 6% (95% CI: 3%-8%) lower among lower-level supervisors and 23% (95% CI: 19%-27%) lower among capitalists than among workers. Patterns were similar for job control alone. However, lower-level supervisors did report elevated job demands, including 14% (95% CI: 10%-17%) greater mean scores than workers. Patterns persisted after thorough confounder adjustment. Our findings suggest job strain may not explain lower-level supervisors' burdens of mental illness and substance use.

UNLABELLED:Social-emotional competence is critical to children's social and school success, prompting interest in understanding factors that promote these skills prior to elementary-school. Cognitive stimulation (e.g., reading, playing) is related to preschool children's social outcomes; However, few studies have examined these associations earlier, or determined whether interventions that encourage cognitive stimulation may enhance children's early social-emotional competencies either directly, or through impact on these behaviors. The present study examined whether cognitive stimulation in infancy predicted social competence in toddlerhood and the impact of a positive parenting intervention on these child outcomes. Mother-infant dyads in the Smart Beginnings (SB) RCT (primarily Hispanic/Latino or Black and from low-income backgrounds) were randomly assigned to treatment or control. SB integrates universal primary prevention in pediatric primary care (PlayReadVIP); and targeted/secondary prevention through home visiting (Family Check-Up). Mothers' cognitive stimulation at 6 months significantly predicted children's social-emotional competence at 24 months. Although there was no direct effect of SB on children's social-emotional competence, there was an indirect effect on children's social competence through maternal cognitive stimulation. Findings suggest that associations between cognitive stimulation and children's social-emotional competence emerge earlier than previously shown, and that positive parenting interventions can support early social-emotional competence through impact on cognitive stimulation. TRIAL REGISTRATION/UNASSIGNED:ClinicalTrials.gov identifier: NCT02459327.

This study examined longitudinal associations between maternal mindful parenting and child social-emotional, behavioral, and language development. Maternal mindful parenting at 18 months was tested for associations with concurrent observed maternal responsivity and lack of punishment toward the child and as a predictor of child internalizing symptoms, externalizing symptoms, social competence and productive language 6 months later, independent of maternal depressive symptoms (a known predictor of both parenting and child outcomes). We also tested whether child negative emotionality (NE) moderated associations between mindful parenting and child outcomes. Participants (N = 316 mothers) were low-income (mean annual income = $19,024), racially and ethnically diverse mothers (48.4% Black; 43.0% Latinx) recruited from Pittsburgh, PA and New York City, NY. Higher mindful parenting was concurrently associated with higher observed maternal responsiveness toward the child and longitudinally associated with all four child outcomes in expected directions; maternal depression was a significant predictor of child internalizing and externalizing symptoms. Contrary to hypotheses, at moderately high levels of child NE, the positive effects of mindful parenting on child outcomes were attenuated. Results provide preliminary evidence that mindful parenting is meaningfully associated with parenting behaviors and early childhood developmental outcomes above and beyond symptoms of maternal depression.

BACKGROUND:Despite fall-related injuries accounting for over two-thirds of older adult trauma injuries, fall-related injuries are more likely to be under-triaged. The Score for Trauma Triage in the Geriatric and Middle-Aged (STTGMA) is an injury risk-triage tool. This study aims to validate STTGMA's accuracy in predicting fall-related mortality among older adult trauma patients and compare its predictive accuracy with the Geriatric Trauma Outcome Score (GTOS) and the Revised Trauma Score (RTS). METHODS:Using a retrospective cohort design, we selected 6,458 older adult trauma patients (aged 65 years and older) from a single institutional trauma database (2017-2023). The primary outcome variable was in-hospital death, measured as a binary variable. The primary predictor variable was the STTGMA score, measured as a continuous variable and a four-level categorical variable. The secondary predictor variables were the GTOS and the RTS. We compared the predictive accuracy (95% confidence interval (CI)) of the STTGMA, GTOS, and RTS. We further assessed the relationships between the STTGMA risk categories and time-to-death and hospital length of stay using multivariable time-varying Cox proportional hazard analysis and multivariable quantile regression analysis, respectively. RESULTS:A total of 130 patients (2.0%) died during admission, and the median hospital length of stay was 2 days. STTGMA exhibited 84% (95% CI: 77.3-89.8) accuracy in predicting in-hospital fall-related mortality, while the GTOS and RTS both exhibited 71% diagnostic accuracies. Compared to the minimal risk category, older adult trauma patients classified as low, moderate, and high risks each had significantly longer hospital stays and adjusted mortality risks, in a dose-response pattern. CONCLUSION/CONCLUSIONS:STTGMA can accurately predict in-hospital mortality and risk-stratify the length of stay and the time to death among older adult trauma patients with fall-related injuries.

BACKGROUND:The COVID-19 pandemic had a significant impact on healthcare delivery. Older adults with multimorbidities were at risk of healthcare disruptions for the management of their chronic conditions. OBJECTIVE:To characterize healthcare disruptions during the COVID-19 healthcare shutdown and recovery period (March 7, 2020-October 6, 2020) and their effects on disease management among older adults with multimorbidities who were patients of NYC Health + Hospitals (H + H), the largest municipal safety-net system in the United States. DESIGN/METHODS:Observational. PATIENTS/METHODS:Patients aged 50 + with hypertension or diabetes and at least one other comorbidity, at least one H + H ambulatory visit in the six months before COVID-19 pandemic onset (March 6, 2020), and at least one visit in the post-acute shutdown period (October 7, 2020 to December 31, 2023). MAIN MEASURES/METHODS:We characterized disruption in care (defined as no ambulatory or telehealth visits during the acute shutdown) and estimated the effect of disruption on blood pressure control, hemoglobin A1c (HbA1c), and low-density lipoprotein (LDL) cholesterol using difference-in-differences models. KEY RESULTS/RESULTS:Out of 73,889 individuals in the study population, 12.5% (n = 9,202) received no ambulatory or telehealth care at H + H during the acute shutdown. Low pre-pandemic healthcare utilization, Medicaid insurance, and self-pay were independent predictors of care disruption. In adjusted analyses, the disruption group had a 3.0-percentage point (95% CI: 1.2-4.8) greater decrease in blood pressure control compared to those who received care. Disruption did not have a significant impact on mean HbA1c or LDL. CONCLUSIONS:Care disruption was associated with declines in blood pressure control, which while clinically modest, could impact risk of cardiovascular outcomes if sustained. Disruption did not affect HbA1c or LDL. Telehealth mitigated impacts of the pandemic on care disruption and subsequent disease management. Targeted outreach to those at risk of care disruption is needed during future crises.

Mobile health (mHealth) tools can be used to deliver nonpharmacologic therapies to patients with migraine. However, mHealth studies often report poor treatment adherence. Neuroscience Education Therapy (NET), behavioral economics, and Digital Navigators have the potential to increase treatment adherence and thereby improve remote migraine self-management. We conducted a 6-month prospective pilot randomized controlled trial testing if a multi-component package of behavioral interventions increased treatment adherence among patients using one of two different mHealth migraine self-management programs (low-intensity program consisting only of a headache diary versus high-intensity program consisting of a headache diary and behavioral exercises). Our outcomes were the number of diary entries and behavioral exercises completed/week captured via back-end analytics of the mHealth application. We also compared our adherence data at 90-days (a secondary endpoint to assess the durability of the effect) with adherence data from similar published studies without the adherence-enhancing package. We enrolled 26 participants (n = 15 low intensity group, n = 11 high-intensity group). During the 6-week intervention period, we had a median of 7 headache diary entries/week in both groups and a median of 6 days/week of behavioral exercises in the high-intensity group. The rate of adherence with the adherence-enhancing package included was 2.9-8x higher compared to the median rates of the behavioral exercises to historical controls. With use of NET, behavioral economics, and digital navigators, participants achieved higher levels of adherence to both self-management programs compared to prior remote migraine self-management studies. Therefore, these tools may be beneficial to improving adherence to migraine self-management programs.

Previous studies have developed proteomic aging clocks to estimate biological age and predict mortality and age-related diseases. However, these earlier clocks were based on cross-sectional data, capturing only the cumulative aging burden at a single time point but were unable to reflect the dynamic trajectory of biological aging over time. We constructed a longitudinal proteomic aging index (LPAI) using data from 4684 plasma proteins measured by the SomaScan 5K Array across three visits in the Atherosclerosis Risk in Communities (ARIC) study (ages 67-90 at last visit). Our two-step approach applied functional principal component analysis (FPCA) to capture protein-level change patterns over time, followed by elastic net penalized Cox regression for protein selection. LPAI was constructed in a randomly selected training set of ARIC participants (N = 2954), tested among the remaining ARIC participants (N = 1267), and validated externally in Multi-Ethnic Study of Atherosclerosis (MESA) participants (N = 3726, ages 53-94 at last exam). Using Cox proportional hazards model, higher LPAI was associated with increased all-cause mortality (HR = 2.50, 95% CI: [2.15, 2.92] per SD), CVD mortality (HR = 1.79, 95% CI: [1.34, 2.39] per SD), and cancer mortality (HR = 1.96, 95% CI: [1.45, 2.64] per SD) risk in ARIC, with statistically significant and directionally consistent associations also observed in MESA. Additionally, higher LPAI was associated with increased multimorbidity and frailty. This study demonstrates the feasibility of developing biological aging measures from longitudinal proteomics data and supports LPAI as a biomarker for aging-related health risks.