Faculty Bibliography

BACKGROUND:Epigenetic modifications linked to biological aging, like DNA methylation (DNAm), may serve as biomarkers for future cardiometabolic disease risk. However, existing studies have focused on older adults, overlooking the early-life origins of cardiometabolic health. METHODS:Among 378 participants from the CHAMACOS (Center for the Health Assessment of Mothers and Children of Salinas) study, we measured DNAm repeatedly from birth to age 18 years to calculate 4 epigenetic aging (EA) biomarkers: Horvath, Skin & Blood, Intrinsic epigenetic age, and DNAm Telomere Length (DNAmTL). We then developed a novel measure of cumulative EA spanning from birth to age 18 years. Using multinomial logistic and multivariable linear regression models, we examined associations between cumulative EA and several indicators of cardiometabolic health at 18 years. RESULTS:We observed an increased risk of obesity with an interquartile range increase in cumulative EA by Horvath (relative risk [RR], 2.61 [95% CI, 1.79-3.80]), Skin & Blood (RR, 2.76 [95% CI, 1.89-4.03]), and Intrinsic epigenetic age (RR, 1.61 [95% CI, 1.11-2.34]), whereas DNAm TL decreased obesity risk (RR, 0.32 [95% CI, 0.22 -0.45]). Similarly, cumulative EA was associated with higher body mass index, waist circumference, body fat percentage, systolic blood pressure, mean arterial pressure, and resting pulse/heart rate at age 18 years. CONCLUSIONS:Cumulative EA throughout childhood predicts young adult cardiometabolic health and may signal increased risk for later cardiometabolic disease, highlighting the value of life-course epigenetic clocks as biomarkers for early-life health interventions.

BACKGROUND:Fall injury is a sentinel event for mortality among older adults, and activity intensity may play a role in mitigating this outcome. This study assessed the relationship between activity intensity and all-cause mortality following fall injury among community-dwelling U.S. older adults. METHODS:For this retrospective cohort study, we pooled 12 years of data from the National Health Interview Survey and identified older adults (aged 65 years and older) who sustained fall injuries (N = 2454). The outcome variable was time to death following a fall injury. We defined activity intensity as a binary variable, none-to-low and normal-to-high, using the American Heart Association's weekly 500 Metabolic Equivalent of Task (MET) as a cutoff. We controlled for sociodemographic, healthcare access, and health characteristics; performed survey-weighted Cox proportional hazard regression analysis; and reported the adjusted mortality risks (plus 95% confidence interval (CI)). RESULTS:The survey comprised 2454 older adults with fall injuries, representing 863,845 US older adults. The population was predominantly female (68%), non-Hispanic White (85%), and divorced/separated (54%). During the follow-up period, 45% of the study population died. Approximately 81% of the study population had low activity levels. However, between 2006 and 2017, the proportion of the study population with low physical activity decreased from 90% to 67%. After adjusting for sociodemographic, healthcare access, and health characteristics, none-to-low activity intensity was associated with 50% increased mortality risk (aHR: 1.50; 95% CI: 1.20-1.87). CONCLUSIONS:Promoting higher physical activity levels may significantly reduce the all-cause mortality risk following fall injury among older adults.

Between May 2020 and December 2021, there were 159,872 drug overdose deaths in the US. Higher eviction rates have been associated with higher overdose mortality. Amid the economic turmoil caused by the COVID-19 pandemic, 43 states and Washington, DC, implemented eviction moratoria of varying durations. These moratoria reduced eviction filing rates, but their impact on fatal drug overdoses remains unexplored. We evaluated the effect of these policies on county-level overdose death rates by focusing on the dates the state eviction moratoria were lifted. We obtained mortality data from NCHS and eviction moratoria dates from the COVID-19 US State Policy Database. We employed a longitudinal targeted minimum-loss-based estimation with Super Learner to flexibly estimate the average treatment effect (ATE) of never lifting the moratoria. Lifting state eviction moratoria was associated with a 0.14 per 100,000 higher rate of monthly overdose mortality (95%CI: -0.03, 0.32), although confidence intervals were wide and included zero. Eviction moratoria may not be sufficient to prevent overdose mortality during crises such as the COVID-19 pandemic.

BACKGROUND:Inferring risk for malignant transformation (MT) in patients with lesions diagnosed as mild or moderate oral epithelial dysplasia (low-grade OED) remains challenging. We developed two models assessing the risk of progression to high-grade OED (severe dysplasia or carcinoma in situ) or OSCC in patients with low-grade OED lesions. METHODS:We included demographic, risk habit and clinical data from participants with low-grade OED lesions enrolled in the BC Oral Cancer Prevention Program's Oral Cancer Prediction Longitudinal study. Cox proportional hazard models were fit to estimate the effects of anatomic site and toluidine blue findings and adjusted for confounders, as both are associated with MT in the literature but without a North American-specific cohort analysis. Our primary model included both variables of interest. A secondary model included only anatomic site since toluidine blue is not in widespread use. RESULTS:Five hundred and thirty-four participants with 605 lesions met final inclusion criteria, with 339 mild and 266 moderate OED at baseline. In the primary model, lesions at a high-risk anatomic site or with positive toluidine blue staining were associated with a 2.6 and 2.4-fold increased risk of progression, respectively. In the second model that did not incorporate toluidine blue, high-risk anatomic site remained a highly associated risk factor (2.7-fold increased risk of progression). CONCLUSION/CONCLUSIONS:Lesion anatomic site is associated with higher risk of MT for the general practitioner, while a specialist with access to toluidine blue results can assume additional risk associated with positive staining. These models may inform decisions for surveillance and intervention for OED.

OBJECTIVES/OBJECTIVE:We aimed to describe pediatric firearm incidents treated at 6 New York City public trauma hospitals over a 5-year period. METHODS:We conducted a retrospective, multi-institutional, descriptive study of firearm-related incidents among patients below 18 years treated at 6 municipal trauma centers in New York City from July 1, 2016, to June 30, 2021. We used trauma registries, electronic health records (EHR), and geospatial analysis, supplemented with Gun Violence Archive (GVA) and New York Police Department data to characterize and map incidents, excluding missing data. RESULTS:Of n=176 patients, data on injury intent and circumstances were unavailable for 13% (n=22) and 22% (n=38), respectively. Most were male (n=161, 91%), Black (n=133, 76%), and adolescents (median 16 y, IQR: 15, 17) who sustained nonfatal (n=166, 94%) assaults (n=151, 98%). Limited available data suggests that identified assailants were unknown to the unintentional victims of community violence. Incidents largely occurred on weekdays (n=133, 76%); between 15:00 and 20:59 (n=72, 42%); and outside a residential home (n=149, 93%), including sidewalk/street (n=85, 53%) and playground/park/basketball court (n=25, 16%). The most common circumstances were running/jogging/walking outside (n=54, 39%), altercation involvement (n=32, 23%), and drive-by (n=27, 20%). Fifty-four percent (n=72) of incidents occurred within 0.2 miles of public housing in 3 primary geospatial clusters. GVA and New York Police Department databases suggest between 39% and 46% capture of relevant incidents. CONCLUSIONS:Regional gun violence data suffers from a lack of standardization and missingness across sources. Nonetheless, triangulating available data from trauma registries, EHR, GVA, and geospatial analysis, we found that most pediatric patients were Black, adolescent, unintended victims who sustained assaults on weekdays, outside a home, and within 0.2 miles of public housing in 3 primary clusters. These results may inform hospital data surveillance and ongoing evidence-based prevention strategies.

BACKGROUND:To encourage high-quality, reduced-cost care for total joint arthroplasty (TJA), the Centers of Medicare & Medicaid Services mandated a pay-for-performance model, the Comprehensive Care for Joint Replacement (CJR), as part of the Patient Protection and Affordable Care Act (PPACA). The CJR incentivizes cost containment, and it was anticipated that its implementation would reduce access to TJA for high-cost populations. Patients with end-stage kidney disease (ESKD) undergoing kidney replacement therapy (dialysis and kidney transplant) are costly compared with healthier patients, but it was unknown whether this population lost access to hip and knee replacement because of CJR implementation. This population allows study of whether TJA is accessible for medically complex patients whose risk of surgical complications has been mitigated, as kidney transplantation improves outcomes compared with dialysis, allowing evaluation as to whether access improved when patients crossed over from dialysis to transplantation. Because all patients with ESKD are included in a mandated national registry, we can quantify whether access changed for patients who underwent dialysis and transplantation. QUESTIONS/PURPOSES/OBJECTIVE:(1) How did the rate of TJA change amid the shift to bundled payments for patients with ESKD receiving dialysis? (2) How did the rate of TJA change amid the shift to bundled payments for patients with ESKD after kidney transplant? METHODS:This was an observational cohort study from 2008 to 2018 using the United States Renal Data System, a mandatory national registry that allows for the opportunity to study all individuals with ESKD. During the study period, we identified 1,324,614 adults undergoing routine dialysis and 187,212 adult kidney transplant recipients; after exclusion for non-Medicare primary insurance (n = 785,224 for dialysis and 78,011 for transplant), patients who were 100 years or older (n = 79 and 0, respectively), those who resided outside of 50 US states and Puerto Rico (n = 781 and 87, respectively), missing dialysis status for the dialysis cohort (n = 8658), and multiorgan transplant recipients for the transplant cohort (n = 2442), our study population was 40% (529,872) of patients who underwent routine dialysis and 57% (106,672) of adult kidney transplant recipients, respectively. TJA was ascertained using Medicare Severity Diagnosis Related Groups and ICD-9 and ICD-10 codes. We divided the study period by PPACA (January 1, 2014, to March 31, 2016) and CJR (April 1, 2016, to December 31, 2018) implementation and compared the incidence of TJA by era using mixed-effects Poisson regression adjusting for calendar time and clinical and demographic variables. RESULTS:After adjustment for linear temporal trend and patient case mix, there was no evidence of association between policy implementation and the incidence of TJA. In the dialysis cohort, the adjusted incidence rate ratio (IRR) for TJA was 1.06 (95% confidence interval [CI] 0.98 to 1.14; p = 0.2) comparing PPACA with the previous period and 1.02 (95% CI 0.96 to 1.08; p = 0.6) comparing CJR with the previous periods. Similarly, in the transplant cohort, the adjusted IRR for TJA was 0.82 (95% CI 0.67 to 1.02; p = 0.07) comparing PPACA with the previous period and 1.10 (95% CI 0.94 to 1.28; p = 0.9) comparing CJR with the previous periods. CONCLUSION/CONCLUSIONS:There was no loss in access to TJA for medically complex patients receiving kidney replacement therapy. The increase in TJA incidence for patients after kidney transplant and decrease for patients receiving dialysis suggest that surgeons continued to provide care for higher risk patients whose risk of morbidity or mortality with total joint replacement has been maximally improved after transplantation. LEVEL OF EVIDENCE/METHODS:Level III, prognostic study.

IMPORTANCE/UNASSIGNED:Despite evidence of clinical benefits and guidelines recommending first-line treatment intensification (TI) for metastatic castration-sensitive prostate cancer (mCSPC), the majority of patients do not receive it. OBJECTIVE/UNASSIGNED:To identify barriers to and facilitators of first-line TI. DESIGN, SETTING, AND PARTICIPANTS/UNASSIGNED:The IMPLEMENT study (December 2022 to August 2024) comprised 3 phases and used a mixed-methods, qualitative and quantitative approach. US-based urologists and oncologists who were primary treaters for 1 or more patients with mCSPC in the past 6 months, had been practicing for 2 to 35 years, spent 50% or more of their time in direct patient care, and were able to provide informed consent were included. EXPOSURE/UNASSIGNED:Phase 1 consisted of semistructured interviews based on the Theoretical Domains Framework. Phase 2 consisted of a discrete choice experiment to identify priority barriers and helpful resources. Phase 3 consisted of cocreation sessions to ideate potential solutions to underutilization based on the findings of the previous phases. MAIN OUTCOMES AND MEASURES/UNASSIGNED:The primary outcome in phase 1 was barriers to and facilitators of first-line TI, as identified through thematic analysis. The primary outcome of phase 2 was perceived helpfulness of potential resources for first-line TI decisions, measured with a coefficient of helpfulness [CoH] for each resource. The primary outcome of phase 3 was potential solutions to increase TI uptake, as cocreated and ranked by urologists and oncologists. RESULTS/UNASSIGNED:In total, 352 participants were included in IMPLEMENT, with 36 in phase 1 (33 men [92%]; mean [range] years in practice, 19 [5-34]), 302 in phase 2 (253 men [84%]; mean [range] years in practice, 18 [4-35]), and 14 in phase 3 (12 men [86%]; mean [range], years in practice, 20 [8-35]). In each phase, one-half of participants were oncologists and one-half were urologists (18 urologists and 18 oncologists in phase 1, 151 urologists and 151 oncologists in phase 2, and 7 urologists and 7 oncologists in phase 3). In phase 1, 5 domains had the greatest perceived influence on intensification: memory, attention, and decision processes; environmental context and resources; knowledge; beliefs about consequences; and social or professional role. Urologists more commonly reported barriers to intensification, while oncologists more commonly reported facilitators. In phase 2, urologists found decision-support tools most helpful (CoH, 3.27; 95% CI, 2.90-3.65), while oncologists preferred databases of posttreatment options (CoH, 2.58; 95% CI, 2.29-2.89) and clinical trial summaries (CoH, 2.41; 95% CI, 2.14-2.69). In phase 3, cross-specialty tumor boards were ranked by both specialties as the best solution to address TI underutilization. CONCLUSIONS AND RELEVANCE/UNASSIGNED:This study using a mixed-methods approach with quantitative and qualitative components found that the issues underlying TI underutilization were numerous and multifactorial; the barriers encountered by physicians and the resources to help address them varied by specialty. These findings offer insights into physician-supported strategies that could help improve rates of first-line TI for mCSPC in the US.

IMPORTANCE/UNASSIGNED:The emergency department (ED) is a critical point of contact within the health care system and an opportunity to initiate nonpharmacologic migraine treatment. OBJECTIVE/UNASSIGNED:To examine whether progressive muscle relaxation (PMR) smartphone-based migraine self-management improved patient-reported outcomes for migraine compared with enhanced usual care. DESIGN, SETTING, AND PARTICIPANTS/UNASSIGNED:A randomized clinical trial of the smartphone application RELAXaHEAD with and without PMR. Patients aged 18 to 65 years visiting New York University Langone Health EDs for headache who met migraine criteria and self reported 4 or more migraine days per month were recruited from June 2019 to October 2021 with follow-up at 3 months. Data were analyzed from June 2022 to June 2025. INTERVENTION/UNASSIGNED:Participants in the intervention group were asked to listen to the app-based PMR for 60 days. Participants in the control group were asked to use the app as a symptom diary. MAIN OUTCOMES AND MEASURES/UNASSIGNED:Primary outcome was change in migraine-related disability (MIDAS). Secondary outcomes were change in migraine-specific quality of life (MSQv2) and monthly headache days (MHDs). Adherence (number of days of diary use, PMR use and total minutes of PMR use over 90-day period) was measured using back-end analytics. RESULTS/UNASSIGNED:Of the 94 patients (median [IQR] age, 33 [26-45] years; 57 [82.6%] female) randomized (48 control patients and 46 PMR patients), 69 of 94 (73%) had 1 or more follow-up MIDAS scores and constituted the modified intent-to-treat population (35 control patients and 34 PMR patients). The mean (SD) change in MIDAS scores from baseline to 3 months (last observation carried forward [LOCF] used if missing 3-month follow-up data) differed between groups (PMR, 25.09 [29.64] vs control, 6.86 [59.61]; P = .01). PMR had nearly double the number of respondents improving by 5 or more MIDAS points (28 of 34 [82.4%] vs 16 of 35 [45.7%] respondents; P = .002). There was no difference in MSQv2 domains from baseline to LOCF between PMR and control (mean [SD] role function preventive domain for PMR, 16.9 [24.5] vs control, 11.3 [25.9]); emotional function domain (mean [SD] for PMR, 26.5 [26.9] vs control, 19.8 [38.5]); and role function restrictive domain (mean [SD] for PMR, 18.1 [22.7] vs control, 18.7 [26.8]). Mean (SD) change in MHDs (baseline to 3 months) did not differ between groups (PMR, 2.9 [8.0]; 23 days vs control, -1.6 [6.5]; 25 days). CONCLUSION AND RELEVANCE/UNASSIGNED:A PMR-based self-management program offered to patients with migraine after ED discharge yielded clinically significant reductions in migraine-related disability. TRIAL REGISTRATION/UNASSIGNED:ClinicalTrials.gov Identifier: NCT04281030.

INTRODUCTION/BACKGROUND:Esophageal adenocarcinoma (EAC) develops through histopathological stages, including Barrett's esophagus (BE). We analyzed the associations between plasma levels of one-carbon metabolism factors and risks of long-segment BE or EAC. METHODS:Plasma levels were measured from an Irish population-based case-control study [Factors INfluencing the Barrett's Adenocarcinoma Relationship (FINBAR) study; 204 long-segment BE cases, 211 EAC cases, and 251 controls]. A "methyl replete score" was derived by assigning a score of 0 (< median) or 1 (> median) to the levels of three dietary methyl donors (methionine, choline, and betaine) and summing across the metabolites. Multinomial logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the associations between EAC or BE and sex-specific quartiles or score using the lowest level as the reference category and adjusted for potential confounders. RESULTS:Highest methionine, betaine, vitamin B6 (PLP), and choline levels were all associated with 62-82% reduced risks of EAC (ptrends <0.001). Conversely, S-adenosylmethionine (SAM), the SAM/S-adenosylhomocysteine (SAH) ratio, total homocysteine (tHcy), and cystathionine were associated with a greater than two-fold increased EAC risk. A higher methyl replete score was associated with reduced EAC risk (OR 0·33; 95%CI: 0·16-0·66). The highest versus lowest plasma methionine levels were borderline statistically significantly associated long-segment BE (OR 0·55; 95%CI: 0·28-1·07), but all other associations were null. CONCLUSIONS:Several biomarkers of one-carbon metabolism are associated with EAC risk, particularly markers of dietary methyl group donors. Future studies to replicate and prospectively evaluate these markers are warranted.