Faculty Bibliography

The objective of this study was to explore the buffering effect of support on the association between stress and postpartum depression (PPD) among immigrant women. We surveyed 223 Chinese pregnant or postpartum (within one year post-delivery) immigrant women in New York City. Surveys were conducted in English, Simplified Chinese or Mandarin, March-June 2021. PPD was measured with the Edinburgh PPD scale (EPDS); scores of 13 or higher indicate probable depression. Perceived stress was measured with one question, "How often did you feel stressed in the past week?"; responses were collapsed into a binary measure: Never/Rarely and Sometimes/Often/Always. Support was assessed with a general question about perception of receiving needed support and the Patient-Reported Outcomes Measurement Information System (PROMIS) V2.0 Short Form Informational, Instrumental, and Emotional Support measures. Bivariate and multivariable general linear regression models assessed the relationship among stress, support, and PPD. The EPDS mean score was 11.9 (95%CI:11.1-12.7) and 50% (95%CI: 42-57%) had EPDS scores ≥ 13, indicative of serious symptoms; 56% felt stressed in the past week and 37% reported getting needed support. Among women without perceived needed support, mean EPDS scores were higher among women who were stressed compared with women who were not (adjusted mean difference (aMD) 5.4; 95%CI:3.3-7.5); the association between stress and EPDS score was attenuated among women with needed support (aMD 1.1; 95%CI:-1.0, 3.1). Similar patterns held for emotional and instrumental support. Perceived and social support attenuated the association between perceived stress and depression symptoms among Chinese immigrant women. Enhancing support may be effective in countering the impact of stressors on PPD.

INTRODUCTION/BACKGROUND:Fentanyl-related deaths involving stimulants have increased in the US, but little is known about nonfatal overdoses involving use. We examined national trends in nonfatal fentanyl-related exposures involving co-use of cocaine or methamphetamine. METHODS:In this cross-sectional analysis, data from US poison centers were used to estimate annual trends in reported exposures involving fentanyl and stimulant use from 2015 to 2023. Cases included patients aged ≥13 with exposures involving intentional misuse or "abuse" of fentanyl where nonfatal adverse effects occurred (n=13,173). Co-exposure trends were examined, and multivariable logistic regression models were used to estimate how region and medical outcome severity were associated with (1) fentanyl-cocaine use (vs. fentanyl, no cocaine use) and (2) fentanyl-methamphetamine use (vs. fentanyl, no methamphetamine use). RESULTS:Between 2015 and 2023, among fentanyl-related exposures, cocaine use increased from 1.3% to 10.0% (669.2% increase, p<.001) and methamphetamine use increased from 1.5% to 10.8% (620.0% increase, p<.001). Exposures in the Northeast were associated with higher odds of cocaine co-use, while exposures in the Midwest, South, and West were associated with higher odds of methamphetamine co-use. Compared to those with less severe effects, those with a major (life-threatening) effect had higher odds of cocaine co-use, but lower odds of methamphetamine co-use. CONCLUSIONS:Similar to drug-related mortality trends, nonfatal fentanyl poisonings involving co-use of cocaine or methamphetamine increased in recent years and became increasingly widespread. Differences in experience of life-threatening adverse effects linked to different stimulants suggests varying risk according to which stimulant is involved.

IMPORTANCE/UNASSIGNED:In the context of the US opioid crisis, factors associated with the prevalence of opioid use disorder (OUD) must be identified to aid prevention and treatment. State medical cannabis laws (MCL) and recreational cannabis laws (RCL) are potential factors associated with OUD prevalence. OBJECTIVE/UNASSIGNED:To examine changes in OUD prevalence associated with MCL and RCL enactment among veterans treated at the Veterans Health Administration (VHA) and whether associations differed by age or chronic pain. DESIGN, SETTING, AND PARTICIPANTS/UNASSIGNED:Using VHA electronic health records from January 2005 to December 2022, adjusted yearly prevalences of OUD were calculated, controlling for sociodemographic characteristics, receipt of prescription opioids, other substance use disorders, and time-varying state covariates. Staggered-adoption difference-in-difference analyses were used for estimates and 95% CIs for the relationship between MCL and RCL enactment and OUD prevalence. The study included VHA patients aged 18 to 75 years. The data were analyzed in December 2023. MAIN OUTCOME AND MEASURES/UNASSIGNED:International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) or International Statistical Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) OUD diagnoses. RESULTS/UNASSIGNED:From 2005 to 2022, most patients were male (86.7.%-95.0%) and non-Hispanic White (70.3%-78.7%); the yearly mean age was 61.9 to 63.6 years (approximately 3.2 to 4.5 million patients per year). During the study period, OUD decreased from 1.12% to 1.06% in states without cannabis laws, increased from 1.13% to 1.19% in states that enacted MCL, and remained stable in states that also enacted RCL. OUD prevalence increased significantly by 0.06% (95% CI, 0.05%-0.06%) following MCL enactment and 0.07% (95% CI, 0.06%-0.08%) after RCL enactment. In patients aged 35 to 64 years and 65 to 75 years, MCL and RCL enactment was associated with increased OUD, with the greatest increase after RCL enactment among older adults (0.12%; 95% CI, 0.11%-0.13%). Patients with chronic pain had even larger increases in OUD following MCL (0.08%; 95% CI, 0.07%-0.09%) and RCL enactment (0.13%; 95% CI, 0.12%-0.15%). Consistent with overall findings, the largest increases in OUD occurred among patients with chronic pain aged 35 to 64 years following the enactment of MCL and RCL (0.09%; 95% CI, 0.07%-0.11%) and adults aged 65 to 75 years following RCL enactment (0.23%; 95% CI, 0.21%-0.25%). CONCLUSIONS AND RELEVANCE/UNASSIGNED:The results of this cohort study suggest that MCL and RCL enactment was associated with greater OUD prevalence in VHA patients over time, with the greatest increases among middle-aged and older patients and those with chronic pain. The findings did not support state cannabis legalization as a means of reducing the burden of OUD during the ongoing opioid epidemic.

BACKGROUND/UNASSIGNED:Maternal sustained smoking during pregnancy is associated with thousands of differentially methylated CpGs in newborns, but impacts of other prenatal tobacco smoking exposures remain unclear. OBJECTIVE/UNASSIGNED:To identify differential DNA methylation in newborns from maternal sustained smoking and less studied prenatal smoking exposures (i.e., maternal exposure to secondhand smoke [SHS] exposure during pregnancy, maternal quitting before pregnancy, paternal smoking around conception, paternal quitting before pregnancy). METHODS/UNASSIGNED:We conducted a large meta-analysis of prenatal tobacco smoking exposures and epigenome-wide newborn blood DNA methylation through the Pregnancy And Childhood Epigenetics Consortium (PACE). Across 19 cohorts, 11,175 parent-newborn pairs contributed information on at least one prenatal smoking exposure, mostly from questionnaires. Maternal blood or urine cotinine measurements, available in a few studies, provided objective data on maternal SHS and smoking during pregnancy. Primary analyses used Illumina450K methylation data; secondary analyses in 5 cohorts examined CpGs unique to the EPIC array. RESULTS/UNASSIGNED:) was associated with paternal former smoking. Forty-one novel genes were identified using maternal cotinine measurements compared to questionnaire. In EPIC unique analyses (n=3,415), differential methylation was observed with maternal sustained smoking (211 CpGs), maternal SHS (5 CpGs), and paternal former smoking (4 CpGs). Smoking-associated CpGs in blood were strongly enriched for functional elements across multiple tissues. CONCLUSIONS/UNASSIGNED:Maternal sustained smoking has the largest impact on newborn DNA methylation, suggesting a strong influence of the intrauterine environment. We observed minimal impacts for less studied exposures including SHS, maternal former smoking and paternal smoking. https://doi.org/10.1289/EHP16303.

Response to immune checkpoint inhibitors (ICIs) in metastatic melanoma (MM) varies among patients, and current baseline biomarkers predicting treatment outcomes are limited. As mitochondrial (MT) metabolism has emerged as an important regulator of host immune function, we explored the association of host MT genetics (MT haplogroups) with ICI efficacy in 1,225 ICI-treated patients with MM from the clinical trial CheckMate-067 and the International Germline Immuno-Oncology Melanoma Consortium. We discovered and validated significant associations of MT haplogroup T (HG-T) with resistance to anti-programmed cell death protein-1-based ICI (both single-agent and combination) and have shown that HG-T is independent from established tumor predictors. We also found that patients belonging to HG-T exhibit a unique nivolumab-resistant baseline peripheral CD8⁺ T cell repertoire compared to other MT haplogroups, providing, to our knowledge, the first link between MT inheritance, host immunity and ICI resistance. The study proposes a host blood-based biomarker with stand-alone clinical value predicting ICI efficacy and points to an ICI-resistance mechanism associated with MT metabolism, with clinical relevance in immuno-oncology.

Algorithmic bias occurs when predictive model performance varies meaningfully across sociodemographic classes, exacerbating systemic healthcare disparities. NYC Health + Hospitals, an urban safety net system, assessed bias in two binary classification models in our electronic medical record: one predicting acute visits for asthma and one predicting unplanned readmissions. We evaluated differences in subgroup performance across race/ethnicity, sex, language, and insurance using equal opportunity difference (EOD), a metric comparing false negative rates. The most biased classes (race/ethnicity for asthma, insurance for readmission) were targeted for mitigation using threshold adjustment, which adjusts subgroup thresholds to minimize EOD, and reject option classification, which re-classifies scores near the threshold by subgroup. Successful mitigation was defined as 1) absolute subgroup EODs <5 percentage points, 2) accuracy reduction <10%, and 3) alert rate change <20%. Threshold adjustment met these criteria; reject option classification did not. We introduce a Supplementary Playbook outlining our approach for low-resource bias mitigation.

Policy Points We can leverage data science and artificial intelligence to inform state and local resource allocation for overdose prevention. Data science and artificial intelligence can help us answer four questions: (1) What is the impact of laws on access to interventions and overdose risk? (2) Where should interventions be targeted? (3) Which types of demographic subgroups benefit the most and the least from interventions? and (4) Which types of interventions should they invest in for each setting and population? Advances in data science and artificial intelligence can accelerate the pace at which we can answer these critical questions and help inform an effective overdose prevention response.

AIMS/OBJECTIVE:To characterize changes in continuous glucose monitoring (CGM)-derived time in tight range (TIR) measures in individuals with prediabetes or non-insulin-treated type 2 diabetes undergoing dietary weight loss intervention and to quantify the association between weight loss and TIR improvement. METHODS:) were analysed. The association between weight change and TIR change adjusted for demographic and clinical covariates was computed using linear regression. RESULTS:. There were no associations between weight loss and change in any overnight TIR measure. CONCLUSION/CONCLUSIONS:in individuals with prediabetes and non-insulin-treated type 2 diabetes undergoing dietary intervention. The daytime time in tight range measures can complement traditional markers like HbA1c, offering a more comprehensive view of glycaemic variations during dietary weight loss programmes for individuals with prediabetes and type 2 diabetes not on insulin.

BACKGROUND:A majority of the 8.9 million Americans with opioid misuse have mild or no symptoms of opioid use disorder (OUD), but they may be at elevated risk of developing more severe OUD, overdose, or other health consequences of opioid use. The "Subthreshold Opioid Use Disorder Prevention"(STOP) Trial is evaluating a collaborative care intervention for risky opioid use in primary care. Here, we describe baseline characteristics of participants to understand their needs and assess the generalizability of the sample. METHODS:Recruitment at five primary care sites spanned March 2021-May 2023. Adult patients who screened positive for subthreshold OUD (current illicit or non-medical opioid use without meeting DSM-5 criteria for moderate-severe OUD) were eligible. Baseline assessments measured self-reported demographic characteristics, other substance use, pain, and physical and mental health symptoms. Descriptive statistics summarize characteristics of the enrolled sample across sites. RESULTS:Among the 202 participants, the majority identified as female (63.4%), white (70.8%), and non-Hispanic (96.5%), with mean age 55.7 (SD: 12.7) years. Nearly half (49.0%) had problem or high-risk use of prescription opioids, and most received a prescription for opioid medication in the past six months (74.8%). Many participants reported current problem use or high-risk use of alcohol (47.0%) or cannabis (31.2%). Approximately one-third endorsed mental health symptoms, including moderate-severe anxiety (35.6%), depression (31.2%), or sleep disturbance (29.7%), and 20.3% reported a past suicide attempt. In the prior six months, 14.7% had experienced a nonfatal overdose. Moderate-severe pain was reported by 63.4%, and 60.4% rated their general health as fair or poor. CONCLUSIONS:Patients with subthreshold OUD had high rates of polysubstance use and comorbidities that may present challenges to reducing risky opioid use. The STOP trial presents an opportunity to detect and address subthreshold OUD in a cohort with considerable medical and social needs, within primary care settings. CLINICAL TRIALS REGISTRATION/BACKGROUND:ClinicalTrials.gov NCT04218201.

PURPOSE/OBJECTIVE:To assess whether slit-scanning specular microscopy (CellChek C; Konan Medical) can repeatedly image the same corneal location using anatomic landmarks (posterior corneal rings and corneal undulations) and unique cells identified during imaging. METHODS:A total of 203 eyes (113 patients) with and without corneal pathology were imaged to assess the prevalence of anatomic landmarks. A subcohort of 20 healthy eyes was used to identify unique cells adjacent to anatomic landmarks. Landmarks were then used to locate the same cells on repeat imaging approximately 1 week later. Endothelial cell density (ECD), coefficient of variation, and percent hexagonality were calculated. Intraclass correlation coefficient and 95% limits of agreement were used to measure variability and reproducibility of imaging. RESULTS:Approximately 91% of eyes had either posterior corneal rings or undulations present. Undulations were more common than posterior corneal rings in both healthy and diseased corneas. Among subcohort eyes, unique cells were found adjacent to anatomic landmarks in 100% of eyes. Landmarks were used to reimage the same cells in 75% of eyes. There was minimal variation in ECD, coefficient of variation, and hexagonality; intraclass correlation coefficient and 95% confidence intervals were 0.891 [0.715-0.962], 0.612 [0.179-0.849], and 0.793 [0.499-0.925], respectively. The 95% limits of agreement for ECD was -359.9-260.98. CONCLUSIONS:Landmarks identified with slit-scanning specular microscopy allowed reliable reimaging of the same endothelial location, providing a powerful tool to better understand the role of the peripheral endothelium in health and disease.