Faculty Bibliography

BACKGROUND:Cannabis consumption modalities such as smoking, vaping, and consumption of edibles differ in pharmacokinetics and potency, and vary by demographic characteristics. Data linking real-world consumption modality patterns to use frequency and cannabis use disorder (CUD) remain limited. METHODS:Latent class analysis (LCA) was applied to identify modality-based classes using data from 17,732 adults reporting past 30-day cannabis use on the 2022-2023 National Survey on Drug Use and Health. Multinomial logistic regression delineated associations of class membership with demographic characteristics, cannabis use frequency, and the presence/severity of CUD. RESULTS:LCA yielded four classes based on each modality likelihood: primary smoking (48.2 %), smoking and vaping (20.5 %), mainly edibles (16.9 %), and polymodal use (14.4 %). Compared to adults aged ≥ 50, those aged 18-25 years were more likely to belong to the smoking and vaping (aRRR = 2.52, 95 % CI: 1.77-3.61) or polymodal classes (aRRR = 3.58, 95 % CI: 2.48-5.18). Females were more likely to be in the mainly edibles class (aRRR = 1.78, 95 % CI: 1.48-2.13). Daily cannabis use was more likely among polymodal (aRRR = 2.67, 95 % CI: 2.25-3.17) and less likely among mainly edibles (aRRR = 0.49, 95 % CI: 0.35-0.68) classes, relative to the primary smoking class. Compared to the primary smoking class, risk of having CUD was higher among people in the smoking and vaping class, and in the polymodal class, but lower in the mainly edibles class. CONCLUSIONS:Cannabis use modalities were associated with differences regarding demographic characteristics and severity of use. Future interventions could account for route-specific use to improve prevention and harm reduction efforts.

OBJECTIVES/OBJECTIVE:To estimate past-year prevalence and correlates of major depressive episode (MDE), characterize mental health treatment utilization, and identify barriers to care among community-dwelling US adults aged ≥50. DESIGN/METHODS:Cross-sectional analysis of a nationally representative survey. SETTING/METHODS:Noninstitutionalized US population. PARTICIPANTS/METHODS:20,580 respondents aged ≥50 from 2022 to 2023 National Survey on Drug Use and Health. MEASUREMENTS/METHODS:We estimated past-year MDE prevalence and delineated demographic and past-year substance use correlates; examined mental health treatment utilization among individuals with MDE; and identified barriers to care among untreated individuals. RESULTS:An estimated 4.6% (95% confidence interval: 4.2-5.2) of adults aged ≥50 experienced past-year MDE. In multivariable analyses, higher odds were estimated among females, divorced/separated or widowed individuals, college-educated individuals, and those with alcohol use disorder, cannabis use (with or without use disorder), and prescription opioid or tranquilizer/sedative misuse. Lower odds were estimated among adults aged ≥65, Non-Hispanic Black individuals, and those with income ≥$50,000. Among those with MDE, 66.2% received any mental health treatment. In bivariable comparisons, adults aged ≥65 were less likely than those aged 50-64 to receive outpatient mental health services (38.7% versus 50.1%, p = 0.032) and to report perceived unmet need for treatment (8.8% versus 23.3%, p = 0.019). Among untreated individuals with perceived unmet need, barriers to treatment were attitudinal (86.2%; e.g., thought could handle without treatment), access-related (73.1%), and financial (48.6%). CONCLUSIONS:MDE is prevalent among older adults with heterogeneity across demographic and substance use factors. Treatment disparities and high barrier rates highlight the need for targeted interventions in this population.

Gun violence is a pervasive and multifaceted public health problem. This study describes a novel application of group model building-a process that centers stakeholder voices to describe a complex problem-to investigate drivers of gun violence and design community-led interventions for prevention in New Haven, Connecticut. We recruited community leaders to participate in 2 group model building sessions in New Haven. Discussions and diagrams created during the sessions were used to produce a causal loop diagram illustrating proposed relationships between gun violence and other variables. Our resulting "iceberg model" illustrates how short-term and visible responses to gun violence "above the surface," such as incarceration and policing, may only transiently decrease gun violence. Long-term, downstream effects of "above the surface" responses may ultimately increase gun violence and are summarized in 3 layers "under the surface," which examine the effects of incarceration and lack of re-entry support, vulnerability to stress and social stigmatization, and community-police relations and community safety, respectively. This study demonstrates the value of using group model building to design community-driven interventions for gun violence prevention, as well as reiterates the importance of targeting structural causes of gun violence. This work has informed TRUE HAVEN, a multi-level intervention that addresses community gun violence in New Haven.

BACKGROUND/UNASSIGNED:Early childhood is a critical window for cardiac development, yet the impact of prenatal factors and early growth patterns on heart structure and function in children with structurally normal hearts remains incompletely described. This study investigates the roles of birth weight (BW), gestational age (GA), birthweight-for-gestational-age (BW/GA) z-score, and weight gain z-score in shaping cardiac dimensions. METHODS/UNASSIGNED:-scores for cardiac dimensions and volumes were used to standardize for body surface area (BSA). BW, BW/GA z-score, GA, and weight gain z-score were analyzed as predictors of these parameters. RESULTS/UNASSIGNED:Higher weight gain z-score was independently associated with smaller cardiac dimension z-scores, particularly in the aortic root, ascending aorta, left atrium diameter, left ventricular internal diameter at end-diastole, left ventricular internal diameter at end-systole, end-systolic volume, end-diastolic volume, and left ventricular mass. While birth characteristics influenced some cardiac parameters, postnatal weight gain emerged as a more significant predictor of cardiac size. Ejection fraction and fractional shortening were not influenced by the predictors in our analysis. CONCLUSIONS/UNASSIGNED:Our findings suggest that postnatal weight gain was more consistently associated with cardiac structure z-scores than anthropometric characteristics at birth. Specifically, contractile myocardial thicknesses were relatively stable across weight gain patterns, whereas vascular structures showed inverse scaling with higher weight gain.

Adverse social determinants of health (SDOH) associate with greater heart failure (HF) risk. Among 9879 community-based participants of the Atherosclerosis Risk in Communities (ARIC) cohort study, we assessed 4955 plasma proteins using an aptamer-based platform (SomaLogic). We derived an SDOH factor comprising income, education, and area deprivation index (ADI) in Black and white participants. Proteins associated with this factor at Bonferroni significance were tested for associations with incident HF using multivariable Cox proportional hazard models. Among Black participants, 36 proteins were associated with both the SDOH factor and incident HF, 126 were among white participants, and 12 were shared between race strata. Eight of these demonstrated significant mediation effect in causal mediation models. Key results were replicated in 49,396 participants in UK Biobank. Mendelian randomization and colocalization suggested a potentially causal effect of C1q tumor necrosis factor-related protein 1 (C1QTNF1), an adiponectin paralog, on HF. We demonstrate protein biomarkers associated with SDOH burden and HF risk.

INTRODUCTION/UNASSIGNED:"Positive" outcomes such as flourishing and personal recovery are important predictors of physical health, mental illness, quality of life, and all-cause mortality. However, behavioral health outcome measures often emphasize symptom reduction, while overlooking "positive" outcomes. The objective of this study is to describe (1) the outcomes most important to individuals with major depressive disorder (MDD) and (2) "positive" outcomes and psychiatric symptoms in a real-world sample of young adults with MDD. MATERIALS AND METHODS/UNASSIGNED:Forty-three participants aged 18-35 with a diagnosis of MDD receiving outpatient behavioral health treatment in an urban safety-net psychiatry department completed online surveys identifying factors most important to recovery and standardized measures of flourishing, personal recovery, functioning, and symptoms of depression and anxiety. RESULTS/UNASSIGNED:Most participants (61.9%) had high symptoms of depression (Patient Health Questionnaire-8 (PHQ-8) ≥ 10), 16.7% were flourishing (Flourishing Scale ≥ 48), and 41.9% had high personal recovery (Brief INSPIRE-O ≥ 50). Factors ranked as "most important" for personal recovery included coping well with stressful events (39.5%), functioning well (34.9%), and having hopes and dreams for the future (30.2%). Notably, among individuals with low depressive symptoms, 60.0% reported low flourishing and 31.3% reported low personal recovery. CONCLUSIONS/UNASSIGNED:Individuals with MDD value a diverse range of outcomes, and exhibit a large variation in levels of depressive symptoms and characteristics of "positive" mental health. Aligning outcome tracking with patient-defined goals may provide a more comprehensive understanding of overall mental health.

Synthetic cathinones are a chemically diverse class of novel stimulants that continue to emerge in the U.S. and globally. Trends in overall and specific synthetic cathinone availability in the U.S. (as indicated by seizures) remain poorly characterized. We analyzed annual counts of reports submitted from 2010-2024 to the U.S. Drug Enforcement Administration's National Forensic Laboratory Information System (NFLIS). We grouped reports into chemical subclasses of beta-keto methylenedioxyamphetamines ("-ylones"), pyrrolidinophenones ("pyrros"), and beta-keto amphetamines ("-drones"). Temporal trends in total reports and subclasses were modeled using negative binomial regression spline models. To further contextualize subclass trends, we descriptively examined the contribution of individual synthetic cathinones over time. Between 2010 and 2024, 178,892 synthetic cathinone reports were submitted to NFLIS, of which 73.3% were classified as -ylones, 19.9% as pyrros, 5.2% as -drones, and 1.6% as other. 68.7% of total reports were from the South, with 33.5% from Florida. Nationally, total reports increased sharply in 2010-2013, declined mid-period, rose again from 2019-2020, and then stabilized. Additional regional and temporal heterogeneity was noted across subclasses. We identified patterns of rapid emergence and replacement of individual compounds within subclasses, particularly within the -ylone subclass. Overall, we found substantial temporal, regional, and subclass-specific variation in synthetic cathinone reports to NFLIS from 2010-2024, largely driven by reports from the South and from successive cycles of replacement of -ylones. These findings emphasize the need to strengthen forensic and epidemiological surveillance of the evolving synthetic cathinone landscape in the U.S.

INTRODUCTION/BACKGROUND:There are multiple human papillomavirus (HPV)-related disparities experienced by sexual and gender minority (SGM) populations in the United States (U.S.), including higher rates of some HPV-associated cancers, lower rates of HPV vaccination among certain subgroups, and higher rates of healthcare discrimination. METHODS:We conducted a national cross-sectional survey of U.S. primary care clinicians (physicians and advanced practice providers [APPs]) in 2024 to examine HPV vaccination recommendation practices for SGM patients. Participants responded to a series of six clinical vignettes which varied by patients' sexual orientation, sex assigned at birth, and gender identity. RESULTS:The sample (n = 483) was primarily non-Hispanic (93%), White (74%), physicians (56%), and did not practice in a rural/frontier community (70%). Across the vignettes, regardless of patient characteristics, 59-69% reported they would always recommend the HPV vaccine; whereas 9-19% reported they would recommend the HPV vaccine often (50-79% of the time). The vast majority were highly consistent in recommendation likelihood across vignettes. Greater likelihood of recommending the HPV vaccine was observed for APPs versus physicians (p = 0.016), female clinicians versus males (p < 0.001), and non-Hispanic White clinicians versus other racial/ethnic groups (p = 0.006). CONCLUSIONS:In summary, participants generally reported high likelihood of recommending the HPV vaccine, with recommendations differing very little by patient sex, sexual orientation, or gender identity.

Prior studies suggest fluoride exposure in drinking water above 1500 μg/L is associated with lower child cognition, but evidence is limited at lower exposure levels and in U.S. populations. We evaluated whether prenatal exposure to fluoride in regulated public drinking water was associated with cognition in a pooled U.S. cohort. We analyzed observational data from the Environmental influences on Child Health Outcomes (ECHO) Cohort, including 2514 children born 2006-2019 across 17 sites in 23 states. Individual prenatal time-weighted average public water fluoride concentrations were estimated by linking census tract-level concentrations to residential addresses across pregnancy. Fluid and crystallized cognition were assessed using NIH Toolbox scores. Generalized estimating equation models estimated adjusted mean differences using restricted cubic spline and linear change-point models. Individual prenatal time-weighted average water fluoride concentrations ranged from < 1.0-1940.0 μg/L (mean = 396.9 μg/L). Cubic spline models showed significant inverse associations for fluid cognition above 1107.0 μg/L. Linear change-point models identified 675 μg/L as the best-fitting change-point for fluid cognition; above this value, fluid scores were 0.67 points lower (95% CI, -0.92, -0.42) per 100 μg/L higher fluoride. These findings indicate that prenatal fluoride exposure in regulated public water is nonlinearly associated with lower fluid cognition scores in U.S. children at concentrations below current WHO and U.S. EPA thresholds.