Faculty Bibliography

BACKGROUND:Ketamine's potential for treating depression has drawn increased clinical interest in recent years. However, despite growing therapeutic use, recreational use among individuals with depression remain underexplored. METHODS:We analyzed data from the 2015-2022 National Survey on Drug Use and Health focusing on adults in the US. Trends in past-year ketamine use, overall and by depression status, were estimated separately for 2015-2019 and 2021-2022 due to methodological changes in the survey. We also delineated correlates of ketamine use in each period, focusing on depression, sociodemographic characteristics, and other past-year drug use. RESULTS:Overall ketamine use prevalence increased from 2015 to 2019 (from 0.11 % to 0.20 %, an 81.8 % increase, p < 0.01) and from 2021 to 2022 (from 0.20 % to 0.28 %, a 40.0 % increase, p < 0.05). From 2015 to 2019, use increased among adults with and without depression (by 139.3 % [p < 0.05] and 66.7 % [p < 0.05], respectively), while from 2021 to 2022, an increase occurred only among those without depression (by 38.9 %, p < 0.05). Multivariable models revealed that depression was associated with increased odds of ketamine use in 2015-2019 (aOR = 1.80, 95 % CI: 1.12-2.89) but not in later years. New sociodemographic correlates emerged in 2021-2022, including adults aged 26-34 and those with a college degree being at higher odds for use. Various drugs (especially ecstasy/MDMA and gamma-hydroxybutyrate) were consistently associated with higher odds of use. CONCLUSION/CONCLUSIONS:We identified differential patterns and correlates of ketamine use over time. Shifts may be related to the evolving ketamine landscape and/or changing survey methodology. Monitoring of use patterns is crucial to inform prevention and harm reduction strategies.

Traumatic brain injury (TBI) is a leading cause of death and disability worldwide and a major global health concern. In the United States (US), individuals of Black or African American racial identity experience disproportionately higher rates of TBI and suffer from worse post-injury outcomes. Contemporary research agendas have largely overlooked or excluded Black populations, resulting in the continued marginalization of Black patient populations in TBI studies, thereby limiting the generalizability of ongoing research to patients in the US and around the world. This review aims to highlight what is currently known, and identify knowledge gaps, in research on molecular biomarkers associated with TBI in Black populations. A PubMed literature search was conducted to identify studies that investigate molecular biomarkers associated with TBI outcomes that include participants of Black racial identity and those of African ancestry. Studies identified for this review investigate biomarkers associated with TBI outcomes through a lens that specifically examines race, ethnicity, or ancestry. Most studies focused on blood- or cerebrospinal fluid-derived protein biomarkers. Studies identified statistical variation in S100ß, ubiquitin C-terminal hydrolase-L1, amyloid-ß, and tau across participant race, either at baseline or following TBI. Additionally, several studies identified genetic polymorphisms associated with TBI outcomes related to apolipoprotein E, ANKK1, and COMT polymorphism and TBI outcome and identified allele frequency variation across population ancestry. The role of race and ancestry on biomarkers associated with TBI outcome remains indeterminate and subsequent work is still required to understand the implications for patients with TBI.

INTRODUCTION/BACKGROUND:Maternal undernutrition and inflammation in utero may significantly impact the neurodevelopmental potential of offspring. However, few studies have investigated the effects of pregnancy interventions on long-term child growth and development. This study will examine the effects of prenatal nutrition and infection management interventions on long-term growth and neurodevelopmental outcomes of offspring. METHODS:The Enhancing Nutrition and Antenatal Infection Treatment ('ENAT') study (ISRCTN15116516) was a pragmatic, open-label, 2×2 factorial, randomised clinical effectiveness study implemented in 12 rural health centres in Amhara, Ethiopia. The study enrolled 2399 pregnant women who were randomised to receive routine care, an enhanced nutrition package (iron and folic acid, monthly household supply of iodised salt, and micronutrient-fortified balanced energy protein supplement for undernourished women), an enhanced infection management package (genitourinary tract infection screening and treatment, and enhanced deworming), or both packages. In the present Longitudinal Infant Development and Growth study, a subset of 480 children of mothers from ENAT will be recruited equally from each of the four study arms and visited at 12, 18, and 24 months of postnatal age. We will evaluate a range of domains and deploy multiple measures to assess child neurodevelopment, including resting electroencephalography and visual evoked potentials, Hammersmith Infant Neurological Examination, eye-tracking, Bayley Scales of Infant and Toddler Development (Bayley-III), and Magnetic Resonance Imaging (MRI). DISCUSSION/CONCLUSIONS:This study will advance understanding of the impact of nutrition and inflammation in pregnancy on long-term offspring neurodevelopment. This study aims to fill a critical knowledge gap on the benefits of prenatal interventions to promote the health of mothers and their offspring. ETHICS AND DISSEMINATION/BACKGROUND:This study was approved by the Institutional Review Boards of Addis Continental Institute of Public Health (ACIPH/IRB/002/2022) and Mass General Brigham (2023P000461). Results will be disseminated to local and international stakeholders. TRIAL REGISTRATION NUMBER/BACKGROUND:NCT06296238.

IMPORTANCE/UNASSIGNED:Infant growth predicts long-term obesity and cardiovascular disease. Previous interventions designed to prevent obesity in the first 2 years of life have been largely unsuccessful. Obesity prevalence is high among traditional racial and ethnic minority groups. OBJECTIVE/UNASSIGNED:To compare the effectiveness of adding a digital childhood obesity prevention intervention to health behavior counseling delivered by pediatric primary care clinicians. DESIGN, SETTING, AND PARTICIPANTS/UNASSIGNED:Individually randomized, parallel-group trial conducted at 6 US medical centers and enrolling patients shortly after birth. To be eligible, parents spoke English or Spanish, and children were born after 34 weeks' gestational age. Study enrollment occurred between October 2019 and January 2022, with follow-up through January 2024. INTERVENTIONS/UNASSIGNED:In the clinic-based health behavior counseling (clinic-only) group, pediatric clinicians used health literacy-informed booklets at well-child visits to promote healthy behaviors (n = 451). In the clinic + digital intervention group, families also received health literacy-informed, individually tailored, responsive text messages to support health behavior goals and a web-based dashboard (n = 449). MAIN OUTCOMES AND MEASURES/UNASSIGNED:The primary outcome was child weight-for-length trajectory over 24 months. Secondary outcomes included weight-for-length z score, body mass index (BMI) z score, and the percentage of children with overweight or obesity. RESULTS/UNASSIGNED:Of 900 randomized children, 86.3% had primary outcome data at the 24-month follow-up time point; 143 (15.9%) were Black, non-Hispanic; 405 (45.0%) were Hispanic; 185 (20.6%) were White, non-Hispanic; and 165 (18.3%) identified as other or multiple races and ethnicities. Children in the clinic + digital intervention group had a lower mean weight-for-length trajectory, with an estimated reduction of 0.33 kg/m (95% CI, 0.09 to 0.57) at 24 months. There was also an adjusted mean difference of -0.19 (95% CI, -0.37 to -0.02) for weight-for-length z score and -0.19 (95% CI, -0.36 to -0.01) for BMI z score. At age 24 months, 23.2% of the clinic + digital intervention group compared with 24.5% of the clinic-only group had overweight or obesity (adjusted risk ratio, 0.91 [95% CI, 0.70 to 1.17]) based on the Centers for Disease Control and Prevention criteria of BMI 85th percentile or greater. At that age, 7.4% of the clinic + digital intervention group compared with 12.7% of the clinic-only group had obesity (adjusted risk ratio, 0.56 [95% CI, 0.36 to 0.88]). CONCLUSIONS AND RELEVANCE/UNASSIGNED:A health literacy-informed digital intervention improved child weight-for-length trajectory across the first 24 months of life and reduced childhood obesity at 24 months. The intervention was effective in a racially and ethnically diverse population that included groups at elevated risk for childhood obesity. TRIAL REGISTRATION/UNASSIGNED:ClinicalTrials.gov Identifier: NCT04042467.

INTRODUCTION/BACKGROUND:E-cigarettes (ECs) may be an effective harm reduction strategy for individuals with conditions like chronic obstructive pulmonary disease (COPD), asthma, coronary artery disease (CAD), and peripheral arterial disease (PAD) who smoke combustible cigarettes (CCs). Our aim was to examine how individuals with chronic conditions transition from CCs to ECs and its impact on health outcomes. METHODS:In a pilot randomized controlled trial (RCT), patients with COPD, asthma, CAD/PAD who currently smoke CCs and have not used nicotine replacement therapy (NRT) or ECs in the past 14 days were randomized to receive ECs or combination NRT with behavioral counselling. Disease symptoms, acceptability/satisfaction (TSQM-9) and feasibility, and cigarettes per day (CPD), and/or EC use were collected at baseline, 3-, and 6-months. Descriptive statistics and a linear regression were conducted to explore changes in CPD and chronic condition-specific assessments (CAT, SAQ-7, ACT) that assess COPD, asthma, and CAD/PAD symptom change. RESULTS:At 3-months, the EC group (n=63, mean CPD=9±11) reduced their CPD by 54% vs. 60% in the NRT group (n=58, mean CPD=7±6), p=0.56. At 6-months, 17.5% had switched completely to ECs while 23% quit smoking in the NRT arm. CAT scores showed a significant 6-point reduction in the EC arm (p=0.03). Participants scored an average of 69±27 for EC effectiveness, 87±23 for convenience, and 75±27 for overall satisfaction. CONCLUSIONS:This pilot study suggests that ECs may be a safer alternative for chronic condition patients using CCs and warrants further research on expected smoking cessation/reduction among individuals who use ECs. IMPLICATIONS/CONCLUSIONS:The findings from this pilot RCT hold significant implications with chronic conditions such as COPD, asthma, CAD and PAD who smoke CCs. The observed reduction in cigarettes per day and improvement in respiratory symptoms suggest that switching to ECs appears feasible and acceptable among those with chronic diseases. These results suggest that ECs may offer an alternative for individuals struggling to quit CC smoking through existing pharmacotherapies. This study supports further exploration of switching to ECs as a harm reduction strategy among CC users who have been unsuccessful at quitting by other means.

INTRODUCTION/BACKGROUND:Early lung cancer screening (LCS) through low-dose CT (LDCT) is crucial but underused due to various barriers, including incomplete or inaccurate patient smoking data in the electronic health record and limited time for shared decision-making. The objective of this trial is to investigate a patient-centred intervention, MyLungHealth, delivered through the patient portal. The intervention is designed to improve LCS rates through increased identification of eligible patients and informed decision-making. METHODS AND ANALYSIS/METHODS:MyLungHealth is a multisite pragmatic trial, involving University of Utah Health and New York University Langone Health primary care clinics. The MyLungHealth intervention was developed using a user-centred design process, informed by patient and provider focus groups and interviews. The intervention's effectiveness will be evaluated through a patient-randomised trial, comparing the combined use of MyLungHealth and DecisionPrecision+ (a provider-focused shared decision-making intervention) against DecisionPrecision+ alone. The first study hypothesis is that among patients aged 50-79 with uncertain LCS eligibility (eg, 10-19 pack-years or unknown pack-years or unknown quit date for individuals who used to smoke), MyLungHealth eligibility questionnaires will result in increased identification of LCS-eligible patients (n~26 729 patients). The second study hypothesis is that among patients aged 50-79 with documented LCS eligibility (20+ pack-years, quit within the last 15 years if individuals who used to smoke, and no recent screening or screening discussion), MyLungHealth education will result in increased LDCT ordering (n~4574 patients). Primary outcomes will be identification of LCS-eligible patients among individuals with uncertain LCS eligibility and LDCT ordering rates among individuals with documented LCS eligibility. ETHICS AND DISSEMINATION/BACKGROUND:The protocol was approved by the University of Utah Institutional Review Board (# 00153806). The patient data collected for this study will not be shared publicly due to the sensitive nature of the patient health information and the fact that we will not be obtaining written informed consent to allow public sharing of their data. Results will be disseminated through peer-reviewed publications. TRIAL REGISTRATION NUMBER/BACKGROUND:Clinicaltrials.gov, NCT06338592.

BACKGROUND:In cohort studies with time-to-event outcomes, covariates of interest often have values that change over time. The classical Cox regression model can handle time-dependent covariates but assumes linear effects on the log hazard function, which can be limiting in practice. Furthermore, when multiple correlated covariates are studied, it is of great interest to model their joint effects by allowing a flexible functional form and to delineate their relative contributions to survival risk. METHODS:Motivated by the World Trade Center (WTC)-exposed Fire Department of New York cohort study, we proposed a partial-linear single-index Cox (PLSI-Cox) model to investigate the effects of repeatedly measured metabolic syndrome indicators on the risk of developing WTC lung injury associated with particulate matter exposure. The PLSI-Cox model reduces the dimensionality of covariates while providing interpretable estimates of their effects. The model's flexible link function accommodates nonlinear effects on the log hazard function. We developed an iterative estimation algorithm using spline techniques to model the nonparametric single-index component for potential nonlinear effects, followed by maximum partial likelihood estimation of the parameters. RESULTS:Extensive simulations showed that the proposed PLSI-Cox model outperformed the classical time-dependent Cox regression model when the true relationship was nonlinear. When the relationship was linear, both the PLSI-Cox model and classical time-dependent Cox regression model performed similarly. In the data application, we found a possible nonlinear joint effect of metabolic syndrome indicators on survival risk. Among the different indicators, BMI had the largest positive effect on the risk of developing lung injury, followed by triglycerides. CONCLUSION/CONCLUSIONS:The PLSI-Cox models allow for the evaluation of nonlinear effects of covariates and offer insights into their relative importance and direction. These methods provide a powerful set of tools for analyzing data with multiple time-dependent covariates and survival outcomes, potentially offering valuable insights for both current and future studies.

Sexually minoritized men (SMM), transgender women (TW), and particularly Black SMM and Black TW may be disproportionately impacted by alcohol-related problems. Few studies have empirically examined neighborhood factors that may contribute to alcohol use, specifically among these populations. Using data from the N2 longitudinal cohort study in Chicago, IL, survey data from the second wave of longitudinal assessment (n = 126) and GPS mobility data from enrollment were used to evaluate neighborhood alcohol outlet availability, neighborhood disorder, and neighborhood poverty as correlates of individual alcohol use. Neighborhood exposures were measured using 200-m-derived activity space areas, created from GPS data, using publicly accessible geospatial contextual data. Separate multivariable quasi-poison regression models tested for association between neighborhood alcohol outlet density (AOD), measured separately for on-premise (e.g., bars) and off-premise consumption outlets (e.g., liquor stores), neighborhood poverty (defined as the percentage of neighborhood areas at 150% or greater of the US poverty line), exposure to vacant buildings, and neighborhood violent crime density. Separate analytical models found no significant effect between alcohol use and exposure to on-premise consumption venue AOD (risk ratio (RR) = 0.99, p = 0.57), off-premise consumption AOD (RR = 0.94, p = 0.56), neighborhood poverty (RR = 1.04, p = 0.07), or neighborhood violent crime (RR = 1.00, p = 0.94). Exposure to higher levels of vacant buildings (RR = 1.03, p = 0.04) was found to be significantly associated with increased alcohol use. Among this population, opposed to geospatial access, neighborhood measurements indicative of disorder may have a greater influence on shaping alcohol use.

INTRODUCTION/BACKGROUND:E-cigarettes (ECs) and heated tobacco products (HTPs) are recent arrivals to the nicotine product market in the Middle East, which are rapidly growing in popularity in the region. There is a lack of surveillance data at the country-level on use of these products and factors associated with their use. METHODS:This study analyzed a subset of data from the UAE Healthy Future Study, a population-based cohort study of the Emirati population, to determine the factors associated with EC and HTP use among a sample of Emirati adults (≥ 18 years). The baseline assessment and supplementary questionnaires, conducted from 2016 to 2023, included data on combustible tobacco use, EC, and HTP use and sociodemographic characteristics. RESULTS:Of the 2,041 individuals who answered questions on EC use, 32% reported ever using them. Of 521 people providing data on HTP, 30% reported ever using them. After adjusting for age, sex, education, perceived harms and perceived addictiveness of EC, current EC use was associated with baseline combustible tobacco smoking (aOR = 27.63, 95% confidence interval [CI] 14.39, 53.06), users of a younger age (aOR=0.91, 95%CI 0.88, 0.95), and users of male sex (OR = 2.15, 95% CI 1.21, 3.81). Current HTP use was less common, but was also associated with baseline combustible tobacco use. CONCLUSIONS:Use of ECs and HTPs was more common among those who used combustible tobacco. Future research should examine use trajectories among those who do and do not smoke, as well as uptake of these products among youth. IMPLICATIONS/CONCLUSIONS:Non-combustible nicotine products are growing in popularity in the Middle East Region. Our study found that EC and HTP use is associated with baseline combustible tobacco use and that concurrent users may use them to cut down on their combustible tobacco use. Continued comprehensive population-based monitoring of all tobacco and nicotine products, especially EC and HTP use, will provide current data to aid in appropriately informing public health and harm reduction messages and programming.