Faculty Bibliography

HIV pre-exposure prophylaxis (PrEP) is a highly effective prevention strategy, yet awareness, knowledge, and willingness to use it among people who inject drugs (PWID) remains inadequate despite widespread eligibility. Stigma, particularly HIV-stigmatizing beliefs and attitudes, may be a key barrier to engagement at early stages of the PrEP care continuum. We examine how HIV-stigmatizing beliefs and attitudes affect PrEP awareness, knowledge, and willingness among PWID. We surveyed 262 HIV-negative PWID in Los Angeles and Denver (2021-2023) and used structural equation modeling to examine associations between HIV-stigmatizing beliefs and attitudes (11-item validated scale with α = 0.899 and 1-factor structure) and three early PrEP outcomes: awareness, knowledge, and willingness, while controlling for race/ethnicity, gender, housing status, and conducted sub-analyses on willingness to use long-acting injectable PrEP. HIV-stigmatizing beliefs and attitudes were significantly associated with lower PrEP awareness (β - 0.212, p < 0.001) and less accurate knowledge (β - 0.179, p = 0.006). Accurate knowledge was associated with greater willingness to use PrEP (β 0.175, p = 0.027). Black, Indigenous, and Other Persons of Color (BIPOC) participants reported higher HIV-stigmatizing beliefs and attitudes than non-Hispanic White participants (β 0.196, p = 0.003). Over half (56%) of participants were willing to take daily oral PrEP once informed, and many were interested in long-acting injectable PrEP. HIV-stigmatizing beliefs and attitudes are associated with lower PrEP care continuum engagement among PWID, particularly through limiting awareness and understanding of PrEP. BIPOC participants reported higher levels of stigmatizing attitudes, suggesting that broader structural and intersectional stigma may shape PrEP engagement, consistent with prior research. Interventions to increase PrEP uptake should address both individual- and structural-level stigma and consider leveraging peer networks and community supports to foster resilience and improve equitable access to HIV prevention tools.

An important goal of precision medicine is to personalize medical treatment by identifying individuals who are most likely to benefit from a specific treatment. The likely responder (LR) framework, which identifies a subpopulation where treatment response is expected to exceed a certain clinical threshold, plays a role in this effort. However, the LR framework, and more generally, data-driven subgroup analyses, often fail to account for uncertainty in the estimation of model-based data-driven subgrouping. We propose a simple two-stage approach that integrates subgroup identification with subsequent subgroup-specific inference on treatment effects. We incorporate model estimation uncertainty from the first stage into subgroup-specific treatment effect estimation in the second stage, by utilizing Bayesian posterior distributions from the first stage. We evaluate our method through simulations, demonstrating that the proposed Bayesian two-stage model produces better calibrated confidence intervals than naïve approaches. We apply our method to an international COVID-19 treatment trial, which shows substantial variation in treatment effects across data-driven subgroups.

PURPOSE/OBJECTIVE:Fertility preservation (FP) is essential for adolescents and young adults (AYAs) with cancer aged 15-39, yet gaps persist in guideline-concordant care. Despite American Society of Clinical Oncology (ASCO)'s 2018 recommendations, clinician and systemic barriers hinder timely FP counseling. Allied health care professionals (AHPs) play a critical role in supporting patient education and support. This study examined AHPs' conceptualizations of optimal FP care, assessed alignment with ASCO guidelines, and identified facilitators and barriers to implementation. METHODS:This study analyzed data from Cohort 4 (2020) of the Enriching Communication Skills for Health Professionals in Oncofertility (ECHO) program, an 8-week web-based training for AHPs on AYA reproductive health communication. A directed content analysis was used to qualitatively examine factors influencing FP care delivery. Multilevel themes were analyzed to identify potential mechanisms to facilitate optimal FP care, resources needed for implementation, and barriers to FP patient education. RESULTS:Among 130 AHPs (92% female, 72% White), most were social workers (29%) or oncology nurses (25%), working in academic cancer centers (49%). Alignment with ASCO guidelines was observed in fertility risk discussions (72%) and specialist referrals (56%). Key facilitators included patient education (46%), clinician training (48%), and interdisciplinary collaboration (47%). Primary barriers identified were systemic challenges (20%), including financial constraints, limited institutional resources, and time pressures. CONCLUSION/CONCLUSIONS:AHPs demonstrated strong commitment to advancing FP care for AYAs with some alignment to ASCO guidelines. Persistent gaps in psychosocial support and system-level resources highlight the need for expanded clinician education, stronger interdisciplinary networks, and institutional prioritization to ensure equitable, developmentally appropriate FP care.

Oxidative stress, an imbalance between reactive oxygen species and antioxidants, has been linked to impaired placental function and suboptimal fetal growth, yet trimester-specific associations remain poorly understood. We examined 561 mother-infant pairs from The Infant Development and Environmental Study (TIDES), measuring maternal urinary biomarkers of DNA oxidation (8- hydroxydeoxyguanosine (8-OHdG)), lipid peroxidation (malondialdehyde (MDA), and F2-isoprostanes), and protein oxidation (dityrosine (diY)) at first and second trimesters. Using generalized linear models, we examined prospective associations between oxidative stress and ultrasound-derived growth velocities. Early pregnancy oxidative stress biomarkers were persistently associated with reduced second and third trimester growth velocities. First trimester lipid peroxidation markers (8-PGF2α, 15-PGF2α, and 8,15-PGF2α) were associated with slower estimated fetal weight growth velocity in both second trimester (-0.81, -0.93, and -1.72 g/week per log-unit increase, respectively) and third trimester (-4.25, -5.60, and -6.74 g/week). Similarly, first trimester 8-OHdG and diY were associated with both second trimester (-1.31 and -1.17 g/week, respectively) and third trimester estimated fetal weight velocity (-8.01 and -6.75 g/week, respectively). Second trimester 8-OHdG and MDA were associated with slower third trimester estimated fetal weight velocity (-8.57 and -9.25 g/week, respectively). These results provide novel insights into trimester-specific associations between oxidative stress and fetal growth.

BACKGROUND/UNASSIGNED:Adolescent blood pressure guidelines rely on expert consensus because evidence on cardiovascular outcomes is limited. This study aimed to examine the link between adolescent blood pressure indices and early cardiovascular events. METHODS/UNASSIGNED:We conducted a cohort study among 902 741 adolescents aged 16 to 19 years who were evaluated for mandatory service from 1979 to 2019, excluding those with preexisting cardiometabolic conditions. Individuals were followed until 50 or death or insurance loss or December 31, 2021, whichever occurred first. Exposures included baseline blood pressure and American Academy of Pediatrics categories: normal (<120/<80), elevated (120/<80-129/<80), stage 1 (130/80-139/89), stage 2 (≥140/90), and hypertension (clinical diagnosis). The primary outcome was incident cardiovascular events (ischemic heart disease or cerebrovascular disease). Hazard ratios were estimated using Cox models adjusted for demographic, socioeconomic, and clinical confounders. RESULTS/UNASSIGNED:During over 18 million person-years of follow-up, 6305 cardiovascular disease events were recorded, yielding an incidence rate of 0.35 per 1000 person-years. Increased diastolic, systolic, and mean arterial blood pressure were significantly associated with increased risk. Compared with the Normal group, adjusted hazard ratios for cardiovascular disease were 1.14 (95% CI, 1.08-1.22) for stage 1, 1.31 (1.20-1.44) for stage 2, and 2.42 (1.87-3.12) for hypertension. Risk in the stage 1 category was particularly sensitive to diastolic blood pressure. CONCLUSIONS/UNASSIGNED:Higher blood pressure indices during adolescence were strongly associated with an elevated risk of early cardiovascular disease, highlighting the potential need to refine current guidelines to better reflect cardiovascular risk.

BACKGROUND:Reductions in blood pressure (BP) control among patients with hypertension were observed early in the COVID-19 pandemic. The degree to which BP control may have returned to prepandemic levels is unknown. METHODS:Individuals aged 18 to 85 years with hypertension from 17 health systems participating in the National Patient-Centered Clinical Research Network were identified using electronic health record data collected as part of routine care. BP control (percentage of patients whose most recent BP measurement was <140/<90 mm Hg) was estimated in a series of 12-month rolling measurement periods from 2017 through 2022 (January 1, 2017 through December 31, 2017; April 1, 2017 through March 31, 2018; … January 1, 2022 through December 31, 2022). Differences in average BP control between 2022 (January 1, 2022 through December 31, 2022) and 2019 (January 1, 2019 through December 31, 2019) were estimated overall (adjusted for age, sex, and race and ethnicity) and by race and ethnicity (adjusted for age and sex). RESULTS:Our sample included 1 193 314 persons with hypertension in 2019 (48.9% aged 65-85 years, 52.9% men, 66.2% non-Hispanic White) and 1 499 418 individuals in 2022 (50.6% aged 65-85 years, 47.1% men, 62.7% non-Hispanic White). The weighted average BP control dropped from 65.3% in 2019 to 61.8% in 2020 and then partially recovered to 62.6% in 2022 (adjusted mean difference, -2.6 percentage points [95% CI, -5.0 to -0.2]). Non-Hispanic Asian individuals experienced the largest temporal drop in BP control, declining from 68.4% in 2019 to 63.9% in 2022. CONCLUSIONS:BP control was disrupted during the COVID-19 pandemic and had not fully rebounded to prepandemic levels by the end of 2022. Continued surveillance is needed to determine whether the decline in BP control will persist and will result in future adverse cardiovascular events.

BACKGROUND AND AIM/UNASSIGNED:Extended-release injectable naltrexone (XR-Naltrexone) is an effective treatment for opioid use disorder (OUD); however, initiation can be challenging as it requires an opioid-free period. This exploratory analysis examines patient characteristics associated with successful initiation of XR-Naltrexone in the National Drug Abuse Treatment Clinical Trials Network (CTN-0051) Extended-Release Naltrexone versus Buprenorphine for Opioid Treatment (X:BOT) trial. METHODS/UNASSIGNED:Patient demographics and clinical variables associated with successful XR-Naltrexone initiation were examined among 283 participants with OUD randomized to XR-Naltrexone in the X:BOT trial. Variables included severity of opioid use, characteristics of opioid and other substance use, treatment history, psychiatric history, baseline depression, and pain. Logistic regression models were used to estimate the effect of variables on the odds of induction success. RESULTS/UNASSIGNED:204 (72%) of 283 participants randomized to receive XR-Naltrexone completed successful induction. Housing status and pain were significantly associated with XR-Naltrexone induction status. Reported homelessness was significantly associated with higher odds of successful XR-Naltrexone induction (OR: 2.31; 95% CI: 1.12, 4.76). Individuals that reported moderate or extreme pain on the EuroQoL had half the odds of successful induction compared to those without pain (OR: 0.49; 95% CI: 0.27, 0.89). CONCLUSIONS/UNASSIGNED:Among patients with OUD initiating treatment on inpatient units, homelessness was associated with greater likelihood of successfully initiating XR-Naltrexone, while chronic pain was associated with lower likelihood of XR-Naltrexone initiation. Future research on XR-Naltrexone initiation should consider tailoring treatment based on housing status and other social determinants, and evaluation and management of pain.

OBJECTIVE:Pediatric Long COVID (LC) is an infection-associated chronic condition following SARS-CoV-2 infection. While research has begun to elucidate clinical phenotypes, functional impacts are not well described. METHODS:Cross-sectional data from the NIH-funded Researching COVID to Enhance Recovery (RECOVER) pediatric observational cohort was analyzed to assess associations in school-age children (6 to 11 years) and adolescents (12 to 17 years) between LC and caregiver-reported school-related functional outcomes. LC was defined using RECOVER age group-specific symptom-based LC research indices. The primary outcome was worsening of child grades. Secondary outcomes included difficulty paying attention, limited fun with friends, and having an Individualized Education Program (IEP). Using age-stratified analyses, children with and without LC were matched based on age, sex, and dates of infection and enrollment, to estimate risk ratios (RRs) between LC and each outcome. RESULTS:The cohort included 1,976 children (406 school-age, 1,570 adolescent). 18% of school-age children and 29% of adolescents with LC had reported worsened grades, compared to 7% and 11% without LC, respectively [school-age: adjusted RR 2.18 (95% CI: 1.15-4.11); adolescent: adjusted RR 2.39 (95% CI: 1.86-3.06)]. In both age groups, children with LC were more likely to have difficulty paying attention, limited fun with friends, and IEPs. CONCLUSIONS:LC in school-age children and adolescents was negatively associated with functional school-related outcomes, including academic performance, attention, and peer interactions. As LC affects a substantial proportion of U.S. children, these findings highlight the urgent need to develop, provide, and evaluate school-related services for children and adolescents with LC.