Faculty Bibliography

BACKGROUND AND OBJECTIVES/OBJECTIVE:Genetics represent a nonmodifiable risk factor for Alzheimer disease (AD), with 60%-80% heritability. Midlife hypertension is a modifiable risk factor for both dementia and death. Our primary objective was to determine how genetic risk for AD modifies the association between hypertension and dementia. METHODS:The Atherosclerosis Risk in Communities Study is an ongoing community-based prospective cohort study of 4 US centers. We analyzed White and Black participants free of dementia at age 55 years with genotypes and blood pressure measured at visit 1 (1987-1989). Three genetic risk groups (low, medium, high) were defined based on tertiles of a race-specific AD polygenic risk score. Dementia was ascertained through cognitive testing, informant interviews, hospitalization, codes and death records. Death was ascertained through the National Death Index. We examined the association of midlife hypertension with incident dementia within 3 genetic risk groups using Cox proportional-hazards and cumulative incidence function estimations. We used age 55 years as the time origin, with left truncation to allow entry at ages older than 55 years; age on December 31, 2022, was the administrative censoring date. RESULTS:Among 8,931 White and 2,666 Black participants, the median follow up time was 26.6 and 23.8 years, the mean age was 54.0/53.5 years, and 53.0%/62.5% were female, respectively. After adjusting for demographics, midlife hypertension was significantly associated with dementia incidence across all genetic risk groups among White participants (low risk hazard ratio [HR] 1.29; 95% CI 1.07-1.55, medium risk HR 1.34; 95% CI 1.13-1.58, high risk HR 1.19; 95% CI 1.03-1.38) and among Black participants at high genetic risk (HR 1.31; 95% CI 1.04-1.66). Associations for low and medium genetic risk Black participants were consistent but not statistically significant. There were no significant differences in association of hypertension with dementia by AD genetic risk group. Individuals with hypertension had a 0%-2% higher probability of developing dementia by age 80 and a 6%-13% lower probability of dementia-free survival to age 80 years vs those without hypertension, across race and genetic risk groups. DISCUSSION/CONCLUSIONS:Genetic risk for AD does not modify the association between hypertension and dementia. These data support the fact that all individuals with hypertension are likely to benefit from antihypertensive treatment.

BACKGROUND AND OBJECTIVES/OBJECTIVE:GLP-1-based medications have rapidly reshaped the landscape of obesity treatment. Semaglutide was approved for obesity treatment in 2021 in the US and 2022 in Europe, sparking global interest, and the GLP-1/GIP dual-agonist tirzepatide has demonstrated even greater efficacy. However, survey-based data on who uses or considers these medications-particularly across socioeconomic groups, BMI categories, and weight management experiences-remain limited. SUBJECTS/METHODS/METHODS:A nationally representative online survey of Finnish adults (n = 1729, of which 1693 were included) was conducted in June 2025 via a market research company using quota sampling. Use and awareness of GLP-1 medications for obesity were measured with a single item listing widely known brands-Ozempic, Wegovy, Zepbound, and Mounjaro-to aid recognition. In regression analyses, current, past, and potential users (n = 322) were combined. RESULTS:In total, 3.5% reported current and 2.0% past use, and 13.5% expressed interest in future use. Notably, ~40% of individuals with obesity reported no interest. Bivariate analysis showed that current use was more common among women, those aged 50-69, those with household income exceeding €70,000, individuals with higher BMI, frequent weight loss attempts, experiences of weight-based discrimination, and self-blame. Multivariable analysis showed that current, past, and potential use had strongest associations with BMI ≥30.0 kg/m², repeated or persistent weight loss attempts, experiences of discriminatory treatment due to weight, self-blaming thoughts and hopeful perceptions of GLP-1 medications. Concern about serious health risks was associated with lower likelihood of use or interest. CONCLUSIONS:GLP-1-based medications are gaining recognition, but uptake remains heterogeneous and many individuals with obesity remain uninterested. Concerns about potential health risks persist. Attitudes toward these medications are shaped not only by weight status but also by prior weight management experiences and perceptions. Clinical communication should be sensitive to these factors.

BACKGROUND:There are limited studies on telehealth use patterns among patients with prostate cancer. OBJECTIVE:We assessed the patterns of delivery of care for prostate cancer management in the Veterans Health Administration (VHA). DESIGN/METHODS:A retrospective observational cohort study from January 2016 to February 2023. PARTICIPANTS/METHODS:Data were from the VHA's Corporate Data Warehouse (CDW). Veterans with a new diagnosis of prostate cancer were included in the study. Those who died within 1 year of diagnosis, had missing staging information, or had no prostate-specific antigen (PSA), biopsy, or treatment recorded within 2 years of initial diagnosis were excluded. MAIN MEASURES/METHODS:Veterans were categorized into watchful waiting, active surveillance, and active treatment management groups based on subsequent care received and categorized into National Comprehensive Cancer Network (NCCN) risk categories. We categorized outpatient urology or oncology visits as telephone-based, video-based, or in-person using administrative stop codes. We used logistic regression models to evaluate the characteristics associated with at least one video/virtual visit. KEY RESULTS/RESULTS:In total, 60,381 Veterans were included in the study (20.3% low risk, 49.8% intermediate risk, and 29.8% high risk). Even during the COVID-19 pandemic, less than 6% and 9% of Veterans had at least one urology or oncology video visit, respectively, in the first year after diagnosis across all management groups. In the regression model, Veterans aged 60 and older were less likely to have video visits for both urology and oncology. In contrast, living in urban areas, being diagnosed during the COVID-19 pandemic, and being in the intermediate NCCN risk group were associated with higher odds of having at least one video visit in both specialties. CONCLUSIONS:Despite improvements in telehealth use among Veterans with prostate cancer, telehealth utilization, particularly video visits, remains low, warranting attention from leadership and policymakers.

BACKGROUND:Emerging evidence suggests endocrine disrupting chemicals, including bisphenols and phthalates, may affect behavioral development in children and adolescents. Risk behavior constitutes a potentially sex hormone sensitive behavioral construct. Here, we examined longitudinal associations of phthalate and bisphenol exposure with performance-based tasks and self-reported risk-taking behaviors. METHODS:Within a population-based birth cohort in the Netherlands, urinary bisphenols and phthalate metabolite concentrations were measured in women during pregnancy (three times, n = 1379) and in children (once at 6 years, n = 775). At 10 years, child risk-taking behavior was assessed with the computerized experimental Columbia Card Task (CCT). At 14 years, adolescents completed a computerized self-assessment of real-life risk-taking behaviors. Linear regression and hurdle models adjusted for confounders were applied in the whole sample and stratified by sex at birth. RESULTS:After multiple testing correction, no associations in all children or in boys were found for prenatal or childhood phthalate exposure with the average CCT-score. In girls, prenatal mono-isobutyl phthalate was associated with a higher average CCT-score, indicting more risk-taking (B per 10-fold increase in creatinine-adjusted average prenatal levels = 2.10, 95% CI: 0.69,3.52). No associations were observed for bisphenol exposure nor for self-reported risk-taking. CONCLUSIONS:Prenatal phthalate exposure was associated with more risk-taking in an experimental task at 10 years-of-age in girls only. The task reflects risky decision-making, which may be a hormonally sensitive construct. Risky decision making potentially precedes real-life risk-taking, which was captured by the self-reported measure and was limited in this young sample.

INTRODUCTION/BACKGROUND:Identifying individuals who undergo cognitive decline is vital to the success of prevention trials that aim to slow cognitive decline. Yet, the benefits of using blood-based biomarkers of neurodegeneration, as well as amyloid and tau, to enrich population-based prevention trials have not been quantified. METHODS: = 552). RESULTS:Elevated plasma biomarker levels identified dementia-free older adults with faster cognitive decline. By selecting participants with Quanterix SiMoA measurements of neurofilament light > 30.65 pg/mL, the sample size needed to detect a 33% reduction in cognitive decline in a clinical trial decreased by 57%. DISCUSSION/CONCLUSIONS:Clinical trials can use plasma biomarkers as a screening tool to increase statistical power.

In the past decade, interest in studying psychedelic compounds as potential therapeutic agents has resurged. These studies carefully exclude individuals at risk for developing psychotic symptoms in response to psychedelic use. Given the potential for psychedelics to be established as treatments in psychiatry, it is important to more robustly understand their link with psychosis and schizophrenia spectrum disorders (SSDs). In this narrative review, we examine the historical and theoretical relationship between psychedelic drugs and SSDs, including the origins of the psychotomimetic hypothesis. For key psychedelic compounds, we review their phenomenological manifestations in relation to the experiential alterations characteristic of SSDs, revealing both areas of overlap and important qualitative differences that challenge the uniform psychotomimetic classification. We also review putative neural mechanisms underlying altered experiential states associated with psychedelic use and SSDs, with attention to serotonergic, dopaminergic, and glutamatergic contributions. Clinical evidence demonstrates that psychedelics can exacerbate pre-existing psychotic illness and may trigger psychosis in vulnerable individuals, though the magnitude of these risks remains inadequately quantified. However, phenomenological and mechanistic distinctions suggest that potential therapeutic applications may exist for carefully selected symptoms (negative symptoms, depression) in stable patients using low-dose, controlled approaches. Based on published work, we provide recommendations regarding psychosis-related risk and potential avenues for the treatment of SSDs as psychedelics gain traction as therapeutics.

BACKGROUND:Methadone is the gold standard treatment for opioid use disorder (OUD). In the U.S., methadone is usually only available through licensed opioid treatment programs (OTPs), but a 2021 federal rule provided an opportunity for OTPs to provide methadone on mobile medication units (MMUs). MMUs operate under the license of an OTP and are subject to complex regulatory requirements. New York State provided grant funding to support OTPs to adopt MMUs, aligned with the broader goal to improve methadone access statewide. This study explored barriers and facilitators to MMU implementation across New York State from the perspectives of treatment staff and administrators. METHODS:We conducted semi-structured interviews between June 2024 and June 2025 with 16 staff from four OTPs that adopted MMUs and one residential treatment program served by an MMU. Interviews were audio-recorded, transcribed, and analyzed using a hybrid deductive-inductive thematic analysis approach to identify implementation barriers and facilitators. RESULTS:Staff described a variety of potential models for using MMUs to expand access. In New York City, MMUs were used to serve a residential substance use program. In upstate NY, MMUs were deployed to reduce travel distance in counties with few OTP options. Key facilitators of MMU implementation included leadership persistence in the face of community pushback, creativity and workarounds in the face of logistical hurdles, and support from the state agency. Key barriers included community resistance to MMUs, unclear or inconsistent guidance from the Drug Enforcement Administration, and a variety of operational challenges, such as vehicle maintenance and workforce shortages. Staff generally were positive about the opportunity to use MMUs to address access challenges. CONCLUSIONS:MMUs provide a novel approach to expand methadone access, particularly to populations not currently served by brick-and-mortar OTPs. Early implementers can provide important lessons about how to manage start-up challenges, which can guide later adopters.

KEY POINTS/CONCLUSIONS:In this cohort study of 720,348 adults referred for kidney transplantation from 2014 to 2025, only 48% were evaluated and 19% were waitlisted. Progression from referral to evaluation, waitlisting and kidney transplantation was limited by individual, center-level, and geographic factors. Some centers evaluated and waitlisted patients at rates far below the national average, and low-volume centers had lower rates of transplantation. BACKGROUND:Kidney transplantation is a cost-effective, lifesaving treatment of kidney failure, compared with dialysis. Unfortunately, most patients with kidney failure never undergo transplantation. METHODS:Using Epic Cosmos electronic health record data on all patients referred for kidney transplantation from 2014 to 2025, we assessed the stage-specific progression and attrition in the process of evaluation, waitlisting, and kidney transplantation. Center-level and individual (socioeconomic, geographic, and insurance status) factors associated with access to evaluation, waitlisting, and kidney transplantation were characterized using modified Poisson regression. RESULTS:Among 720,348 referred candidates, the median age was 55 years (interquartile range [IQR], 42-64); 47% of patients were White, 52% were male, and 87% were English speaking. Eighty-five percent of patients lived in urban areas. Of the referred candidates, 48% initiated evaluation, 19% were waitlisted, and 10% ultimately underwent transplantation. Among the referred patients who initiated evaluation, the median (IQR) time to evaluation initiation was two (1-4) months after referral; among the patients who were waitlisted, the median (IQR) time to waitlisting was four (2-9) months after evaluation initiation. Patients who were never married (0.94; 95% confidence interval [CI], 0.93 to 0.94), had severe obesity (0.70; 95% CI, 0.69 to 0.72), or were from rural zip codes (relative risk, 0.98; 95% CI, 0.97 to 1.00) were less likely to initiate evaluation. Low-volume centers had lower relative rates of transplantation (0.92; 95% CI, 0.88 to 0.96). In centers with documentation for nonprogression to evaluation, reasons for removal included not meeting criteria/not a candidate (18%), patient decision (13%), unable to contact (12%), death (4%), and financial/insurance complications (7%). CONCLUSIONS:Our study shows substantial attrition before kidney transplant waitlisting.