Faculty Bibliography

BACKGROUND/UNASSIGNED:The ketamine landscape in the USA is rapidly shifting, especially given recent increases in off-label prescribing of ketamine as a psychiatric treatment. Research is needed to determine the extent to which illicit ketamine is available, nonmedically used, and associated with morbidity and mortality in the USA. METHODS/UNASSIGNED:This observational study used eight unique annual repeated cross-sectional datasets to examine illicit ketamine availability (using seizure data as a proxy), use, and consequences of use, including self-reported nonmedical use among noninstitutionalized individuals aged ≥12 years (2006-2014, 2015-2019, and 2021-2023) and among 12th grade students (2000-2023). Further, it assessed reported ketamine-related poisonings (1991-2023) and mortalities (2020-2023), diversion of undispensed pharmaceutical ketamine (2008-2024), drug seizures testing positive for ketamine (2001-2024), and the number and total weight of ketamine seizures from two additional law enforcement agencies (2017-2024 and 2019-2024). Piecewise linear regression models were used to estimate annual trends. FINDINGS/UNASSIGNED:Nonmedical ketamine use among individuals aged ≥12 years increased between 2021 (0.19%) and 2023 (0.34%) (b [slope] = 0.08 [SE = 0.001], p = 0.0072). Regarding reported poisonings, there was initial increase from 1994 to 2000 (from 0.17 to 1.40 per 1,000,000 population; b = 0.20 [SE = 0.02], p < 0.0001), a decrease through 2003 (0.58 per 1,000,000 population; b = -0.34 [SE = 0.08, p = 0.0002) and an increase from 2017 through 2023 (from 0.76 to 1.54 per 1,000,000 population; b = 0.12 [SE = 0.03], p = 0.0002). The number of reported diversions increased from 2008 (n = 23) to 2017 (n = 202) (b = 18.72 [SE = 2.20], p < 0.0001) and again from 2021 (n = 183) to 2024 (n = 286) (b = 39.00 [SE = 12.04], p < 0.0001). Regarding seizures, there was an increase in ketamine reports to one agency from 2015 (n = 1448) through 2024 (n = 4008) (b = 201.41 [SE = 57.83], p = 0.0023). In another source, there was an increase in seizures from 2022 (n = 247) through 2024 (n = 502) (b = 127.50 [SE = 10.40], p = 0.0003). Rates of ketamine-involved deaths did not significantly shift between 2020 and 2023. Nonmedical use declined among 12th grade students, first from 2000 (2.49%) through 2005 (1.61%) (b = -0.19 [SE = 0.06], p = 0.0039] and then again from 2005 through 2023 (0.9%) (b = -0.04 [SE = 0.01], p = 0.0019). INTERPRETATION/UNASSIGNED:Ketamine poisonings, pharmaceutical diversion, and seizures have increased; trends in nonmedical ketamine use vary. Prevention and harm reduction are needed as use and morbidity are expected to continue to increase. FUNDING/UNASSIGNED:National Institute on Drug Abuse at the National Institutes of Health.

BACKGROUND:on dementia may be more severe in this population. METHODS:and dementia risk factors using a Wald test. Models were adjusted for confounders, including social determinants of health. RESULTS:was associated with 1.90-fold higher odds of global cognitive impairment (95% CI: 1.48-2.46), and 3.29-fold higher risk of dementia (95% CI: 1.14-9.55). CONCLUSION/CONCLUSIONS:neighborhoods should discuss cognitive assessments and ways to increase physical activity with providers.

BACKGROUND:Carnobacterium maltaromaticum and Faecalibacterium prausnitzii induce de novo gut synthesis of vitamin D to inhibit colorectal carcinogenesis in mice. Magnesium (Mg) treatment increases circulating vitamin D and Mg homeostasis is dependent on TRPM7 genotype. OBJECTIVE:We hypothesize that Mg treatment increases gut C. maltaromaticum and F. prausnitzii and the effect differs by TRPM7 polymorphism. METHODS:The Personalized Prevention of Colorectal Cancer Trial is a double-blind, precision-based randomized controlled trial with 240 participants randomized by both treatment and TRPM7 genotype. Stool, rectal swabs, and rectal mucosa were collected. RESULTS:Of 239 participants that completed the trial, 226 with valid microbiome data were analyzed (treatment n=112, placebo n=114). The interaction between treatment and TRPM7 genotype was only significant for C. maltaromaticum (p=0.001) and F. prausnitzii (p=0.02) in rectal swabs. In a stratified analysis by TRPM7 genotype without the missense variant, Mg treatment compared to placebo significantly increased abundance of C. maltaromaticum (0.217±0.615 (23.01%) compared to -0.065±0.588 (-6.30%); P=0.006) and F. prausnitzii (0.105±0.817 (2.13%) compared to -0.095±0.856 (-1.92%); P =0.04) in rectal swabs. The effect on C. maltaromaticum remained after multiple comparisons (Q=0.05 for C. maltaromaticum across all sample types and genotypes). In those with the TRPM7 missense variant, Mg decreased C. maltaromaticum, but not F. prausnitzii, compared to placebo in rectal swabs (-0.065±0.511 (-6.54%) compared to 0.133±0.503 (13.30%); adjusted P=0.04). The effect did not remain after FDR correction. Mg treatment's effect on C. maltaromaticum in rectal swabs primarily appeared in females, and the treatment-genotype interaction remained significant. CONCLUSION/CONCLUSIONS:In individuals with adequate TRPM7 function, Mg supplementation increases abundance of C. maltaromaticum and F. prausnitzii. CLINICAL TRIAL REGISTRY/BACKGROUND:This trial was registered on ClinicalTrials.gov as NCT04229992 (https://clinicaltrials.gov/study/NCT04229992?term=NCT04229992&rank=1). The parent study is registered as NCT03265483, and another relevant study is registered as NCT01105169.

BACKGROUND:Studies examining the association of chronic kidney disease (CKD) with cancer risk have demonstrated conflicting results. METHODS:This was an individual participant data meta-analysis including 54 international cohorts contributing to the CKD Prognosis Consortium. Included cohorts had data on albuminuria [urine albumin-to-creatinine ratio (ACR)], estimated glomerular filtration rate (eGFR), overall and site-specific cancer incidence, and established risk factors for cancer. Included participants were aged 18 years or older, without previous cancer or kidney failure. RESULTS:Among 1,319,308 individuals, the incidence rate of overall cancer was 17.3 per 1000 person-years. Higher ACR was positively associated with cancer risk [adjusted hazard ratio 1.08 (95% CI 1.06-1.10) per 8-fold increase in ACR]. No association of eGFR with overall cancer risk was seen. For site-specific cancers, lower eGFR was associated with urological cancer and multiple myeloma, whereas higher ACR was associated with many cancer types (kidney, head/neck, colorectal, liver, pancreas, bile duct, stomach, larynx, lung, hemolymphatic, leukaemia, and multiple myeloma). Results were similar in a 1-year landmark analysis. DISCUSSION/CONCLUSIONS:Albuminuria, but not necessarily eGFR, was independently associated with the subsequent risk of cancer. Our results warrant an investigation into mechanisms that explain the link between albuminuria and cancer.

OBJECTIVE:To evaluate urinalysis testing patterns within the Veterans Health Administration (VHA), estimate the proportion and likelihood of patients who completed a urinalysis to have microscopic hematuria (MH), and explore how urinalysis testing patterns may influence MH detection. METHODS:This was a retrospective cross-sectional study using VHA data. We identified adult patients without a known urologic cancer history who had at least 1 outpatient visit at any VHA site and at least 1 interpretable urinalysis performed in 2015. The factors associated with the number or urinalyses performed on each patient and associations with the presence of MH were investigated. RESULTS:Among 5,719,966 adults, 39% completed a urinalysis. Variation in the proportion of patients who completed urinalyses was highest by age, among patients with hypertension and diabetes, and by region. Of patients who underwent urinalysis and had no prior genitourinary cancer history, 54% did not have an interpretable urinalysis result. Among patients with at least one interpretable microscopic urinalysis, 37% had MH. This was more common among older patients, females, current smokers, and patients with more comorbidities. Variation in the likelihood of patients having MH remained after adjusting for multiple factors and when contextualized by urinalysis completion and interpretability patterns. CONCLUSION/CONCLUSIONS:The number of urinalyses performed in the VHA system is remarkably high. Detection of MH is influenced by the frequency of urinalysis testing and interpretability of results. The presence and detection of MH varies by factors which should be considered when adjudicating the need for further evaluation of MH.

PURPOSE/OBJECTIVE:In adolescents (12-17 years), it is unknown whether COVID-19 vaccination reduces progression from COVID-19 to Long COVID (LC) beyond preventing SARS-CoV-2 infection. We assessed the effect of vaccination among SARS-CoV-2 infected adolescents. METHODS AND RESULTS/RESULTS:Participants were recruited from over 60 US healthcare and community settings. The exposure was any COVID-19 vaccination 6 months prior to infection. The outcome was LC defined using the LC research index. Vaccinated (n = 724) and unvaccinated (n = 507) adolescents were matched on sex, infection date, and enrollment date. The risk of LC was 36 % lower (95 % CI, 17 %, 50 %) in vaccinated compared to unvaccinated participants. CONCLUSIONS:Vaccination reduces the risk of LC. Given the profound impact LC can have on the health and well-being of adolescents and the limited availability of treatments during this developmental stage, this supports vaccination as a strategy for preventing LC by demonstrating an important secondary prevention effect.

BACKGROUND:Community-clinical linkage models (CCLM) display significant potential to address the unique, multi-level type 2 diabetes risk factors facing minoritized communities, such as South Asian Americans. However, there lacks a systematic, longitudinal evaluation of how such tailored CCLMs can be better implemented in dynamic, real-world settings. This study aims to leverage multi-partner insights, collected in real time, to explore the barriers and facilitators to implement a South Asian American diabetes management and prevention intervention (the DREAM intervention). METHODS:The DREAM intervention, a two-arm randomized controlled trial, was implemented from 2019-2022; partners involved in its implementation were interviewed annually to understand their experiences of the program. Implementation partners included community health workers (CHWs), participating healthcare providers, community advisory board (CAB) partners, and research staff. The interview guide and subsequent deductive qualitative analysis was informed by the Consolidated Framework for Implementation Research (CFIR). RESULTS:Overall, 78 interviews were conducted across four waves (2019-2022) with 5 research staff, 8 CHWs, 18 providers/clinic staff, and 12 CAB partners. CHWs adapted intervention characteristics by tailoring curriculum and implementation to patient needs, including personalized goal setting and shifting to remote delivery with COVID-19-related content. At the individual level, participants' occupations, family dynamics, and technological capacity shaped engagement, while changing social, financial, and health contexts over time required CHWs to continually adjust support. Within the inner setting, partner roles and resource availability fluctuated, yet structured and consistent meetings facilitated communication and problem-solving. Outer setting influences, including shifting government and universities policies and the COVID-19 pandemic, required repeated adaptations, while CAB partnerships expanded community connections and services over time. Process-related findings underscored the evolving role of CHWs and research staff in planning and fidelity, with training shifting toward peer mentorship to build capacity. CONCLUSION/CONCLUSIONS:Findings revealed the pivotal role of programmatic adaptability and robust partner engagement in navigating dynamic contexts to support the diabetes needs of minoritized communities. The real-time, longitudinal approach taken for data collection and analysis was crucial in understanding how intervention changes were implemented and experienced, providing a model for similar implementation assessments.

Inaccurate information about prostate cancer is widespread on online social networks in English and Spanish and spans a variety of topics from prevention and screening to treatment and survivorship. Clinicians should raise awareness that social media can be a source of misinformation about prostate cancer, preemptively address prevalent myths, and actively participate in public dissemination of evidence-based information.

Household chaos has been shown to be an important predictor across multiple domains of children's development, with both direct associations and indirect associations through changes in parenting practices. Yet, little is known about these associations among immigrant families. Data from the Children, Community, and Caregivers (C3) Study of the larger Together Growing Strong place-based initiative among predominantly Chinese and Latine immigrant families in the Sunset Park neighborhood of Brooklyn, New York were used to examine cross-sectional associations between household chaos and child behavior and receptive vocabulary at child ages 4 and 6 (N = 187). The STROBE checklist for cross-sectional research was adhered to. Linear regression models were used to examine unique contributions of variables, as well as structural equation modeling to examine mediation through parenting stress. As a supplemental exploratory analysis, differences in associations between household chaos and child behavior and language by race/ethnicity were further examined. There were significant positive associations between household chaos and parental reports of children's problem behavior (β = 0.21, 95% CI [0.07-0.35]) and significant negative associations between household chaos and direct assessments of children's receptive vocabulary (β=-0.21, 95% CI [-0.37 - -0.04]). Further, there were indirect associations of household chaos through parenting stress for child problem behavior only (β = 0.11, 95% CI [0.05-0.17]). The results for the main linear regression models and mediation models were primarily driven by Chinese families. Implications for predictors of child development in immigrant populations and the enduring salience of household chaos are discussed.