Faculty Bibliography

INTRODUCTION/BACKGROUND:The impact of maternal SARS-CoV-2 infection on fetal brain development during pregnancy remains unclear. Prior research has associated other antenatal infections with adverse neurodevelopmental outcomes in offspring. OBJECTIVE:To compare neurodevelopmental outcomes in infants born to mothers infected with SARS-CoV-2 during pregnancy (COVID+) to infants without congenital exposure (COVID-). METHODS:This study included 77 COVID+ infants and 157 COVID- infants assessed at 6 and/or 12 months. Outcomes were based on maternal self-report, observed infant behavior and brain fMRI. RESULTS:Overall, COVID+ and COVID- infant groups showed no significant differences across a range of neurobehavioral measures. However, analyses not adjusted for multiple comparisons revealed differences: fewer night awakenings at 6 (t(154) = 2.24, p < 0.03) and 12 months (t(107) = 1.94, p < 0.05), and reduced duration of orienting at 12 months (t(55.38) = 2.15, p < 0.04) in COVID+ infants. Neural differences were noted in posterior-anterior midline, insular-frontal, insular-posterior cingulate, and frontal-cingulate regions at an uncorrected threshold of p < 0.01. CONCLUSION/CONCLUSIONS:This study of multi-level infant development suggests that infants born to mothers infected with COVID during pregnancy are not experiencing harmful effects of that exposure. IMPACT/CONCLUSIONS:This study contributes comprehensive data on infant neurodevelopmental outcomes following prenatal SARS-CoV-2 exposure, evaluating a wide range of behavioral and neural measures to address gaps in previous research. Findings suggest that congenital exposure to SARS-CoV-2 does not result in significant neurodevelopmental impairments in infants, offering reassurance amidst concerns about potential long-term effects of maternal prenatal COVID-19 infection. Results indicate that any observed differences, such as fewer night awakenings and functional neural connectivity patterns, may reflect a more mature developmental profile in the exposed group. Continued longitudinal research is necessary to understand behaviorally relevant and lasting neurodevelopmental effects of prenatal SARS-CoV-2 exposure.

BACKGROUND:Estimated glomerular filtration rate (eGFR) using creatinine (eGFRcr), cystatin C (eGFRcys), or both (eGFRcr-cys) is not sufficiently accurate in many settings, often due to non-glomerular filtration rate (GFR) determinants of the filtration markers. In principle, using a panel of endogenous markers (panel eGFR) could reduce the impact of non-GFR determinants of each marker, improving the accuracy of eGFR. Using global untargeted metabolomics, we previously identified 33 endogenous metabolites that correlate highly with measured GFR. METHODS:A LC-MS/MS measurement procedure was developed to quantify 11 endogenous metabolites from serum and plasma. The assay was evaluated in 99 participants with measured GFR (mGFR) from 2 research studies, including a subgroup of 51 participants with large errors in eGFRcr and large discordance between eGFRcr and eGFRcys. Performance of eGFR models using single metabolites and all metabolites (panel eGFR-11) compared to mGFR was assessed by leave-one-out cross-validated root mean square error (RMSE). RESULTS:Assay CV for single metabolites ranged from 1.1% to 6.3% over the course of 21 days. RMSE of eGFR in single metabolite models ranged from 0.184 to 0.324. RMSEs for panel eGFR-11, eGFRcr, and eGFRcr-cys were 0.195, 0.251, and 0.201, respectively, and 0.155, 0.290, and 0.203, respectively, in the subgroup with large errors and large discordance. CONCLUSIONS:A precise metabolite (LC-MS/MS) measurement procedure shows promise for more accurate GFR estimation when eGFRcr is unreliable, offering a potential new confirmatory test for GFR evaluation.

The U.S. Drug Enforcement Administration (DEA) proposed a rule in which they intend to place the psychedelic phenethylamines 2,5-dimethoxy-4-chloroamphetamine (DOC) and 2,5-dimethoxy-4-iodoamphetamine (DOI) into Schedule I of the Controlled Substances Act. We examined the epidemiology of use and availability of these substances. We examined national trends in seizures of these compounds (which indicate availability) using DEA National Forensic Laboratory Information System (NFLIS) and High Intensity Drug Trafficking Areas (HIDTA) data. We also examined the prevalence of self-reported use on the National Survey of Drug Use and Health (NSDUH), a nationally representative sample of noninstitutionalized individuals aged ≥12 in the United States. The scientific literature was also systematically searched for reports of poisonings linked to use. Between 2005 and 2024, NFLIS received 795 submissions of drugs testing positive for DOC, with a peak of 152 in 2012. There was then a decrease through 2024, with only two submissions containing DOC in 2023-2024. Forty submissions contained DOI, with no submissions testing positive in 2019-2024. Three DOC seizures were recorded by HIDTA in 2017-2021, with none in 2022-2024. HIDTA had no recorded seizures of DOI. Between 2005 and 2023, there were 37 and 10 type-in mentions of lifetime DOC and DOI use, respectively, in NSDUH responses, suggesting a lifetime prevalence of < 0.01% among the noninstitutionalized U.S. population. We located three reports of poisonings linked to DOC use (in 2008-2024) and none linked to DOI use. Availability, recreational use, and poisoning related to the use of DOC and especially DOI appear to be rare.

BACKGROUND:The United States has one of the highest incarceration rates in the world. Prior incarceration is associated with adverse health effects. While the era of "mass incarceration" began in 1973, little work has focused on older adults, whose lives have spanned the five decades of mass incarceration. METHODS:We conducted a cross-sectional analysis using data on adults 50 or older from the nationally representative Family History of Incarceration Survey to test the independent association between prior incarceration and self-reported physical and mental health. In logistic regression models, we controlled for age, gender, race/ethnicity, education, income, employment, and marital status. We also tested for effect modification by race/ethnicity, gender, and time since last incarceration, as well as financial and social wellbeing. RESULTS:Among 1318 older adults, 21% had been incarcerated. Formerly incarcerated older adults were more likely to be men; non-Hispanic Black or "other" race/ethnicity; meet criteria for disability; be unmarried; and have lower income and education compared with those never incarcerated. In fully adjusted models, prior incarceration was independently associated with greater odds of reporting "fair" or "poor" physical health (aOR:1.88, 95% CI: 1.19-2.98; p = 0.007). Prior incarceration was associated with reporting "fair" or "poor" mental health after adjusting for demographic covariates (aOR: 2.12, 95% CI: 1.24-3.65; p = 0.006) but was nonsignificant after adding socioeconomic covariates. Length of time from last incarceration did not moderate the observed association, meaning that even those incarcerated > 10 years ago had poor self-reported health. Financial wellbeing moderated the association between incarceration and mental health. CONCLUSION/CONCLUSIONS:Prior incarceration is a social determinant of health for older adults, even those with distant incarceration history, and is strongly associated with current poverty and meeting criteria for disability. Further research is needed to understand the mechanisms of these associations and means to mitigate health harms associated with prior incarceration.

BACKGROUND:Fall injury is a sentinel event for mortality among older adults, and activity intensity may play a role in mitigating this outcome. This study assessed the relationship between activity intensity and all-cause mortality following fall injury among community-dwelling U.S. older adults. METHODS:For this retrospective cohort study, we pooled 12 years of data from the National Health Interview Survey and identified older adults (aged 65 years and older) who sustained fall injuries (N = 2454). The outcome variable was time to death following a fall injury. We defined activity intensity as a binary variable, none-to-low and normal-to-high, using the American Heart Association's weekly 500 Metabolic Equivalent of Task (MET) as a cutoff. We controlled for sociodemographic, healthcare access, and health characteristics; performed survey-weighted Cox proportional hazard regression analysis; and reported the adjusted mortality risks (plus 95% confidence interval (CI)). RESULTS:The survey comprised 2454 older adults with fall injuries, representing 863,845 US older adults. The population was predominantly female (68%), non-Hispanic White (85%), and divorced/separated (54%). During the follow-up period, 45% of the study population died. Approximately 81% of the study population had low activity levels. However, between 2006 and 2017, the proportion of the study population with low physical activity decreased from 90% to 67%. After adjusting for sociodemographic, healthcare access, and health characteristics, none-to-low activity intensity was associated with 50% increased mortality risk (aHR: 1.50; 95% CI: 1.20-1.87). CONCLUSIONS:Promoting higher physical activity levels may significantly reduce the all-cause mortality risk following fall injury among older adults.

Estimating causal effects in the presence of spillover among individuals within a social network poses challenges due to missing information. Spillover effects refer to the impact of an intervention on individuals not directly exposed themselves but connected to intervention recipients within the network. In network-based studies, outcomes may be missing due to study termination or participant dropout, termed censoring. We introduce an inverse probability censoring weighted estimator which extends the inverse probability weighted estimator for network-based observational studies to handle possible outcome censoring. We prove the consistency and asymptotic normality of the proposed estimator and derive a closed-form estimator for its asymptotic variance. Applying the inverse probability censoring weighted estimator, we assess spillover effects in a network-based study of a nonrandomized intervention with outcome censoring. A simulation study evaluates the finite-sample performance of the inverse probability censoring weighted estimator, demonstrating its effectiveness with sufficiently large sample sizes and number of connected subnetworks. We then employ the method to assess spillover effects of community alerts on self-reported human immunodeficiency virus risk behavior among people who inject drugs and their contacts in the Transmission Reduction Intervention Project (TRIP), from 2013 to 2015, Athens, Greece. Results suggest that community alerts may help reduce human immunodeficiency virus risk behavior for both the individuals who receive them and others in their network, possibly through shared information. In this study, we found that the risk of human immunodeficiency virus behavior was reduced by increasing the proportion of a participant's immediate contacts exposed to community alerts.

Between May 2020 and December 2021, there were 159,872 drug overdose deaths in the US. Higher eviction rates have been associated with higher overdose mortality. Amid the economic turmoil caused by the COVID-19 pandemic, 43 states and Washington, DC, implemented eviction moratoria of varying durations. These moratoria reduced eviction filing rates, but their impact on fatal drug overdoses remains unexplored. We evaluated the effect of these policies on county-level overdose death rates by focusing on the dates the state eviction moratoria were lifted. We obtained mortality data from NCHS and eviction moratoria dates from the COVID-19 US State Policy Database. We employed a longitudinal targeted minimum-loss-based estimation with Super Learner to flexibly estimate the average treatment effect (ATE) of never lifting the moratoria. Lifting state eviction moratoria was associated with a 0.14 per 100,000 higher rate of monthly overdose mortality (95%CI: -0.03, 0.32), although confidence intervals were wide and included zero. Eviction moratoria may not be sufficient to prevent overdose mortality during crises such as the COVID-19 pandemic.

BACKGROUND:Cardiovascular disease is the most common cause of morbidity and mortality in kidney transplant recipients. Screening for coronary disease is frequently required prior to kidney transplantation, but coronary intervention has not been shown to be beneficial except in complex coronary artery disease. The likelihood of finding significant coronary artery disease and the benefits of routine pre-transplant screening are uncertain. METHODS:We performed a systematic review and meta-analysis. Medline & Embase were searched to identify manuscripts published between 1998 and 2024 reporting the results of pre-transplant screening. The primary endpoints were the frequency of detecting significant coronary lesions for which there are AHA class 1 indications for revascularization: a) >50% left main stenosis; or b) multi-vessel disease with ejection fraction < 35% during pre-kidney transplant screening. Secondary endpoints included frequency of detecting multivessel disease, proximal left anterior descending artery (LAD) disease, and number of patients who underwent invasive coronary angiography. Meta-regression was used to explore outcome heterogeneity according to the presence of hypertension, diabetes, and age. RESULTS:We identified 1273 studies out of which 44 met eligibility criteria. The mean prevalence of class 1 indications was 2%, although the heterogeneity was high with estimates ranging from 0% to 17%. Estimated prevalence of proximal LAD disease was 2% and left main stenosis was 1%, whereas 10% of patients had multi-vessel coronary artery disease, and 35% were referred for invasive angiography. There was no evidence of significant heterogeneity according to sex of the population or prevalence of diabetes or hypertension. CONCLUSIONS:Identification of class I indications for revascularization during pre-transplant coronary screening was rare.

BACKGROUND:Inferring risk for malignant transformation (MT) in patients with lesions diagnosed as mild or moderate oral epithelial dysplasia (low-grade OED) remains challenging. We developed two models assessing the risk of progression to high-grade OED (severe dysplasia or carcinoma in situ) or OSCC in patients with low-grade OED lesions. METHODS:We included demographic, risk habit and clinical data from participants with low-grade OED lesions enrolled in the BC Oral Cancer Prevention Program's Oral Cancer Prediction Longitudinal study. Cox proportional hazard models were fit to estimate the effects of anatomic site and toluidine blue findings and adjusted for confounders, as both are associated with MT in the literature but without a North American-specific cohort analysis. Our primary model included both variables of interest. A secondary model included only anatomic site since toluidine blue is not in widespread use. RESULTS:Five hundred and thirty-four participants with 605 lesions met final inclusion criteria, with 339 mild and 266 moderate OED at baseline. In the primary model, lesions at a high-risk anatomic site or with positive toluidine blue staining were associated with a 2.6 and 2.4-fold increased risk of progression, respectively. In the second model that did not incorporate toluidine blue, high-risk anatomic site remained a highly associated risk factor (2.7-fold increased risk of progression). CONCLUSION/CONCLUSIONS:Lesion anatomic site is associated with higher risk of MT for the general practitioner, while a specialist with access to toluidine blue results can assume additional risk associated with positive staining. These models may inform decisions for surveillance and intervention for OED.