Faculty Bibliography

OBJECTIVE:Colorectal cancer (CRC) is the third leading cause of cancer death among both men and women in the United States. CRC-related events may increase media coverage and public attention, boosting awareness and prevention. This study examined associations between several types of CRC events (including unplanned celebrity cancer deaths and planned events like national CRC awareness months, celebrity screening behavior, and screening guideline changes) and news coverage, Twitter discussions, and Google search trends about CRC and CRC screening. METHODS:We analyzed data from U.S. national news media outlets, posts scraped from Twitter, and Google Trends on CRC and CRC screening during a three-year period from 2020 to 2022. We used burst detection methods to identify temporal spikes in the volume of news, tweets, and search after each CRC-related event. RESULTS:There is a high level of heterogeneity in the impact of celebrity CRC events. Celebrity CRC deaths were more likely to precede spikes in news and tweets about CRC overall than CRC screening. Celebrity screening preceded spikes in news and tweets about screening but not searches. Awareness months and screening guideline changes did precede spikes in news, tweets, and searches about screening, but these spikes were inconsistent, not simultaneous, and not as large as those events concerning most prominent public figures. CONCLUSIONS:CRC events provide opportunities to increase attention to CRC. Media and public health professionals should actively intervene during CRC events to increase emphasis on CRC screening and evidence-based recommendations.

BACKGROUND:The Bridging Income Generation with Group Integrated Care (BIGPIC) trial in rural Kenya showed that integrating usual care with group medical visits or microfinance interventions reduced systolic blood pressure and cardiovascular risk in participants. We aimed to estimate the incremental cost-effectiveness of three BIGPIC interventions for a modelled cohort and by sex, as well as the cost of implementing these interventions. METHODS:For this analysis, we used data collected during the BIGPIC trial, a four-group, cluster-randomised trial conducted in the western Kenyan catchment area of the Academic Model Providing Access to Healthcare. BIGPIC enrolled participants from 24 rural health facilities in rural western Kenya aged 35 years or older with either increased blood pressure or diabetes. Participants were assigned to receive either usual care, group medical visits, microfinance, or a combination of group medical visits and microfinance (GMV-MF). Our model estimated the incremental cost-effectiveness of the three BIGPIC interventions via seven health states (ie, a hypertensive state, five chronic cardiovascular-disease states, and a death state) by simulating transitions between health states for a hypothetical cohort of individuals with hypertension on the basis of QRISK3 scores. In every cycle, participants accrued costs and disability-adjusted life-years (DALYs) associated with their health state. Incremental cost-effectiveness ratios (ICERs) were calculated for the entire modelled cohort and by sex by dividing the incremental cost by the incremental effectiveness of the next most expensive intervention. The main outcome of this analysis was ICERs for each intervention evaluated. This analysis is registered at ClinicalTrials.gov (NCT02501746). FINDINGS/RESULTS:Between Feb 6, 2017, and Dec 29, 2019, 2890 people were recruited to the BIGPIC trial. 2020 (69·9%) of 2890 participants were female and 870 (30·1%) were male. At baseline, mean QRISK3 score was 11·5 (95% CI 11·1-11·9) for the trial population, 11·9 (11·5-12·2) for male participants, and 11·3 (11·0-11·6) for female participants. For the population of Kenya, group medical visits were estimated to cost US$7 more per individual than usual care and result in 0·005 more DALYs averted (ICER $1455 per DALY averted). Microfinance was estimated to cost $19 more than group medical visits but was only estimated to avert 0·001 more DALYs. Relative to group medical visits, GMV-MF was estimated to cost $29 more and avert 0·009 more DALYs ($3235 per DALY averted). Relative to usual care, GMV-MF was estimated to cost $37 more and avert 0·014 more DALYs ($2601 per DALY averted). In the first year of the intervention, usual care was estimated to be the least expensive intervention to implement ($87 per participant; $10 238 per health-facility catchment area [HFCA]), then group medical visits ($99 per participant; $12 268 per HFCA), then microfinance ($120 per participant; $14 172 per HFCA), with GMV-MF estimated to be the most expensive intervention to implement ($139 per participant; $16 913 per HFCA). INTERPRETATION/CONCLUSIONS:Group medical visits and GMV-MF were estimated to be cost-effective strategies to improve blood-pressure control in rural Kenya. However, which intervention to pursue depends on resource availability. Policy makers should consider these factors, in addition to sex differences in programme effectiveness, when selecting optimal implementation strategies. FUNDING/BACKGROUND:US National Institutes of Health.

While immune function is known to play a mechanistic role in Alzheimer's disease (AD), whether immune proteins in peripheral circulation influence the rate of amyloid-β (Aβ) progression - a central feature of AD - remains unknown. In the Baltimore Longitudinal Study of Aging, we quantified 942 immunological proteins in plasma and identified 32 (including CAT [catalase], CD36 [CD36 antigen], and KRT19 [keratin 19]) associated with rates of cortical Aβ accumulation measured with positron emission tomography (PET). Longitudinal changes in a subset of candidate proteins also predicted Aβ progression, and the mid- to late-life (20-year) trajectory of one protein, CAT, was associated with late-life Aβ-positive status in the Atherosclerosis Risk in Communities (ARIC) study. Genetic variation that influenced plasma levels of CAT, CD36 and KRT19 predicted rates of Aβ accumulation, including causal relationships with Aβ PET levels identified with two-sample Mendelian randomization. In addition to associations with tau PET and plasma AD biomarker changes, as well as expression patterns in human microglia subtypes and neurovascular cells in AD brain tissue, we showed that 31 % of candidate proteins were related to mid-life (20-year) or late-life (8-year) dementia risk in ARIC. Our findings reveal plasma proteins associated with longitudinal Aβ accumulation, and identify specific peripheral immune mediators that may contribute to the progression of AD pathophysiology.

Measures of selective constraint on genes have been used for many applications, including clinical interpretation of rare coding variants, disease gene discovery and studies of genome evolution. However, widely used metrics are severely underpowered at detecting constraints for the shortest ~25% of genes, potentially causing important pathogenic mutations to be overlooked. Here we developed a framework combining a population genetics model with machine learning on gene features to enable accurate inference of an interpretable constraint metric, s_het. Our estimates outperform existing metrics for prioritizing genes important for cell essentiality, human disease and other phenotypes, especially for short genes. Our estimates of selective constraint should have wide utility for characterizing genes relevant to human disease. Finally, our inference framework, GeneBayes, provides a flexible platform that can improve the estimation of many gene-level properties, such as rare variant burden or gene expression differences.

Studies have recently begun to explore the potential long-term health impacts of homeownership policies implemented in the New Deal era. We investigated the association between assigned grades of lending risk by the Home Owners' Load Corporation (HOLC) maps from the 1930s and present-day prevalence of three cardiovascular risk factors (diabetes and obesity in 2020, and hypertension in 2019), estimated at the census tract level in the United States. To minimize potential confounding, we adjusted for sociodemographic data from the time period when HOLC maps were made. We calculated propensity scores (predicted probability of receiving a HOLC grade) and created a pseudo-population using inverse probability weighting. We then employed marginal structural models to estimate prevalence differences comparing A vs. B, B vs. C, and C vs. D HOLC grades. Adjusting only for regions, a less desirable HOLC grade was associated with higher estimated prevalence rates of present-day cardiovascular risk factors; however, most differences were no longer significant after applying propensity score methods. The one exception was that the prevalence of diabetes, hypertension, and obesity were all higher in C vs. B graded census tracts, while no differences were observed for C and D and A and B comparisons. These results contribute to a small body of evidence that suggests historical "yellowlining" (as C grade was in color yellow) may have had persistent impacts on neighborhood-level cardiovascular risk factors 80 years later.

OBJECTIVE/UNASSIGNED:The purpose of this study was to determine whether social support from extended family and church members moderate the association between chronic stress exposure and sleep quality in a nationally representative sample of African American adults. DESIGN/UNASSIGNED:Data from African American respondents aged 18 and older were drawn from the National Survey of American Life-Reinterview. The analytic sample for this study included 1,372 African American adults who attended religious services at least a few times a year, as the church-based relationship measures were only assessed for these individuals. Self-reported sleep quality was assessed by sleep satisfaction, trouble falling asleep, and restless sleep. Chronic stress exposure was measured by a nine-item index. OLS and logistic regression were used to estimate the relationship between chronic stress exposure, extended family and church relationships, and sleep quality. RESULTS/UNASSIGNED:The data indicated that chronic stress exposure was associated with decreased sleep satisfaction, increased likelihood of trouble falling asleep and restless sleep. Receiving emotional support from family and more frequent contact with church members were associated with decreased restless sleep. Emotional family support moderated the associations between chronic stress exposure and trouble falling asleep and restless sleep. The positive associations between chronic stress exposure and these two sleep quality measures were attenuated among respondents who received high levels of emotional support from their family. CONCLUSIONS/UNASSIGNED:Together, these findings underscore the detriment of chronic stress exposure to African Americans' sleep quality and suggest that extended family members are effective stress coping resources and play an important role in this population's sleep quality.

PURPOSE/OBJECTIVE:The premature infant brain may be particularly vulnerable to anesthesia effects, but there is conflicting evidence on the association between anesthesia exposure and developmental outcomes. Twin studies can control for confounding factors. A twin cohort of premature twins provides internal control of difficulty to measure confounders and delivers added power to a study examining the effects of anesthesia on neurodevelopmental outcomes. METHODS:We conducted a retrospective cohort study of sets of premature twins and multiples born at an academic medical center, in which 1 member of the set was exposed to general anesthesia. The primary outcome was the composite scores using Bayley Scale of Infant and Toddler Development III performed at age 6 months to 18 months. Unpaired and paired analyses were performed with linear regression models, Wilcoxon signed rank test, and Mann-Whitney U test. RESULTS:We identified 81 children born at less than 32 weeks gestation within 39 sets of twins and 1 set of triplets for a total of 18 paired observations. All of the exposed infants had a single exposure to general anesthesia. There was no significant association between anesthesia exposure and a diagnosis of developmental delay (OR = 0.8; 95% confidence interval, 0.2-3.2; p = 0.99). Regression models demonstrated no association between anesthesia exposure and cognitive (96.67 vs 97.50; p = 0.74), language (98.33 vs 98.61; p = 0.94), or motor (96.25 vs 96.44; p = 0.91) composite Bayley scores. There was no association between duration of anesthesia and the 3 composite Bayley scores ( p = 0.33; p = 0.40; p = 0.74). CONCLUSION/CONCLUSIONS:Using a premature twin cohort with discordant exposure to anesthesia, our data did not demonstrate any association between anesthesia exposure and developmental delay in this vulnerable population of premature infants.

INTRODUCTION/BACKGROUND:While morbidity and mortality related to synthetic opioids such as illicitly manufactured fentanyl (IMF) are monitored in the U.S., there has been a lack of national survey data focusing on use. Survey data are important as self-report can help estimate prevalence of use among living persons. METHODS:Data were examined from the 2022 National Survey on Drug Use and Health, a nationally representative probability sample of noninstitutionalized individuals age ≥12 in the U.S. (N=59,069). Prevalence and correlates of past-year use of IMF were estimated. Data were analyzed in 2024. RESULTS:The estimated prevalence of past-year IMF use was 0.23% (95% confidence interval [CI]: 0.17-0.31). Compared to no past-year use, individuals were at increased odds for IMF use if proxy-diagnosed with use disorder involving use of cannabis (aOR=3.72, 95% CI: 1.34-10.32), cocaine (aOR=11.96, 95% CI: 4.78-29.93), methamphetamine (aOR=5.60, 95% CI: 1.65-19.02), heroin (aOR=20.56, 95% CI: 8.90-47.52), and/or prescription opioids (aOR=10.65, 95% CI: 3.54-32.03). (Mis)use without use disorder was only significant for prescription opioids (aOR=5.77, 95% CI: 2.55-13.06). Those receiving treatment for substance use in the past year were also at increased odds for use (aOR=5.79, 95% CI: 2.58-13.00). CONCLUSIONS:Prevalence of IMF use is rare in the general U.S. POPULATION/METHODS:While past-year (mis)use of other drugs (without use disorder) was not consistently associated with IMF use, cannabis, cocaine, methamphetamine, heroin, and prescription opioid use disorder was associated with higher odds of IMF use, suggesting that more "severe" use of various drugs is more of a risk factor than use.

A large body of research has documented racial/ethnic disparities in childhood obesity in the United States (US) but less work has sought to understand differences within racial groups. Longitudinal studies are needed to describe BMI trajectories across development, particularly for Black children from immigrant families who have been underrepresented in childhood obesity research. The current study utilizes BMI data collected longitudinally from ages 5 to 8 years and growth mixture modeling to (1) identify and visualize growth patterns among Black children from primarily Caribbean immigrant families, and (2) to compare these patterns to growth trajectories among Black children from US-born families. First, we identified four classes or trajectories of growth for Black children from immigrant families. The largest trajectory (70% of the sample) maintained non-overweight throughout the study period. A second trajectory developed overweight by age 8 (25%). Two small trajectory groups demonstrated high rates of moderate and severe obesity-i.e., specifically, a trajectory of accelerated weight gain ending in moderate/severe obesity (3%), and a trajectory of early severe obesity with BMI decreasing slightly with age (2%). We identified a very similar four class/trajectory model among Black children from US-born families, and compared the model to the one for children from immigrant families using multi-group growth mixture modeling. We found that the patterns of growth did not differ significantly between the populations, with two notable exceptions. Among Black children from immigrant families, ∼ 5% were classified into the two heavier BMI trajectories, compared to ∼ 11% of children from US-born families. Additionally, among children with an accelerated weight gain trajectory, children from immigrant families had lower BMIs on average at each time point than children from US-born families. These findings describe the multiple trajectories of weight gain among Black children from immigrant families and demonstrate that although these trajectories are largely similar to those of Black children from US-born families, the differences provide some evidence for lower obesity risk among Black children from immigrant families compared to Black children from US-born families. As this study is the first to describe BMI trajectories for Black children from immigrant families across early and middle childhood, future work is needed to replicate these results and to explore differences in heavier weight trajectories between children from immigrant and US-born families.