Faculty Bibliography

RATIONALE/BACKGROUND:Abrupt air quality improvements have followed the closure or dramatic emission control of large air pollution sources. These "natural experiments" provide ideal opportunities to assess the real-world health benefits of air quality improvements. The shutdown of the Shenango coking plant, a significant fossil-fuel pollution source located on an island in the Ohio River near Pittsburgh, PA, presented such an opportunity to test for changes in respiratory health in the local community following the closure. OBJECTIVES/OBJECTIVE:To identify and quantify the immediate and/or longer-term changes in respiratory hospitalizations and emergency department (ED) visits among the population residing near the Shenango coke plant at the time of its closure. METHODS:We acquired data for respiratory hospitalizations and ED visit counts by residents living in zip codes surrounding the plant, as well as at comparison control sites, three years before and after the shutdown date. The immediate and longer-term changes of respiratory health outcomes were tested with an interrupted time series model, and compared with external control sites and internal control outcomes. MEASUREMENTS AND MAIN RESULTS/RESULTS:We found the closure of the Shenango plant was associated with an immediate 20.5% (95% CI: 12.8%-27.6%) decrease for weekly respiratory ED visits, and an immediate 41.2% (95% CI: 14.4%-59.9%) decrease in pediatric asthma ED visits, followed by an additional 4% per month longer-term downward trend. Longer-term reductions, as compared to pre-closure trends, were also observed for chronic obstructive pulmonary disease hospitalizations. CONCLUSIONS:Our study provides strong confirmation that reductions in fossil-fuel-related air pollution produce both short and longer-term respiratory health benefits. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/).

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.

BACKGROUND:We previously reported that individuals with the Transient receptor potential melastatin 7 (TRPM7) GA/AA genotype and consumed diets high in Ca:Mg ratio had an increased risk of colorectal polyps. OBJECTIVE:The aim was to identify if the gut microbiota plays a role in the association of TRPM7 genotype, Ca:Mg intake ratio and risk of colorectal polyps. METHODS:We analyzed the gut microbiota of 240 participants in a double-blind 2x2 factorial (TRPM7 genotype and Ca:Mg intake ratios) randomized trial by sequencing the stool, rectal swab, and rectal mucosa tissue samples of each participant. RESULTS:The gut microbiota of participants with the GA genotype significantly differed from those with the GG genotype in all three sample types, with an altered abundance of Prevotella and Bacteroides in swab samples. Prevotella in rectal mucosa and Bacteroides in swab were associated with an increased risk of metachronous colorectal polyps. Optimizing high diet Ca:Mg ratios to 2.3 through Mg supplementation resulted in a reduced abundance of Prevotella in rectal swabs and Bacteroides in stool samples. We identified multiple microbes in all three sample types linked to the risk of metachronous colorectal polyps. CONCLUSIONS:Our findings indicate that the gut microbiota in stool, rectal swab and mucosa are associated with the risk of metachronous colorectal polyps, and diet changes could modify the abundance of TRPM7-related microbes. CLINICAL TRIAL REGISTRATION/BACKGROUND:The study was registered as NCT01105169 at ClinicalTrials.gov: https://clinicaltrials.gov/study/NCT01105169.

BACKGROUND:The association of PREVENT-HF (Predicting Risk of Cardiovascular Events-Heart Failure) risk estimates with preclinical heart failure (HF) and whether preclinical HF measures add to the predictive utility of PREVENT-HF remain undefined. OBJECTIVES/OBJECTIVE:The aims of this study were to evaluate the association between PREVENT-HF risk estimates and preclinical HF, to examine how preclinical HF measures correspond to absolute HF risk within PREVENT-HF categories, and to determine whether they provide predictive value beyond the PREVENT-HF score. METHODS:The authors performed a prospective analysis of 2,714 ARIC (Atherosclerosis Risk In Communities) Visit 5 participants <80 years of age, without baseline cardiovascular disease. Preclinical HF was defined by elevated cardiac biomarkers (N-terminal of pro-b-type natriuretic peptide ≥125 pg/mL or high-sensitivity cardiac troponin T ≥22 ng/L/≥14 ng/L in men/women) and/or abnormal echocardiographic findings. Within PREVENT-HF 10-year risk categories (<7.5%, ≥7.5% to <10%, ≥10% to <15%, ≥15% to <20%, and ≥20%), we assessed preclinical HF prevalence and compared 10-year HF incidence rates for those with and without preclinical HF. We assessed changes in predictive utility by adding preclinical HF measures to PREVENT-HF. RESULTS:The mean age was 74 years, with 63% women, and 22% Black adults. Higher PREVENT-HF risk was associated with higher preclinical HF prevalence, with the highest prevalence of combined elevated biomarkers plus abnormal echocardiograms (37%) in those with PREVENT-HF ≥20%. Over a median follow-up of 9.9 years, 262 HF events occurred. Within PREVENT-HF categories, preclinical HF measures were strongly associated with absolute HF risk: among those with PREVENT-HF ≥20%, HF incidence rates (per 1,000 person-years) were 9.5 with no preclinical HF and 51.5 with elevated biomarkers plus abnormal echocardiography. Adding cardiac biomarkers to PREVENT-HF improved risk discrimination (C statistic change 0.69 to 0.75; P < 0.001) and reclassification (categorical Net Reclassification Index: 0.17; 95% CI: 0.09-0.26), with modest further improvement from adding echocardiographic measures. CONCLUSIONS:Preclinical HF measures indicate higher absolute HF risk within PREVENT-HF categories and enhance HF risk prediction.

Older (aged ≥55 years) kidney transplant (KT) recipients diagnosed with a sleep disorder after transplantation may be at increased risk for developing dementia. Using the United States Renal Data System/Medicare claims (2010-2020), we identified 16 573 older KT recipients with a functioning graft 1-year post-KT. First-time sleep disorders and newly prescribed sleep medications were ascertained within the first year post-KT. We used cause-specific hazard models to estimate the adjusted hazard ratio of diagnosed dementia with inverse probability of treatment weights. Overall, 3615 (21.8%) KT recipients were newly diagnosed with sleep disorders. Recipients diagnosed with a sleep disorder had a 1.32-fold increased risk for dementia (95% CI:1.15-1.51); those with insomnia had a 1.56-fold increased risk (95% CI:1.20-2.03). Of those diagnosed with insomnia, only 7.5% underwent cognitive behavioral therapy for insomnia. Of the recipients, 12.9% with a sleep disorder were prescribed sleep medications. Recipients prescribed sleep medication had a 1.44-fold increased risk for dementia (95% CI:1.16-1.77). Those prescribed zolpidem, the most commonly prescribed medication (80.1%), had a 1.41-fold increased risk (95% CI:1.12-1.78) for dementia; those prescribed other sleep medications had 3.13-fold (95% CI:1.41-6.98) increased risk for dementia. Post-KT sleep disorders are modifiable dementia risk factors; medication-associated dementia risk should be weighed against other therapies such as cognitive behavioral therapy for insomnia during management.

INTRODUCTION/BACKGROUND:Sleep, depression, stress, and neighborhood support are independently linked to cognition, but how these factors interact when sleep quality is poor remains understudied. METHODS:We analyzed cross-sectional baseline data from 233 adults aged ≥ 65 years in the Aging Adult Brain Connectome study. Sleep quality, depressive symptoms, stress, and neighborhood support were assessed with validated scales, and cognition was measured using the Preclinical Alzheimer's Cognitive Composite (PACC). Models tested two- and three-way interactions, adjusting for sociodemographics. RESULTS:Poor sleep quality was associated with lower PACC scores (β = -0.57, p = 0.002). This association was even more pronounced in older adults who also had depressive symptoms (β = -0.09, p < 0.001) or increased stress (β = -0.31, p < 0.001). This effect was attenuated by greater neighborhood support (interaction estimates 0.007-0.021, all p ≤ 0.014). DISCUSSION/CONCLUSIONS:Poor sleep quality was associated with lower cognition, compounded by psychosocial burden and buffered by neighborhood support. HIGHLIGHTS/CONCLUSIONS:Poor sleep quality worsened late-life cognitive performance in older adults. Depressive symptoms and stress further worsened the effect of poor sleep on cognitive performance. Neighborhood support buffered negative sleep-psychosocial impacts on cognitive performance.

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.