Faculty Bibliography

Context: Chemicals used in plastics have been described to contribute to disease and disability, but attributable fractions have not been quantified to assess specific contributions. Without this information, interventions proposed as part of the Global Plastics Treaty cannot be evaluated for potential benefits. Objective: To accurately inform the tradeoffs involved in the ongoing reliance on plastic production as a source of economic productivity in the United States, we calculated the attributable disease burden and cost due to chemicals used in plastic materials in 2018. Methods: We first analyzed the existing literature to identify plastic-related fractions (PRF) of disease and disability for specific polybrominated diphenylethers (PBDE), phthalates, bisphenols, and polyfluoroalkyl substances and perfluoroalkyl substances (PFAS). We then updated previously published disease burden and cost estimates for these chemicals in the United States to 2018. By uniting these data, we computed estimates of attributable disease burden and costs due to plastics in the United States. Results: We identified PRFs of 97.5% for bisphenol A (96.25-98.75% for sensitivity analysis), 98% (96%-99%) for di-2-ethylhexylphthalate, 100% (71%-100%) for butyl phthalates and benzyl phthalates, 98% (97%-99%) for PBDE-47, and 93% (16%-96%) for PFAS. In total, we estimate $249 billion (sensitivity analysis: $226 billion-$289 billion) in plastic-attributable disease burden in 2018. The majority of these costs arose as a result of PBDE exposure, though $66.7 billion ($64.7 billion-67.3 billion) was due to phthalate exposure and $22.4 billion was due to PFAS exposure (sensitivity analysis: $3.85-$60.1 billion). Conclusion: Plastics contribute substantially to disease and associated social costs in the United States, accounting for 1.22% of the gross domestic product. The costs of plastic pollution will continue to accumulate as long as exposures continue at current levels. Actions through the Global Plastics Treaty and other policy initiatives will reduce these costs in proportion to the actual reductions in chemical exposures achieved.

IMPORTANCE/UNASSIGNED:Despite increasing obesity rates in adolescents, data regarding early kidney sequelae are lacking. OBJECTIVE/UNASSIGNED:To assess the association between adolescent body mass index (BMI) and early chronic kidney disease (CKD) in young adulthood (<45 years of age). DESIGN, SETTING, AND PARTICIPANTS/UNASSIGNED:This cohort study linked screening data of mandatory medical assessments of Israeli adolescents to data from a CKD registry of a national health care system. Adolescents who were aged 16 to 20 years; born since January 1, 1975; medically evaluated for mandatory military service through December 31, 2019; and insured by Maccabi Healthcare Services were assessed. Individuals with kidney pathology, albuminuria, hypertension, dysglycemia, or missing blood pressure or BMI data were excluded. Body mass index was calculated as weight in kilograms divided by height in meters squared and categorized by age- and sex-matched percentiles according to the US Centers for Disease Control and Prevention. Follow-up started at the time of medical evaluation or January 1, 2000 (whichever came last), and ended at early CKD onset, death, the last day insured, or August 23, 2020 (whichever came first). Data analysis was performed from December 19, 2021, to September 11, 2023. MAIN OUTCOMES AND MEASURES/UNASSIGNED:Early CKD, defined as stage 1 to 2 CKD by moderately or severely increased albuminuria, with an estimated glomerular filtration rate of 60 mL/min/1.73 m2 or higher. RESULTS/UNASSIGNED:Of 629 168 adolescents evaluated, 593 660 (mean [SD] age at study entry, 17.2 [0.5] years; 323 293 [54.5%] male, 270 367 [45.5%] female) were included in the analysis. During a mean (SD) follow-up of 13.4 (5.5) years for males and 13.4 (5.6) years for females, 1963 adolescents (0.3%) developed early CKD. Among males, the adjusted hazard ratios were 1.8 (95% CI, 1.5-2.2) for adolescents with high-normal BMI, 4.0 (95% CI, 3.3-5.0) for those with overweight, 6.7 (95% CI, 5.4-8.4) for those with mild obesity, and 9.4 (95% CI, 6.6-13.5) for those with severe obesity. Among females, the hazard ratios were 1.4 (95% CI, 1.2-1.6) for those with high-normal BMI, 2.3 (95% CI, 1.9-2.8) for those with overweight, 2.7 (95% CI, 2.1-3.6) for those with mild obesity, and 4.3 (95% CI, 2.8-6.5) for those with severe obesity. The results were similar when the cohort was limited to individuals who were seemingly healthy as adolescents, individuals surveyed up to 30 years of age, or those free of diabetes and hypertension at the end of the follow-up. CONCLUSIONS AND RELEVANCE/UNASSIGNED:In this cohort study, high BMI in late adolescence was associated with early CKD in young adulthood. The risk was also present in seemingly healthy individuals with high-normal BMI and before 30 years of age, and a greater risk was seen among those with severe obesity. These findings underscore the importance of mitigating adolescent obesity rates and managing risk factors for kidney disease in adolescents with high BMI.

Virtual care, including synchronous and asynchronous telehealth, remote patient monitoring, and the collection and interpretation of patient-generated health data (PGHD), has the potential to transform healthcare delivery and increase access to care. The Veterans Health Administration (VHA) Office of Health Services Research and Development (HSR&D) convened a State-of-the-Art (SOTA) Conference on Virtual Care to identify future virtual care research priorities. Participants were divided into three workgroups focused on virtual care access, engagement, and outcomes. In this article, we report the findings of the Outcomes Workgroup. The group identified virtual care outcome areas with sufficient evidence, areas in need of additional research, and areas that are particularly well-suited to be studied within VHA. Following a rigorous process of literature review and consensus, the group focused on four questions: (1) What outcomes of virtual care should we be measuring and how should we measure them?; (2) how do we choose the "right" care modality for the "right" patient?; (3) what are potential consequences of virtual care on patient safety?; and (4) how can PGHD be used to benefit provider decision-making and patient self-management?. The current article outlines key conclusions that emerged following discussion of these questions, including recommendations for future research.

Rapidly advancing evidence documents that a broad array of synthetic chemicals found ubiquitously in the environment contribute to disease and disability across the lifespan. Although the early literature focused on early life exposures, endocrine-disrupting chemicals (EDCs) are now understood to contribute substantially to chronic disease in adulthood, especially metabolic, cardiovascular, and reproductive consequences as well as endocrine cancers. The contribution to mortality is substantial, with over 90,000 deaths annually and at least $39 billion/year in lost economic productivity in the United States (US) due to exposure to certain phthalates that are used as plasticizers in food packaging. Importantly, exposures are disproportionately high in low-income and minoritized populations, driving disparities in these conditions. Though non-Hispanic Blacks and Mexican Americans comprise 12.6% and 13.5% of the US population, they bear 16.5% and 14.6% of the disease burden due to EDCs, respectively. Many of these exposures can be modified through safe and simple behavioral changes supported by proactive government action to both limit known hazardous exposures and to proactively screen new industrial chemicals prior to their use. Routine healthcare maintenance should include guidance to reduce EDC exposures, and a recent report by the Institute of Medicine suggests that testing be conducted, particularly in populations heavily exposed to perfluoroalkyl substances-chemicals used in nonstick coatings as well as oil- and water-resistant clothing.

OBJECTIVE:To evaluate the efficacy of a multimodal intervention in reducing CT pulmonary angiography (CTPA) overutilization in the evaluation of suspected pulmonary embolism in the emergency department (ED). METHODS:Previous mixed-methods analysis of barriers to guideline-concordant CTPA ordering results was used to develop a provider-focused behavioral intervention consisting of a clinical decision support tool and an audit and feedback system at a multisite, tertiary academic network. The primary outcome (guideline concordance) and secondary outcomes (yield and CTPA and D-dimer order rates) were compared using a pre- and postintervention design. ED encounters for adult patients from July 5, 2017, to January 3, 2019, were included. Fisher's exact tests and statistical process control charts were used to compare the pre- and postintervention groups for each outcome. RESULTS:Of the 201,912 ED patient visits evaluated, 3,587 included CTPA. Guideline concordance increased significantly after the intervention, from 66.9% to 77.5% (P < .001). CTPA order rate and D-dimer order rate also increased significantly, from 17.1 to 18.4 per 1,000 patients (P = .035) and 30.6 to 37.3 per 1,000 patients (P < .001), respectively. Percent yield showed no significant change (12.3% pre- versus 10.8% postintervention; P = .173). Statistical process control analysis showed sustained special-cause variation in the postintervention period for guideline concordance and D-dimer order rates, temporary special-cause variation for CTPA order rates, and no special-cause variation for percent yield. CONCLUSION/CONCLUSIONS:Our success in increasing guideline concordance demonstrates the efficacy of a mixed-methods, human-centered approach to behavior change. Given that neither of the secondary outcomes improved, our results may demonstrate potential limitations to the guidelines directing the ordering of CTPA studies and D-dimer ordering.

OBJECTIVE/UNASSIGNED:HbA1c is an insensitive marker for assessing real-time dysglycemia in obesity. This study investigated whether 1-h plasma glucose level (1-h PG) ≥155 mg/dL (8.6 mmol/L) during an oral glucose tolerance test (OGTT) and continuous glucose monitoring (CGM) measurement of glucose variability (GV) better reflected dysglycemia than HbA1c after weight loss from metabolic and bariatric surgery. METHODS/UNASSIGNED:This was a prospective cohort study of 10 participants with type 2 diabetes compared with 11 participants with non-diabetes undergoing sleeve gastrectomy (SG). At each research visit; before SG, and 6 weeks and 6 months post-SG, body weight, fasting lipid levels, and PG and insulin concentrations during an OGTT were analyzed. Mean amplitude of glycemic excursions (MAGE), a CGM-derived GV index, was analyzed. RESULTS/UNASSIGNED:-cell function, remained reduced in the diabetes group when compared to the non-diabetes group. CONCLUSIONS/UNASSIGNED:-cell dysfunction and the potential residual risk of diabetes complications.

BACKGROUND:This study aimed to identify contextual factors associated with life satisfaction during the COVID-19 pandemic for adolescents with mental, emotional, behavioral, and developmental (MEBD) disabilities. METHODS:Data were collected from a sample of 1084 adolescents aged 11-21 years from April 2020 to August 2021. This cross-sectional study used a sequential machine learning workflow, consisting of random forest regression and evolutionary tree regression, to identify subgroups of adolescents in the Environmental influences on Child Health Outcomes (ECHO) consortium who demonstrated enhanced vulnerability to lower life satisfaction as described by intersecting risk factors, protective factors, and MEBD disabilities. RESULTS:Adolescents with a history of depression, anxiety, autism, and attention-deficit/hyperactivity disorder were particularly susceptible to decreased life satisfaction in response to unique combinations of stressors experienced during the COVID-19 pandemic. These stressors included decreased social connectedness, decreased family engagement, stress related to medical care access, pandemic-related traumatic stress, and single-caregiver households. CONCLUSION/CONCLUSIONS:Findings from this study highlight the importance of interventions aimed specifically at increasing adolescent social connectedness, family engagement, and access to medical support for adolescents with MEBD disabilities, particularly in the face of stressors, such as a global pandemic. IMPACT/CONCLUSIONS:Through a machine learning process, we identified contextualized risks associated with life satisfaction among adolescents with neurodevelopmental disabilities during the COVID-19 pandemic. The COVID-19 pandemic resulted in large-scale social disruptions for children and families. Such disruptions were associated with worse mental health outcomes in the general pediatric population, but few studies have examined specific subgroups who may be at heightened risk. We endeavored to close that gap in knowledge. This study highlights the importance of social connectedness, family engagement, and access to medical support as contributing factors to life satisfaction during the COVID-19 pandemic for adolescents with neurodevelopmental disabilities.

The prevalence of youth-onset type 2 diabetes (T2D) and childhood obesity has been rising steadily¹, producing a growing public health concern¹ that disproportionately affects minority groups². The genetic basis of youth-onset T2D and its relationship to other forms of diabetes are unclear³. Here we report a detailed genetic characterization of youth-onset T2D by analysing exome sequences and common variant associations for 3,005 individuals with youth-onset T2D and 9,777 adult control participants matched for ancestry, including both males and females. We identify monogenic diabetes variants in 2.4% of individuals and three exome-wide significant (P < 2.6 × 10^-6) gene-level associations (HNF1A, MC4R, ATXN2L). Furthermore, we report rare variant association enrichments within 25 gene sets related to obesity, monogenic diabetes and β-cell function. Many youth-onset T2D associations are shared with adult-onset T2D, but genetic risk factors of all frequencies-and rare variants in particular-are enriched within youth-onset T2D cases (5.0-fold increase in the rare variant and 3.4-fold increase in common variant genetic liability relative to adult-onset cases). The clinical presentation of participants with youth-onset T2D is influenced in part by the frequency of genetic risk factors within each individual. These findings portray youth-onset T2D as a heterogeneous disease situated on a spectrum between monogenic diabetes and adult-onset T2D.