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Rationale: Identifying the root causes of racial disparities in childhood asthma is critical for health equity. Objectives: To determine whether the racist policy of redlining in the 1930s led to present-day disparities in childhood asthma by increasing community-level poverty and decreasing neighborhood socioeconomic position (SEP). Methods: We categorized census tracts at the birth address of participants from the Children's Respiratory and Environmental Workgroup birth cohort consortium into categories A, B, C, and D as defined by the Home Owners Loan Corporation, with D being the highest perceived risk. Surrogates of present-day neighborhood-level SEP were determined for each tract, including the percentage of low-income households, the CDC's Social Vulnerability Index, and other tract-level variables. We performed causal mediation analysis, which, under the assumption of no unmeasured confounding, estimates the direct and mediated pathways by which redlining may cause asthma disparities through tract-level mediators adjusting for individual-level covariates. Measurements and Main Results: Of 4,849 children, the cumulative incidence of asthma through age 11 was 26.6%, and 13.2% resided in census tracts with a Home Owners Loan Corporation grade of D. In mediation analyses, residing in Grade-D tracts (adjusted odds ratio = 1.03 [95% confidence interval = 1.01, 1.05]) was significantly associated with childhood asthma, with 79% of this increased risk mediated by percentage of low-income households; results were similar for the Social Vulnerability Index and other tract-level variables. Conclusions: The historical structural racist policy of redlining led to present-day asthma disparities in part through decreased neighborhood SEP. Policies aimed at reversing the effects of structural racism should be considered to create more just, equitable, and healthy communities. [ABSTRACT FROM AUTHOR]

Dietary flavanols are food constituents found in certain fruits and vegetables that have been linked to cognitive aging. Previous studies suggested that consumption of dietary flavanols might specifically be associated with the hippocampal-dependent memory component of cognitive aging and that memory benefits of a flavanol intervention might depend on habitual diet quality. Here, we tested these hypotheses in the context of a large-scale study of 3,562 older adults, who were randomly assigned to a 3-y intervention of cocoa extract (500 mg of cocoa flavanols per day) or a placebo [(COcoa Supplement and Multivitamin Outcomes Study) COSMOS-Web, NCT04582617]. Using the alternative Healthy Eating Index in all participants and a urine-based biomarker of flavanol intake in a subset of participants [n = 1,361], we show that habitual flavanol consumption and diet quality at baseline are positively and selectively correlated with hippocampal-dependent memory. While the prespecified primary end point testing for an intervention-related improvement in memory in all participants after 1 y was not statistically significant, the flavanol intervention restored memory among participants in lower tertiles of habitual diet quality or habitual flavanol consumption. Increases in the flavanol biomarker over the course of the trial were associated with improving memory. Collectively, our results allow dietary flavanols to be considered in the context of a depletion-repletion paradigm and suggest that low flavanol consumption can act as a driver of the hippocampal-dependent component of cognitive aging. [ABSTRACT FROM AUTHOR]

Aims: Cardiac arrhythmias have been associated with intense solar and geomagnetic activity (SGA) and exposures to air pollution.Methods and Results: We examined whether oscillations of SGA can modify the effect of hourly exposures to air pollutants on atrial fibrillation ≥30 s (AF) risk in patients with dual-chamber implantable cardioverter-defibrillators. The effects of SGA on ambient particulate matter <2.5 µm (PM2.5), black carbon (BC), ultrafine particles (PN), and associations with AF were assessed. Measures of SGA included solar wind proton density (SW), total interplanetary magnetic field strength (IMF), and Kp index, a measure of global geomagnetic activity. Overall time lags between 0 and 24 h, periods of increased SGA (>50th percentile in IMF, SW, and Kp index) enhanced the effects of all three air pollutants on AF, while during periods of reduced SGA the associations were considerably weaker or absent. During periods of intense SW 6 h prior to an AF event, the odds ratio (OR) for PM2.5 exposure per interquartile range (IQR) of 5.6 µg/m3 was 1.7 [95% confident interval (CI) 1.3-2.3, P = 0.0001]. For periods of reduced SW, the OR for PM2.5 exposure per IQR was 1.2 (95% CI 0.9-1.5; P = 0.27). There were similar effects for PN and BC exposures. In patients with multiple AF events per hour, the associations with air pollutants during intense SGA were even greater.Conclusion: The effects of air pollutants up to 24 h before AF events were enhanced during periods of increased SGA. Our results suggest that these effects may account for variation in AF risk. [ABSTRACT FROM AUTHOR]

Context: The effect of daily vitamin D supplementation on the serum concentration of vitamin D (the parent compound) may offer insight into vitamin D disposition. Objective: To assess the total serum vitamin D response to vitamin D3 supplementation and whether it varies according to participant characteristics. To compare results with corresponding results for total serum 25-hydroxyvitamin D [25(OH)D], which is used clinically and measured in supplementation trials. Design: Exploratory study within a randomized trial. Intervention: 2000 International Units of vitamin D3 per day (or matching placebo). Setting: Community-based. Participants: 161 adults (mean ± SD age 70 ± 6 years; 66% males) with type 2 diabetes. Main Outcome Measures: Changes in total serum vitamin D and total serum 25(OH)D concentrations from baseline to year 2. Results: At baseline, there was a positive, nonlinear relation between total serum vitamin D and total serum 25(OH)D concentrations. Adjusted effects of supplementation were a 29.2 (95% CI: 24.3, 34.1) nmol/L increase in serum vitamin D and a 33.4 (95% CI: 27.7, 39.2) nmol/L increase in serum 25(OH)D. Among those with baseline 25(OH)D < 50 compared with ≥ 50 nmol/L, the serum vitamin D response to supplementation was attenuated (15.7 vs 31.2 nmol/L; interaction P-value = 0.02), whereas the serum 25(OH)D response was augmented (47.9 vs 30.7 nmol/L; interaction P-value = 0.05). Conclusions: Vitamin D3 supplementation increases total serum vitamin D and 25(OH) D concentrations with variation according to baseline 25(OH)D, which suggests that 25-hydroxylation of vitamin D3 is more efficient when serum 25(OH)D concentration is low. [ABSTRACT FROM AUTHOR]

Rationale: Race-based estimates of pulmonary function in children could influence the evaluation of asthma in children from racial and ethnic minoritized backgrounds., Objectives: To determine if race-neutral (GLI-Global) versus race-specific (GLI-Race-Specific) reference equations differentially impact spirometry evaluation of childhood asthma., Methods: The analysis included 8,719 children aged 5 to <12 years from 27 cohorts across the United States grouped by parent-reported race and ethnicity. We analyzed how the equations affected forced expiratory volume in 1 second (FEV 1 ), forced vital capacity (FVC), and FEV 1 /FVC z-scores. We used multivariable logistic models to evaluate associations between z-scores calculated with different equations and asthma diagnosis, emergency department (ED) visits, and hospitalization., Measurements and Main Results: For Black children, the GLI-Global vs. Race-Specific equations estimated significantly lower z-scores for FEV 1 and FVC but similar values for FEV 1 /FVC, thus increasing the proportion of children classified with low FEV 1 by 14%. While both equations yielded strong inverse relationships between FEV 1 and FEV 1 /FVC z-scores and asthma outcomes, these relationships varied across racial and ethnic groups (p<0.05). For any given FEV 1 or FEV 1 /FVC z-score, asthma diagnosis and ED visits were higher among Black and Hispanic versus White children (p<0.05). For FEV 1 , GLI-Global equations estimated asthma outcomes that were more uniform across racial and ethnic groups., Conclusions: Parent-reported race and ethnicity influenced relationships between lung function and asthma outcomes. Our data show no advantage to race-specific equations for evaluating childhood asthma, and the potential for race-specific equations to obscure lung impairment in disadvantaged children strongly supports using race-neutral equations.

Place-based exposures, termed "geomarkers", are powerful determinants of health but are often understudied because of a lack of open data and integration tools. Existing DeGAUSS (Decentralized Geomarker Assessment for Multisite Studies) software has been successfully implemented in multi-site studies, ensuring reproducibility and protection of health information. However, DeGAUSS relies on transporting geomarker data, which is not feasible for high-resolution spatiotemporal data too large to store locally or download over the internet. We expanded the DeGAUSS framework for high-resolution spatiotemporal geomarkers. Our approach stores data subsets based on coarsened location and year in an online repository, and appropriate subsets are downloaded to complete exposure assessment locally using exact date and location. We created and validated two free and open-source DeGAUSS containers for estimation of high-resolution, daily ambient air pollutant exposures, transforming published exposure assessment models into computable exposures for geomarker assessment at scale., (©2023 AMIA - All rights reserved.)

Background: Reduced 25-hydroxyvitamin D (25[OH]D) metabolism and secondary hyperparathyroidism are common with lower estimated glomerular filtration rate (eGFR) and may contribute to cardiovascular disease and cancer risk., Methods: We assessed for heterogeneity by baseline eGFR of the effects of vitamin D 3 on cardiovascular and cancer outcomes in the Vitamin D and Omega-3 Trial (VITAL). Participants were randomized to 2000 IU vitamin D 3 and/or 1 g Ω -3 fatty acids daily using a placebo-controlled, two-by-two factorial design (5.3 years follow-up). Primary study end points were incident major cardiovascular events and invasive cancer. Changes in serum 25(OH)D and parathyroid hormone (PTH) were examined., Results: Baseline eGFR was available for 15,917 participants. Participants' mean age was 68 years, and 51% were women. Vitamin D 3 resulted in higher serum 25(OH)D compared with placebo (difference in change 12.5 ng/ml; 95% CI, 12 to 13.1 ng/ml), without heterogeneity by eGFR ( P interaction, continuous eGFR=0.2). Difference in change in PTH between vitamin D 3 and placebo was larger with lower eGFR ( P interaction=0.05): -6.9 (95% CI, -10.5 to -3.4), -5.8 (95% CI, -8.3 to -3.4), -4 (95% CI, -5.9 to -2.2), and -3.8 (95% CI, -5.6 to -2) pg/ml for eGFR <60, 60-74, 75-89, and ≥90 ml/min per 1.73 m 2 , respectively. Effects of vitamin D 3 supplementation on cardiovascular events ( P interaction=0.61) and cancer ( P interaction=0.89) did not differ by eGFR: HR=1.14 (95% CI, 0.73 to 1.79), HR=1.06 (95% CI, 0.75 to 1.5), HR=0.92 (95% CI, 0.67 to 1.25), and HR=0.92 (95% CI, 0.66 to 1.27) across eGFR categories for cardiovascular events and HR=1.63 (95% CI, 1.03 to 2.58), HR=0.85 (95% CI, 0.64 to 1.11), HR=0.84 (95% CI, 0.68 to 1.03), and 1.11 (95% CI, 0.92 to 1.35) for cancer, respectively., Conclusions: We observed no significant heterogeneity by baseline eGFR in the effects of vitamin D 3 supplementation versus placebo on cardiovascular or cancer outcomes, despite effects on 25(OH)D and PTH concentrations., Competing Interests: J.E. Buring reports that her spouse is on the scientific advisory board of Pharmavite, which provided pills for the trial. I.H. de Boer reports consultancy for AstraZeneca, Bayer, Boehringer-Ingelheim, Boehringer-Ingelheim/Lilly, Cyclerion Therapeutics, Ironwood Pharmaceuticals, George Clinical, Gilead, Goldfinch Bio, Medscape, and Otsuka; research funding from DexCom; honoraria from the National Institutes of Health; and an advisory or leadership role for the Clinical Journal of the American Society of Nephrology (deputy editor), Contemporary Clinical Trials (associate editor), and Kidney Disease Improving Global Outcomes (clinical practice guideline co-chair). A.N. Hoofnagle reports consultancy for Kilpatrick Townsend & Stockton LLP; ownership interest in Seattle Genetics; research funding from Waters; patents or royalties from SISCAPA Assay Technologies; an advisory or leadership role for Clinical Chemistry (associate editor); and other interests or relationships as an expert witness for Kilpatrick, Townsend, and Stockton, LLC. J.E. Manson reports research funding from the National Institutes of Health during the conduct of the study and grants from the National Institutes of Health outside the submitted work. M.L. Melamed reports consultancy for Guidepoint Global Consulting; an advisory or leadership role for the American Board of Internal Medicine Nephrology Exam Committee; and other interests or relationships with the New York Society of Nephrology. S. Mora reports consultancy for Pfizer, and an advisory or leadership role for the International Society of Atherosclerosis (treasurer). H.D. Sesso reports research funding from GSK Consumer Healthcare, Mars Edge, and Pure Encapsulations; and honoraria from BASF. R. Thadhani reports consultancy for Alnylum, Bayer, the US Food and Drug Administration Fresenius Medical Care North America, Kaneka, and Thermo Fisher Scientific; ownership interest in Aggamin LLC, Comanche Pharma, Hero Health, and Tvardi; research funding from Thermo Fisher Scientific; honoraria from Alnylum, Bayer, and Thermo Fisher Scientific; patents or royalties from Gravity Diagnostics, Thermo Fisher Scientific, and UpToDate; and an advisory or leadership role for Aggamin LLC and Vifor Pharma. L.R. Zelnick reports consultancy for the Veterans Medical Research Foundation, and an advisory or leadership role for the Clinical Journal of the American Society of Nephrology (statistical editor). All remaining authors have nothing to disclose., (Copyright © 2022 by the American Society of Nephrology.)

Importance: In the United States, Black and Hispanic children have higher rates of asthma and asthma-related morbidity compared with White children and disproportionately reside in communities with economic deprivation., Objective: To determine the extent to which neighborhood-level socioeconomic indicators explain racial and ethnic disparities in childhood wheezing and asthma., Design, Setting, and Participants: The study population comprised children in birth cohorts located throughout the United States that are part of the Children's Respiratory and Environmental Workgroup consortium. Cox proportional hazard models were used to estimate hazard ratios (HRs) of asthma incidence, and logistic regression was used to estimate odds ratios of early and persistent wheeze prevalence accounting for mother's education, parental asthma, smoking during pregnancy, child's race and ethnicity, sex, and region and decade of birth., Exposures: Neighborhood-level socioeconomic indicators defined by US census tracts calculated as z scores for multiple tract-level variables relative to the US average linked to participants' birth record address and decade of birth. The parent or caregiver reported the child's race and ethnicity., Main Outcomes and Measures: Prevalence of early and persistent childhood wheeze and asthma incidence., Results: Of 5809 children, 46% reported wheezing before age 2 years, and 26% reported persistent wheeze through age 11 years. Asthma prevalence by age 11 years varied by cohort, with an overall median prevalence of 25%. Black children (HR, 1.47; 95% CI, 1.26-1.73) and Hispanic children (HR, 1.29; 95% CI, 1.09-1.53) were at significantly increased risk for asthma incidence compared with White children, with onset occurring earlier in childhood. Children born in tracts with a greater proportion of low-income households, population density, and poverty had increased asthma incidence. Results for early and persistent wheeze were similar. In effect modification analysis, census variables did not significantly modify the association between race and ethnicity and risk for asthma incidence; Black and Hispanic children remained at higher risk for asthma compared with White children across census tracts socioeconomic levels., Conclusions and Relevance: Adjusting for individual-level characteristics, we observed neighborhood socioeconomic disparities in childhood wheeze and asthma. Black and Hispanic children had more asthma in neighborhoods of all income levels. Neighborhood- and individual-level characteristics and their root causes should be considered as sources of respiratory health inequities.

Aims: Cardiac arrhythmias have been associated with intense solar and geomagnetic activity (SGA) and exposures to air pollution., Methods and Results: We examined whether oscillations of SGA can modify the effect of hourly exposures to air pollutants on atrial fibrillation ≥30 s (AF) risk in patients with dual-chamber implantable cardioverter-defibrillators. The effects of SGA on ambient particulate matter <2.5 µm (PM2.5), black carbon (BC), ultrafine particles (PN), and associations with AF were assessed. Measures of SGA included solar wind proton density (SW), total interplanetary magnetic field strength (IMF), and Kp index, a measure of global geomagnetic activity. Overall time lags between 0 and 24 h, periods of increased SGA (>50th percentile in IMF, SW, and Kp index) enhanced the effects of all three air pollutants on AF, while during periods of reduced SGA the associations were considerably weaker or absent. During periods of intense SW 6 h prior to an AF event, the odds ratio (OR) for PM2.5 exposure per interquartile range (IQR) of 5.6 µg/m3 was 1.7 [95% confident interval (CI) 1.3-2.3, P = 0.0001]. For periods of reduced SW, the OR for PM2.5 exposure per IQR was 1.2 (95% CI 0.9-1.5; P = 0.27). There were similar effects for PN and BC exposures. In patients with multiple AF events per hour, the associations with air pollutants during intense SGA were even greater., Conclusion: The effects of air pollutants up to 24 h before AF events were enhanced during periods of increased SGA. Our results suggest that these effects may account for variation in AF risk., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions, please email: journals.permissions@oup.com.)