Area-Level Social Vulnerability and Severe COVID-19: A Case-Control Study Using Electronic Health Records from Multiple Health Systems in the Southeastern Pennsylvania Region.

Knowledge about neighborhood characteristics that predict disease burden can be used to guide equity-based public health interventions or targeted social services. We used a case-control design to examine the association between area-level social vulnerability and severe COVID-19 using electronic health records (EHR) from a regional health information hub in the greater Philadelphia region. Severe COVID-19 cases (n = 15,464 unique patients) were defined as those with an inpatient admission and a diagnosis of COVID-19 in 2020. Controls (n = 78,600; 5:1 control-case ratio) were a random sample of individuals who did not have a COVID-19 diagnosis from the same geographic area. Retrospective data on comorbidities and demographic variables were extracted from EHR and linked to area-level social vulnerability index (SVI) data using ZIP codes. Models adjusted for different sets of covariates showed incidence rate ratios (IRR) ranging from 1.15 (95% CI, 1.13-1.17) in the model adjusted for individual-level age, sex, and marital status to 1.09 (95% CI, 1.08-1.11) in the fully adjusted model, which included individual-level comorbidities and race/ethnicity. The fully adjusted model indicates that a 10% higher area-level SVI was associated with a 9% higher risk of severe COVID-19. Individuals in neighborhoods with high social vulnerability were more likely to have severe COVID-19 after accounting for comorbidities and demographic characteristics. Our findings support initiatives incorporating neighborhood-level social determinants of health when planning interventions and allocating resources to mitigate epidemic respiratory diseases, including other coronavirus or influenza viruses.

Serum zinc concentration and dietary zinc intake in relation to cognitive function: an analysis of the REasons for Geographic and Racial Differences in Stroke (REGARDS) cohort.

PURPOSE: There are several pathways by which zinc may be a modifiable factor to slow age-related cognitive decline. We investigated the associations between serum and dietary zinc and cognitive impairment in a longitudinal cohort. METHODS: We used data from the REasons for Geographic and Racial Differences in Stroke (REGARDS) Cohort (n = 30,239) and the REGARDS Trace Element Study (n = 2666). Baseline serum zinc concentrations (2003-2007) were measured using inductively coupled plasma mass spectrometry. Baseline dietary zinc intake was measured via the Block food frequency questionnaire. Serum zinc concentrations and dietary zinc intake were categorized into quartiles. The outcome of interest was impairment on the Six-Item Screener (SIS), a measure of global cognitive functioning administered annually. The Enhanced Cognitive Battery (ECB), a more comprehensive series of tests assessing memory and fluency, was administered every two years and considered a secondary outcome. Associations between zinc and incident impairment were assessed using multivariable logistic regression. RESULTS: Among 2065 participants with serum zinc data, 184 individuals developed impairment over 10 years of follow-up. In adjusted models, there was no significant association between serum zinc and impairment as assessed by the SIS or the ECB. Among 18,103 participants who had dietary data, 1424 experienced incident impairment on the SIS. Dietary zinc intake was not significantly associated with impairment as assessed by the SIS or the ECB in adjusted models. CONCLUSION: Findings from this U.S. cohort did not support the hypothesis that serum zinc concentration or dietary zinc intake is associated with the risk of cognitive impairment.

Teaching children pedestrian safety in virtual reality via smartphone: a noninferiority randomized clinical trial.

OBJECTIVE: To evaluate whether child pedestrian safety training in a smartphone-based virtual reality (VR) environment is not inferior to training in a large, semi-immersive VR environment with demonstrated effectiveness. METHODS: Five hundred 7- and 8-year-old children participated; 479 were randomized to one of two conditions: Learning to cross streets in a smartphone-based VR or learning in a semi-immersive kiosk VR. The systems used identical virtual environments and scenarios. At baseline, children's pedestrian skills were assessed in both VR systems and through a vehicle approach estimation task (judging speed/distance of oncoming traffic on monitor). Training in both conditions comprised at least six 30-min sessions in the randomly assigned VR platform and continued for up to 25 visits until adult-level proficiency was obtained. Following training and again 6 months later, children completed pedestrian safety assessments identical to baseline. Three outcomes were considered from assessments in each VR platform: Unsafe crossings (collisions plus close calls), time to contact (shortest time between child and oncoming simulated traffic), and missed opportunities (unselected safe opportunities to cross). RESULTS: Participants achieved adult-level street-crossing skill through VR training. Training in a smartphone-based VR system was generally not inferior to training in a large semi-immersive VR system. There were no adverse effects. CONCLUSIONS: Seven- and 8-year-old children can learn pedestrian safety through VR-based training, including training in a smartphone-based VR system. Combined with recent meta-analytic results, the present findings support broad implementation and dissemination of child pedestrian safety training through VR, including smartphone-based VR systems.

Rural versus Urban Residence in Adulthood and Incident Cognitive Impairment.

INTRODUCTION: Rural versus urban living is a social determinant of cognitive health. We estimated the association of rural versus urban residence in the USA with incident cognitive impairment (ICI) and assessed effect heterogeneity by sociodemographic, behavioral, and clinical factors. METHODS: The Reasons for Geographic and Racial Differences in Stroke Study (REGARDS) is a population-based prospective observational cohort of 30,239 adults, 57% female, 36% Black, aged 45+ years, sampled from 48 contiguous states in the USA in 2003-2007. We analyzed 20,878 participants who at baseline were cognitively intact with no history of stroke and had ICI assessed on average 9.4 years later. We classified participants' home addresses at baseline as urban (population ≥50,000), large rural (10,000-49,999), or small rural (≤9,999) by Rural-Urban Commuting Area codes. We defined ICI as ≥1.5 SD below the mean on at least 2 of the following tests: word list learning, word list delayed recall, and animal naming. RESULTS: Participants' home addresses were 79.8% urban, 11.7% large rural, and 8.5% small rural. ICI occurred in 1,658 participants (7.9%). Small rural residents had higher odds of ICI than urban residents, adjusted for age, sex, race, region, and education (OR = 1.34 [95% CI: 1.10, 1.64]), and after further adjustment for income, health behaviors, and clinical characteristics (OR = 1.24 [95% CI: 1.02, 1.53]). Former smoking versus never, nondrinking versus light alcohol drinking, no exercise versus ≥4 times/week, CES-D depressive symptom score of 2 versus 0, and fair versus excellent self-rated health had stronger associations with ICI in small rural areas than in urban areas. For example, in urban areas, lack of exercise was not associated with ICI (OR = 0.90 [95% CI: 0.77, 1.06]); however, lack of exercise combined with small rural residence was associated with 1.45 times the odds of ICI compared with ≥4 bouts of exercise/week in urban areas (95% CI: 1.03, 2.03). Overall, large rural residence was not associated with ICI; however, black race, hypertension, and depressive symptoms had somewhat weaker associations with ICI, and heavy alcohol drinking a stronger association with ICI, in large rural areas than in urban areas. CONCLUSION: Small rural residence was associated with ICI among USA adults. Further research to better understand why rural residents are at higher risk for developing ICI and mechanisms to ameliorate that risk will support efforts to advance rural public health.

Associations between PM2.5 and O3 exposures and new onset type 2 diabetes in regional and national samples in the United States.

BACKGROUND: Exposure to particulate matter ≤2.5 µm in diameter (PM2.5) and ozone (O3) has been linked to numerous harmful health outcomes. While epidemiologic evidence has suggested a positive association with type 2 diabetes (T2D), there is heterogeneity in findings. We evaluated exposures to PM2.5 and O3 across three large samples in the US using a harmonized approach for exposure assignment and covariate adjustment. METHODS: Data were obtained from the Veterans Administration Diabetes Risk (VADR) cohort (electronic health records [EHRs]), the Reasons for Geographic and Racial Disparities in Stroke (REGARDS) cohort (primary data collection), and the Geisinger health system (EHRs), and reflect the years 2003-2016 (REGARDS) and 2008-2016 (VADR and Geisinger). New onset T2D was ascertained using EHR information on medication orders, laboratory results, and T2D diagnoses (VADR and Geisinger) or report of T2D medication or diagnosis and/or elevated blood glucose levels (REGARDS). Exposure was assigned using pollutant annual averages from the Downscaler model. Models stratified by community type (higher density urban, lower density urban, suburban/small town, or rural census tracts) evaluated likelihood of new onset T2D in each study sample in single- and two-pollutant models of PM2.5 and O3. RESULTS: In two pollutant models, associations of PM2.5, and new onset T2D were null in the REGARDS cohort except for in suburban/small town community types in models that also adjusted for NSEE, with an odds ratio (95% CI) of 1.51 (1.01, 2.25) per 5 µg/m3 of PM2.5. Results in the Geisinger sample were null. VADR sample results evidenced nonlinear associations for both pollutants; the shape of the association was dependent on community type. CONCLUSIONS: Associations between PM2.5, O3 and new onset T2D differed across three large study samples in the US. None of the results from any of the three study populations found strong and clear positive associations.

Assessing the association between food environment and dietary inflammation by community type: a cross-sectional REGARDS study.

BACKGROUND: Communities in the United States (US) exist on a continuum of urbanicity, which may inform how individuals interact with their food environment, and thus modify the relationship between food access and dietary behaviors. OBJECTIVE: This cross-sectional study aims to examine the modifying effect of community type in the association between the relative availability of food outlets and dietary inflammation across the US. METHODS: Using baseline data from the REasons for Geographic and Racial Differences in Stroke study (2003-2007), we calculated participants' dietary inflammation score (DIS). Higher DIS indicates greater pro-inflammatory exposure. We defined our exposures as the relative availability of supermarkets and fast-food restaurants (percentage of food outlet type out of all food stores or restaurants, respectively) using street-network buffers around the population-weighted centroid of each participant's census tract. We used 1-, 2-, 6-, and 10-mile (~ 2-, 3-, 10-, and 16 km) buffer sizes for higher density urban, lower density urban, suburban/small town, and rural community types, respectively. Using generalized estimating equations, we estimated the association between relative food outlet availability and DIS, controlling for individual and neighborhood socio-demographics and total food outlets. The percentage of supermarkets and fast-food restaurants were modeled together. RESULTS: Participants (n = 20,322) were distributed across all community types: higher density urban (16.7%), lower density urban (39.8%), suburban/small town (19.3%), and rural (24.2%). Across all community types, mean DIS was - 0.004 (SD = 2.5; min = - 14.2, max = 9.9). DIS was associated with relative availability of fast-food restaurants, but not supermarkets. Association between fast-food restaurants and DIS varied by community type (P for interaction = 0.02). Increases in the relative availability of fast-food restaurants were associated with higher DIS in suburban/small towns and lower density urban areas (p-values < 0.01); no significant associations were present in higher density urban or rural areas. CONCLUSIONS: The relative availability of fast-food restaurants was associated with higher DIS among participants residing in suburban/small town and lower density urban community types, suggesting that these communities might benefit most from interventions and policies that either promote restaurant diversity or expand healthier food options.

Duration of employment within occupations and incident stroke in a US general population cohort 45 years of age or older (REGARDS study).

BACKGROUND: The work environment can contribute to the risk of cardiovascular diseases (CVD) including stroke. Our objective was to identify occupations with elevated risk of stroke within the Reasons for Geographic and Racial Differences in Stroke (REGARDS) cohort. METHODS: We analyzed incident stroke outcomes (ischemic and hemorrhagic strokes) from 2003 to 2020 and employment characteristics of 13,659 adults aged ≥45 years enrolled in a national population-based cohort study. Using a modified Poisson regression approach, we estimated the relative risks (RRs) and the associated 95% confidence intervals (CI) of stroke in relation to years of employment within each occupation coded using the US Census two-digit Standard Occupation Code. Models were adjusted for Framingham Stroke Risk Score, region, race, age, and body mass index. We conducted stratified analysis by sex, employment time period (pre-1975 vs. post-1975), and region. RESULTS: Workers in the following occupations had a greater risk of stroke with longer duration of employment (per decade): protective service (RR: 2.35, 95% CI: 1.11, 4.97), food preparation and service (RR: 1.51, 95% CI: 1.05, 2.19), and transportation and material moving (RR: 1.30, 95% CI: 1.00, 1.69). The stroke risk in these occupations was disproportionately elevated in men, and differed by region and employment time period. CONCLUSIONS: Longer employment in protective service, food preparation and serving, and transportation and materials moving occupations may increase the risk of stroke. Surveillance may uncover specific work-related risk factors in these occupations, leading to interventions to reduce the burden of stroke among US workers.

Comparing Global and Spatial Composite Measures of Neighborhood Socioeconomic Status Across US Counties.

Area-level neighborhood socioeconomic status (NSES) is often measured without consideration of spatial autocorrelation and variation. In this paper, we compared a non-spatial NSES measure to a spatial NSES measure for counties in the USA using principal component analysis and geographically weighted principal component analysis (GWPCA), respectively. We assessed spatial variation in the loadings using a Monte Carlo randomization test. The results indicated that there was statistically significant variation (p = 0.004) in the loadings of the spatial index. The variability of the census variables explained by the spatial index ranged from 60 to 90%. We found that the first geographically weighted principal component explained the most variability in the census variables in counties in the Northeast and the West, and the least variability in counties in the Midwest. We also tested the two measures by assessing the associations with county-level diabetes prevalence using data from the CDC's US Diabetes Surveillance System. While associations of the two NSES measures with diabetes did not differ for this application, the descriptive results suggest that it might be important to consider a spatial index over a global index when constructing national county measures of NSES. The spatial approach may be useful in identifying what factors drive the socioeconomic status of a county and how they vary across counties. Furthermore, we offer suggestions on how a GWPCA-based NSES index may be replicated for smaller geographic scopes.

The associations between prenatal phthalate exposure measured in child meconium and cognitive functioning of 12-month-old children in two cohorts at elevated risk for adverse neurodevelopment.

BACKGROUND: Phthalate metabolites in gestational-maternal urine represents short-term maternal exposure, but meconium, the newborn's first stool may better capture cumulative fetal exposure. We quantified phthalate metabolites in meconium from two cohorts of children at higher risk of adverse neurodevelopment and evaluated associations with their cognitive function at 12 months. METHODS: Meconium phthalate metabolites were quantified in the Safe Passage Study (SPS), N = 720, a pregnancy cohort with high community-levels of prenatal alcohol use, and the Early Autism Risk Longitudinal Investigation (EARLI), N = 236, a high familial autism risk pregnancy cohort. EARLI also had second and third trimester (T2/T3) maternal urine for exposure assessment. Molar sum of di (2-ethylhexyl) (∑DEHP) metabolites and an anti-androgenic score (AAS) using mono-isobutyl, mono-n-butyl, monobenzyl (MBZP), and DEHP metabolites were computed. Cognitive function was assessed at 12 months using the Mullen Scales of Early Learning-Composite (ELC). Multivariable linear regression assessed associations between loge-transformed metabolites and ELC. Quadratic terms explored nonlinearity and interaction terms of metabolite by child's sex examined effect modification. RESULTS: In SPS, MBzP (ßLinear = -6.73; 95% CI: 12.04, -1.42; ßquadratic = 1.95; 0.27, 3.62) and mono (2-ethyl-5-carboxypentyl), (ßLinear = -3.81; -7.53, -0.27; ßquadratic = 0.93; 0.09, 1.77) had U-shaped associations with ELC. In EARLI, T2 urine mono-carboxyisononyl was associated with linear decrease in ELC, indicating lower cognitive function. Interaction with sex was suggested (P < 0.2) for several urine metabolites, mostly indicating negative association between phthalates and ELC among girls but reversed among boys. Only mono-isononyl phthalate and ∑DEHP had consistent main effect associations across matrixes and cohorts, but similar interaction with sex was observed for meconium-measured ∑DEHP, AAS, MBzP, and mono (2-ethylhexyl) in both cohorts. CONCLUSIONS: Few phthalate metabolites were consistently associated with children's cognitive function, but a similar set of meconium metabolites from both cohorts displayed sex-specific associations. Gestational phthalate exposure may have sexually-dimorphic associations with early cognitive function in children at higher risk for adverse neurodevelopment.

Forty-Year Shifting Distribution of Systolic Blood Pressure With Population Hypertension Treatment and Control.

BACKGROUND: Hypertension awareness, treatment, and control programs were initiated in the United States during the 1960s and 1970s. Whereas blood pressure (BP) control in the population and subsequent reduced hypertension-related disease risks have improved since the implementation of these interventions, it is unclear whether these BP changes can be generalized to diverse and high-risk populations. This report describes the 4-decade change in BP levels for the population in a high disease risk southeastern region of the United States. The objective is to determine the magnitude of the shift in systolic BP (SBP) among Blacks and Whites from the Southeast between 1960 and 2005 with the assessment of the unique population cohorts. METHODS: A multicohort study design compared BPs from the CHS (Charleston Heart Study) and ECHS (Evans County Heart Study) in 1960 and the REGARDS study (Reasons for Geographic and Racial Differences in Stroke) 4 decades later. The analyses included participants ≥45 years of age from CHS (n=1323), ECHS (n=1842), and REGARDS (n=6294) with the main outcome of SBP distribution. RESULTS: Among Whites 45 to 54 years of age, the median SBP was 18 mm Hg (95% CI, 16-21 mm Hg) lower in 2005 than 1960. The median shift was a 45 mm Hg (95% CI, 37-51 mm Hg) decline for those ≥75 years of age. The shift was larger for Blacks, with median declines of 38 mm Hg (95% CI, 32-40 mm Hg) at 45 to 54 years of age and 50 mm Hg (95% CI, 33-60 mm Hg) for ages ≥75 years. The 95th percentile of SBP decreased 60 mm Hg for Whites and 70 mm Hg for Blacks. CONCLUSIONS: The results of the current analyses of the unique cohorts in the Southeast confirm the improvements in population SBP levels since 1960. This assessment provides new evidence of improvement in SBP, suggesting that strategies and programs implemented to improve hypertension treatment and control have been extraordinarily successful for both Blacks and Whites residing in a high-risk region of the United States. Severe BP elevations commonly observed in the 1960s have been nearly eliminated, with the current 75th percentile of BP generally less than the 25th percentile of BP in 1960.

Serum Zinc Levels and Incidence of Ischemic Stroke: The Reasons for Geographic and Racial Differences in Stroke Study.

BACKGROUND AND PURPOSE: Despite zinc's role as an antioxidant and anti-inflammatory agent, prospective studies relating zinc levels to ischemic stroke risk are lacking. To examine the association between serum zinc levels and incidence of ischemic stroke in a US population. METHODS: Using a case-cohort study nested within the Reasons for Geographic and Racial Differences in Stroke cohort, participants were randomly selected from the Reasons for Geographic and Racial Differences in Stroke cohort to generate a sub-cohort (n=2346). All incident ischemic stroke cases as of September 2012 (n=660) were included, with 62 incident cases overlapping in the sub-cohort. Serum zinc levels were measured at baseline. Barlow-weighted Cox's proportional hazards regression models were used to calculate multivariable-adjusted hazard ratios and the corresponding 95% CI of ischemic stroke by serum zinc levels. RESULTS: The median zinc level for the sub-cohort was 121.19 µg/dL (interquartile range, 104.86-140.39 µg/dL). Serum zinc levels were inversely associated with incidence of ischemic stroke after adjustment for potential confounders (quartile 4 versus quartile 1: hazard ratio, 0.78 [95% CI, 0.61-0.98], P=0.03 for trend). When stratified by prespecified factors (sex, race, region), only sex showed a significant modification (P=0.03 for interaction). The inverse association was more pronounced among females (quartile 4 versus quartile 1: hazard ratio, 0.58 [95% CI, 0.41-0.84], P<0.01 for trend) than males (quartile 4 versus quartile 1: hazard ratio, 1.08 [95% CI, 0.78-1.51], P=0.92 for trend). CONCLUSIONS: Serum zinc concentration was inversely associated with incidence of ischemic stroke, especially among women, indicating that low zinc levels may be a risk factor for ischemic stroke.

Lifecourse socioeconomic position and diabetes incidence in the REasons for Geographic and Racial Differences in Stroke (REGARDS) study, 2003 to 2016.

Low socioeconomic position (SEP) across the lifecourse is associated with Type 2 diabetes (T2DM). We examined whether these economic disparities differ by race and sex. We included 5448 African American (AA) and white participants aged ≥45 years from the national (United States) REasons for Geographic and Racial Differences in Stroke (REGARDS) cohort without T2DM at baseline (2003-07). Incident T2DM was defined by fasting glucose ≥126 mg/dL, random glucose ≥200 mg/dL, or using T2DM medications at follow-up (2013-16). Derived SEP scores in childhood (CSEP) and adulthood (ASEP) were used to calculate a cumulative (CumSEP) score. Social mobility was defined as change in SEP. We fitted race-stratified logistic regression models to estimate the association between each lifecourse SEP indicator and T2DM, adjusting for covariates; additionally, we tested SEP-sex interactions. Over a median of 9.0 (range 7-14) years of follow-up, T2DM incidence was 167.1 per 1000 persons among AA and 89.9 per 1000 persons among white participants. Low CSEP was associated with T2DM incidence among AA (OR = 1.61; 95%CI 1.05-2.46) but not white (1.06; 0.74-2.33) participants; this was attenuated after adjustment for ASEP. In contrast, low CumSEP was associated with T2DM incidence for both racial groups. T2DM risk was similar for stable low SEP and increased for downward mobility when compared with stable high SEP in both groups, whereas upward mobility increased T2DM risk among AAs only. No differences by sex were observed. Among AAs, low CSEP was not independently associated with T2DM, but CSEP may shape later-life experiences and health risks.

Correlates of a southern diet pattern in a national cohort study of blacks and whites: the REasons for Geographic And Racial Differences in Stroke (REGARDS) study.

The Southern dietary pattern, derived within the REasons for Geographic And Racial Differences in Stroke (REGARDS) cohort, is characterised by high consumption of added fats, fried food, organ meats, processed meats and sugar-sweetened beverages and is associated with increased risk of several chronic diseases. The aim of the present study was to identify characteristics of individuals with high adherence to this dietary pattern. We analysed data from REGARDS, a national cohort of 30 239 black and white adults ≥45 years of age living in the USA. Dietary data were collected using the Block 98 FFQ. Multivariable linear regression was used to calculate standardised beta coefficients across all covariates for the entire sample and stratified by race and region. We included 16 781 participants with complete dietary data. Among these, 34·6 % were black, 45·6 % male, 55·2 % resided in stroke belt region and the average age was 65 years. Black race was the factor with the largest magnitude of association with the Southern dietary pattern (Δ = 0·76 sd, P < 0·0001). Large differences in Southern dietary pattern adherence were observed between black participants and white participants in the stroke belt and non-belt (stroke belt Δ = 0·75 sd, non-belt Δ = 0·77 sd). There was a high consumption of the Southern dietary pattern in the US black population, regardless of other factors, underlying our previous findings showing the substantial contribution of this dietary pattern to racial disparities in incident hypertension and stroke.

Serum magnesium concentration and incident cognitive impairment: the reasons for geographic and racial differences in stroke study.

PURPOSE: To examine the prospective association between serum Mg level and the incidence of cognitive impairment. METHODS: A random sub-cohort (n = 2063) from the Reasons for Geographic and Racial Differences in Stroke (REGARDS) cohort was included in this study. Baseline serum Mg concentration was measured using inductively coupled plasma mass spectrometry. According to the current reference interval of serum magnesium (0.75-0.95 mmol/L), we classified participants below the interval as Level 1 and used it as the referent. The rest of the study population were equally divided into three groups, named Level 2 to 4. Incident cognitive impairment was identified using the Six-Item Screener. Multivariable-adjusted odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were estimated using logistic regression models. RESULTS: After adjustment for potential confounders, an inverse threshold association between serum Mg level and incident cognitive impairment was observed. Compared to those with hypomagnesemia (Level 1: < 0.75 mmol/L), the relative odds of incident cognitive impairment was reduced by 41% in the second level [OR (95% CI) = 0.59 (0.37, 0.94)]; higher serum Mg level did not provide further benefits [Level 3 and 4 versus Level 1: OR (95% CI) = 0.54 (0.34, 0.88) and 0.59 (0.36, 0.96), P for linear trend = 0.08]. CONCLUSIONS: Findings from this prospective study suggest that sufficient Mg status within the normal range may be beneficial to cognitive health in the US general population.

Prenatal air pollution exposure and neurodevelopment: A review and blueprint for a harmonized approach within ECHO.

BACKGROUND: Air pollution exposure is ubiquitous with demonstrated effects on morbidity and mortality. A growing literature suggests that prenatal air pollution exposure impacts neurodevelopment. We posit that the Environmental influences on Child Health Outcomes (ECHO) program will provide unique opportunities to fill critical knowledge gaps given the wide spatial and temporal variability of ECHO participants. OBJECTIVES: We briefly describe current methods for air pollution exposure assessment, summarize existing studies of air pollution and neurodevelopment, and synthesize this information as a basis for recommendations, or a blueprint, for evaluating air pollution effects on neurodevelopmental outcomes in ECHO. METHODS: We review peer-reviewed literature on prenatal air pollution exposure and neurodevelopmental outcomes, including autism spectrum disorder, attention deficit hyperactivity disorder, intelligence, general cognition, mood, and imaging measures. ECHO meta-data were compiled and evaluated to assess frequency of neurodevelopmental assessments and prenatal and infancy residential address locations. Cohort recruitment locations and enrollment years were summarized to examine potential spatial and temporal variation present in ECHO. DISCUSSION: While the literature provides compelling evidence that prenatal air pollution affects neurodevelopment, limitations in spatial and temporal exposure variation exist for current published studies. As >90% of the ECHO cohorts have collected a prenatal or infancy address, application of advanced geographic information systems-based models for common air pollutant exposures may be ideal to address limitations of published research. CONCLUSIONS: In ECHO we have the opportunity to pioneer unifying exposure assessment and evaluate effects across multiple periods of development and neurodevelopmental outcomes, setting the standard for evaluation of prenatal air pollution exposures with the goal of improving children's health.

Injuries on the Youth Soccer (Football) Field: Do Additional Referees Reduce Risk? Randomized Crossover Trial.

OBJECTIVE: Youth soccer injury can be prevented through various means, but few studies consider the role of referees. Following previous research suggesting children take fewer risks when supervised intensely, this randomized crossover trial evaluated whether risky play and injuries decrease under supervision from three referees instead of one referee. METHODS: Youth soccer clubs serving a metropolitan U.S. area participated. Boys' and girls' clubs at under age 10 (U10) and under age 11 (U11) levels were randomly assigned such that when the same clubs played each other twice in the same season, they played once with one referee and once with three referees. A total of 98 games were videotaped and subsequently coded to obtain four outcomes: collisions between players, aggressive fouls (involving physical player-to-player contact) called by the referee(s) on the field, aggressive fouls judged by trained coders, and injuries requiring adult attention or play stoppage. RESULTS: Poisson mixed model results suggest players in the 98 games committed fewer aggressive fouls, as identified independently by referees (rate ratio [RR] 0.58; 95% confidence interval [CI] 0.35-0.96) and by researchers (RR 0.67; 95% CI 0.50-0.90), when there were three referees versus one referee. Collisions (RR 0.98; 95% CI 0.86-1.12) and injury rates (RR 1.15; 95% CI 0.60-2.19) were similar across conditions. CONCLUSION: When the same youth soccer clubs played with three referees rather than one, they committed fewer aggressive fouls. More intense supervision created better rule adherence. Injury rates were unchanged with increased supervision. Results raise questions concerning whether financial investment in additional referees on youth soccer fields yields safety benefits.

The effect of time spent outdoors during summer on daily blood glucose and steps in women with type 2 diabetes.

This study investigated changes in glycemic control following a small increase in time spent outdoors. Women participants with type 2 diabetes (N = 46) wore an iBUTTON temperature monitor and a pedometer for 1 week and recorded their morning fasting blood glucose (FBG) daily. They went about their normal activities for 2 days (baseline) and were asked to add 30 min of time outdoors during Days 3-7 (intervention). Linear mixed effects models were used to test whether morning FBG values were different on days following intervention versus baseline days, and whether steps and/or heat exposure changed. Results were stratified by indicators of good versus poor glycemic control prior to initiation of the study. On average, blood glucose was reduced by 6.1 mg/dL (95% CI - 11.5, - 0.6) on mornings after intervention days after adjusting for age, BMI, and ambient weather conditions. Participants in the poor glycemic control group (n = 16) experienced a 15.8 mg/dL decrease (95% CI - 27.1, - 4.5) in morning FBG on days following the intervention compared to a 1.6 mg/dL decrease (95%CI - 7.7, 4.5) for participants in the good glycemic control group (n = 30). Including daily steps or heat exposure did not attenuate the association between intervention and morning FBG. The present study suggests spending an additional 30 min outdoors may improve glycemic control; however, further examination with a larger sample over a longer duration and determination of mediators of this relationship is warranted.

PCSK9 Variants, Low-Density Lipoprotein Cholesterol, and Neurocognitive Impairment: Reasons for Geographic and Racial Differences in Stroke Study (REGARDS).

BACKGROUND: Despite concerns about adverse neurocognitive events raised by prior trials, pharmacological PCSK9 (proprotein convertase subtilisin/kexin type-9) inhibition was not associated with neurocognitive effects in a recent phase 3 randomized trial. PCSK9 loss-of-function (LOF) variants that result in lifelong exposure to lower levels of low-density lipoprotein cholesterol can provide information on the potential long-term effects of lower low-density lipoprotein cholesterol on neurocognitive impairment and decline. METHODS: We investigated the association between PCSK9 LOF variants and neurocognitive impairment and decline among black REGARDS study (Reasons for Geographic and Racial Differences in Stroke) participants with (n=241) and without (n=10 454) C697X or Y142X LOF variants. Neurocognitive tests included the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) battery (Word List Learning, World List Delayed Recall, Semantic Animal Fluency) and Six-Item Screener (SIS) assessments, administered longitudinally during follow-up. Neurocognitive impairment was defined as a score ≥1.5 SD below age, sex, and education-based stratum-specific means on 2 or 3 CERAD assessments or, separately, a score <5 on any SIS assessment at baseline or during follow-up. Neurocognitive decline was assessed using standardized continuous scores on individual neurocognitive tests. RESULTS: The mean sample age was 64 years (SD, 9), 62% were women, and the prevalence of neurocognitive impairment at any assessment was 6.3% by CERAD and 15.4% by SIS definitions. Adjusted odds ratios for neurocognitive impairment for participants with versus without PCSK9 LOF variants were 1.11 (95% confidence interval [CI], 0.58-2.13) using the CERAD battery and 0.89 (95% CI, 0.61-1.30) using the SIS assessment. Standardized average differences in individual neurocognitive assessment scores over the 5.6-year (range, 0.1-9.1) study period ranged between 0.07 (95% CI, -0.06 to 0.20) and -0.07 (95% CI, -0.18 to 0.05) among participants with versus without PCSK9 LOF variants. Patterns of neurocognitive decline were similar between participants with and without PCSK9 LOF variants (all P>0.10). Odds ratios for neurocognitive impairment per 20 mg/dL low-density lipoprotein cholesterol decrements were 1.02 (95% CI, 0.96-1.08) and 0.99 (95% CI, 0.95-1.02) for the CERAD and SIS definitions of impairment, respectively. CONCLUSIONS: These results suggest that lifelong exposure to low PCSK9 levels and cumulative exposure to lower levels of low-density lipoprotein cholesterol are not associated with neurocognitive effects in blacks.

An Investigation of Selection Bias in Estimating Racial Disparity in Stroke Risk Factors.

Selection due to survival or attrition might bias estimates of racial disparities in health, but few studies quantify the likely magnitude of such bias. In a large national cohort with moderate loss to follow-up, we contrasted racial differences in 2 stroke risk factors, incident hypertension and incident left ventricular hypertrophy, estimated by complete-case analyses, inverse probability of attrition weighting, and the survivor average causal effect. We used data on 12,497 black and 17,660 white participants enrolled in the United States (2003-2007) and collected incident risk factor data approximately 10 years after baseline. At follow-up, 21.0% of white participants and 23.0% of black participants had died; additionally 22.0% of white participants and 28.4% of black participants had withdrawn. Individual probabilities of completing the follow-up visit were estimated using baseline demographic and health characteristics. Adjusted risk ratio estimates of racial disparities from complete-case analyses in both incident hypertension (1.11, 95% confidence interval: 1.02, 1.21) and incident left ventricular hypertrophy (1.02, 95% confidence interval: 0.84, 1.24) were virtually identical to estimates from inverse probability of attrition weighting and survivor average causal effect. Despite racial differences in mortality and attrition, we found little evidence of selection bias in the estimation of racial differences for these incident risk factors.

C-reactive protein and stroke risk in blacks and whites: The REasons for Geographic And Racial Differences in Stroke cohort.

BACKGROUND: C-reactive protein (CRP) is an inflammatory biomarker used in vascular risk prediction, though with less data in people of color. Blacks have higher stroke incidence and also higher CRP than whites. We studied the association of CRP with ischemic stroke risk in blacks and whites. METHODS: REGARDS, an observational cohort study, recruited and followed 30,239 black and white Americans 45 years and older for ischemic stroke. We calculated hazard ratios and 95% CIs of ischemic stroke by CRP category (<1, 1-3, 3-10, and ≥10 mg/L) adjusted for age, sex and stroke risk factors. RESULTS: There were 292 incident ischemic strokes among blacks and 439 in whites over 6.9 years of follow-up. In whites, the risk was elevated for CRP in the range from 3 to 10 mg/L and even higher for CRP >10 mg/L, whereas in blacks, an association was only seen for CRP >10 mg/L. Considered as a continuous variable, the risk factor-adjusted hazard ratios per SD higher lnCRP were 1.18 (95% CI 1.09-1.28) overall, 1.14 (95% CI 1.00-1.29) in blacks, and 1.22 (95% CI 1.10-1.35) in whites. Spline regression analysis visually confirmed the race difference in the association. CONCLUSIONS: CRP may not be equally useful in stroke risk assessment in blacks and whites. Confirmation, similar study for coronary heart disease, and identification of reasons for these racial differences require further study.