An Updated Evaluation of Atrazine-Cancer Incidence Associations among Pesticide Applicators in the Agricultural Health Study Cohort.

BACKGROUND: Atrazine is a common agricultural herbicide in the United States. Few epidemiologic studies have evaluated cancer risks. Previous analyses within the Agricultural Health Study (AHS) have found some evidence of associations with cancer at some sites. OBJECTIVE: We updated exposure information, incident cases, and follow-up time to assess the associations between atrazine use and cancer at specific sites in the AHS. METHODS: Information about lifetime pesticide use was reported at enrollment (1993-1997) and follow-up (1999-2005). Among 53,562 pesticide applicators in North Carolina and Iowa, we identified 8,915 incident cases through cancer registry linkages through 2014 (North Carolina)/2017 (Iowa). We used Poisson regression to evaluate the association between ever/never and intensity-weighted lifetime days of atrazine use and incident cancer risk controlling for several confounders. We also evaluated lagged exposures and age-stratified risk. RESULTS: Approximately 71.2% of applicators reported ever using atrazine, which was associated with lung cancer [rate ratios (RR)=1.24; 95% confidence interval (CI): 1.04, 1.46]. Aggressive prostate cancer risk was increased in the highest quartile (RRQ4=1.20; 95% CI: 0.95, 1.52; p-trend=0.19), particularly among those <60 years old (RRQ4=3.04; 95% CI: 1.61, 5.75; p-trend<0.001; p-interaction=0.04). Among applicators <50 years of age, ever-atrazine use was associated with non-Hodgkin lymphoma (NHL) (RR=2.43; 95% CI: 1.10, 5.38; p-interaction=0.60). For soft tissue sarcoma, there was an elevated risk in the highest tertile of exposure (RRT3: 2.54; 95% CI: 0.97, 6.62; p-trend=0.31). In analyses with exposure lagged by 25 years, there was an elevated risk of pharyngeal (RRT3=3.04; 95% CI: 1.45, 6.36; p-trend=0.07) and kidney (RRQ4=1.62; 95% CI: 1.15, 2.29; p-trend<0.005) cancers. DISCUSSION: We observed suggestive associations with some malignancies in overall, age-specific, and lagged analyses. Associations with aggressive prostate cancer and NHL were apparent among those diagnosed at younger ages and with cancers of the pharynx and kidney, and soft tissue sarcomas were observed in lagged analyses. Further work is needed to confirm these observed associations and elucidate potential underlying mechanisms. https://doi.org/10.1289/EHP13684.

Inclement Weather and Risk of Missing Scheduled Hemodialysis Appointments among Patients with Kidney Failure.

BACKGROUND: Nonadherence to hemodialysis appointments could potentially result in health complications that can influence morbidity and mortality. We examined the association between different types of inclement weather and hemodialysis appointment adherence. METHODS: We analyzed health records of 60,135 patients with kidney failure who received in-center hemodialysis treatment at Fresenius Kidney Care clinics across the Northeastern US counties during 2001-2019. County-level daily meteorological data on rainfall, hurricane and tropical storm events, snowfall, snow depth, and wind speed were extracted using National Oceanic and Atmosphere Agency data sources. A time-stratified case-crossover study design with conditional Poisson regression was used to estimate the effect of inclement weather exposures within the Northeastern US region. We applied a distributed lag nonlinear model framework to evaluate the delayed effect of inclement weather for up to 1 week. RESULTS: We observed positive associations between inclement weather and missed appointment (rainfall, hurricane and tropical storm, snowfall, snow depth, and wind advisory) when compared with noninclement weather days. The risk of missed appointments was most pronounced during the day of inclement weather (lag 0) for rainfall (incidence rate ratio [RR], 1.03 per 10-mm rainfall; 95% confidence interval [CI], 1.02 to 1.03) and snowfall (RR, 1.02; 95% CI, 1.01 to 1.02). Over 7 days (lag 0-6), hurricane and tropical storm exposures were associated with a 55% higher risk of missed appointments (RR, 1.55; 95% CI, 1.22 to 1.98). Similarly, 7-day cumulative exposure to sustained wind advisories was associated with 29% higher risk (RR, 1.29; 95% CI, 1.25 to 1.31), while wind gusts advisories showed a 34% higher risk (RR, 1.34; 95% CI, 1.29 to 1.39) of missed appointment. CONCLUSIONS: Inclement weather was associated with higher risk of missed hemodialysis appointments within the Northeastern United States. Furthermore, the association between inclement weather and missed hemodialysis appointments persisted for several days, depending on the inclement weather type.

Combined effects of air pollution and extreme heat events among ESKD patients within the Northeastern United States.

BACKGROUND: Increasing number of studies have linked air pollution exposure with renal function decline and disease. However, there is a lack of data on its impact among end-stage kidney disease (ESKD) patients and its potential modifying effect from extreme heat events (EHE). METHODS: Fresenius Kidney Care records from 28 selected northeastern US counties were used to pool daily all-cause mortality (ACM) and all-cause hospital admissions (ACHA) counts. County-level daily ambient PM2.5 and ozone (O3) were estimated using a high-resolution spatiotemporal coupled climate-air quality model and matched to ESKD patients based on ZIP codes of treatment sites. We used time-stratified case-crossover analyses to characterize acute exposures using individual and cumulative lag exposures for up to 3 days (Lag 0-3) by using a distributed lag nonlinear model framework. We used a nested model comparison hypothesis test to evaluate for interaction effects between air pollutants and EHE and stratification analyses to estimate effect measures modified by EHE days. RESULTS: From 2001 to 2016, the sample population consisted of 43,338 ESKD patients. We recorded 5217 deaths and 78,433 hospital admissions. A 10-unit increase in PM2.5 concentration was associated with a 5% increase in ACM (rate ratio [RRLag0-3]: 1.05, 95% CI: 1.00-1.10) and same-day O3 (RRLag0: 1.02, 95% CI: 1.01-1.03) after adjusting for extreme heat exposures. Mortality models suggest evidence of interaction and effect measure modification, though not always simultaneously. ACM risk increased up to 8% when daily ozone concentrations exceeded National Ambient Air Quality Standards established by the United States, but the increases in risk were considerably higher during EHE days across lag periods. CONCLUSION: Our findings suggest interdependent effects of EHE and air pollution among ESKD patients for all-cause mortality risks. National level assessments are needed to consider the ESKD population as a sensitive population and inform treatment protocols during extreme heat and degraded pollution episodes.

Assessing proximate intermediates between ambient temperature, hospital admissions, and mortality in hemodialysis patients.

BACKGROUND: Typical thermoregulatory responses to elevated temperatures among healthy individuals include reduced blood pressure and perspiration. Individuals with end-stage kidney disease (ESKD) are susceptible to systemic fluctuations caused by ambient temperature changes that may increase morbidity and mortality. We investigated whether pre-dialysis systolic blood pressure (preSBP) and interdialytic weight gain (IDWG) can independently mediate the association between ambient temperature, all-cause hospital admissions (ACHA), and all-cause mortality (ACM). METHODS: The study population consisted of ESKD patients receiving hemodialysis treatments at Fresenius Medical Care facilities in Philadelphia County, PA, from 2011 to 2019 (n = 1981). Within a time-to-event framework, we estimated the association between daily maximum dry-bulb temperature (TMAX) and, as separate models, ACHA and ACM during warmer calendar months. Clinically measured preSBP and IDWG responses to temperature increases were estimated using linear mixed effect models. We employed the difference (c-c') method to decompose total effect models for ACHA and ACM using preSBP and IDWG as time-dependent mediators. Covariate adjustments for exposure-mediator and total and direct effect models include age, race, ethnicity, blood pressure medication use, treatment location, preSBP, and IDWG. We considered lags up to two days for exposure and 1-day lag for mediator variables (Lag 2-Lag 1) to assure temporality between exposure-outcome models. Sensitivity analyses for 2-day (Lag 2-only) and 1-day (Lag 1-only) lag structures were also conducted. RESULTS: Based on Lag 2- Lag 1 temporal ordering, 1 °C increase in daily TMAX was associated with increased hazard of ACHA by 1.4% (adjusted hazard ratio (HR), 1.014; 95% confidence interval, 1.007-1.021) and ACM 7.5% (adjusted HR, 1.075, 1.050-1.100). Short-term lag exposures to 1 °C increase in temperature predicted mean reductions in IDWG and preSBP by 0.013-0.015% and 0.168-0.229 mmHg, respectively. Mediation analysis for ACHA identified significant indirect effects for all three studied pathways (preSBP, IDWG, and preSBP + IDWG) and significant indirect effects for IDWG and conjoined preSBP + IDWG pathways for ACM. Of note, only 1.03% of the association between temperature and ACM was mediated through preSBP. The mechanistic path for IDWG, independent of preSBP, demonstrated inconsistent mediation and, consequently, potential suppression effects in ACHA (-15.5%) and ACM (-6.3%) based on combined pathway models. Proportion mediated estimates from preSBP + IDWG pathways achieved 2.2% and 0.3% in combined pathway analysis for ACHA and ACM outcomes, respectively. Lag 2 discrete-time ACM mediation models exhibited consistent mediation for all three pathways suggesting that 2-day lag in IDWG and preSBP responses can explain 2.11% and 4.41% of total effect association between temperature and mortality, respectively. CONCLUSION: We corroborated the previously reported association between ambient temperature, ACHA and ACM. Our results foster the understanding of potential physiological linkages that may explain or suppress temperature-driven hospital admissions and mortality risks. Of note, concomitant changes in preSBP and IDWG may have little intermediary effect when analyzed in combined pathway models. These findings advance our assessment of candidate interventions to reduce the impact of outdoor temperature change on ESKD patients.

Association of Extreme Heat Events With Hospital Admission or Mortality Among Patients With End-Stage Renal Disease.

Importance: Extreme heat events (EHEs) are increasing in frequency, duration, and intensity, and this trend is projected to continue as part of ongoing climate change. There is a paucity of data regarding how EHEs may affect highly vulnerable populations, such as patients with end-stage renal disease (ESRD). Such data are needed to inform ESRD patient management guidelines in a changing climate. Objectives: To investigate the association between EHEs and the risk of hospital admission or mortality among patients with ESRD and further characterize how this risk may vary among races/ethnicities or patients with preexisting comorbidities. Design, Setting, and Participants: This study used hospital admission and mortality records of patients with ESRD who underwent hemodialysis treatment at Fresenius Kidney Care clinics in Boston, Massachusetts; Philadelphia, Pennsylvania; or New York, New York, from January 1, 2001, to December 31, 2012. Data were analyzed using a time-stratified case-crossover design with conditional Poisson regression to investigate associations between EHEs and risk of hospital admission or mortality among patients with ESRD. Data were analyzed from July 1, 2017, to March 31, 2019. Exposures: Calendar day- and location-specific 95th-percentile maximum temperature thresholds were calculated using daily meteorological data from 1960 to 1989. These thresholds were used to identify EHEs in each of the 3 cities during the study. Main Outcomes and Measures: Daily all-cause hospital admission and all-cause mortality among patients with ESRD. Results: The study included 7445 patients with ESRD (mean [SD] age, 61.1 [14.1] years; 4283 [57.5%] men), among whom 2953 deaths (39.7%) and 44 941 hospital admissions (mean [SD], 6.0 [7.5] per patient) were recorded. Extreme heat events were associated with increased risk of same-day hospital admission (rate ratio [RR], 1.27; 95% CI, 1.13-1.43) and same-day mortality (RR, 1.31; 95% CI, 1.01-1.70) among patients with ESRD. There was some heterogeneity in risk, with patients in Boston showing statistically significant increased risk for hospital admission (RR, 1.15; 95% CI, 1.00-1.31) and mortality (RR, 1.45; 95% CI, 1.04-2.02) associated with cumulative exposure to EHEs, while such risk was absent among patients with ESRD in Philadelphia. While increases in risks were similar among non-Hispanic black and non-Hispanic white patients, findings among Hispanic and Asian patients were less clear. After stratifying by preexisting comorbidities, cumulative lag exposure to EHEs was associated with increased risk of mortality among patients with ESRD living with congestive heart failure (RR, 1.55; 95% CI, 1.27-1.89), chronic obstructive pulmonary disease (RR, 1.60; 95% CI, 1.24-2.06), or diabetes (RR, 1.83; 95% CI, 1.51-2.21). Conclusions and Relevance: In this study, extreme heat events were associated with increased risk of hospital admission or mortality among patients with ESRD, and the association was potentially affected by geographic region and race/ethnicity. Future studies with larger populations and broader geographic coverage are needed to better characterize this variability in risk and inform ESRD management guidelines and differential risk variables, given the projected increases in the frequency, duration, and intensity of EHEs.

A Local View of Informal Urban Environments: a Mobile Phone-Based Neighborhood Audit of Street-Level Factors in a Brazilian Informal Community.

Street-level environment characteristics influence the health behaviors and safety of urban residents, and may particularly threaten health within informal communities. However, available data on how such characteristics vary within and among informal communities is limited. We sought to adapt street audit strategies designed to characterize the physical environment for use in a large informal community, Rio das Pedras (RdP) located in Rio de Janeiro, Brazil. A smartphone-based systematic observation protocol was used to gather street-level information for a high-density convenience sample of street segments (N = 630, estimated as 86% of all street segments in the community). We adapted items related to physical disorder and physical deterioration. Measures selected to illustrate the approach include the presence of the following: (1) low-hanging or tangled wires, (2) litter, (3) structural evidence of sinking, and (4) an unpleasant odor. Intercept-only spatial generalized additive models (GAM) were used to evaluate and visualize spatial variation within the RdP community. We also examined how our estimates and conclusions about spatial variation might have been affected by lower-density sampling from random subsets street observations. Random subsets were selected to determine the robustness of study results in scenarios with sparser street sampling. Selected characteristics were estimated to be present for between 18% (unpleasant odor) to 59% (low-hanging or tangled wires) of the street segments in RdP; estimates remain similar (± 6%) when relying on a random subset created to simulate lower-density spatial sampling. Spatial patterns of variation based on predicted probabilities across RdP differed by indicator. Structural sinking and low-hanging or tangled wires demonstrated relatively consistent spatial distribution patterns across full and random subset sample sizes. Smartphone-based systematic observations represent an efficient and potentially feasible approach to systematically studying neighborhood environments within informal communities. Future deployment of such tools will benefit from incorporating data collection across multiple time points to explore reliability and quantify neighborhood change. These tools can prove useful means to assess street-level exposures that can be modifiable health determinants across a wide range of informal urban settings. Findings can contribute to improved urban planning and provide useful information for identifying potential locations for neighborhood-scaled interventions that can improve living conditions for residents in Rio das Pedras.