Epidemiology Evidence for Health Effects of 150 per- and Polyfluoroalkyl Substances: A Systematic Evidence Map.

BACKGROUND: Per- and polyfluoroalkyl substances (PFAS) comprise a large class of chemicals with widespread use and persistence in the environment and in humans; however, most of the epidemiology research has focused on a small subset. OBJECTIVES: The aim of this systematic evidence map (SEM) is to summarize the epidemiology evidence on approximately 150 lesser studied PFAS prioritized by the EPA for tiered toxicity testing, facilitating interpretation of those results as well as identification of priorities for risk assessment and data gaps for future research. METHODS: The Populations, Exposure, Comparators, and Outcomes (PECO) criteria were intentionally broad to identify studies of any health effects in humans with information on associations with exposure to the identified PFAS. Systematic review methods were used to search for literature that was screened using machine-learning software and manual review. Studies meeting the PECO criteria underwent quantitative data extraction and evaluation for risk of bias and sensitivity using the Integrated Risk Information System approach. RESULTS: 193 epidemiology studies were identified, which included information on 15 of the PFAS of interest. The most commonly studied health effect categories were metabolic (n=37), endocrine (n=30), cardiovascular (30), female reproductive (n=27), developmental (n=26), immune (n=22), nervous (n=21), male reproductive (n=14), cancer (n=12), and urinary (n=11) effects. In study evaluation, 120 (62%) studies were considered High/Medium confidence for at least one outcome. DISCUSSION: Most of the PFAS in this SEM have little to no epidemiology data available to inform evaluation of potential health effects. Although exposure to the 15 PFAS that had data was fairly low in most studies, these less-studied PFAS may be used as replacements for "legacy" PFAS, leading to potentially greater exposure. It is impractical to generate epidemiology evidence to fill the existing gaps for all potentially relevant PFAS. This SEM highlights some of the important research gaps that currently exist. https://doi.org/10.1289/EHP11185.

Acute health effects associated with satellite-determined cyanobacterial blooms in a drinking water source in Massachusetts.

BACKGROUND: The occurrence of cyanobacterial blooms in freshwater presents a threat to human health. However, epidemiological studies on the association between cyanobacterial blooms in drinking water sources and human health outcomes are scarce. The objective of this study was to evaluate if cyanobacterial blooms were associated with increased emergency room visits for gastrointestinal (GI), respiratory and dermal illnesses. METHODS: Satellite-derived cyanobacteria cell concentrations were estimated in the source of drinking water for the Greater Boston area, during 2008-2011. Daily counts of hospital emergency room visits for GI, respiratory and dermal illnesses among drinking water recipients were obtained from an administrative record database. A two-stage model was used to analyze time-series data for an association between cyanobacterial blooms and the occurrence of illnesses. At the first stage, predictive autoregressive generalized additive models for Poisson-distributed outcomes were fitted to daily illness count data and daily predictive variables. At the second stage, residuals from the first stage models were regressed against lagged categorized cyanobacteria concentration estimates. RESULTS: The highest cyanobacteria concentration (above the 75th percentile) was associated with an additional 4.3 cases of respiratory illness (95% confidence interval: 0.7, 8.0, p = 0.02, n = 268) compared to cyanobacteria concentrations below the 50th percentile in a two-day lag. There were no significant associations between satellite derived cyanobacterial concentrations and lagged data on GI or dermal illnesses. CONCLUSION: The study demonstrated a significant positive association between satellite-derived cyanobacteria concentrations in source water and respiratory illness occurring 2 days later. Future studies will require direct measures of cyanotoxins and health effects associated with exposure to cyanobacteria-impacted drinking water sources.

Emergency Department Visits for Acute Gastrointestinal Illness After a Major Water Pipe Break in 2010.

BACKGROUND: When a water pipe breaks, contaminants can enter the drinking water system and cause waterborne illnesses such as acute gastrointestinal illness. In May 2010, a major water pipe broke near Boston, MA, and a boil water order was issued to nearly two million residents. METHODS: Using a case-crossover study design, we examined the association between the water pipe break and subsequent emergency department visits for acute gastrointestinal illness. We identified cases of illness according to ICD-9-CM diagnosis codes and selected control dates 2 weeks before and after each case. We estimated the risk of visiting the emergency department during the 0-3 and 4-7 days after the water pipe break using conditional logistic regression models. RESULTS: Our analysis included 5,726 emergency department visits for acute gastrointestinal illness from 3 April 2010 to 5 June 2010. Overall, there was a 1.3-fold increased odds for visiting the emergency department for acute gastrointestinal illness during the 0-3 days after the water pipe break (odds ratio [OR] = 1.3; 95% confidence interval [CI] = 1.1, 1.4) compared with referent dates selected 2 weeks before and after. During the 4-7 days after the break, the association diminished overall (OR = 1.1; 95% CI = 0.96, 1.2). However, in communities over 12 miles from the break, the 4- to 7-day association was elevated (OR = 1.4; 95% CI = 1.1, 1.8). CONCLUSIONS: This study suggests that a major water pipe break was associated with emergency department visits for acute gastrointestinal illness, particularly during the 0-3 days after the break, when a boil water order was in effect.

Erratum: "Sanitary Sewer Overflows and Emergency Room Visits for Gastrointestinal Illness: Analysis of Massachusetts Data, 2006-2007".

[This corrects the article DOI: 10.1289/EHP2048.].

Sanitary Sewer Overflows and Emergency Room Visits for Gastrointestinal Illness: Analysis of Massachusetts Data, 2006-2007.

BACKGROUND: Sanitary sewer overflows (SSOs) occur when untreated sewage is discharged into water sources before reaching the treatment facility, potentially contaminating the water source with gastrointestinal pathogens. OBJECTIVES: The objective of this paper is to assess associations between SSO events and rates of gastrointestinal (GI) illness in Massachusetts. METHODS: A case-crossover study design was used to investigate association between SSO events and emergency room (ER) visits with a primary diagnosis of gastrointestinal (GI) illness in Massachusetts for 2006-2007. ER visits for GI were considered exposed if an SSO event occurred in the county of residence within three hazard periods, 0-4 d, 5-9 d, or 10-14 d, before the visit. A time-stratified bidirectional design was used to select control days for each ER visit on the same day of the week during the same month. Fixed effect logistic regression models were used to estimate the risk of ER visits following the SSO event. RESULTS: During the study period, there were 270 SSO events for northeastern Massachusetts and 66,460 ER admissions with GI illness listed as the primary diagnostic code. The overall odds ratio (OR) for ER visits for GI illness was 1.09 [95% confidence interval (CI): 1.03, 1.16] in the 10-14 d period following an SSO event, with positive ORs for all age groups and for three of the four counties. The 0-4 d and 5-9 d periods following an SSO event were not associated with ER visits for GI illness overall, and associations by county or age were inconsistent. CONCLUSIONS: We demonstrated an association between SSO events and ER visits for GI illness using a case-crossover study design. In light of the aging water infrastructure in the United States and the expected increase in heavy rainfall events, our findings suggest a potential health impact associated with sewage overflows. https://doi.org/10.1289/EHP2048.

Extreme precipitation and emergency room visits for influenza in Massachusetts: a case-crossover analysis.

BACKGROUND: Influenza peaks during the wintertime in temperate regions and during the annual rainy season in tropical regions - however reasons for the observed differences in disease ecology are poorly understood. We hypothesize that episodes of extreme precipitation also result in increased influenza in the Northeastern United States, but this association is not readily apparent, as no defined 'rainy season' occurs. Our objective was to evaluate the association between extreme precipitation (≥ 99th percentile) events and risk of emergency room (ER) visit for influenza in Massachusetts during 2002-2008. METHODS: A case-crossover analysis of extreme precipitation events and influenza ER visits was conducted using hospital administrative data including patient town of residence, date of visit, age, sex, and associated diagnostic codes. Daily precipitation estimates were generated for each town based upon data from the National Oceanic and Atmospheric Administration. Odds ratio (OR) and 95% confidence intervals (CI) for associations between extreme precipitation and ER visits for influenza were estimated using conditional logistic regression. RESULTS: Extreme precipitation events were associated with an OR = 1.23 (95%CI: 1.16, 1.30) for ER visits for influenza at lag days 0-6. There was significant effect modification by race, with the strongest association observed among Blacks (OR = 1.48 (1.30, 1.68)). CONCLUSIONS: We observed a positive association between extreme precipitation events and ER visits for influenza, particularly among Blacks. Our results suggest that influenza is associated with extreme precipitation in a temperate area; this association could be a result of disease ecology, behavioral changes such as indoor crowding, or both. Extreme precipitation events are expected to increase in the Northeastern United States as climate change progresses. Additional research exploring the basis of this association can inform potential interventions for extreme weather events and influenza transmission.

A Prospective Study of Marine Phytoplankton and Reported Illness Among Recreational Beachgoers in Puerto Rico, 2009.

BACKGROUND: Blooms of marine phytoplankton may adversely affect human health. The potential public health impact of low-level exposures is not well established, and few prospective cohort studies of recreational exposures to marine phytoplankton have been conducted. OBJECTIVE: We evaluated the association between phytoplankton cell counts and subsequent illness among recreational beachgoers. METHODS: We recruited beachgoers at Boquerón Beach, Puerto Rico, during the summer of 2009. We conducted interviews at three time points to assess baseline health, water activities, and subsequent illness. Daily water samples were quantitatively assayed for phytoplankton cell count. Logistic regression models, adjusted for age and sex, were used to assess the association between exposure to three categories of phytoplankton concentration and subsequent illness. RESULTS: During 26 study days, 15,726 individuals successfully completed all three interviews. Daily total phytoplankton cell counts ranged from 346 to 2,012 cells/mL (median, 712 cells/mL). The category with the highest (≥ 75th percentile) total phytoplankton cell count was associated with eye irritation [adjusted odds ratio (OR) = 1.30; 95% confidence interval (CI): 1.01, 1.66], rash (OR = 1.27; 95% CI: 1.02, 1.57), and earache (OR = 1.25; 95% CI: 0.88, 1.77). In phytoplankton group-specific analyses, the category with the highest Cyanobacteria counts was associated with respiratory illness (OR = 1.37; 95% CI: 1.12, 1.67), rash (OR = 1.32; 95% CI: 1.05, 1.66), eye irritation (OR = 1.25; 95% CI: 0.97, 1.62), and earache (OR = 1.35; 95% CI: 0.95, 1.93). CONCLUSIONS: We found associations between recreational exposure to marine phytoplankton and reports of eye irritation, respiratory illness, and rash. We also found that associations varied by phytoplankton group, with Cyanobacteria having the strongest and most consistent associations. CITATION: Lin CJ, Wade TJ, Sams EA, Dufour AP, Chapman AD, Hilborn ED. 2016. A prospective study of marine phytoplankton and reported illness among recreational beachgoers in Puerto Rico, 2009. Environ Health Perspect 124:477-483; http://dx.doi.org/10.1289/ehp.1409558.

Flooding and Clostridium difficile Infection: A Case-Crossover Analysis.

Clostridium difficile is a bacterium that can spread by water. It often causes acute gastrointestinal illness in older adults who are hospitalized and/or receiving antibiotics; however, community-associated infections affecting otherwise healthy individuals have become more commonly reported. A case-crossover study was used to assess emergency room (ER) and outpatient visits for C. difficile infection following flood events in Massachusetts from 2003 through 2007. Exposure status was based on whether or not a flood occurred prior to the case/control date during the following risk periods: 0-6 days, 7-13 days, 14-20 days, and 21-27 days. Fixed-effects logistic regression was used to estimate the risk of diagnosis with C. difficile infection following a flood. There were 129 flood events and 1575 diagnoses of C. difficile infection. Among working age adults (19-64 years), ER and outpatient visits for C. difficile infection were elevated during the 7-13 days following a flood (Odds Ratio, OR = 1.69; 95% Confidence Interval, CI: 0.84, 3.37). This association was more substantial among males (OR = 3.21; 95% CI: 1.01-10.19). Associations during other risk periods were not observed (p < 0.05). Although we were unable to differentiate community-associated versus nosocomial infections, a potential increase in C. difficile infections should be considered as more flooding is projected due to climate change.

Flooding and emergency room visits for gastrointestinal illness in Massachusetts: a case-crossover study.

INTRODUCTION: Floods and other severe weather events are anticipated to increase as a result of global climate change. Floods can lead to outbreaks of gastroenteritis and other infectious diseases due to disruption of sewage and water infrastructure and impacts on sanitation and hygiene. Floods have also been indirectly associated with outbreaks through population displacement and crowding. METHODS: We conducted a case-crossover study to investigate the association between flooding and emergency room visits for gastrointestinal illness (ER-GI) in Massachusetts for the years 2003 through 2007. We obtained ER-GI visits from the State of Massachusetts and records of floods from the National Oceanic and Atmospheric Association's Storm Events Database. ER-GI visits were considered exposed if a flood occurred in the town of residence within three hazard periods of the visit: 0-4 days; 5-9 days; and 10-14 days. A time-stratified bi-directional design was used for control selection, matching on day of the week with two weeks lead or lag time from the ER-GI visit. Fixed effect logistic regression models were used to estimate the risk of ER-GI visits following the flood. RESULTS AND CONCLUSIONS: A total of 270,457 ER-GI visits and 129 floods occurred in Massachusetts over the study period. Across all counties, flooding was associated with an increased risk for ER-GI in the 0-4 day period after flooding (Odds Ratio: 1.08; 95% Confidence Interval: 1.03-1.12); but not the 5-9 days (Odds Ratio: 0.995; 95% Confidence Interval: 0.955-1.04) or the 10-14 days after (Odds Ratio: 0.966, 95% Confidence Interval: 0.927-1.01). Similar results were observed for different definitions of ER-GI. The effect differed across counties, suggesting local differences in the risk and impact of flooding. Statewide, across the study period, an estimated 7% of ER-GI visits in the 0-4 days after a flood event were attributable to flooding.

Accuracy and reliability of self-reported weight and height in the Sister Study.

OBJECTIVE: To assess the accuracy and reliability of self-reported weight and height and identify the factors associated with reporting accuracy. DESIGN: Analysis of self-reported and measured weight and height from participants in the Sister Study (2003-2009), a nationwide cohort of 50 884 women aged 35-74 years in the USA with a sister with breast cancer. SETTING: Weight and height were reported via computer-assisted telephone interview (CATI) and self-administered questionnaires, and measured by examiners. SUBJECTS: Early enrolees in the Sister Study. There were 18 639 women available for the accuracy analyses and 13 316 for the reliability analyses. RESULTS: Using weighted kappa statistics, comparisons were made between CATI responses and examiner measures to assess accuracy and CATI and questionnaire responses to assess reliability. Polytomous logistic regression evaluated factors associated with over- or under-reporting. Compared with measured values, agreement was 96 % for reported height (±1 inch (±2·5 cm); weighted κ = 0·84) and 67 % for weight (±3 lb (±1·36 kg); weighted κ = 0·92). Obese women (BMI ≥ 30 kg/m2) were more likely than normal-weight women to under-report weight by ≥5 % and underweight women (BMI < 18·5 kg/m2) were more likely to over-report. Among normal-weight and overweight women (18·5 kg/m2 ≤ BMI < 30 kg/m2), weight cycling and lifetime weight difference ≥50 lb (≥22·68 kg) were associated with over-reporting. CONCLUSIONS: US women in the Sister Study were reasonably reliable and accurate in reporting weight and height. Women with normal-range BMI reported most accurately. Overweight and obese women and those with weight fluctuations were less accurate, but even among obese women, few under-reported their weight by >10 %.

Intestinal parasites in Kaposi sarcoma patients in Uganda: indication of shared risk factors or etiologic association.

Kaposi sarcoma (KS) is endemic in Uganda and shares several risk factors with intestinal parasite infestation, including rural residence, contact with surface water, and walking barefoot, however, the significance of these ecologic relationships is unknown. We investigated these relationships among 1,985 Ugandan patients with cancer. Odds ratios (OR) were calculated using logistic regression. KS patients had higher carriage of Strongyloides stercoralis larvae (OR 2.1, 95% CI 1.2-3.7) and lower carriage of hookworm ova (0.6, 0.4-1.0) and Entamoeba coli cysts (0.7, 0.5-1.0), after adjusting for region of residence, age, gender, and diagnosis. While our findings may be due to confounding, they are compatible with shared risk factors or etiological association between parasites and KS, and warrant well-designed follow up studies.