Outbreak Linked to Morel Mushroom Exposure - Montana, 2023.

During March-April 2023, a total of 51 persons reported mild to severe gastrointestinal illness after eating at restaurant A in Bozeman, Montana. The outbreak resulted in multiple severe outcomes, including three hospitalizations and two deaths. After an inspection and temporary restaurant closure, the Montana Department of Public Health and Human Services and Montana's Gallatin City-County Health Department collaborated with CDC to conduct a matched case-control study among restaurant patrons to help identify the source of the outbreak. Consumption of morel mushrooms, which are generally considered edible, was strongly associated with gastrointestinal illness. A dose-response relationship was identified, and consumption of raw morel mushrooms was more strongly associated with illness than was consumption of those that were at least partially cooked. In response to the outbreak, educational public messaging regarding morel mushroom preparation and safety was shared through multiple media sources. The investigation highlights the importance of prompt cross-agency communication and collaboration, the utility of epidemiologic studies in foodborne disease outbreak investigations, and the need for additional research about the impact of morel mushroom consumption on human health. Although the toxins in morel mushrooms that might cause illness are not fully understood, proper preparation procedures, including thorough cooking, might help to limit adverse health effects.

A case-cohort study of per- and polyfluoroalkyl substance concentrations and incident prostate cancer in the cancer prevention Study-II LifeLink cohort study.

INTRODUCTION: Per- and polyfluoroalkyl substances (PFAS) are environmentally persistent, potentially carcinogenic chemicals. Previous studies investigating PFAS exposure and prostate cancer yielded mixed findings. We aimed to investigate associations between PFAS exposure and incident prostate cancer in a large cohort of U.S. men, overall and by selected demographic, lifestyle, and medical-related characteristics. METHODS: We conducted a case-cohort study among Cancer Prevention Study-II LifeLink Cohort participants who, at baseline (1998-2001), had serum specimens collected and no prior cancer diagnosis. The study included all men diagnosed with prostate cancer (n = 1610) during follow-up (baseline-June 30, 2015) and a random sub-cohort of 500 men. PFAS concentrations [perfluorohexane sulfonic acid (PFHxS), perfluorooctane sulfonate (PFOS), perfluorononanoic acid (PFNA), and perfluorooctanoic acid (PFOA)] were measured in stored serum specimens. We used multivariable Cox proportional hazards models to estimate associations between PFAS concentrations and prostate cancer, overall and by selected characteristics (grade, stage, family history, age, education, smoking status, and alcohol consumption). RESULTS: Prostate cancer hazards were slightly higher among men with concentrations in the highest (Q4) vs lowest quartile (Q1) for PFHxS [hazard ratio (HR) (95% CI): 1.18 (0.88-1.59)] and PFOS [HR (95% CI): 1.18 (0.89-1.58)], but not for PFNA or PFOA. However, we observed heterogeneous associations by age, family history of prostate cancer (PFHxS), alcohol consumption (PFHxS), and education (PFNA). For example, no meaningful associations were observed among men aged <70 years at serum collection, but among men aged ≥70 years, HRs (95% CIs) comparing Q4 to Q1 were PFHxS 1.54 (1.02-2.31) and PFOS 1.62 (1.08-2.44). No meaningful heterogeneity in associations were observed by tumor grade or stage. CONCLUSIONS: Our findings do not clearly support an association between the PFAS considered and prostate cancer. However, positive associations observed in some subgroups, and consistently positive associations observed for PFHxS warrant further investigation.

Characterizing the Role of International Graduates of the Epidemic Intelligence Service in Increasing the Epidemiological Capacity and Diversity of the United States Public Health Workforce.

CONTEXT: A trained and diverse public health workforce is needed to respond to public health threats. The Epidemic Intelligence Service (EIS) is an applied epidemiology training program. Most EIS officers are from the United States, but some are from other countries and bring unique perspectives and skills. OBJECTIVES/EVALUATION: To characterize international officers who participated in the EIS program and describe their employment settings after training completion. DESIGN: International officers were people who participated in EIS and who were not US citizens or permanent residents. We analyzed data from EIS's application database during 2009-2017 to describe officers' characteristics. We used data from the Centers for Disease Control and Prevention's (CDC's) workforce database for civil servants and EIS exit surveys to describe jobs taken after program completion. MAIN OUTCOME MEASURES: We described the characteristics of the international officers, jobs taken immediately after program completion, and duration of employment at CDC. RESULTS: Among 715 officers accepted in EIS classes of 2009-2017, 85 (12%) were international applicants, with citizenships from 40 different countries. Forty (47%) had 1 or more US postgraduate degrees, and 65 (76%) were physicians. Of 78 (92%) international officers with available employment data, 65 (83%) reported taking a job at CDC after program completion. The remaining took a public health job with an international entity (6%), academia (5%), or other jobs (5%). Among 65 international officers who remained working at CDC after graduation, the median employment duration was 5.2 years, including their 2 years in EIS. CONCLUSIONS: Most international EIS graduates remain at CDC after program completion, which strengthens the diversity and capacity of CDC's epidemiological workforce. Further evaluations are needed to determine the effects of pulling away crucial talent from other countries needing experienced epidemiologists and to what extent retaining those persons can benefit public health globally.

PFAS and cancer, a scoping review of the epidemiologic evidence.

BACKGROUND: The number of studies addressing per- and polyfluoroalkyl substances (PFAS) and cancer is increasing. Many communities have had water contaminated by PFAS, and cancer is one of the important community concerns related to PFAS exposure. OBJECTIVES: We critically reviewed the evidence relating to PFAS and cancer from an epidemiologic standpoint to highlight directions for future research that would be the most likely to meaningfully increase knowledge. METHODS: We conducted a search in PubMed for studies of cancer and PFAS (through 9/20/2020). We identified epidemiologic studies that provided a quantitative estimate for some measure of the association between PFAS and cancer. Here, we review that literature, including several aspects of epidemiologic study design that impact the usefulness of study results. RESULTS: We identified 16 cohort (or case-cohort) studies, 10 case-control studies (4 nested within cohorts and 6 non-nested), 1 cross sectional study and 1 ecologic study. The cancer sites with the most evidence of an association with PFAS are testicular and kidney cancer. There are also some suggestions in a few studies of an association with prostate cancer, but the data are inconsistent. DISCUSSION: Each study's design has strengths and limitations. Weaknesses in study design and methods can, in some cases, lead to questionable associations, but in other cases can make it more difficult to detect true associations, if they are present. Overall, the evidence for an association between cancer and PFAS remains sparse. A variety of studies with different strengths and weaknesses can be helpful to clarify associations between PFAS and cancer. Long term follow-up of large-sized cohorts with large exposure contrasts are most likely to be informative.

Association Between CMS Quality Ratings and COVID-19 Outbreaks in Nursing Homes - West Virginia, March 17-June 11, 2020.

Nursing homes are high-risk settings for outbreaks of SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19) (1,2). During the COVID-19 pandemic, U.S. health departments worked to improve infection prevention and control (IPC) practices in nursing homes to prevent outbreaks and limit the spread of COVID-19 in affected facilities; however, limited resources have hampered health departments' ability to rapidly provide IPC support to all nursing homes within their jurisdictions. Since 2008, the Centers for Medicare & Medicaid Services (CMS) has published health inspection results and quality ratings based on their Five-Star Quality Rating System for all CMS-certified nursing homes (3); these ratings might be associated with facility-level risk factors for COVID-19 outbreaks. On April 17, 2020, West Virginia became the first state to mandate and conduct COVID-19 testing for all nursing home residents and staff members to identify and reduce transmission of SARS-CoV-2 in these settings (4). West Virginia's census of nursing home outbreaks was used to examine associations between CMS star ratings and COVID-19 outbreaks. Outbreaks, defined as two or more cases within 14 days (with at least one resident case), were identified in 14 (11%) of 123 nursing homes. Compared with 1-star-rated (lowest rated) nursing homes, the odds of a COVID-19 outbreak were 87% lower among 2- to 3-star-rated facilities (adjusted odds ratio [aOR] = 0.13, 95% confidence interval [CI] = 0.03-0.54) and 94% lower among 4- to 5-star-rated facilities (aOR = 0.06, 95% CI = 0.006-0.39). Health departments could use star ratings to help identify priority nursing homes in their jurisdictions to inform the allocation of IPC resources. Efforts to mitigate outbreaks in high-risk nursing homes are necessary to reduce overall COVID-19 mortality and associated disparities. Moreover, such efforts should incorporate activities to improve the overall quality of life and care of nursing home residents and staff members and address the social and health inequities that have been recognized as a prominent feature of the COVID-19 pandemic in the United States (5).

Racial and Ethnic Disparities Among COVID-19 Cases in Workplace Outbreaks by Industry Sector - Utah, March 6-June 5, 2020.

Improved understanding of the overall distribution of workplace coronavirus disease 2019 (COVID-19) outbreaks by industry sector could help direct targeted public health action; however, this has not been described. The Utah Department of Health (UDOH) analyzed COVID-19 surveillance data to describe workplace outbreaks by industry sectors. In this report, workplaces refer to non-health care, noncongregate-living, and noneducational settings. As of June 5, 2020, UDOH reported 277 COVID-19 outbreaks, 210 (76%) of which occurred in workplaces. Approximately 12% (1,389 of 11,448) of confirmed COVID-19 cases in Utah were associated with workplace outbreaks. The 210 workplace outbreaks occurred in 15 of 20 industry sectors;* nearly one half of all workplace outbreaks occurred in three sectors: Manufacturing (43; 20%), Construction (32; 15%) and Wholesale Trade (29; 14%); 58% (806 of 1,389) of workplace outbreak-associated cases occurred in these three sectors. Although 24% of Utah's workforce in all 15 affected sectors identified as Hispanic or Latino (Hispanic) or a race other than non-Hispanic white (nonwhite†) (1), 73% (970 of 1,335) of workplace outbreak-associated COVID-19 cases were in persons who identified as Hispanic or nonwhite. Systemic social inequities have resulted in the overrepresentation of Hispanic and nonwhite workers in frontline occupations where exposure to SARS-CoV-2, the virus that causes COVID-19, might be higher (2); extra vigilance in these sectors is needed to ensure prevention and mitigation strategies are applied equitably and effectively to workers of racial and ethnic groups disproportionately affected by COVID-19. Health departments can adapt workplace guidance to each industry sector affected by COVID-19 to account for different production processes and working conditions.

Long-Term Supportive Housing is Associated with Decreased Risk for New HIV Diagnoses Among a Large Cohort of Homeless Persons in New York City.

It is unknown whether providing housing to persons experiencing homelessness decreases HIV risk. Housing, including access to preventive services and counseling, might provide a period of transition for persons with HIV risk factors. We assessed whether the new HIV diagnosis rate was associated with duration of supportive housing. We linked data from a cohort of 21,689 persons without a previous HIV diagnosis who applied to a supportive housing program in New York City (NYC) during 2007-2013 to the NYC HIV surveillance registry. We used time-dependent Cox modeling to compare new HIV diagnoses among recipients of supportive housing (defined a priori, for program evaluation purposes, as persons who spent > 7 days in supportive housing; n = 6447) and unplaced applicants (remainder of cohort), after balancing the groups on baseline characteristics with propensity score weights. Compared with unplaced applicants, persons who received ≥ 3 continuous years of supportive housing had decreased risk for new HIV diagnosis (HR 0.10; CI 0.01-0.99). Risk of new HIV diagnosis decreased with longer duration placement in supportive housing. Supportive housing might aid in primary HIV prevention.

Estimating Acute Cardiorespiratory Effects of Ambient Volatile Organic Compounds.

BACKGROUND: The health effects of ambient volatile organic compounds (VOCs) have received less attention in epidemiologic studies than other commonly measured ambient pollutants. In this study, we estimated acute cardiorespiratory effects of ambient VOCs in an urban population. METHODS: Daily concentrations of 89 VOCs were measured at a centrally-located ambient monitoring site in Atlanta and daily counts of emergency department visits for cardiovascular diseases and asthma in the five-county Atlanta area were obtained for the 1998-2008 period. To understand the health effects of the large number of species, we grouped these VOCs a priori by chemical structure and estimated the associations between VOC groups and daily counts of emergency department visits in a time-series framework using Poisson regression. We applied three analytic approaches to estimate the VOC group effects: an indicator pollutant approach, a joint effect analysis, and a random effect meta-analysis, each with different assumptions. We performed sensitivity analyses to evaluate copollutant confounding. RESULTS: Hydrocarbon groups, particularly alkenes and alkynes, were associated with emergency department visits for cardiovascular diseases, while the ketone group was associated with emergency department visits for asthma. CONCLUSIONS: The associations observed between emergency department visits for cardiovascular diseases and alkenes and alkynes may reflect the role of traffic exhaust, while the association between asthma visits and ketones may reflect the role of secondary organic compounds. The different patterns of associations we observed for cardiovascular diseases and asthma suggest different modes of action of these pollutants or the mixtures they represent.

Evaluation of individual and area-level factors as modifiers of the association between warm-season temperature and pediatric asthma morbidity in Atlanta, GA.

INTRODUCTION: Previous studies have found associations between respiratory morbidity and high temperatures; however, few studies have explored associations in potentially sensitive sub-populations. METHODS: We evaluated individual and area-level factors as modifiers of the association between warm-season (May-Sept.) temperature and pediatric respiratory morbidity in Atlanta. Emergency department (ED) visit data were obtained for children, 5-18 years old, with primary diagnoses of asthma or respiratory disease (diagnoses of upper respiratory infections, bronchiolitis, pneumonia, chronic obstructive pulmonary disease, asthma, or wheeze) in 20-county Atlanta during 1993-2012. Daily maximum temperature (Tmax) was acquired from the automated surface observing station at Atlanta Hartsfield International Airport. Poisson generalized linear models were used to estimate rate ratios (RR) between daily Tmax and asthma or respiratory disease ED visits, controlling for time and meteorology. Tmax effects were estimated for single-day lags of 0-6 days, for 3-, 5-, and 7-day moving averages and modeled with cubic terms to allow for non-linear relationships. Effect modification by individual factors (sex, race, insurance status) and area-level socioeconomic status (SES; ZIP code levels of poverty, education, and the neighborhood deprivation index) was examined via stratification. RESULTS: Estimated RRs for Tmax and pediatric asthma ED visits were positive and significant for lag days 1-5, with the strongest single day association observed on lag day 2 (RR=1.06, 95% CI: 1.03, 1.09) for a change in Tmax from 27°C to 32°C (25th to 75th percentile). For the moving average exposure periods, associations increased as moving average periods increased. We observed stronger RRs between Tmax and asthma among males compared to females, non-white children compared to white children, children with private insurance compared to children with Medicaid, and among children living in high compared to low SES areas. Associations between Tmax and respiratory disease ED visits were weak and non-significant (p-value>0.05). CONCLUSIONS: Results suggest socio-demographic factors (race/ethnicity, insurance status, and area-level SES) may confer vulnerability to temperature-related pediatric asthma morbidity. Our findings of weaker associations among children with Medicaid compared to other health insurance types and among children living in low compared to high SES areas run counter to our belief that children from disadvantaged households or ZIP codes would be more vulnerable to the respiratory effects of temperature. The potential reasons for these unexpected results are explored in the discussion.

Ozone and childhood respiratory disease in three US cities: evaluation of effect measure modification by neighborhood socioeconomic status using a Bayesian hierarchical approach.

BACKGROUND: Ground-level ozone is a potent airway irritant and a determinant of respiratory morbidity. Susceptibility to the health effects of ambient ozone may be influenced by both intrinsic and extrinsic factors, such as neighborhood socioeconomic status (SES). Questions remain regarding the manner and extent that factors such as SES influence ozone-related health effects, particularly across different study areas. METHODS: Using a 2-stage modeling approach we evaluated neighborhood SES as a modifier of ozone-related pediatric respiratory morbidity in Atlanta, Dallas, & St. Louis. We acquired multi-year data on emergency department (ED) visits among 5-18 year olds with a primary diagnosis of respiratory disease in each city. Daily concentrations of 8-h maximum ambient ozone were estimated for all ZIP Code Tabulation Areas (ZCTA) in each city by fusing observed concentration data from available network monitors with simulations from an emissions-based chemical transport model. In the first stage, we used conditional logistic regression to estimate ZCTA-specific odds ratios (OR) between ozone and respiratory ED visits, controlling for temporal trends and meteorology. In the second stage, we combined ZCTA-level estimates in a Bayesian hierarchical model to assess overall associations and effect modification by neighborhood SES considering categorical and continuous SES indicators (e.g., ZCTA-specific levels of poverty). We estimated ORs and 95% posterior intervals (PI) for a 25 ppb increase in ozone. RESULTS: The hierarchical model combined effect estimates from 179 ZCTAs in Atlanta, 205 ZCTAs in Dallas, and 151 ZCTAs in St. Louis. The strongest overall association of ozone and pediatric respiratory disease was in Atlanta (OR = 1.08, 95% PI: 1.06, 1.11), followed by Dallas (OR = 1.04, 95% PI: 1.01, 1.07) and St. Louis (OR = 1.03, 95% PI: 0.99, 1.07). Patterns of association across levels of neighborhood SES in each city suggested stronger ORs in low compared to high SES areas, with some evidence of non-linear effect modification. CONCLUSIONS: Results suggest that ozone is associated with pediatric respiratory morbidity in multiple US cities; neighborhood SES may modify this association in a non-linear manner. In each city, children living in low SES environments appear to be especially vulnerable given positive ORs and high underlying rates of respiratory morbidity.

Perfluorooctanoic acid exposure and natural menopause: A longitudinal study in a community cohort.

INTRODUCTION: Perfluorooctanoic acid (PFOA), a suspected endocrine disruptor, is a bio-persistent chemical found at low levels in the serum of nearly all U.S. residents. Early menopause has been positively associated with serum PFOA in prior cross-sectional studies. METHODS: We conducted a longitudinal analysis of age at menopause among women, aged ≥40 years, (N=8759) in a Mid-Ohio Valley community cohort, exposed to high PFOA levels via contaminated drinking water. Using estimated retrospective year-specific serum PFOA concentrations (1951-2011), we examined the associations between PFOA, as cumulative exposure or year-specific serum estimates, and natural menopause using a Cox proportional hazards models. As participants were initially recruited in 2005-2006, we also analyzed the cohort prospectively (i.e., from the time of enrollment), using both modeled cumulative PFOA, and PFOA serum levels measured in 2005-2006. Women with hysterectomy (a competing risk) were either censored or excluded from the analysis. RESULTS: Neither in the retrospective nor the prospective cohort did we find a significant (at α=0.05) trend between PFOA exposure and natural menopause. The non-significant, hazard ratios by quintile of increasing cumulative serum PFOA were 1.00 (referent), 1.00, 1.09, 1.05 and 1.06 (trend test for log cumulative exposure: p=0.37) with hysterectomies censored, and 1.00 (referent), 1.06, 1.13, 1.09 and 1.11 (trend test for log cumulative exposure: p=0.85) with hysterectomies excluded. Year-specific serum estimates were also not associated with early menopause. CONCLUSION: Our data suggest that earlier age at menopause is not associated with PFOA exposure.

Warm season temperatures and emergency department visits in Atlanta, Georgia.

PURPOSE: Extreme heat events will likely increase in frequency with climate change. Heat-related health effects are better documented among the elderly than among younger age groups. We assessed associations between warm-season ambient temperature and emergency department (ED) visits across ages in Atlanta during 1993-2012. METHODS: We examined daily counts of ED visits with primary diagnoses of heat illness, fluid/electrolyte imbalances, renal disease, cardiorespiratory diseases, and intestinal infections by age group (0-4, 5-18, 19-64, 65+years) in relation to daily maximum temperature (TMX) using Poisson time series models that included cubic terms for TMX at single-day lags of 0-6 days, controlling for maximum dew-point temperature, time trends, week day, holidays, and hospital participation periods. We estimated rate ratios (RRs) and 95% confidence intervals (CI) for TMX changes from 27°C to 32°C (25th to 75th percentile) and conducted extensive sensitivity analyses. RESULTS: We observed associations between TMX and ED visits for all internal causes, heat illness, fluid/electrolyte imbalances, renal diseases, asthma/wheeze, diabetes, and intestinal infections. Age groups with the strongest observed associations were 65+years for all internal causes [lag 0 RR (CI)=1.022 (1.016-1.028)] and diabetes [lag 0 RR=1.050 (1.008-1.095)]; 19-64 years for fluid/electrolyte imbalances [lag 0 RR=1.170 (1.136-1.205)] and renal disease [lag 1 RR=1.082 (1.065-1.099)]; and 5-18 years for asthma/wheeze [lag 2 RR=1.059 (1.030-1.088)] and intestinal infections [lag 1 RR=1.120 (1.041-1.205)]. CONCLUSIONS: Varying strengths of associations between TMX and ED visits by age suggest that optimal interventions and health-impact projections would account for varying heat health impacts across ages.

Perfluorooctanoic acid and chronic kidney disease: Longitudinal analysis of a Mid-Ohio Valley community.

INTRODUCTION: Perfluorooctanoic acid (PFOA) is an environmentally persistent chemical found at low-levels in the serum of almost all U.S. residents. Chronic kidney disease (CKD) has been positively associated with serum PFOA in prior cross-sectional studies and in one occupational mortality study, while other investigations have found no association between kidney function and PFOA. METHODS: We conducted a longitudinal analysis of chronic kidney disease among adults, aged ≥20 years, (N=32,254) in a Mid-Ohio Valley community cohort, exposed to high PFOA levels from contaminated drinking water. Estimated retrospective yearly serum PFOA concentrations (1951-2011) were previously modeled in this population. Information about lifetime history of CKD diagnosis was collected during surveys in 2008-2011; self-reported CKD diagnoses were validated through medical record review. Using a Cox proportional hazards model, we retrospectively examined the association between validated adult onset CKD, and modeled PFOA exposure, from time of first exposure. We also analyzed data for the cohort prospectively, among people with no CKD diagnosis prior to enrollment in a baseline survey in 2005-2006. Both the full cohort and a non-diabetic subset were analyzed, retrospectively and prospectively. RESULTS: Neither in retrospective nor in prospective analyses did we find a significant (α=0.05) trend between PFOA exposure and CKD. In the full cohort, estimated hazard ratios by quintile of cumulative serum PFOA in the retrospective analysis were 1.00 (referent), 1.26, 1.12, 1.12 and 1.24 (trend test for log cumulative exposure: p=0.80). CONCLUSION: Our analyses suggest that CKD is not associated with exposure to PFOA.

Modification of Traffic-related Respiratory Response by Asthma Control in a Population of Car Commuters.

BACKGROUND: Effects of traffic-related exposures on respiratory health are well documented, but little information is available about whether asthma control influences individual susceptibility. We analyzed data from the Atlanta Commuter Exposure study to evaluate modification of associations between rush-hour commuting, in- vehicle air pollution, and selected respiratory health outcomes by asthma control status. METHODS: Between 2009 and 2011, 39 adults participated in Atlanta Commuter Exposure, and each conducted two scripted rush-hour highway commutes. In-vehicle particulate components were measured during all commutes. Among adults with asthma, we evaluated asthma control by questionnaire and spirometry. Exhaled nitric oxide, forced expiratory volume in 1 second (FEV1), and other metrics of respiratory health were measured precommute and 0, 1, 2, and 3 hours postcommute. We used mixed effects linear regression to evaluate associations between commute-related exposures and postcommute changes in metrics of respiratory health by level of asthma control. RESULTS: We observed increased exhaled nitric oxide across all levels of asthma control compared with precommute measurements, with largest postcommute increases observed among participants with below-median asthma control (2 hours postcommute: 14.6% [95% confidence interval {CI} = 5.7, 24.2]; 3 hours postcommute: 19.5% [95% CI = 7.8, 32.5]). No associations between in-vehicle pollutants and percent of predicted FEV1 were observed, although higher PM2.5 was associated with lower FEV1 % predicted among participants with below-median asthma control (3 hours postcommute: -7.2 [95% CI = -11.8, -2.7]). CONCLUSIONS: Level of asthma control may influence respiratory response to in-vehicle exposures experienced during rush-hour commuting.

A cohort incidence study of workers exposed to perfluorooctanoic acid (PFOA).

OBJECTIVES: Determine if perfluorooctanoic acid (PFOA) is associated with an incident disease in an occupational cohort. METHODS: We interviewed 3713 workers or their next of kin in 2008-2011, and sought medical records for self-reported disease. These workers were a subset of a previously studied cohort of 32,254 community residents and workers. We estimated historical PFOA serum levels via a job-exposure matrix based on over 2000 serum measurements. Non-occupational exposure from drinking water was also estimated. Lifetime serum cumulative dose (combining occupational and non-occupational exposure) was our exposure metric. We studied 17 disease outcomes with more than 20 validated cases. RESULTS: The median measured serum level was 113 ng/mL in 2005 (n=1881), compared with 4 ng/mL in the US. Ulcerative colitis (10-year lag) showed a significant trend (p≤0.05) with increasing dose (quartile rate ratios (RRs)=1.00, 3.00, 3.26, 6.57, n=28, p for trend=0.05), similar to earlier findings in the community study. Rheumatoid arthritis (no lag) showed a positive trend in a categorical trend test (RRs=1.00, 2.11, 4.08, 4.45, n=23, p for trend=0.04). Positive non-significant trends were also observed for prostate cancer, non-hepatitis liver disease and male hypothyroidism, which have been implicated in other studies. A significant negative trend was found for bladder cancer and asthma with medication. No marked trends were seen for high cholesterol, which had been seen in the community study. CONCLUSIONS: Ulcerative colitis and rheumatoid arthritis were positively linked to PFOA exposure among workers. Data were limited by small numbers, under-representation of hard-to-trace decedents and few low-exposed referents.

Disease fatality and bias in survival cohorts.

OBJECTIVES: Simulate how the effect of exposure on disease occurrence and fatality influences the presence and magnitude of bias in survivor cohorts, motivated by an actual survivor cohort under study. METHODS: We simulated a cohort of 50,000 subjects exposed to a disease-causing exposure over time and followed forty years, where disease incidence was the outcome of interest. We simulated this 'inception' cohort under different assumptions about the effect of exposure on disease occurrence and fatality after disease occurrence. We then created a corresponding 'survivor' (or 'cross-sectional') cohort, where cohort enrollment took place at a specific date after exposure began in the inception cohort; subjects dying prior to that enrollment date were excluded. The disease of interest caused all deaths in our simulations, but was not always fatal. In the survivor cohort, person-time at risk began before enrollment for all subjects who did not die prior to enrollment. We compared exposure-disease associations in each inception cohort to those in corresponding survivor cohorts to determine how different assumptions impacted bias in the survivor cohorts. All subjects in both inception and survivor cohorts were considered equally susceptible to the effect of exposure in causing disease. We used Cox proportional hazards regression to calculate effect measures. RESULTS: There was no bias in survivor cohort estimates when case fatality among diseased subjects was independent of exposure. This was true even when the disease was highly fatal and more highly exposed subjects were more likely to develop disease and die. Assuming a positive exposure-response in the inception cohort, survivor cohort rate ratios were biased downwards when case fatality was greater with higher exposure. CONCLUSIONS: Survivor cohort effect estimates for fatal outcomes are not always biased, although precision can decrease.

Associations between ambient air pollutant mixtures and pediatric asthma emergency department visits in three cities: a classification and regression tree approach.

BACKGROUND: Characterizing multipollutant health effects is challenging. We use classification and regression trees to identify multipollutant joint effects associated with pediatric asthma exacerbations and compare these results with those from a multipollutant regression model with continuous joint effects. METHODS: We investigate the joint effects of ozone, NO2 and PM2.5 on emergency department visits for pediatric asthma in Atlanta (1999-2009), Dallas (2006-2009) and St. Louis (2001-2007). Daily concentrations of each pollutant were categorized into four levels, resulting in 64 different combinations or "Day-Types" that can occur. Days when all pollutants were in the lowest level were withheld as the reference group. Separate regression trees were grown for each city, with partitioning based on Day-Type in a model with control for confounding. Day-Types that appeared together in the same terminal node in all three trees were considered to be mixtures of potential interest and were included as indicator variables in a three-city Poisson generalized linear model with confounding control and rate ratios calculated relative to the reference group. For comparison, we estimated analogous joint effects from a multipollutant Poisson model that included terms for each pollutant, with concentrations modeled continuously. RESULTS AND DISCUSSION: No single mixture emerged as the most harmful. Instead, the rate ratios for the mixtures suggest that all three pollutants drive the health association, and that the rate plateaus in the mixtures with the highest concentrations. In contrast, the results from the comparison model are dominated by an association with ozone and suggest that the rate increases with concentration. CONCLUSION: The use of classification and regression trees to identify joint effects may lead to different conclusions than multipollutant models with continuous joint effects and may serve as a complementary approach for understanding health effects of multipollutant mixtures.

Perfluorooctanoic acid exposure and thyroid disease in community and worker cohorts.

BACKGROUND: Perfluorooctanoic acid (PFOA) was released from a mid-Ohio River Valley chemical plant, exposing the surrounding community to PFOA for >50 years, primarily through drinking water. Toxicological studies and some previous human studies have suggested that PFOA can disrupt thyroid homeostasis. We examined the association between PFOA and thyroid disease among community members and plant workers. METHODS: Participants completed health surveys during 2008-2011. Yearly serum PFOA concentrations were estimated for each participant starting at birth or in 1952, whichever came later. We used Cox proportional hazard models, stratified by birth year, to assess adult thyroid disease hazard in relation to time-varying yearly or cumulative (sum of yearly estimates) estimated PFOA serum concentration, controlling for sex, race, education, smoking, and alcohol use. RESULTS: Of 32,254 participants, 3,633 reported functional thyroid disease (excluding neoplasms, congenital disease, nodules without functional changes, cysts, and unspecified type). Analyses were restricted to 2109 cases of functional thyroid disease with thyroid prescription medication use and validation through medical record review. In analyses starting at age 20 years or in 1952, thyroid disease hazard ratios across cumulative exposure quintiles were 1.00, 1.24, 1.27, 1.36, and 1.37 among women and 1.00, 1.12, 0.83, 1.01, and 1.05 among men (log-linear trend tests: P = 0.03 and P = 0.85, respectively); similar results were observed for yearly exposure. Associations were observed for hyperthyroidism and hypothyroidism among women. Some subanalyses also suggested an increased hazard of hypothyroidism among men. CONCLUSIONS: Higher PFOA exposure was associated with incident functional thyroid disease in this large cohort with high exposure.

PFOA and PFOS serum levels and miscarriage risk.

BACKGROUND: Serum concentrations of perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS) were assessed in relation to miscarriage in a population of mid-Ohio River Valley residents highly exposed to PFOA through contaminated drinking water. METHODS: Serum PFOA and PFOS concentrations were measured in 1129 women in 2005-2006 who reported pregnancy outcomes in follow-up interviews between 2008 and 2011. In the analysis, we included 1438 reported live births, stillbirths, and miscarriages with estimated conception dates after the serum measurements. Preconception serum levels of PFOA and PFOS were analyzed in relation to miscarriage using logistic regression and generalized estimating equations. RESULTS: There was little evidence of association between PFOA and miscarriage. For PFOS, when including all reported prospective pregnancies, the odds ratio of miscarriage per log ng/ml increase was 1.21 (95% confidence interval = 0.94-1.55); in subanalyses restricted to each woman's first pregnancy conceived after the serum measurement, the odds ratio was 1.34 (1.02-1.76). Categorical analyses showed elevated odds ratios for the top 4 quintiles relative to the first quintile, without a monotonic trend. Positive associations between PFOS and miscarriage were strongest among nulligravid pregnancies. CONCLUSIONS: In this prospective study of miscarriage in a population exposed to high levels of PFOA and background levels of PFOS, we found little evidence of association with serum levels of PFOA and limited evidence of association with serum levels of PFOS.

Joint effects of ambient air pollutants on pediatric asthma emergency department visits in Atlanta, 1998-2004.

BACKGROUND: Because ambient air pollution exposure occurs as mixtures, consideration of joint effects of multiple pollutants may advance our understanding of the health effects of air pollution. METHODS: We assessed the joint effect of air pollutants on pediatric asthma emergency department visits in Atlanta during 1998-2004. We selected combinations of pollutants that were representative of oxidant gases and secondary, traffic, power plant, and criteria pollutants, constructed using combinations of criteria pollutants and fine particulate matter (PM2.5) components. Joint effects were assessed using multipollutant Poisson generalized linear models controlling for time trends, meteorology, and daily nonasthma upper respiratory emergency department visit counts. Rate ratios (RRs) were calculated for the combined effect of an interquartile range increment in each pollutant's concentration. RESULTS: Increases in all of the selected pollutant combinations were associated with increases in warm-season pediatric asthma emergency department visits (eg, joint-effect RR = 1.13 [95% confidence interval = 1.06-1.21] for criteria pollutants, including ozone, carbon monoxide, nitrogen dioxide, sulfur dioxide, and PM2.5). Cold-season joint effects from models without nonlinear effects were generally weaker than warm-season effects. Joint-effect estimates from multipollutant models were often smaller than estimates based on single-pollutant models, due to control for confounding. Compared with models without interactions, joint-effect estimates from models including first-order pollutant interactions were largely similar. There was evidence of nonlinear cold-season effects. CONCLUSIONS: Our analyses illustrate how consideration of joint effects can add to our understanding of health effects of multipollutant exposures and also illustrate some of the complexities involved in calculating and interpreting joint effects of multiple pollutants.