Vaughn Barry

Perfluorooctanoic Acid (PFOA) Exposures and Incident Cancers among Adults Living near a Chemical Plant

Background: Perfluorooctanoic acid (PFOA) is a synthetic chemical ubiquitous in the serum of U.S. residents. It causes liver, testicular, and pancreatic tumors in rats. Human studies are sparse. Objective: We examined cancer incidence in Mid-Ohio Valley residents exposed to PFOA in drinking water due to chemical plant emissions. Methods: The cohort consisted of adult community residents who resided in contaminated water districts or worked at a local chemical plant. Most participated in a 2005–2006 baseline survey in which serum PFOA was measured. We interviewed the cohort in 2008–2011 to obtain further medical history. Retrospective yearly PFOA serum concentrations were estimated for each participant from 1952 through 2011. Self-reported cancers were validated through medical records and cancer registry review. We estimated the association between cancer and cumulative PFOA serum concentration using proportional hazards models. Results: Participants (n = 32,254) reported 2,507 validated cancers (21 different cancer types). Estimated cumulative serum PFOA concentrations were positively associated with kidney and testicular cancer [hazard ratio (HR) = 1.10; 95% CI: 0.98, 1.24 and HR = 1.34; 95% CI: 1.00, 1.79, respectively, for 1-unit increases in ln-transformed serum PFOA]. Categorical analyses also indicated positive trends with increasing exposures for both cancers: for kidney cancer HRs for increasing exposure quartiles were 1.0, 1.23, 1.48, and 1.58 (linear trend test p = 0.18) and for testicular cancer, HRs were 1.0, 1.04, 1.91, 3.17 (linear trend test p = 0.04). Conclusions: PFOA exposure was associated with kidney and testicular cancer in this population. Because this is largely a survivor cohort, findings must be interpreted with caution, especially for highly fatal cancers such as pancreatic and lung cancer. Citation: Barry V, Winquist A, Steenland K. 2013. Perfluorooctanoic acid (PFOA) exposures and incident cancers among adults living near a chemical plant. Environ Health Perspect 121:1313–1318; http://dx.doi.org/10.1289/ehp.1306615

Early life perfluorooctanoic acid (PFOA) exposure and overweight and obesity risk in adulthood in a community with elevated exposure.

BACKGROUND Infants and young children may be susceptible to developmental effects of perfluorooctanoic acid (PFOA) exposure. Two previous studies, one that examined a general population exposed to environmental PFOA levels and one conducted in mice exposed to experimental PFOA levels, found that early life exposure was associated with higher body mass index (BMI) in adulthood and effects may be stronger in women than in men. OBJECTIVES Examine whether elevated early life PFOA exposure was associated with adult BMI among a group of mid-Ohio valley residents exposed to a wide range of early life PFOA levels due to emissions from a chemical plant. METHODS The cohort consisted of 8764 adults aged 20-40 years who reported height and weight on a survey between 2008 and 2011. Annual retrospective early life PFOA serum concentrations were estimated for each participant based on residential history and nearby chemical plant emissions as well as background exposure not originating from the facility. We defined early life exposure as the estimated average PFOA serum concentration over the first three years of life. We examined the association between early life PFOA exposure and adult overweight (BMI ≥ 25 kg/m(2)) and obesity (BMI ≥ 30 kg/m(2)) risk using logistic and linear regression models. RESULTS Nearly half the participants (45%) had early life PFOA exposure serum concentration estimates above background levels. Using participants who were exposed only to background PFOA levels as the referent category with quintiles of exposure above background, adjusted odds ratios (and 95% confidence intervals) for overweight risk by increasing exposure category for women were 1.0 (ref), 1.0 (0.8, 1.3), 1.0 (0.8, 1.2), 1.0 (0.8, 1.2), 0.9 (0.7, 1.1), and 0.9 (0.7, 1.1) and for men were 1.0 (ref), 0.9 (0.6, 1.1), 1.0 (0.7, 1.3), 1.0 (0.8, 1.4), 0.7 (0.5, 0.9), and 0.9 (0.7, 1.1). Odds ratios for adult obesity risk were similar. Regression coefficients from linear models using BMI as a continuous outcome showed no association between early life PFOA exposure and adult BMI. CONCLUSIONS Elevated levels of PFOA exposure in early life were not associated with overweight and obesity risk in adulthood and results did not vary by sex.

Responsiveness of PROMIS® Pediatric Measures to Hospitalizations for Sickle Pain and Subsequent Recovery.

The Patient‐Reported Outcomes Measurement Information System® (PROMIS®) created pediatric self‐report scales measuring a variety of health attributes (domains), but their responsiveness to changes in health status has not yet been determined in children with sickle cell disease (SCD).

Initial Evaluation of the Pediatric PROMIS® Health Domains in Children and Adolescents With Sickle Cell Disease.

The Patient Reported Outcomes Measurement Information System (PROMIS®) has developed pediatric self‐report scales measuring several unidimensional health attributes (domains) suitable for use in clinical research, but these measures have not yet been validated in sickle cell disease (SCD).

Hydroxyurea effectiveness in children and adolescents with sickle cell anemia: A large retrospective, population-based cohort

The clinical efficacy of hydroxyurea in patients with sickle cell anemia (SCA) has been well established. However, data about its clinical effectiveness in practice is limited. We evaluated the clinical effectiveness of hydroxyurea in a large pediatric population using a retrospective cohort, pre‐post treatment study design to control for disease severity selection bias. The cohort included children with SCA (SS, Sβ0thalassemia) who received care at Childrens Healthcare of Atlanta (CHOA) and who initiated hydroxyurea in 2009‐2011. Children on chronic transfusions, or children with inadequate follow up data and/or children who had taken hydroxyurea in the 3 years prior were excluded. For each patient healthcare utilization, laboratory values, and clinical outcomes for the 2‐year period prior to hydroxyurea initiation were compared to those 2 years after initiation. Of 211 children with SCA who initiated hydroxyurea in 2009–2011, 134 met eligibility criteria. After initiation of hydroxyurea, rates of hospitalizations, pain encounters, and emergency department visits were reduced by 47% (<0.0001), 36% (P = 0.0001) and 43% (P < 0.0001), respectively. Average hemoglobin levels increased by 0.7 g/dl (P < 0.0001). Hydroxyurea effectiveness was similar across gender, insurance types and age, although there was a slightly greater reduction in hospitalizations in younger children. Am. J. Hematol. 92:77–81, 2017.

Distress in patients with bleeding disorders: a single institutional cross-sectional study.

Distress may affect a patients ability to cope with and manage disease.

A cohort mortality study of lead-exposed workers in the USA, Finland and the UK

Objectives To investigate further whether inorganic lead is a carcinogen among adults, or associated with increased blood pressure and kidney damage, via a large mortality study. Methods We conducted internal analyses via Cox regression of mortality in three cohorts of lead-exposed workers with blood lead (BL) data (USA, Finland, UK), including over 88 000 workers and over 14 000 deaths. Our exposure metric was maximum BL. We also conducted external analyses using country-specific background rates. Results The combined cohort had a median BL of 26 µg/dL, a mean first-year BL test of 1990 and was 96% male. Fifty per cent had more than one BL test (mean 7). Significant (p<0.05) positive trends, using the log of each worker’s maximum BL, were found for lung cancer, chronic obstructive pulmonary disease (COPD), stroke and heart disease, while borderline significant trends (0.05≤p≤0.10) were found for bladder cancer, brain cancer and larynx cancer. Most results were consistent across all three cohorts. In external comparisons, we found significantly elevated SMRs for those with BLs>40 µg/dL; for bladder, lung and larynx cancer; and for COPD. In a small subsample of the US cohort (n=115) who were interviewed, we found no association between smoking and BL. Conclusions We found strong positive mortality trends, with increasing BL level, for several outcomes in internal analysis. Many of these outcomes are associated with smoking, for which we had no data. A borderline trend was found for brain cancer, not associated with smoking.

Physician trust and depression influence adherence to factor replacement: a single‐centre cross‐sectional study

Poor adherence to factor replacement therapy among patients with haemophilia can lead to joint bleeding and eventual disability.

Determining Adherence to Quality Indicators in Sickle Cell Anemia Using Multiple Data Sources.

INTRODUCTION Advances in primary prophylaxis have resulted in improved outcomes for patients with sickle cell anemia (SCA; i.e., hemoglobin SS- and Sβ(0)-thalassemia). Standard prophylactic measures include a first pneumococcal polysaccharide vaccine (PPV) and transcranial Doppler ultrasound (TCD) at age 2 years. Though efficacious, evidence suggests that delivery of these interventions is suboptimal. This study reports adherence to these measures and examines concordance across various data sources, using Registry and Surveillance for Hemoglobinopathies project data. METHODS Retrospective database and SCA center chart review identified children with SCA aged 24-36 months between January 1, 2004, and December 31, 2008. PPV and TCD administration were determined through Medicaid and Childrens Health Insurance Program administrative claims data, medical record review, and Georgia Registry of Immunization Transaction and Services. Analysis was conducted in 2015. RESULTS A total of 125 children met inclusion criteria. Forty-five (36.0%) children had documentation of both interventions, whereas 19 (15.2%) had no documentation of either intervention. Sixty-one (48.8%) children obtained only one intervention. Of these, more were likely to have had PPV than TCD (77.0% vs 23.0%, respectively, p<0.001). Agreement between claims data and medical record review was moderate for PPV (κ=0.55) and substantial for TCD (κ=0.74). CONCLUSIONS No single, reliable data source for tracking standard of care for children with SCA statewide was found. According to study data, prophylaxis measures were not universally implemented during the surveillance period. Further research is needed to adequately track changes over time, determine risk groups, and develop methods of evaluating important metrics.

Characterization of the concentration-response curve for ambient ozone and acute respiratory morbidity in 5 US cities

Although short-term exposure to ambient ozone (O3) can cause poor respiratory health outcomes, the shape of the concentration-response (C-R) between O3 and respiratory morbidity has not been widely investigated. We estimated the effect of daily O3 on emergency department (ED) visits for selected respiratory outcomes in 5 US cities under various model assumptions and assessed model fit. Population-weighted average 8-h maximum O3 concentrations were estimated in each city. Individual-level data on ED visits were obtained from hospitals or hospital associations. Poisson log-linear models were used to estimate city-specific associations between the daily number of respiratory ED visits and 3-day moving average O3 levels controlling for long-term trends and meteorology. Linear, linear-threshold, quadratic, cubic, categorical, and cubic spline O3 C-R models were considered. Using linear C-R models, O3 was significantly and positively associated with respiratory ED visits in each city with rate ratios of 1.02–1.07 per 25 ppb. Models suggested that O3-ED C-R shapes were linear until O3 concentrations of roughly 60 ppb at which point risk continued to increase linearly in some cities for certain outcomes while risk flattened in others. Assessing C-R shape is necessary to identify the most appropriate form of the exposure for each given study setting.