Introduction.
Perfluorooctanoic acid (PFOA) has been associated with kidney cancer in human studies.
Methods.
We conducted a pooled analysis of two large studies of PFOA and renal cell carcinoma (RCC, the most common type of kidney cancer); one from the National Cancer Institute (NCI) ( 324 cases and controls), and a second from the C8 Science Panel (103 cases and 511 controls). Serum PFOA levels were estimated a median of 8 years before diagnosis. Analyses were conducted via conditional logistic regression. Lifetime risk of kidney cancer per unit serum PFOA concentration and per unit dose were calculated.
Results.
The 25th, 50th and 75th percentiles of serum PFOA levels were 4.8, 7.3, and 23.9 ng/ml for the pooled analysis. The preferred model for the pooled data was a two-piece linear spline model (knot at 12.5 ng/ml serum PFOA); the log odds of RCC increased 0.1349 per 1 ng/ml increase in serum PFOA up to the knot (eg, an OR of 2.02 (1.45–2.80) from the median to the knot), and was flat thereafter. The estimated lifetime excess risk (cancer slope factor) with an exposure of 1 ng/ml was 0.0018, similar to the excess risk of 0.0026 recently reported by CalEPA based on different methods. Assuming a serum half-life of 2.3 years and a distribution volume of 170 mL/kg for PFOA, our results are equivalent to 0.0128 per ng/kg/d of PFOA intake. To limit excess lifetime kidney cancer risk to 1/1,000,000, our data suggest a limit of 0.0015 ng/L (0.0015 ppt) for PFOA in drinking water, similar to CalEPA’s proposed Public Health Goal and the new US EPA Drinking Water Health Advisory.
Conclusions.
Our results correspond reasonably well with cancer slope factors developed by other investigators using published summary data, and suggest drinking water limits similar to new recommendations by the US EPA.
by
Elvira Vaclavik Bräuner;
Zorana Jovanovic Andersen;
Marie Frederiksen;
Ina Olmer Specht;
Karin Sørig Hougaard;
Niels Ebbehøj;
Janice Bailey;
Aleksander Giwercman;
Nelson Steenland;
Matthew Paul Longnecker;
Jens Peter Bonde
Polychlorinated-biphenyls (PCBs) were introduced in the late 1920s and used until the 1970s when they were banned in most countries due to evidence of environmental build-up and possible adverse health effects. However they still persist in the environment, indoors and in humans. Indoor air in contaminated buildings may confer airborne exposure markedly above background regional PCB levels. To date, no epidemiological studies have assessed the health effects from exposure to semi-volatile PCBs in the indoor environment. Indoor air PCBs are generally less chlorinated than PCBs that are absorbed via the diet, or via past occupational exposure; therefore their health effects require separate risk assessment. Two separate cohorts of individuals who have either attended schools (n = 66,769; 26% exposed) or lived in apartment buildings (n = 37,185; 19% exposed), where indoor air PCB concentrations have been measured were created. An individual estimate of long-term airborne PCB exposure was assigned based on measurements. The cohorts will be linked to eight different national data sources on mortality, school records, residential history, socioeconomic status, and chronic disease and reproductive outcomes. The linking of indoor air exposures with health outcomes provides a dataset unprecedented worldwide. We describe a project, called HESPERUS (Health Effects of PCBs in Residences and Schools), which will be the first study of the long term health effects of the lower-chlorinated, semi-volatile PCBs in the indoor environment.
OBJECTIVES: To assess the effect of modulation of the renin-angiotensin system (RAS) on conversion to Alzheimer's disease (AD) and cognitive decline in people with mild cognitive impairment (MCI) and the effect of the permeability of the blood-brain barrier (BBB) and race on the potential relationship between the RAS and AD.
DESIGN: Analysis of data from AD centers funded by the National Alzheimer's Coordinating Center, National Institute on Aging.
SETTING: Alzheimer's Disease Centers.
PARTICIPANTS: Individuals receiving antihypertensive medications who had MCI at baseline and had cognitive assessments on at least two follow-up visits (N = 784; mean age 75 l 48/% male).
MEASUREMENTS: Conversion to AD and cognitive and functional decline.
RESULTS: Four hundred eighty-eight participants were receiving RAS-acting antihypertensive medications. RAS-acting medication users were less likely to convert to AD (33% vs 40%; P =.04) and had slower decline on the Clinical Dementia Rating Sum of Boxes (CDR-SOB, P =.005) and Digit Span Forward (P =.02) than nonusers. BBB-crossing RAS-acting medications were associated with slower cognitive decline on the CDR-SOB, (P =.009), the Mini-Mental State Examination (MMSE), (P =.001), and the Boston Naming test (P =.002). RAS-acting medications were associated with cognitive benefits more in African Americans than in Caucasians (MMSE, P =.05; category fluency, P =.04; Digit Span Backward, P =.03).
CONCLUSION: RAS-acting medication users were less likely to convert to AD. BBB permeability may produce additional cognitive benefit, and African Americans may benefit more from RAS modulation than Caucasians. Results highlight the need for trials investigating RAS modulation during prodromal disease stages.
Background: We previously screened 400 elderly Costa Ricans for neurodegenerative disease. Those reporting occupational pesticide exposure (18%) had an increased Parkinson's disease (PD) risk (OR 2.57, 95% CI 0.91-7.26), and worse cognition (Mini-Mental States Exam (MMSE) 24.5 versus 25.9 points, p=0.01). We subsequently measured long-lasting organochlorine pesticides (β-HCH, DDE, DDT, and dieldrin) in a sub-sample ( n=89). Dieldrin and β-HCH have been linked to PD, and DDE to Alzheimer's disease. Methods: We ran regression models for MMSE and tremor-at-rest to assess associations with pesticides in 89 subjects. Results: The percent of β-HCH, DDE, DDT (parent compound for DDE), and dieldrin above their limit of detection (LOD) were 100%, 93%, 75%, and 57%, respectively. Tremor-at-rest was found in 21 subjects, and the mean MMSE was 25. Those who reported occupational pesticide exposure ( n=36) had more detectable dieldrin samples ( p=0.005), and higher mean levels of dieldrin ( p=0.01), than those not reporting exposure. Other pesticides did not differ between those with and without self-reported occupational exposure. There was a positive but non-significant trend of higher risk for tremor-at-rest with higher dieldrin ( p=0.10 for linear trend). Neither DDE nor DDT showed a relationship with MMSE. However, after excluding two outliers with the lowest MMSE scores, higher DDT levels showed some modest association with lower MMSE ( p=0.09 for linear trend). Conclusions: Our data are limited by small sample size. However, dieldrin was high in our population, has been previously linked to PD, and could be partly responsible for the excess PD risk seen in our population.
Background: Several epidemiological cross-sectional studies have found positive associations between serum concentrations of lipids and perfluorooctanoic acid (PFOA, or C8). A longitudinal study should be less susceptible to biases from uncontrolled confounding or reverse causality.
Methods: We investigated the association between within-individual changes in serum PFOA and perfluorooctanesulfonic acid (PFOS) and changes in serum lipid levels (low-density lipoprotein [LDL] cholesterol, high-density lipoprotein cholesterol, total cholesterol, and triglycerides) over a 4.4-year period. The study population consisted of 560 adults living in parts of Ohio and West Virginia where public drinking water had been contaminated with PFOA. They had participated in a cross-sectional study in 2005–2006, and were followed up in 2010, by which time exposure to PFOA had been substantially reduced.
Results: Overall serum concentrations of PFOA and PFOS fell by half from initial geometric means of 74.8 and 18.5 ng/mL, respectively, with little corresponding change in LDL cholesterol (mean increase 1.8%, standard deviation 26.6%). However, there was a tendency for people with greater declines in serum PFOA or PFOS to have greater LDL decrease. For a person whose serum PFOA fell by half, the predicted fall in LDL cholesterol was 3.6% (95% confidence interval = 1.5–5.7%). The association with a decline in PFOS was even stronger, with a 5% decrease in LDL (2.5–7.4%).
Conclusions: Our findings from this longitudinal study support previous evidence from cross-sectional studies of positive associations between PFOA and PFOS in serum and LDL cholesterol.
Objective: To examine associations between inflammation and cognitive performance in African Americans and Caucasians.
Methods: The sample included 59 African Americans and 219 Caucasians ≥50years old who had a baseline visit at the Emory/Georgia Tech Center for Health Discovery and Well Being. Peripheral levels of inflammation (interleukin-6, interleukin-8, C-reactive protein, and tumor necrosis factor-α) were examined in relation to performance on tests of visual processing (Identify the Odd Pattern), attention (Digit Span Forward), visuomotor set shifting (Digit Symbol Substitution), verbal set shifting (Digit Span Backwards), and memory (Recall a Pattern).
Results: Multiple regression models adjusting for potential demographic and vascular/metabolic confounders were conducted, with markers of inflammation included as either continuous or categorical (quartiles) variables. There were significant interactions between IL-8 and race for the Recall a Pattern (p=.006) and the Digit Symbol Substitution (p=.014) tests. Race-specific analyses (using a continuous variable for IL-8) demonstrated slower response times on the Recall a Pattern and Digit Symbol Substitution tests for African Americans but not for Caucasians. Categorical analyses among African Americans indicated that all of the top three quartiles of IL-8 were associated with slower reaction times on the Recall a Pattern test compared to the lowest quartile, while for Digit Symbol, the highest quartile of IL-8 was associated with the slowest cognitive performance.
Conclusions: These preliminary findings suggest a stronger association between IL-8 and cognitive performance in African Americans than Caucasians. This relationship should be further examined in larger samples that are followed over time.
Background: There are no agreed-upon variables for predicting progression from unimpaired cognition to amnestic mild cognitive impairment (aMCI), or from aMCI to Alzheimer's disease (AD). Objective: Use ADNI data to develop a 'Framingham-like' prediction model for a 4-year period. Methods: We developed models using the strongest baseline predictors from six domains (demographics, neuroimaging, CSF biomarkers, genetics, cognitive tests, and functional ability). We chose the best predictor from each domain, which was dichotomized into more versus less harmful. Results: There were 224 unimpaired individuals and 424 aMCI subjects with baseline data on all predictors, of whom 37 (17%) and 150 (35%) converted to aMCI and AD, respectively, during 4 years of follow-up. For the unimpaired, CSF tau/Aβ ratio, hippocampal volume, and a memory score predicted progression. For those aMCI at baseline, the same predictors plus APOE4 status and functional ability predicted progression. Demographics and family history were not important predictors for progression for either group. The fit statistic was good for the unimpaired-aMCI model (C-statistic 0.80) and very good for the aMCI-AD model (C-statistic 0.91). Among the unimpaired, those with no harmful risk factors had a 4-year predicted 2% risk of progression, while those with the most harmful risk factors had a predicted 35% risk. The aMCI subjects with no harmful risk factors had a predicted 1% risk of progression those with all six harmful risk factors had a predicted 90% risk. Conclusion: Our parsimonious model accurately predicted progression from unimpaired to aMCI with three variables, and from aMCI to AD with five variables.
by
Jennifer Estefania Davila Cordova;
Vilma Tapia Aguirre;
Vanessa Vasquez Apestegui;
Luis Ordonez Ibarguen;
Bryan N. Vu;
Nelson Steenland;
Gustavo F. Gonzales Rengifo
Background: Lima is one of the more polluted cities in Latin America. High levels of PM2.5 have been shown to increase health center outpatient visits of respiratory diseases. Methods: Health center outpatient visits for children < 5 years for childhood respiratory disease (acute lower respiratory infections (ALRI), pneumonia and acute bronchiolitis/asthma) from 498 public clinics in Lima were available on a weekly basis from 2011 to 2015 from Peru's Ministry of Health (MINSA). The association between the average weekly concentrations of PM2.5 was evaluated in relation to the number of weekly health center outpatient visits for children. Weekly PM2.5 values were estimated using a recently developed model that combined data observed from ground monitors, with data from space satellite and meteorology. Ground monitoring data came from 10 fixed stations of the Peruvian National Service of Meteorology and Hydrology (SENAMHI) and from 6 mobile stations located in San Juan de Miraflores by Johns Hopkins University. We conducted a time-series analysis using a negative binomial model. Results: We found a significant association between exposure to PM2.5 and all three types of respiratory diseases, across all age groups. For an interquartile increase in PM2.5, we found an increase of 6% for acute lower respiratory infections, an increase of 16-19% for pneumonia, and an increase of 10% for acute bronchiolitis / asthma. Conclusions: Higher emissions of environmental pollutants such as PM2,5 could be a trigger for the increase of health center outpatients visits for respiratory diseases (ALRI, pneumonia and asthma), which are themselves risk factors for mortality for children in Lima province, Peru.
The integration of mental and neurologic services in healthcare is a global priority. The universal Social Security of Costa Rica aspires to develop national screening of neurodegenerative disorders among the elderly, as part of the non-communicable disease agenda. This study assessed the feasibility of routine screening for Parkinson's disease (PD) and Alzheimer's disease (AD) within the public healthcare system of Costa Rica. The population (aged ≥65) in the catchment areas of two primary healthcare clinics was targeted for motor and cognitive screening during routine annual health check-ups. The screening followed a tiered three-step approach, with increasing specificity. Step 1 involved a two-symptom questionnaire (tremor-at-rest; balance) and a spiral drawing test for motor assessment, as well as a three-word recall and animal category fluency test for cognitive assessment. Step 2 (for those failing Step 1) was a 10-item version of the Unified Parkinson Disease Rating Scale and the Mini-Mental State Examination. Step 3 (for those failing Step 2) was a comprehensive neurologic exam with definitive diagnosis of PD, AD, mild cognitive impairment (MCI), other disorders, or subjects who were healthy. Screening parameters and disease prevalence were calculated. Of the 401 screened subjects (80% of target population), 370 (92%), 163 (45%), and 81 (56%) failed in Step 1, Step 2, and Step 3, respectively. Thirty-three, 20, and 35 patients were diagnosed with PD, AD, and MCI, respectively (7 were PD with MCI/AD); 90% were new cases. Step 1 sensitivities of motor and cognitive assessments regarding Step 2 were both 93%, and Step 2 sensitivities regarding definitive diagnosis 100 and 96%, respectively. Specificities for Step 1 motor and cognitive tests were low (23% and 29%, respectively) and for Step 2 tests acceptable (76%, 94%). Based on international data, PD prevalence was 3.7 times higher than expected; AD prevalence was as expected. Proposed protocol adjustments will increase test specificity and reduce administration time. A routine screening program is feasible within the public healthcare system of Costa Rica.
BACKGROUND: Increasingly, risk of bias tools are used to evaluate epidemiologic studies as part of evidence synthesis (evidence integration), often involving meta-analyses. Some of these tools consider hypothetical randomized controlled trials (RCTs) as gold standards. METHODS: We review the strengths and limitations of risk of bias assessments, in particular, for reviews of observational studies of environmental exposures, and we also comment more generally on methods of evidence synthesis. RESULTS: Although RCTs may provide a useful starting point to think about bias, they do not provide a gold standard for environmental studies. Observational studies should not be considered inherently biased vs. a hypothetical RCT. Rather than a checklist approach when evaluating individual studies using risk of bias tools, we call for identifying and quantifying possible biases, their direction, and their impacts on parameter estimates. As is recognized in many guidelines, evidence synthesis requires a broader approach than simply evaluating risk of bias in individual studies followed by synthesis of studies judged unbiased, or with studies given more weight if judged less biased. It should include the use of classical considerations for judging causality in human studies, as well as triangulation and integration of animal and mechanistic data. CONCLUSIONS: Bias assessments are important in evidence synthesis, but we argue they can and should be improved to address the concerns we raise here. Simplistic, mechanical approaches to risk of bias assessments, which may particularly occur when these tools are used by nonexperts, can result in erroneous conclusions and sometimes may be used to dismiss important evidence. Evidence synthesis requires a broad approach that goes beyond assessing bias in individual human studies and then including a narrow range of human studies judged to be unbiased in evidence synthesis. https:// doi.org/10.1289/EHP6980.