Misclassification of causes of death among a small all-autopsied group of former nuclear workers: Death certificates vs. autopsy reports.

The U.S. Transuranium and Uranium Registries performs autopsies on each of its deceased Registrants as a part of its mission to follow up occupationally-exposed individuals. This provides a unique opportunity to explore death certificate misclassification errors, and the factors that influence them, among this small population of former nuclear workers. Underlying causes of death from death certificates and autopsy reports were coded using the 10th revision of the International Classification of Diseases (ICD-10). These codes were then used to quantify misclassification rates among 268 individuals for whom both full autopsy reports and death certificates with legible underlying causes of death were available. When underlying causes of death were compared between death certificates and autopsy reports, death certificates correctly identified the underlying cause of death's ICD-10 disease chapter in 74.6% of cases. The remaining 25.4% of misclassified cases resulted in over-classification rates that ranged from 1.2% for external causes of mortality to 12.2% for circulatory disease, and under-classification rates that ranged from 7.7% for external causes of mortality to 47.4% for respiratory disease. Neoplasms had generally lower misclassification rates with 4.3% over-classification and 13.3% under-classification. A logistic regression revealed that the odds of a match were 2.8 times higher when clinical history was mentioned on the autopsy report than when it was not. Similarly, the odds of a match were 3.4 times higher when death certificates were completed using autopsy findings than when autopsy findings were not used. This analysis excluded cases where it could not be determined if autopsy findings were used to complete death certificates. The findings of this study are useful to investigate the impact of death certificate misclassification errors on radiation risk estimates and, therefore, improve the reliability of epidemiological studies.

Latent bone modelling for estimation of plutonium concentration in skeleton of former nuclear workers.

The skeleton is a major plutonium retention site in the human body. Estimation of the total plutonium activity in the skeleton is a challenging problem. For most tissue donors at the United States Transuranium and Uranium Registries, a limited number of bone samples is available. The skeleton activity is calculated using plutonium activity concentration (Cskel) and skeleton weight. In this study, latent bone modelling was used to estimate Cskel from the limited number of analysed bone samples. Data from 13 non-osteoporotic whole-body donors were used to develop latent bone model (LBM) to estimate Cskel for seven cases with four to eight analysed bone samples. LBM predictions were compared to Cskel estimated using an arithmetic mean in terms of accuracy and precision. For the studied cases, LBM offered a significant reduction of uncertainty of Cskel estimate.

A million persons, a million dreams: a vision for a national center of radiation epidemiology and biology.

BACKGROUND: Epidemiologic studies of radiation-exposed populations form the basis for human safety standards. They also help shape public health policy and evidence-based health practices by identifying and quantifying health risks of exposure in defined populations. For more than a century, epidemiologists have studied the consequences of radiation exposures, yet the health effects of low levels delivered at a low-dose rate remain equivocal. MATERIALS AND METHODS: The Million Person Study (MPS) of U.S. Radiation Workers and Veterans was designed to examine health effects following chronic exposures in contrast with brief exposures as experienced by the Japanese atomic bomb survivors. Radiation associations for rare cancers, intakes of radionuclides, and differences between men and women are being evaluated, as well as noncancers such as cardiovascular disease and conditions such as dementia and cognitive function. The first international symposium, held November 6, 2020, provided a broad overview of the MPS. Representatives from four U.S. government agencies addressed the importance of this research for their respective missions: U.S. Department of Energy (DOE), the Centers for Disease Control and Prevention (CDC), the U.S. Department of Defense (DOD), and the National Aeronautics and Space Administration (NASA). The major components of the MPS were discussed and recent findings summarized. The importance of radiation dosimetry, an essential feature of each MPS investigation, was emphasized. RESULTS: The seven components of the MPS are DOE workers, nuclear weapons test participants, nuclear power plant workers, industrial radiographers, medical radiation workers, nuclear submariners, other U.S. Navy personnel, and radium dial painters. The MPS cohorts include tens of thousands of workers with elevated intakes of alpha particle emitters for which organ-specific doses are determined. Findings to date for chronic radiation exposure suggest that leukemia risk is lower than after acute exposure; lung cancer risk is much lower and there is little difference in risks between men and women; an increase in ischemic heart disease is yet to be seen; esophageal cancer is frequently elevated but not myelodysplastic syndrome; and Parkinson's disease may be associated with radiation exposure. CONCLUSIONS: The MPS has provided provocative insights into the possible range of health effects following low-level chronic radiation exposure. When the 34 MPS cohorts are completed and combined, a powerful evaluation of radiation-effects will be possible. This final article in the MPS special issue summarizes the findings to date and the possibilities for the future. A National Center for Radiation Epidemiology and Biology is envisioned.

Plutonium in Manhattan Project workers: Using autopsy data to evaluate organ content and dose estimates based on urine bioassay with implications for radiation epidemiology.

PURPOSE: Radiation dose estimates in epidemiology typically rely on intake predictions based on urine bioassay measurements. The purpose of this article is to compare the conventional dosimetric estimates for radiation epidemiology with the estimates based on additional post-mortem tissue radiochemical analysis results. METHODS: The comparison was performed on a unique group of 11 former Manhattan Project nuclear workers, who worked with plutonium in the 1940s, and voluntarily donated their bodies to the United States Transuranium and Uranium Registries. RESULTS: Post-mortem organ activities were predicted using different sets of urine data and compared to measured activities. Use of urinalysis data collected during the exposure periods overestimated the systemic (liver+skeleton) deposition of 239Pu by 155±134%, while the average bias from using post-exposure urinalyses was -4±50%. Committed effective doses estimated using early urine data differed from the best estimate by, on average, 196±193%; inclusion of follow-up urine measurements in analyses decreased the mean bias to 0.6±36.3%. Cumulative absorbed doses for the liver, red marrow, bone surface, and brain were calculated for the actual commitment period. CONCLUSION: On average, post-exposure urine bioassay results were in good agreement with post-mortem tissue analyses and were more reliable than results of urine bioassays collected during the exposure.

A Monte Carlo t Test to Evaluate Mesothelioma and Radiation in the US Transuranium and Uranium Registries.

A cluster of nine mesothelioma cases was observed among 341 registrants' deaths in the US Transuranium and Uranium Registries. Descriptive analysis showed that mesothelioma cases had the highest average cumulative external radiation dose compared with lung cancer, other cancer, and noncancer deaths. Further analysis indicated that the mesothelioma cluster was very different demographically from lung cancer, other cancer, and noncancer deaths. Therefore, an internally matched case-control approach was applied to evaluate the differences in an average cumulative external radiation dose between mesothelioma deaths and other causes of death. A Monte Carlo t test was used to examine the statistical significance of the differences. The results showed that there were no significant statistical differences in an average cumulative external radiation dose between mesothelioma and lung cancer, other cancers, or noncancers for the internally matched cases and controls.

Bias in the proportionate mortality ratio analysis of small study populations: a case on analyses of radiation and mesothelioma.

UNLABELLED: Abstract Purpose: To quantify bias in the proportionate mortality ratio (PMR) analysis of small study populations and develop a bias correction methodology. MATERIALS AND METHODS: Bias in the PMR analysis of small study populations is quantified through algebraic derivation. A simulation procedure is developed to evaluate the relationship between bias and study population size. A recently published PMR analysis of radiation and mesothelioma among 329 deceased registrants in the United States Transuranium and Uranium Registries (USTUR) is used as an illustrated example. RESULTS: The proportionate mortality ratios are biased and overestimated in small population studies; the smaller the study population, the larger the overestimation. As such, the average overestimation of PMR for mesothelioma in the analyses of radiation and mesothelioma in USTUR is 7.2% (95% confidence interval = 5.1%, 9.7%); the PMR overestimation is 22.5% (95% confidence interval = 16.8%, 29.1%) when stratified by quartiles of radiation doses. CONCLUSIONS: The degree of PMR small sample bias is mainly determined by the sample size ratio, which is defined as the ratio of the sample size to the number of disease categories in the reference population. Correction for the bias is recommended when the sample size ratio is less than 5. The quantification and correction algorithm of the PMR small sample bias developed in this research supplements the PMR methodology.

Intraindividual stability of human erythrocyte cholinesterase activity.

BACKGROUND: Erythrocyte cholinesterase (RBC-ChE) activities serve as useful and sensitive biomarkers to monitor exposure to cholinesterase-inhibiting substances, such as chemical warfare nerve agents and pesticides. Although the interindividual variation of RBC-ChE is well characterized, the magnitude of intraindividual variation for RBC-ChE remains controversial. An accurate measure of intraindividual variation is critical for establishing the appropriate frequency of RBC-ChE testing. METHODS: We retrospectively tracked the intraindividual variation of RBC-ChE activities among 46 male nerve agent workers from a single US Army depot that participated in a medical surveillance program requiring periodic RBC-ChE monitoring. All RBC-ChE analysis was performed by the same medical laboratory technician by the delta pH method. RESULTS: A mean of 38 and a median of 37 RBC-ChE measurements were available for each worker. The mean duration of employment for these workers was 20 years (median, 21 years). The mean CV for RBC-ChE in this set of 46 workers was 3.9%. Linear regression analysis of the data for each worker resulted in a mean slope of 0.0010 delta pH units/h per year. CONCLUSIONS: RBC-ChE activities increased in each person by a mean of 0.01 delta pH units/h every 10 years, which is a negligible rate. These findings highlight the stability of RBC-ChE activities over time in a given individual and may have important policy implications regarding the appropriate frequency of RBC-ChE testing.

Pesticide measurements from the first national environmental health survey of child care centers using a multi-residue GC/MS analysis method.

The U.S. Department of Housing and Urban Development, in collaboration with the U.S. Consumer Product Safety Commission and the U.S. Environmental Protection Agency, characterized the environments of young children (<6 years) by measuring lead, allergens, and pesticides in a randomly selected nationally representative sample of licensed institutional child care centers. Multi-stage sampling with clustering was used to select 168 child care centers in 30 primary sampling units in the United States. Centers were recruited into the study by telephone interviewers. Samples for pesticides, lead, and allergens were collected at multiple locations in each center by field technicians. Field sampling was conducted from July through October 2001. Wipe samples from indoor surfaces (floors, tabletops, desks) and soil samples were collected at the centers and analyzed using a multi-residue GC/MS analysis method. Based on the questionnaire responses, pyrethroids were the most commonly used pesticides among centers applying pesticides. Among the 63% of centers reporting pesticide applications, the number of pesticides used in each center ranged from 1 to 10 and the frequency of use ranged from 1 to 107 times annually. Numerous organophosphate and pyrethroid pesticides were detected in the indoor floor wipe samples. Chlorpyrifos (0.004-28 ng/cm2), diazinon (0.002-18 ng/cm2), cis-permethrin (0.004-3 ng/cm2), and

A geographic information systems (GIS) and spatial modeling approach to assessing indoor radon potential at local level.

This study integrates residential radon data from previous studies in Southern California (USA), into a geographic information system (GIS) linked with statistical techniques. A difference (p<0.05) is found in the indoor radon in residences grouped by radon-potential zones. Using a novel Monte Carlo approach, we found that the mean distance from elevated-radon residences (concentration>74 Bq m(-3)) to epicenters of large (> 4 Richter) earthquakes was smaller (p<0.0001) than the average residence-to-epicenter distance, suggesting an association between the elevated indoor-radon and seismic activities.

The prevalence of lead-based paint hazards in U.S. housing.

In this study we estimated the number of housing units in the United States with lead-based paint and lead-based paint hazards. We included measurements of lead in intact and deteriorated paint, interior dust, and bare soil. A nationally representative, random sample of 831 housing units was evaluated in a survey between 1998 and 2000; the units and their occupants did not differ significantly from nationwide characteristics. Results indicate that 38 million housing units had lead-based paint, down from the 1990 estimate of 64 million. Twenty-four million had significant lead-based paint hazards. Of those with hazards, 1.2 million units housed low-income families (< 30,000 US dollars/year) with children under 6 years of age. Although 17% of government-supported, low-income housing had hazards, 35% of all low-income housing had hazards. For households with incomes greater than or equal to 30,000 US dollars/year, 19% had hazards. Fourteen percent of all houses had significantly deteriorated lead-based paint, and 16% and 7%, respectively, had dust lead and soil lead levels above current standards of the U.S. Department of Housing and Urban Development and the U.S. Environmental Protection Agency. The prevalence of lead-based paint and hazards increases with age of housing, but most painted surfaces, even in older housing, do not have lead-based paint. Between 2% and 25% of painted building components were coated with lead-based paint. Housing in the Northeast and Midwest had about twice the prevalence of hazards compared with housing in the South and West. The greatest risk occurs in older units with lead-based paint hazards that either will be or are currently occupied by families with children under 6 years of age and are low-income and/or are undergoing renovation or maintenance that disturbs lead-based paint. This study also confirms projections made in 2000 by the President's Task Force on Environmental Health Risks and Safety Risks to Children of the number of houses with lead-based paint hazards. Public- and private-sector resources should be directed to units posing the greatest risk if future lead poisoning is to be prevented.