Mathematical Model to Assess Potential Reduced Specificity When Switching to New Screening Assays at Blood Donation Centers.

BACKGROUND: Switching to new infectious disease blood donor screening assays can precipitate an initial decrease in specificity in an established donor population followed by an increase of specificity, referred to as a "cleaning effect". We developed a mathematical model to simulate this and to measure the stabilization of specificity. METHODS: A modified exponential distribution curve was created to show the impact of donation frequency on the cleaning of the donor pool. Other parameters (e.g., number of donations from repeat donors/donations per month, average and minimum times between donations, retention of regular repeat donors, ratio of false positives for regular repeat donors/first-time donors and specificity of newly introduced assays) were also used to simulate the rise and fall in number of additional false positives. The mathematical model created was compared with real-world data from a South African blood donation center. RESULTS: In the mathematical model, the degree and duration of the cleaning effect were influenced by certain parameters. A longer time interval between donations resulted in a higher number of deferred blood donations than a shorter time interval, if deferred after a 1st, 2nd or 3rd false positive result prior to a stable plateau of specificity. Real-world data on false positive, discarded donations from a South African blood donation center were consistent with numbers from the mathematical model. CONCLUSIONS: The mathematical model can identify and describe any "cleaning effect" observed upon switching to a new infectious disease blood screening assay, allowing affected blood donation centers to prepare and adjust, while specificity is stabilized.

Mortality from cancers of the extra-thoracic airways in relation to radon progeny in the Wismut cohort, 1946-2008.

PURPOSE: Inhalation of radon progeny can cause high lung and respiratory tract radiation doses. The aim of this paper was to examine the relationship between radon progeny and cancers of the extra-thoracic airways in the German uranium miner cohort for an extended follow-up through 2008. METHODS: The cohort included 58,690 workers employed between 1946 and 1989 at the Wismut company. Exposure to radon progeny in Working Level Months (WLM) was determined from a comprehensive job-exposure matrix. The mean (max) cumulative exposure to radon among exposed cohort members (86%) was 280 WLM (3,224 WLM). Internal Poisson regression models were applied to estimate the linear Excess Relative Risk (ERR) per unit of cumulative exposure to radon. RESULTS: A small increase in the mortality from all cancers of the extra-thoracic airways combined with increasing cumulative exposure to radon was found (ERR/100 WLM = 0.036, p = 0.12), based on 234 deaths. The estimated ERR per 100 WLM for relevant cancer sub-groups were: 0.017 (p > 0.5) larynx (n = 94); 0.077 (p = 0.20) pharynx (n = 74); and 0.030 (p > 0.5) tongue and mouth (n = 55). CONCLUSION: RESULTS indicated a small but not statistically significant increase in mortality from cancers of the extra-thoracic airways in relation to radon. Low statistical power and uncontrolled confounding were limitations of this study.

Prostate cancer mortality risk in relation to working underground in the Wismut cohort study of German uranium miners, 1970-2003.

OBJECTIVE: A recent study and comprehensive literature review has indicated that mining could be protective against prostate cancer. This indication has been explored further here by analysing prostate cancer mortality in the German 'Wismut' uranium miner cohort, which has detailed information on the number of days worked underground. DESIGN: An historical cohort study of 58 987 male mine workers with retrospective follow-up before 1999 and prospective follow-up since 1999. SETTING AND PARTICIPANTS: Uranium mine workers employed during the period 1970-1990 in the regions of Saxony and Thuringia, Germany, contributing 1.42 million person-years of follow-up ending in 2003. OUTCOME MEASURE: Simple standardised mortality ratio (SMR) analyses were applied to assess differences between the national and cohort prostate cancer mortality rates and complemented by refined analyses done entirely within the cohort. The internal comparisons applied Poisson regression excess relative prostate cancer mortality risk model with background stratification by age and calendar year and a whole range of possible explanatory covariables that included days worked underground and years worked at high physical activity with γ radiation treated as a confounder. RESULTS: The analysis is based on miner data for 263 prostate cancer deaths. The overall SMR was 0.85 (95% CI 0.75 to 0.95). A linear excess relative risk model with the number of years worked at high physical activity and the number of days worked underground as explanatory covariables provided a statistically significant fit when compared with the background model (p=0.039). Results (with 95% CIs) for the excess relative risk per day worked underground indicated a statistically significant (p=0.0096) small protective effect of -5.59 (-9.81 to -1.36) ×10(-5). CONCLUSION: Evidence is provided from the German Wismut cohort in support of a protective effect from working underground on prostate cancer mortality risk.

Differences in baseline lung cancer mortality between the German uranium miners cohort and the population of the former German Democratic Republic (1960-2003).

A previous analysis of the radon-related lung cancer mortality risk, in the German uranium miners cohort, using Poisson modeling techniques, noted internal (spontaneous) rates that were higher on average than the external rates by 16.5% (95% CI: 9%; 24%). The main purpose of the present paper is to investigate the nature of, and possible reasons for, this difference by comparing patterns in spontaneous lung cancer mortality rates in a cohort of male miners involved in uranium extraction at the former Wismut mining company in East Germany with national male rates from the former German Democratic Republic. The analysis is based on miner data for 3,001 lung cancer deaths, 1.76 million person-years for the period 1960-2003, and national rates covering the same calendar-year range. Simple "age-period-cohort" graphical analyses were applied to assess the main qualitative differences between the national and cohort baseline lung cancer rates. Some differences were found to occur mainly at higher attained ages above 70 years. Although many occupational risk factors may have contributed to these observed age differences, only the effects of smoking have been assessed here by applying the Peto-Lopez indirect method for calculating smoking attributability. It is inferred that the observed age differences could be due to the greater prevalence of smoking and more mature smoking epidemic in the Wismut cohort compared to the general population of the former German Democratic Republic. In view of these observed differences between external population-based rates and internal (spontaneous) cohort baseline lung cancer rates, it is strongly recommended to apply only the internal rates in future analyses of uranium miner cohorts.

Radon and the risk of cancer mortality--internal Poisson models for the German uranium miners cohort.

Uranium mining occurred between 1946 and 1990 at the former Wismut mining company in East Germany. 58,987 male former employees form the largest single uranium miners cohort, which has been followed up for causes of mortality occurring from the beginning of 1946 to the end of 2003. The purpose of this paper is to present the radon exposure related cancer mortality risk based on 20,920 deaths, 2 million person-years, and 6,373 cancers. The latter include 3,016 lung cancers and 3,053 extrapulmonary solid cancers. Internal Poisson regression was used to estimate the excess relative risk (ERR) per unit of cumulative radon exposure in Working Level Months (WLM) for all major sites and for the follow-up period from 1946 to 2003. The simple cohort ERR WLM for lung cancer is 0.20% [95% confidence interval (CI): 0.17%; 0.22%]. The ERR model for lung cancer is linear in radon exposure with exponential effect modifiers that depend on age at median exposure, time since median exposure, and radon exposure-rate. In this model the central estimate of ERR WLM is 1.06% (95% CI: 0.69%; 1.42%) for an age at median exposure of 33 y, a time since median exposure of 11 y, and an exposure-rate of 2.7 WL. This central ERR decreases by 5% for each unit exposure-rate increase. The ERR decreases by 32% with each decade increase in age at median exposure and also decreases by 54% with each decade increase in time since median exposure. The ERR WLM for all extrapulmonary solid cancers combined without effect modification is 0.014% (95% CI: 0.006%; 0.023%). The ERR model for extrapulmonary solid cancer is linear in radon exposure with an exponential effect modifier which depends on age-attained. In this model the central estimate of ERR WLM is 0.040% (95% CI: -0.001%; 0.082%) for an age-attained of 44. The ERR decreases by 37% with each decade increase in age-attained. The highest ERR WLM, after lung, is observed for cancers of the pharynx (0.16%), tongue/mouth (0.045%), and liver (0.04%).

The influence of radon exposures on lung cancer mortality in German uranium miners, 1946-2003.

Extensive uranium extraction took place from 1946 until 1990 at the former Wismut mining company in East Germany. A total of 58,987 male former employees of this company form the largest single uranium miners cohort that has been followed up for causes of mortality occurring from the beginning of 1946 to the end of 2003. The purpose of this study was to investigate and evaluate different forms of models for the radon exposure-related lung cancer mortality risk based on 3,016 lung cancer deaths and 2 million person years. Other exposure covariables such as occupational exposure to external gamma radiation, long-lived radionuclides, arsenic, fine dust and silica dust are available. The standardized mortality ratio for lung cancer is 2.03 (95% CI: 1.96; 2.10). The simple cohort excess relative risk (ERR/WLM) for lung cancer is estimated as 0.0019 (95% CI: 0.0016; 0.0022). The BEIR VI model produced risks similar to those obtained with a selected mathematically continuous ERR model for lung cancer. The continuous model is linear in radon exposure with exponential effect modifiers that depend on the whole range of age at median exposure, time since median exposure, and radon exposure rate. In this model the central estimate of ERR/WLM is 0.0054 (95% CI: 0.0040; 0.0068) for an age at median exposure of 30 years, a time since median exposure of 20 years, and a mean exposure rate of 3 WL. The ERR decreases by 5% for each unit of exposure-rate increase. The ERR decreases by 28% with each decade increase in age at median exposure and also decreases by 51% with each decade increase in time since median exposure. The method of determination of radon exposure (i.e., whether the exposures were estimated or measured) did not play an important role in the determination of the ERR. The other exposure covariables were found to have only minor confounding influences on the ERR/WLM for the finally selected continuous model when included in an additive way.