Annual Burden of Occupationally‐Acquired Influenza Infections in Hospitals and Emergency Departments in the United States

Infections among health‐care personnel (HCP) occur as a result of providing care to patients with infectious diseases, but surveillance is limited to a few diseases. The objective of this study is to determine the annual number of influenza infections acquired by HCP as a result of occupational exposures to influenza patients in hospitals and emergency departments (EDs) in the United States. A risk analysis approach was taken. A compartmental model was used to estimate the influenza dose received in a single exposure, and a dose–response function applied to calculate the probability of infection. A three‐step algorithm tabulated the total number of influenza infections based on: the total number of occupational exposures (tabulated in previous work), the total number of HCP with occupational exposures, and the probability of infection in an occupational exposure. Estimated influenza infections were highly dependent upon the dose–response function. Given current compliance with infection control precautions, we estimated 151,300 and 34,150 influenza infections annually with two dose–response functions (annual incidence proportions of 9.3% and 2.1%, respectively). Greater reductions in infectious were achieved by full compliance with vaccination and IC precautions than with patient isolation. The burden of occupationally‐acquired influenza among HCP in hospitals and EDs in the United States is not trivial, and can be reduced through improved compliance with vaccination and preventive measures, including engineering and administrative controls.     

Use of Markov Chain Monte Carlo Analysis with a Physiologically-Based Pharmacokinetic Model of Methylmercury to Estimate Exposures in U.S. Women of Childbearing Age

A Bayesian approach, implemented using Markov Chain Monte Carlo (MCMC) analysis, was applied with a physiologically‐based pharmacokinetic (PBPK) model of methylmercury (MeHg) to evaluate the variability of MeHg exposure in women of childbearing age in the U.S. population. The analysis made use of the newly available National Health and Nutrition Survey (NHANES) blood and hair mercury concentration data for women of age 16–49 years (sample size, 1,582). Bayesian analysis was performed to estimate the population variability in MeHg exposure (daily ingestion rate) implied by the variation in blood and hair concentrations of mercury in the NHANES database. The measured variability in the NHANES blood and hair data represents the result of a process that includes interindividual variation in exposure to MeHg and interindividual variation in the pharmacokinetics (distribution, clearance) of MeHg. The PBPK model includes a number of pharmacokinetic parameters (e.g., tissue volumes, partition coefficients, rate constants for metabolism and elimination) that can vary from individual to individual within the subpopulation of interest. Using MCMC analysis, it was possible to combine prior distributions of the PBPK model parameters with the NHANES blood and hair data, as well as with kinetic data from controlled human exposures to MeHg, to derive posterior distributions that refine the estimates of both the population exposure distribution and the pharmacokinetic parameters. In general, based on the populations surveyed by NHANES, the results of the MCMC analysis indicate that a small fraction, less than 1%, of the U.S. population of women of childbearing age may have mercury exposures greater than the EPA RfD for MeHg of 0.1 μg/kgg/day, and that there are few, if any, exposures greater than the ATSDR MRL of 0.3 μgg/kgg/day. The analysis also indicates that typical exposures may be greater than previously estimated from food consumption surveys, but that the variability in exposure within the population of U.S. women of childbearing age may be less than previously assumed.     

Physiologically Based Pharmacokinetic Modeling of the Lactational Transfer of Methylmercury

The developmental neurotoxicity of methylmercury (MeHg) in humans has been described following catastrophic events in Minamata Bay, Japan and in Iraq, and following the exposure to lower doses elsewhere in the world. The most common route of MeHg exposure in humans is through the intake of contaminated food, especially fish. Although the precautions against the ingestion of potentially contaminated food during pregnancy are well recognized, precautions against the ingestion of MeHg during lactation are not so uniformly recognized. However, the continued development of the central nervous system during the early postnatal period serves to prolong the period during which this critical system is susceptible to the toxic insult of MeHg. Because no direct method is available to quantitatively assess the lactational transfer of MeHg to humans, a computer-aided simulation method was developed. An available gestational physiologically based pharmacokinetic model was refined and expanded to include parameters and algorithms specific for the elimination of MeHg in breast milk. The predictions of the completed model were compared with experimental data obtained from rodents, and the model parameters were allometrically scaled to humans. Finally, the model was validated by comparing its predictions against the available clinical data for MeHg distribution and elimination in mothers and their nursing infants. This model incorporated current and previous maternal exposures to MeHg to accurately predict the kinetics of MeHg excretion in breast milk and the daily intake by the nursing infant. This model may be used to quantify MeHg intake by the nursing infant, under different rates of maternal MeHg ingestion.     

An Exposure Assessment of Methyl Mercury via Fish Consumption for the Japanese Population

The objective of this article was to propose an exposure assessment model to describe the relationship between fish consumption and body methyl mercury (MeHg) levels in the Japanese population. Individual MeHg intake was estimated by the summation of species-specific fish consumption multiplied by species-specific fish MeHg levels. The distribution of fish consumed by individuals and the MeHg level in each fish species were assigned based on published data from Japanese government institutions. The probability of MeHg intake for a population was accomplished through a Monte Carlo simulation by the random sampling of fish consumption and species-specific MeHg levels. Internal body MeHg levels in blood and hair were estimated using a one-compartment model. Overall, the mean value of MeHg intake for the Japanese population was estimated to be 6.76 μg/day or 0.14 μg/kg body weight per day (bw/day), while the mean value for the hair mercury level was 2.02 μg/g. Compared with the survey data that tabulated hair mercury levels in a cross-section of the Japanese population, the simulation results matched the hair mercury survey data very well for women, but somewhat underestimated for men and all of the population. This exposure assessment model is a useful attempt at further risk assessment with respect to a risk-benefit analysis.     

Effects of Uncertainties on Exposure Estimates to Methylmercury: A Monte Carlo Analysis of Exposure Biomarkers versus Dietary Recall Estimation

This article presents a general model for estimating population heterogeneity and "lack of knowledge" uncertainty in methylmercury (MeHg) exposure assessments using two-dimensional Monte Carlo analysis. Using data from fish-consuming populations in Bangladesh, Brazil, Sweden, and the United Kingdom, predictive model estimates of dietary MeHg exposures were compared against those derived from biomarkers (i.e., [Hg]hair and [Hg]blood). By disaggregating parameter uncertainty into components (i.e., population heterogeneity, measurement error, recall error, and sampling error) estimates were obtained of the contribution of each component to the overall uncertainty. Steady-state diet:hair and diet:blood MeHg exposure ratios were estimated for each population and were used to develop distributions useful for conducting biomarker-based probabilistic assessments of MeHg exposure. The 5th and 95th percentile modeled MeHg exposure estimates around mean population exposure from each of the four study populations are presented to demonstrate lack of knowledge uncertainty about a best estimate for a true mean. Results from a U.K. study population showed that a predictive dietary model resulted in a 74% lower lack of knowledge uncertainty around a central mean estimate relative to a hair biomarker model, and also in a 31% lower lack of knowledge uncertainty around central mean estimate relative to a blood biomarker model. Similar results were obtained for the Brazil and Bangladesh populations. Such analyses, used here to evaluate alternative models of dietary MeHg exposure, can be used to refine exposure instruments, improve information used in site management and remediation decision making, and identify sources of uncertainty in risk estimates.     

A Time‐Dependent Risk Assessment for Broken Compact Fluorescent Lamps

Environmental Protection Agency (EPA) ambient air quality guidelines are meant to limit long‐term exposures of toxins to safe levels. Unfortunately, there is little guidance for what constitutes a safe level from a one‐time (or very infrequent) short exposure(s). In the case of mercury, a review of the derivation of the EPA ambient air quality standard shows that it implicitly assumes a tissue burden model. The time dependence of the tissue burden is commonly described in terms of a half‐life, a modeling assumption that presumes that the decline in the tissue burden after a single exposure can be approximately described as an exponential decay. In this article, we use a simple exponential tissue burden model to derive a time‐dependent no observable adverse effect level (NOAEL) for mercury concentrations in air. The model predicts that tissue body burden will asymptotically approach the EPA air quality level for long exposure times, and reach workplace standard levels for exposures of a few hours. The model was used along with data on mercury levels from experimental work done by the Maine Department of Environmental Protection to evaluate the risks from a broken compact fluorescent lamp in a residential setting. Mercury levels approached the NOAEL only when the debris was left in an almost sealed room. Normal common‐sense cleaning measures: removal of debris to an outside area, and ventilation of the room for several minutes, reduced exposures to less than 1% of the NOAEL.     

Methods and Rationale for Derivation of a Reference Dose for Methylmercury by the U.S. EPA

In 2001, the U.S. Environmental Protection Agency derived a reference dose (RfD) for methylmercury, which is a daily intake that is likely to be without appreciable risk of deleterious effects during a lifetime. This derivation used a series of benchmark dose (BMD) analyses provided by a National Research Council (NRC) panel convened to assess the health effects of methylmercury. Analyses were performed for a number of endpoints from three large longitudinal cohort studies of the neuropsychological consequences of in utero exposure to methylmercury: the Faroe Islands, Seychelles Islands, and New Zealand studies. Adverse effects were identified in the Faroe Islands and New Zealand studies, but not in the Seychelles Islands. The NRC also performed an integrative analysis of all three studies. The EPA applied a total uncertainty factor (UF) of 10 for intrahuman toxicokinetic and toxicodynamic variability and uncertainty. Dose conversion from cord blood mercury concentrations to maternal methylmercury intake was performed using a one-compartment model. Derivation of potential RfDs from a number of endpoints from the Faroe Islands study converged on 0.1 microg/kg/day, as did the integrative analysis of all three studies. EPA identified several areas for which further information or analyses is needed. Perhaps the most immediately relevant is the ratio of cord:maternal blood mercury concentration, as well as the variability around this ratio. EPA assumed in its dose conversion that the ratio was 1.0; however, available data suggest it is perhaps 1.5-2.0. Verification of a deviation from unity presumably would be translated directly into comparable reduction in the RfD. Other areas that EPA identified as significant areas requiring further attention are cardiovascular consequences of methylmercury exposure and delayed neurotoxicity during aging as a result of previous developmental or adult exposure.     

Fault Tree Analysis for Exposure to Refrigerants Used for Automotive Air Conditioning in the United States

A fault tree analysis was used to estimate the number of refrigerant exposures of automotive service technicians and vehicle occupants in the United States. Exposures of service technicians can occur when service equipment or automotive air-conditioning systems leak during servicing. The number of refrigerant exposures of service technicians was estimated to be 135,000 per year. Exposures of vehicle occupants can occur when refrigerant enters passenger compartments due to sudden leaks in air-conditioning systems, leaks following servicing, or leaks caused by collisions. The total number of exposures of vehicle occupants was estimated to be 3,600 per year. The largest number of exposures of vehicle occupants was estimated for leaks caused by collisions, and the second largest number of exposures was estimated for leaks following servicing. Estimates used in the fault tree analysis were based on a survey of automotive air-conditioning service shops, the best available data from the literature, and the engineering judgement of the authors and expert reviewers from the Society of Automotive Engineers Interior Climate Control Standards Committee. Exposure concentrations and durations were estimated and compared with toxicity data for refrigerants currently used in automotive air conditioners. Uncertainty was high for the estimated numbers of exposures, exposure concentrations, and exposure durations. Uncertainty could be reduced in the future by conducting more extensive surveys, measurements of refrigerant concentrations, and exposure monitoring. Nevertheless, the analysis indicated that the risk of exposure of service technicians and vehicle occupants is significant, and it is recommended that no refrigerant that is substantially more toxic than currently available substitutes be accepted for use in vehicle air-conditioning systems, absent a means of mitigating exposure.     

Reanalysis of Dose-Response Data from the Iraqi Methylmercury Poisoning Episode

Applying a hockey stick parametric dose-response model to data on late or retarded development in Iraqi children exposed in utero to methylmercury, with mercury (Hg) exposure characterized by the peak Hg concentration in mothers'hair during pregnancy, Cox et al. calculated the "best statistical estimate" of the threshold for health effects as 10 ppm Hg in hair with a 95% range of uncertainty of between 0 and 13.6 ppm.⁽¹⁾A new application of the hockey stick model to the Iraqi data shows, however, that the statistical upper limit of the threshold based on the hockey stick model could be as high as 255 ppm. Furthermore, the maximum likelihood estimate of the threshold using a different parametric model is virtually zero. These and other analyses demonstrate that threshold estimates based on parametric models exhibit high statistical variability and model dependency, and are highly sensitive to the precise definition of an abnormal response. Consequently, they are not a reliable basis for setting a reference dose (RfD) for methylmercury. Benchmark analyses and statistical analyses useful for deriving NOAELs are also presented. We believe these latter analyses—particularly the benchmark analyses—generally form a sounder basis for determining RfDs than the type of hockey stick analysis presented by Cox et al. However, the acute nature of the exposures, as well as other limitations in the Iraqi data suggest that other data may be more appropriate for determining acceptable human exposures to methylmercury.     

Quantitative Links Between Arsenic Exposure and Influenza A (H1N1) Infection‐Associated Lung Function Exacerbations Risk

The objective of this study was to link arsenic exposure and influenza A (H1N1) infection‐induced respiratory effects to assess the impact of arsenic‐contaminated drinking water on exacerbation risk of A (H1N1)‐associated lung function. The homogeneous Poisson process was used to approximate the related processes between arsenic exposure and influenza‐associated lung function exacerbation risk. We found that (i) estimated arsenic‐induced forced expiratory volume in 1 second (FEV₁) reducing rates ranged from 0.116 to 0.179 mL/μg for age 15–85 years, (ii) estimated arsenic‐induced A (H1N1) viral load increasing rate was 0.5 mL/μg, (iii) estimated A (H1N1) virus‐induced FEV₁ reducing rate was 0.10 mL/logTCID50, and (iv) the relationship between arsenic exposure and A (H1N1)‐associated respiratory symptoms scores (RSS) can be described by a Hill model. Here we showed that maximum RSS at day 2 postinfection for Taiwan, West Bengal (India), and the United States were estimated to be in the severe range of 0.83, 0.89, and 0.81, respectively, indicating that chronic arsenic exposure and A (H1N1) infection together are most likely to pose potential exacerbations risk of lung function, although a 50% probability of lung function exacerbations risk induced by arsenic and influenza infection was within the mild and moderate ranges of RSS at day 1 and 2 postinfection. We concluded that avoidance of drinking arsenic‐containing water could significantly reduce influenza respiratory illness and that need will become increasingly urgent as the novel H1N1 pandemic influenza virus infects people worldwide.     

Evaluation of the Uncertainty in an Oral Reference Dose for Methylmercury Due to Interindividual Variability in Pharmacokinetics

An analysis of the uncertainty in guidelines for the ingestion of methylmercury (MeHg) due to human pharmacokinetic variability was conducted using a physiologically based pharmacokinetic (PBPK) model that describes MeHg kinetics in the pregnant human and fetus. Two alternative derivations of an ingestion guideline for MeHg were considered: the U.S. Environmental Protection Agency reference dose (RfD) of 0.1 g/kg/day derived from studies of an Iraqi grain poisoning episode, and the Agency for Toxic Substances and Disease Registry chronic oral minimal risk level (MRL) of 0.5 g/kg/day based on studies of a fish-eating population in the Seychelles Islands. Calculation of an ingestion guideline for MeHg from either of these epidemiological studies requires calculation of a dose conversion factor (DCF) relating a hair mercury concentration to a chronic MeHg ingestion rate. To evaluate the uncertainty in this DCF across the population of U.S. women of child-bearing age, Monte Carlo analyses were performed in which distributions for each of the parameters in the PBPK model were randomly sampled 1000 times. The 1st and 5th percentiles of the resulting distribution of DCFs were a factor of 1.8 and 1.5 below the median, respectively. This estimate of variability is consistent with, but somewhat less than, previous analyses performed with empirical, one-compartment pharmacokinetic models. The use of a consistent factor in both guidelines of 1.5 for pharmacokinetic variability in the DCF, and keeping all other aspects of the derivations unchanged, would result in an RfD of 0.2 g/kg/day and an MRL of 0.3 g/kg/day.     

Development of a Single-Meal Fish Consumption Advisory for Methyl Mercury

Methyl mercury (meHg) contamination of fish is the leading cause of fish consumption advisories in the United States. These advisories have focused upon repeated or chronic exposure, whereas risks during pregnancy may also exist from a single-meal exposure if the fish tissue concentration is high enough. In this study, acute exposure to meHg from a single fish meal was analyzed by using the one-compartment meHg biokinetic model to predict maternal hair concentrations. These concentrations were evaluated against the mercury hair concentration corresponding to the U.S. Environmental Protection Agency's reference dose (RfD), which is intended to protect against neurodevelopmental effects. The one-compartment model was validated against blood concentrations from three datasets in which human subjects ingested meHg in fish, either as a single meal or multiple meals. Model simulations of the single-meal scenario at different fish meHg concentrations found that concentrations of 2.0 ppm or higher can be associated with maternal hair concentrations elevated above the RfD level for days to weeks during gestation. A single-meal fish concentration cutoff of > or = 2.0 ppm is an important consideration, especially because this single high exposure event might be in addition to a baseline meHg body burden from other types of fish consumption. This type of single-meal advisory requires that fish sampling programs provide data for individual rather than composited fish, and take into account seasonal differences that may exist in fish concentrations.     

Aldrin and Dieldrin: A Reevaluation of the Cancer and Noncancer Dose‐Response Assessments

The dose‐response analyses of cancer and noncancer health effects of aldrin and dieldrin were evaluated using current methodology, including benchmark dose analysis and the current U.S. Environmental Protection Agency (U.S. EPA) guidance on body weight scaling and uncertainty factors. A literature review was performed to determine the most appropriate adverse effect endpoints. Using current methodology and information, the estimated reference dose values were 0.0001 and 0.00008 mg/kg‐day for aldrin and dieldrin, respectively. The estimated cancer slope factors for aldrin and dieldrin were 3.4 and 7.0 (mg/kg‐day)^?1, respectively (i.e., about 5‐ and 2.3‐fold lower risk than the 1987 U.S. EPA assessments). Because aldrin and dieldrin are no longer used as pesticides in the United States, they are presumed to be a low priority for additional review by the U.S. EPA. However, because they are persistent and still detected in environmental samples, quantitative risk assessments based on the best available methods are required. Recent epidemiologic studies do not demonstrate a causal association between aldrin and dieldrin and human cancer risk. The proposed reevaluations suggest that these two compounds pose a lower human health risk than currently reported by the U.S. EPA.     

Total Economic Consequences of an Influenza Outbreak in the United States

Pandemic influenza represents a serious threat not only to the population of the United States, but also to its economy. In this study, we analyze the total economic consequences of potential influenza outbreaks in the United States for four cases based on the distinctions between disease severity and the presence/absence of vaccinations. The analysis is based on data and parameters on influenza obtained from the Centers for Disease Control and the general literature. A state‐of‐the‐art economic impact modeling approach, computable general equilibrium, is applied to analyze a wide range of potential impacts stemming from the outbreaks. This study examines the economic impacts from changes in medical expenditures and workforce participation, and also takes into consideration different types of avoidance behavior and resilience actions not previously fully studied. Our results indicate that, in the absence of avoidance and resilience effects, a pandemic influenza outbreak could result in a loss in U.S. GDP of $25.4 billion, but that vaccination could reduce the losses to $19.9 billion. When behavioral and resilience factors are taken into account, a pandemic influenza outbreak could result in GDP losses of $45.3 billion without vaccination and $34.4 billion with vaccination. These results indicate the importance of including a broader set of causal factors to achieve more accurate estimates of the total economic impacts of not just pandemic influenza but biothreats in general. The results also highlight a number of actionable items that government policymakers and public health officials can use to help reduce potential economic losses from the outbreaks.     

Mercury,Polychlorinated Biphenyls,Selenium, and Fatty Acids in Tribal Fish Harvests of the Upper Great Lakes

The Chippewa Ottawa Resource Authority monitors fish contaminants in Anishinaabe (Great Lake Native American) tribal fisheries. This article updates previously reported trends in two persistent bioaccumulative toxic (PBT) substances that are the primary contributors to consumption advisory limits for these fish: methylmercury (MeHg) and polychlorinated biphenyls (PCBs). Also, we report, for the first time, an analysis of nutritional benefit bioindicators and metrics in these same Upper Great Lakes fish harvests: selenium (Se) and omega‐3 fatty acids (PUFA‐3s). A novel risk/benefit quantification originally presented by Ginsberg et al. is reported here to characterize the tradeoffs between fatty acid benefits and toxic MeHg health outcomes. We also report a Se benefit metric to characterize the possible protective value against MeHg neurotoxicity based on Ralston et al. Congruent with Anishinaabe cultural motivations to consume fish from their ancestral fisheries, nutritional content was high in locally caught fish and, in some respects, superior to farmed/store‐bought fish. These Great Lakes fish still contained levels of PBTs that require careful education and guidance for consumers. However, the contaminant trends suggest that these fish need not be abandoned as important (both culturally and nutritionally) food sources for the Anishinaabe who harvested them.     

An Analysis of the Uncertainties in Estimates of Radon-Induced Lung Cancer

A recent report by the National Academy of Sciences estimates that the radiation dose to the bronchial epithelium, per working level month (WLM) of radon daughter exposure, is about 30% lower for residential exposures than for exposures received in underground mines. Adjusting the previously published BEIR IV radon risk model accordingly, the unit risk for indoor exposures of the general population is about 2.2 x 10(-4) lung cancer deaths (lcd)/WLM. Using results from EPA's National Residential Radon Survey, the average radon level is estimated to be about 1.25 pCi/L, and the annual average exposure about 0.242 WLM. Based on these estimates, 13,600 radon-induced lcd/yr are projected for the United States. A quantitative uncertainty analysis was performed, which considers: statistical uncertainties in the epidemiological studies of radon-exposed miners; the dependence of risk on age at, and time since, exposure; the extrapolation of risk estimates from mines to homes based on comparative dosimetry; and uncertainties in the radon daughter levels in homes and in the average residential occupancy. Based on this assessment of the uncertainties in the unit risk and exposure estimates, an uncertainty range of 7000-30000 lcd/yr is derived.     

Development of Dose‐Response Models to Predict the Relationship for Human Toxoplasma gondii Infection Associated with Meat Consumption

Toxoplasma gondii is a protozoan parasite that is responsible for approximately 24% of deaths attributed to foodborne pathogens in the United States. It is thought that a substantial portion of human T. gondii infections is acquired through the consumption of meats. The dose‐response relationship for human exposures to T. gondii‐infected meat is unknown because no human data are available. The goal of this study was to develop and validate dose‐response models based on animal studies, and to compute scaling factors so that animal‐derived models can predict T. gondii infection in humans. Relevant studies in literature were collected and appropriate studies were selected based on animal species, stage, genotype of T. gondii, and route of infection. Data were pooled and fitted to four sigmoidal‐shaped mathematical models, and model parameters were estimated using maximum likelihood estimation. Data from a mouse study were selected to develop the dose‐response relationship. Exponential and beta‐Poisson models, which predicted similar responses, were selected as reasonable dose‐response models based on their simplicity, biological plausibility, and goodness fit. A confidence interval of the parameter was determined by constructing 10,000 bootstrap samples. Scaling factors were computed by matching the predicted infection cases with the epidemiological data. Mouse‐derived models were validated against data for the dose‐infection relationship in rats. A human dose‐response model was developed as P (d) = 1–exp (–0.0015 × 0.005 × d) or P (d) = 1–(1 + d × 0.003 / 582.414)^?1.479. Both models predict the human response after consuming T. gondii‐infected meats, and provide an enhanced risk characterization in a quantitative microbial risk assessment model for this pathogen.     

Human Dose–Response Data for Francisella tularensis and a Dose‐ and Time‐Dependent Mathematical Model of Early‐Phase Fever Associated with Tularemia After Inhalation Exposure

Military health risk assessors, medical planners, operational planners, and defense system developers require knowledge of human responses to doses of biothreat agents to support force health protection and chemical, biological, radiological, nuclear (CBRN) defense missions. This article reviews extensive data from 118 human volunteers administered aerosols of the bacterial agent Francisella tularensis , strain Schu S4, which causes tularemia. The data set includes incidence of early‐phase febrile illness following administration of well‐characterized inhaled doses of F. tularensis . Supplemental data on human body temperature profiles over time available from de‐identified case reports is also presented. A unified, logically consistent model of early‐phase febrile illness is described as a lognormal dose–response function for febrile illness linked with a stochastic time profile of fever. Three parameters are estimated from the human data to describe the time profile: incubation period or onset time for fever; rise time of fever; and near‐maximum body temperature. Inhaled dose‐dependence and variability are characterized for each of the three parameters. These parameters enable a stochastic model for the response of an exposed population through incorporation of individual‐by‐individual variability by drawing random samples from the statistical distributions of these three parameters for each individual. This model provides risk assessors and medical decisionmakers reliable representations of the predicted health impacts of early‐phase febrile illness for as long as one week after aerosol exposures of human populations to F. tularensis .     

Retrospective Cost-Effectiveness Analyses for Polio Vaccination in the United States

The history of polio vaccination in the United States spans 50 years and includes different phases of the disease, multiple vaccines, and a sustained significant commitment of resources. We estimated cost-effectiveness ratios and assessed the net benefits of polio vaccination applicable at various points in time from the societal perspective and we discounted these back to appropriate points in time. We reconstructed vaccine price data from available sources and used these to retrospectively estimate the total costs of the U.S. historical polio vaccination strategies (all costs reported in year 2002 dollars). We estimate that the United States invested approximately US dollars 35 billion (1955 net present value, discount rate of 3%) in polio vaccines between 1955 and 2005 and will invest approximately US dollars 1.4 billion (1955 net present value, or US dollars 6.3 billion in 2006 net present value) between 2006 and 2015 assuming a policy of continued use of inactivated poliovirus vaccine (IPV) for routine vaccination. The historical and future investments translate into over 1.7 billion vaccinations that prevent approximately 1.1 million cases of paralytic polio and over 160,000 deaths (1955 net present values of approximately 480,000 cases and 73,000 deaths). Due to treatment cost savings, the investment implies net benefits of approximately US dollars 180 billion (1955 net present value), even without incorporating the intangible costs of suffering and death and of averted fear. Retrospectively, the U.S. investment in polio vaccination represents a highly valuable, cost-saving public health program. Observed changes in the cost-effectiveness ratio estimates over time suggest the need for living economic models for interventions that appropriately change with time. This article also demonstrates that estimates of cost-effectiveness ratios at any single time point may fail to adequately consider the context of the investment made to date and the importance of population and other dynamics, and shows the importance of dynamic modeling.     

A Bayesian Model and Stochastic Exposure (Dose) Estimation for Relative Exposure Risk Comparison Involving Asbestos‐Containing Dropped Ceiling Panel Installation and Maintenance Tasks

Assessing exposures to hazards in order to characterize risk is at the core of occupational hygiene. Our study examined dropped ceiling systems commonly used in schools and commercial buildings and lay‐in ceiling panels that may have contained asbestos prior to the mid to late 1970s. However, most ceiling panels and tiles do not contain asbestos. Since asbestos risk relates to dose, we estimated the distribution of eight‐hour TWA concentrations and one‐year exposures (a one‐year dose equivalent) to asbestos fibers (asbestos f/cc‐years) for five groups of workers who may encounter dropped ceilings: specialists, generalists, maintenance workers, nonprofessional do‐it‐yourself (DIY) persons, and other tradespersons who are bystanders to ceiling work. Concentration data (asbestos f/cc) were obtained through two exposure assessment studies in the field and one chamber study. Bayesian and stochastic models were applied to estimate distributions of eight‐hour TWAs and annual exposures (dose). The eight‐hour TWAs for all work categories were below current and historic occupational exposure limits (OELs). Exposures to asbestos fibers from dropped ceiling work would be categorized as “highly controlled” for maintenance workers and “well controlled” for remaining work categories, according to the American Industrial Hygiene Association exposure control rating system. Annual exposures (dose) were found to be greatest for specialists, followed by maintenance workers, generalists, bystanders, and DIY. On a comparative basis, modeled dose and thus risk from dropped ceilings for all work categories were orders of magnitude lower than published exposures for other sources of banned friable asbestos‐containing building material commonly encountered in construction trades.