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OBJECTIVES: To examine the efficacy of an outside-the-boot parachute ankle brace (PAB) in reducing risk of ankle injury to army paratrooper trainees and to identify inadvertent risks associated with PAB use. DESIGN: The authors compared hospitalization rates for ankle, musculoskeletal, and other traumatic injury among 223,172 soldiers trained 1985-2002 in time periods defined by presence/absence of PAB use protocols. Multiple logistic regression analysis estimated adjusted odds ratios (OR) and 95% confidence intervals for injury outcomes, comparing pre and post brace periods to the brace protocol period. SETTING: A research database consisting of training rosters from the US Army Airborne training facility (Fort Benning, GA) occupational, demographic, and hospitalization information. MAIN OUTCOME MEASURES: Injuries were considered training related if they occurred during a five week period starting with first scheduled static line parachute jump and a parachuting cause of injury code appeared in the hospital record. RESULTS: Of 939 parachuting related hospitalizations during the defined risk period, 597 (63.6%) included an ankle injury diagnosis, 198 (21.1%) listed a musculoskeletal (non-ankle) injury, and 69 (7.3%) cited injuries to multiple body parts. Risk of ankle injury hospitalization was higher during both pre-brace (adjusted OR 2.38, 95% CI 1.92 to 2.95) and post-brace (adjusted OR 1.72, 95% CI 1.27 to 2.32) periods compared with the brace protocol period. Odds of musculoskeletal (non-ankle) injury or injury to multiple body parts did not change between the brace and post-brace periods. CONCLUSION: Use of a PAB during airborne training appears to reduce risk of ankle injury without increasing risk of other types of traumatic injury. [ABSTRACT FROM AUTHOR]

Background: Deep venous thrombosis (DVT) is commonly seen among bedridden and postoperative patients. Its association with travel may also make DVT an occupational health risk to otherwise healthy business travelers. We estimated the incidence of and risk factors for DVT among 8,189 World Bank employees and a subset of 4,951 international business travelers.Methods: Occurrence of DVT between 1995 and 1998 was determined using 1) medical insurance claims; 2) Workers' Compensation claims; and 3) intra-office E-mail solicitation followed by interview. For each insurance claim case, 10 controls were randomly selected from among World Bank employees insured during the same month and year as the case's claim was filed, and case-control analyses were performed to identify potential predictors or risk factors for DVT.Results: Thirty individuals filed claims for DVT of the legs (annual incidence rate: 0.9 per 1,000 employees); three of these claims were filed within 30 days after a travel mission. Two employees reported DVT as a Workers' Compensation injury, and five staff with verified DVT participated in interviews. After controlling for age and gender, no association with any travel-related covariate was seen. Results of analyses considering all thrombophlebitis and thromboembolism followed the same pattern. The average annual incidence of DVT occurring within 30 days of mission among traveling staff ranged from 0.10 per 1,000 to 0.25 per 1,000 travelers, depending on the case-finding method.Conclusion: No association between DVT and travel was observed after adjustment for gender and age. These results, however, are preliminary, and due to the rarity of DVT, based on small numbers. [ABSTRACT FROM AUTHOR]

To accurately characterize human health hazards, human, animal, and mechanistic data must be integrated and the relevance to the research question of all three lines of evidence must be considered. Mechanistic data are often critical to the full integration of animal and human data and to characterizing relevance and uncertainty. This novel evidence integration framework (EIF) provides a method for synthesizing data from comprehensive, systematic, quality-based assessments of the epidemiological and toxicological literature, including in vivo and in vitro mechanistic studies. It organizes data according to both the observed human health effects and the mechanism of action of the chemical, providing a method to support evidence synthesis. The disease-based component uses the evidence of human health outcomes studied in the best quality epidemiological literature to organize the toxicological data according to authors' stated purpose, with the pathophysiology of the disease determining the potential relevance of the toxicological data. The mechanism-based component organizes the data based on the proposed mechanisms of effect and data supporting events leading to each endpoint, with the epidemiological data potentially providing corroborating information. The EIF includes a method to cross-classify and describe the concordance of the data, and to characterize its uncertainty. At times, the two methods of organizing the data may lead to different conclusions. This facilitates identification of knowledge gaps and shows the impact of uncertainties on the strength of causal inference.

This analysis uses data from the Community Noise and Health Study developed by Statistics Canada to investigate the association between residential proximity to wind turbines and health-related outcomes in a dataset that also provides objective measures of wind turbine noise. The findings indicate that residential proximity to wind turbines is correlated with annoyance and health-related quality of life measures. These associations differ in some respects from associations with noise measurements. Results can be used to support discussions between communities and wind-turbine developers regarding potential health effects of wind turbines.

Background: Injuries during basic combat training (BCT) impact military health and readiness in the U.S. Army. Identifying risk factors is crucial for injury prevention, but few Army-wide studies to identify risk factors for injury during BCT have been completed to date. This study examines associations between individual and training-related characteristics and injuries during Army BCT., Methods: Using administrative data from the Total Army Injury and Health Outcomes Database (TAIHOD), we identified individuals who apparently entered BCT for the first time between 1 January 2002 and 30 September 2007, based on review of administrative records. Injuries were identified and categorized based on coded medical encounter data. When combined with dates of medical services, we could count injuries per person, identify unique injuries, and identify the quantity and type of medical care delivered. Regression models produced odds ratios (ORs) and 95% confidence intervals (CIs) to identify risk factors for injury during BCT (yes/no), adjusted for potential confounders., Results: Of the 278,045 (83.4%) men and 55,302 (16.6%) women who were apparently first-time trainees, 39.5% (n = 109,760) of men and 60.9% (n = 33,699) of women were injured during training based on over 2 million recorded medical encounters entries. The large cohort yielded statistically significant, small magnitude associations between injury and all individual and training-related covariates for men, and all but medical accession waivers and weight for women. After adjustment, largest magnitude effects among men were due to age > 25 yr vs. 17-18 yr (OR = 1.83, 95% CI: 1.75, 1.91); having been married in the past vs. being single (OR = 1.36, 95% CI: 1.24, 1.49); rank E4-E7 vs. E1 (OR = 0.56, 95% CI: 0.53. 0.59); training at Ft. Jackson (OR = 0.66, 95% CI: 0.64, 0.69), Ft. Leonard Wood (OR = 0.67, 95% CI: 0.65, 0.70), or Ft. Knox (OR = 0.69, 95% CI: 066, 0.72) vs. Ft. Benning. Odds of injury were highest during 2005, 2006, and 2007. After adjustment for weight and body mass index, taller men had higher odds of BCT injury than average height men (OR = 1.08, 95% CI: 1.05, 1.11). Among women, short stature (OR = 1.11; 95% CI: 1.04, 1.19), training at Ft Leonard Wood (OR = 1.10; 95% CI: 1.04, 1.16) and evidence of injury prior to training based on accession waiver (OR = 1.12; 95% CI: 1.00, 1.26) increased injury risk., Conclusions: This Army-wide analysis reveals higher BCT-related injury rates for both men and women than prior studies and identifies risk factors for injuries during BCT. The large data set allows adjustment for many covariates, but because statistical analysis may yield significant findings for small differences, results must be interpreted based on minimally important differences determined by military and medical professionals. Results provide information that may be used to adapt training or medical screening and examination procedures for basic trainees.

Researchers and those responsible for evaluating and implementing policies intended to reduce population harm must assess the potential for both intended and unintended consequences associated with those policies. Such assessments should be based on the combined dimensions of magnitude, and thus likelihood, of shifts in exposure patterns needed to produce a population benefit or harm, and magnitude of the expected population benefit or harm. In response to this assessment need, we provide a conceptual description of the dynamic population modeler, DPM(+1), as well as illustrative analyses that estimate the effects on all-cause mortality, life expectancy, and quality of life-adjusted life expectancy if exposure patterns in the population shift from a higher risk product (e.g., cigarettes) to a lower, or modified, risk tobacco product (MRTP) in specified ways. Estimates from these analyses indicate that, within a single birth cohort, switching completely from cigarette smoking to MRTP use is more likely to lead to a population-level survival benefit than initiating tobacco use with an MRTP instead of cigarettes. This is because tobacco initiation rarely occurs beyond young adulthood, whereas continuing smokers exist in all subsequent age categories, leading to a greater cumulative effect. In addition, complete switching to MRTP use among a small proportion of smokers in each age category offsets the survival deficit caused by unintended shifts in exposure patterns, such as MRTP initiation among never tobacco users followed by transitioning to cigarette smoking and/or cigarette smokers switching to MRTP use instead of quitting., (© 2017 Society for Risk Analysis.)

A physiologically-based pharmacokinetic (PBPK) model (Schroeter et al., 2011) was applied to simulate target tissue manganese (Mn) concentrations following occupational and environmental exposures. These estimates of target tissue Mn concentrations were compared to determine margins of safety (MOS) and to evaluate the biological relevance of applying safety factors to derive acceptable Mn air concentrations. Mn blood concentrations measured in occupational studies permitted verification of the human PBPK models, increasing confidence in the resulting estimates. Mn exposure was determined based on measured ambient air Mn concentrations and dietary data in Canada and the United States (US). Incorporating dietary and inhalation exposures into the models indicated that increases in target tissue concentrations above endogenous levels only begin to occur when humans are exposed to levels of Mn in ambient air (i.e. >10μg/m 3 ) that are far higher than those currently measured in Canada or the US. A MOS greater than three orders of magnitude was observed, indicating that current Mn air concentrations are far below concentrations that would be required to produce the target tissue Mn concentrations associated with subclinical neurological effects. This application of PBPK modeling for an essential element clearly demonstrates that the conventional application of default factors to "convert" an occupational exposure to an equivalent continuous environmental exposure, followed by the application of safety factors, is not appropriate in the case of Mn. PBPK modeling demonstrates that the relationship between ambient Mn exposures and dose-to-target tissue is not linear due to normal tissue background levels and homeostatic controls., (Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.)

This Data in Brief contains results from three different survey logistic regression models comparing risks of self-reported diagnoses of cardiovascular and pulmonary diseases among smokers of menthol and non-menthol cigarettes. Analyses employ data from National Health and Nutrition Examination Survey (NHANES) cycles administered between 1999 and 2012, combined and in subsets. Raw data may be downloaded from the National Center for Health Statistics. Results were not much affected by which covariates were included in the models, but depended strongly on the NHANES cycles included in the analysis. All three models returned elevated risk estimates for three endpoints when they were run in individual NHANES cycles (congestive heart failure in 2001-02; hypertension in 2003-04; and chronic obstructive pulmonary disease in 2005-06), and all three models returned null results for these endpoints when data from 1999-2012 were combined.

Though available evidence is relatively consistent in showing no additional health effects among smokers due to menthol in cigarettes, two studies reported conflicting results for stroke risk using different subsets of NHANES data. We investigated reasons for the differences in these reports by analyzing NHANES cycles conducted between 1999 and 2012, combined and in subsets. Adjusted odds ratios (AOR) and 95% confidence intervals (CI) from three different survey logistic regression models compare risk of reported stroke diagnoses among menthol and non-menthol cigarette smokers. Depending on timeframe, about 1150 to 8000 U.S. adults (aged ≥ 20 years) who smoked on ≥ 1 of the last 30 days had complete data for cigarette type and all covariates included in each model. Results were not much affected by which covariates were included in the models, but depended strongly on the NHANES cycles included in the analysis. Using NHANES 1999-2012 data combined, AORs and 95% CIs for stroke comparing menthol with non-menthol cigarette smokers were 0.95 (95% CI: 0.65, 1.37), 0.85 (95% CI: 0.59, 1.23) or 0.86 (95% CI: 0.59, 1.25). Collectively, findings illustrate the need for fully reporting research and analytical methods, especially when analyses are meant to develop evidence intended for regulatory decision-making., (Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.)

Objectives: Training-related injury is a threat to military health and readiness. Prevalence of potential risk factors for training-related injury can change with U.S. Army recruitment goals and may influence basic combat training (BCT) injury rates. This article describes challenges of using administrative data to identify a trainee cohort and describes demographic and training characteristics across the five BCT locations., Methods: Data from the Total Army Injury and Health Outcomes Database were used to identify a U.S. Army-wide cohort of first-time trainees from January 1, 2002 to September 30, 2007 and describe its characteristics., Results: The cohort includes 368,102 first-time trainees. The annual number starting BCT increased from 52,187 in 2002 to 68,808 in 2004. The proportion of males increased from 81.57% in 2003 to 83.84% in 2007. Mean (SD) age increased from 20.67 (3.55) years in 2002 to 20.94 (3.65) years in 2007. Mean (SD) body mass index increased from 24.53 (3.56) kg/m(2) in 2002 to 24.94 (3.84) kg/m(2) in 2006. Other characteristics fluctuated by year, including proportions of race/ethnicity, accession waivers, and confirmed graduates., Conclusions: Fluctuations in trainee characteristics warrant further analysis of potential influence on BCT injury rates. For research uses, careful acquisition of administrative data is needed., (Reprint & Copyright © 2014 Association of Military Surgeons of the U.S.)

Context: Approximately one quarter of men and half of women in U.S. Army basic combat training experience an injury. Preventing basic combat training-related injuries would reduce associated human and economic costs and discharges from the Army. Identification of risk factors for such injuries is a crucial step toward their prevention. Although some research has begun to address this need, prior studies of risk factors for training-related injury have not been reviewed systematically. This study systematically reviews the literature on risk factors for injury during U.S. Army basic combat training., Evidence Acquisition: Original studies of risk factors for injury during U.S. Army basic combat training published since 1990 in peer-reviewed journals were identified using PubMed and manual searches of reference lists. This search was last performed in May 2013. Nineteen studies met the inclusion criteria., Evidence Synthesis: Methodologic quality and potential for bias were assessed. The findings of 11 studies deemed to be of high or medium quality were synthesized to determine the level of evidence supporting the association between each risk factor studied and risk of injury during basic combat training. Quality assessment and evidence synthesis were performed from June to September 2013., Conclusions: There is strong or moderate evidence supporting association of older age, history of smoking, and self-rated low physical activity level prior to basic combat training with increased risk of training-related injury among male trainees. There is limited, mixed, or insufficient evidence to identify risk factors for injury among female trainees., (Copyright © 2014 American Journal of Preventive Medicine. All rights reserved.)

There are no large-scale, carefully designed cohort studies that provide evidence on whether menthol cigarette use is associated with a differential risk of initiating and/or progressing to increased smoking. However, questions of whether current menthol cigarette smokers initiated smoking at a younger age or are more likely to have transitioned from non-daily to daily cigarette use compared to non-menthol smokers can be addressed using cross-sectional data from U.S. government surveys. Analyses of nationally representative samples of adult and youth smokers indicate that current menthol cigarette use is not associated with an earlier age of having initiated smoking or greater likelihood of being a daily versus non-daily smoker. Some surveys likewise provide information on cigarette type preference (menthol versus non-menthol) among youth at different stages or trajectories of smoking, based on number of days smoked during the past month and/or cigarettes smoked per day. Prevalence of menthol cigarette use does not appear to differ among new, less experienced youth smokers compared to established youth smokers. While there are limitations with regard to inferences that can be drawn from cross-sectional analyses, these data do not suggest any adverse effects for menthol cigarettes on measures of initiation and progression to increased smoking., (Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.)

The National Health and Nutrition Examination Survey, National Survey on Drug Use and Health, National Health Interview Survey and Tobacco Use Supplement to the Current Population Survey provide estimates of the proportions of U.S. smokers who currently use menthol cigarettes, overall and within demographic strata. Among adult past-month, regular and daily smokers, menthol cigarette use ranges from 26% to 30%, with statistically higher proportions of female versus male smokers (8-11 percentage points higher) currently using menthol cigarettes. Compared to adult smokers overall, statistically higher proportions of non-Hispanic Black smokers (72-79%) and statistically lower proportions of non-Hispanic White smokers (19-22%) currently use menthol cigarettes, with no differences among smokers of other race/ethnicity groups (18-20% to 28-30%, depending on the survey). Higher proportions of younger adult past-month, regular and daily smokers (aged 18-25years) currently use menthol cigarettes compared to older adult smokers (aged 26-29years and/or ⩾30years); however, differences are small in magnitude, with the vast majority of adult smokers (70-75%) who currently use menthol cigarettes being aged ⩾30years. Comparisons between youth and adult smokers are provided, although data for youth smokers are less available and provide less consistent patterns of menthol cigarette use., (Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.)

Menthol in cigarettes has been examined for its potential to affect smoking dependence, measured primarily as number of cigarettes smoked per day and time to first cigarette after waking; the ability to quit smoking constitutes an additional measure of dependence. Successful quitting among menthol compared to non-menthol cigarette smokers is difficult to determine from the literature, due in part to the various definitions of quitting used by researchers. Nevertheless, intervention and follow-up studies of smoking cessation treatments generally indicate no differences in quitting success among menthol compared to non-menthol smokers, while cross-sectional studies suggest some differences within race/ethnicity groups. The association between menthol cigarette use and likelihood of being a former versus current smoker was examined based on data from the National Health Interview Survey and Tobacco Use Supplement to the Current Population Survey. Analyses stratified by race/ethnicity and limited to smokers who had quit at least one year prior to survey participation provided inconsistent results with regard to menthol cigarette use and quitting, both within surveys (i.e., comparing race/ethnicity groups) and between surveys (i.e., same race/ethnicity group across surveys). Evidence suggesting the existence or direction of an association between menthol in cigarettes and quitting depended on the data source., (Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.)

Previously published studies provide somewhat inconsistent evidence on whether menthol in cigarettes is associated with increased dependence. The National Health and Nutrition Examination Survey, National Survey on Drug Use and Health, National Health Interview Survey, and Tobacco Use Supplement to the Current Population Survey collect data on current cigarette type preference and primary measures of dependence, and thus allow examination of whether menthol smokers are more dependent than non-menthol smokers. Analyses based on combined data from multiple administrations of each of these four nationally representative surveys, using three definitions for current smokers (i.e., smoked ⩾1day, ⩾10days and daily during the past month), consistently demonstrate that menthol smokers do not report smoking more cigarettes per day than non-menthol smokers. Moreover, two of the three surveys that provide data on time to first cigarette after waking indicate no difference in urgency to smoke among menthol compared to non-menthol smokers, while the third suggests menthol smokers may experience a greater urgency to smoke; estimates from all three surveys indicate that menthol versus non-menthol smokers do not report a higher Heaviness of Smoking Index. Collectively, these findings indicate no difference in dependence among U.S. smokers who use menthol compared to non-menthol cigarettes., (Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.)

We developed a comprehensive, flexible dynamic model that estimates all-cause mortality for a hypothetical cohort. All model input is user-specified. In the base case, members of the cohort may be exposed to a high risk product as they age. The counterfactual scenario includes exposure to both a high risk and a lower risk product. The model sorts the population into age and exposure categories, and applies the appropriate mortality rates to each category. The model tracks individual exposure histories, and estimates, at the end of each modeled age category, the number of survivors in the two exposure scenarios (base case and counterfactual), and the difference between them. Markov Chain Monte Carlo techniques are used to estimate the variability of the results. Model output was compared against US and Swedish life tables using population-specific tobacco exposure transition probabilities derived from the literature, and it produced similar survival estimates., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Context: To protect troops against the use of anthrax as a biological weapon, the US Department of Defense began an anthrax vaccination program in 1998. 14 years after the inception of the vaccination program, there is no evidence suggesting vaccination against anthrax carries long-term health risks for Active Duty Soldiers., Objective: To investigate the association between Anthrax Vaccine Adsorbed (AVA) received while on Active Duty and subsequent disability determined by the Veterans Benefits Administration., Design, Setting and Participants: Case-control study nested in the cohort of all Active Duty personnel known to have separated from the US Army between December 1, 1997 and December 31, 2005. Cases were ≥10% disabled, determined either by the Army prior to separation (N=5846) or by the Veterans Benefits Administration (VBA) after separation (N=148,934). Controls (N=937,705) separated from the Army without disability, and were not receiving pensions from the VBA as of April 2007. Data were from the Total Army Injury and Health Outcomes Database and the VBA Compensation and Pension and Benefits database., Main Outcomes: Disability status (yes/no); for primary disability, percent disabled (≥10%, 20%, >20%) and type of disability., Results: Vaccination against anthrax was four times more likely among disabled Veterans with hostile fire pay records (HFP, a surrogate for deployment). Vaccinated Soldiers with HFP had lower odds of disability separation from the Army 0.89 (0.80, 0.98); there was no association between vaccine and receiving Army disability benefits among those without HFP (OR=1.05, CI: 0.96, 1.14). Vaccination was negatively associated with receiving VA disability benefits for those with HFP (OR=0.66, CI: 0.65, 0.67), but there was little or no association between vaccine and receipt of VA disability benefits for those without HFP (OR=0.95, CI: 0.93, 0.97)., Conclusions: Risk of disability separation from the Army and receipt of disability compensation from the VA were not increased in association with prior exposure to AVA. This study provides evidence that vaccination against anthrax is not associated with long term disability., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Objective: Osteoarthritis of the hip (OA) is a common degenerative disorder of the joint cartilage that presents a major public health problem worldwide. While intrinsic risk factors (e.g, body mass and morphology) have been identified, external risk factors are not well understood. In this systematic review, the evidence for workload as a risk factor for hip OA is summarized and used to derive recommendations for prevention and further research., Methods: Epidemiological studies on workload or occupation and osteoarthritis of the hip were identified through database and bibliography searches. Using pre-defined quality criteria, 30 studies were selected for critical evaluation; six of these provided quantitative exposure data., Results: Study results were too heterogeneous to develop pooled risk estimates by specific work activities. The weight of evidence favors a graded association between long-term exposure to heavy lifting and risk of hip OA. Long-term exposure to standing at work might also increase the risk of hip OA., Conclusions: It is not possible to estimate a quantitative dose-response relationship between workload and hip OA using existing data, but there is enough evidence available to identify job-related heavy lifting and standing as hazards, and thus to begin developing recommendations for preventing hip OA by limiting the amount and duration of these activities. Future research to identify specific risk factors for work-related hip OA should focus on implementing rigorous study methods with quantitative exposure measures and objective diagnostic criteria.

To evaluate the potential for long-term or delayed onset health effects, we extended a previous cohort study of disability separation from the army associated with vaccination against anthrax. Analyses included stratified Cox proportional hazards and multiple logistic regression models. Forty-one percent of 1,001,546 soldiers received at least one anthrax vaccination; 5.21% were evaluated for disability. No consistent patterns or statistically significant differences in risk of disability evaluation, disability determination, or reason for disability were associated with anthrax vaccination. There was a dose-related trend in risk of disability for soldiers with 2 years' service, limited to those entering service in 2000 or later. Divergent patterns in risk suggest confounding by temporal or occupational risks of disability., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Outside-the-boot parachute ankle braces (PABs) worn during US Army paratrooper training have been shown to reduce the risk of severe ankle injuries. In spite of evidence to the contrary, anecdotal reports continue to suggest increases in risk of other types of injury, and the cost of obtaining and periodically replacing the PAB has been used to justify its discontinued use. The authors identified inpatient and outpatient treatment for injuries during US Army paratrooper training. Those undergoing training during two periods when PAB use was mandated had 40% lower risks of ankle injury (brace I, RR=0.60 (95% CI 0.47 to 0.75); brace II, RR=0.62 (95% CI 0.49 to 0.78)), with no difference in risks of other types of injury. There were no differences in risk of ankle injury during periods when brace use was not mandated. The PAB is safe, effective and cost effective.

Manganese (Mn) is an essential element for humans, animals, and plants and is required for growth, development, and maintenance of health. Mn is present in most tissues of all living organisms and is present naturally in rocks, soil, water, and food. High-dose oral, parenteral, or inhalation exposures are associated with increased tissue Mn levels that may lead to development of adverse neurological, reproductive, or respiratory effects. Manganese-induced clinical neurotoxicity is associated with a motor dysfunction syndrome commonly referred to as manganism. Because Mn is an essential element and absorption and excretion are homeostatically regulated, a reasonable hypothesis is that there should be no adverse effects at low exposures. Therefore, there should be a threshold for exposure, below which adverse effects may occur only rarely, if at all, and the frequency of occurrence of adverse effects may increase with higher exposures above that threshold. Lowest-observed-adverse-effect levels (LOAELs), no-observed-adverse-effect levels (NOAELs), and benchmark dose levels (BMDs) have been derived from studies that were conducted to evaluate subclinical neurotoxicity in human occupational cohorts exposed to Mn. Although there is some uncertainty about the predictive value of the subclinical neuromotor or neurobehavioral effects that were observed in these occupational cohort studies, results of the neurological tests were used in risk assessments to establish guidelines and regulations for ambient air levels of Mn in the environment. A discussion of the uncertainties associated with these tests is provided in this review. The application of safety and uncertainty factors result in guidelines for ambient air levels that are lower than the LOAELs, NOAELs, or BMDs from occupational exposure studies by an order of magnitude, or more. Specific early biomarkers of effect, such as subclinical neurobehavioral or neurological changes or magnetic resonance imaging (MRI) changes, have not been established or validated for Mn, although some studies attempted to correlate certain biomarkers with neurological effects. Pharmacokinetic studies with rodents and monkeys provide valuable information about the absorption, bioavailability, and tissue distribution of various Mn compounds with different solubilities and oxidation states in different age groups. These pharmacokinetic studies showed that rodents and primates maintain stable tissue Mn levels as a result of homeostatic mechanisms that tightly regulate absorption and excretion of ingested Mn and limit tissue uptake at low to moderate levels of inhalation exposure. In addition, physiologically based pharmacokinetic (PBPK) models are being developed to provide for the ability to conduct route-to-route extrapolations, evaluate nasal uptake to the central nervous system (CNS), and determine life-stage differences in Mn pharmacokinetics. Such models will facilitate more rigorous quantitative analysis of the available human pharmacokinetic data for Mn and will be used to identify situations that may lead to increased brain accumulation related to altered Mn kinetics in different human populations, and to develop quantitatively accurate predictions of elevated Mn levels that may serve as a basis of dosimetry-based risk assessments. Such dosimetry-based risk assessments will permit for the development of more scientifically refined and robust recommendations, guidelines, and regulations for Mn levels in the ambient environment and occupational settings.

Occupational exposure limits (OELs) for carbon disulfide vary between 1 and 10 ppm worldwide. They are generally based on health effects observed in viscose industry. Publications after the mid-1970s are reviewed to determine whether there is a scientific justification for an OEL below 10 ppm. The exposure situation in viscose industry is governed by long exposure durations, high exposures in past decades, high peak exposures, former analytical procedures underestimating exposure, and shift work. Three approaches were used to define an OEL based on workplace data: (1) Division of a cumulative exposure index by lifetime exposure duration. This approach ignores the possible existence of a threshold and fails to differentiate between brief high and sustained low exposures. (2) Defining the NOEL/LOEL by mean exposure levels. With a wide range of exposures, effects observed at the mean are driven by high exposures underestimating the true NOEL. (3) Assessment of effects observed at workplaces complying with a predefined exposure limit. Without adverse effects at such a limit this should be the starting point to define the OEL. The most important health effects for carbon disulfide are coronary heart disease, coronary risk factors, retinal angiopathy, color discrimination, effects on peripheral nerves, psychophysiological effects, morphological and other central nervous system (CNS) effects, and fertility and hormonal effects. The data generally support an OEL of 10 ppm. Some uncertainties exist for effects on electrocardiogram (ECG), heart rate, retinal microaneurysms (in Japanese workers), peripheral nerve conduction velocities, some psychophysiological parameters, brain magnetic resonance imaging (MRI; hyperintensive spots), and hearing function. Further investigations on workers under defined long-term exposure conditions might help to come to a final conclusion. Finally, the reproductive capacity of female workers may not be adequately protected at exposures around 10 ppm.

This study was conducted to examine whether U.S. Army personnel receiving > or =1 dose of anthrax vaccine adsorbed (AVA) between March 1998 and February 2002 were at higher risk of disability than unvaccinated personnel. We studied a historical cohort study of 716,833 active-duty soldiers (154,456 vaccinated) followed for 4.25 years to determine rates of evaluation for disability discharge. Cox proportional hazards models compared estimated risk of evaluation for disability, accounting for occupation and sociodemographics. Adjusted hazard ratio (HR) and 95% confidence interval (CI) was 0.96 (CI = 0.92-0.99). Separate adjusted HRs for men, women, permanent and temporary disability, musculoskeletal and neurologic conditions were similar, ranging from 0.90 to 1.04. Latency assumptions did not affect results. Anthrax vaccination does not increase risk of disability. This finding may be partially the result of factors influencing selection for vaccination or vaccine tolerance.

In response to concerns about occupational and environmental exposures, and a perceived cluster of amyotrophic lateral sclerosis (ALS) in the community, the mortality experience among 31,811 civilian employees who worked for at least 1 year between 1981 and 2000 at Kelly Air Force Base, Texas was ascertained. A total of 3264 deaths occurred through October 31, 2001. Overall, significant deficits in mortality were observed for all causes of death and all cancers combined. An excess of breast cancer [standardized mortality ratio (SMR) = 216; 95% confidence interval (CI) = 128-341] among blue-collar women was identified, and remained elevated after adjusting for race and ethnicity [rate ratio (RR) = 2.83; 95% CI = 1.50-5.34]. Mortality from motor neuron disease, which includes ALS deaths, was not increased overall (SMR = 0.98; 95% CI = 0.52-1.68), and was lower among blue-collar employees and higher among white-collar employees than expected, based on small numbers. Overall, mortality patterns indicated a healthy worker population and no large increased mortality associated with employment at Kelly Air Force Base.

Aims: To identify sociodemographic and occupational determinants of knee related disability discharge from the US Army among enlisted women, and to investigate effect modification., Methods: A case-control study of 692 cases of knee related disability discharge and 2080 incidence density matched controls nested within the population of all 244 000 enlisted women on active duty in the US Army, 1980-97. We used logistic regression to identify determinants of disability, stratified to explore effect modification by demographic and work characteristics., Results: The risk of disability discharge was twice as high (odds ratio (OR) 2.4, 95% confidence interval (CI): 1.71 to 3.47) for the oldest (33-60 years) versus the youngest (17-21 years) women. Non-whites had lower risk than whites (OR 0.5, 95% CI: 0.41 to 0.60), as did married (OR 0.7, 95% CI: 0.54 to 0.81) relative to non-married women. Those of lower rank (pay grades E1-E3) were at five times the risk of disability discharge compared to those of higher ranks (pay grades E4-E9, OR 5.0, 95% CI: 2.86 to 8.33), while ORs were highest for those with longer duration of service compared to women on active duty for a year or less (OR 1.4, 95% CI: 0.8 to 2.55 after 12 years). Race modified several effects, including that of rank. Age, duration of service, and pay grade were too highly correlated to draw firm conclusions about their independent modifying effects on risk of disability discharge from the Army., Conclusions: Sociodemographic factors had larger effects than occupational characteristics on risk of knee related disability discharge from the US Army. Interactions suggest subgroups at differing risk levels that might be targeted for more detailed investigations.

Objectives: Occupational carbon disulfide (CS(2)) exposure has been associated with a variety of health effects since its introduction in the mid-19th century. Much of the epidemiological interest, especially since the 1960s, has focused on associations with cardiac effects. However, considerable differences in study approach, disease outcome, CS(2) exposure level, and control of confounding factors have produced mixed results and conclusions. This critical review presents a synthesis of the most relevant and best quality studies to better understand these associations., Methods: Using specific criteria to assess methodological and scientific quality, we identified 37 studies with the potential to inform on at least one of the following questions: (1) Has a relationship between CS(2) exposure and coronary heart disease (CHD) mortality been reasonably demonstrated? If so, at what apparent exposure levels has it been observed? (2) Among studies of workers routinely exposed to CS(2) at levels greater than 20 ppm, have any health effects or indicators of CHD been observed consistently? (3) Among occupational groups exposed to CS(2) at levels less than 20 ppm, have any health effects or indicators of CHD been observed consistently?, Results: Several CHD-related effects have been examined relative to various levels of occupational CS(2) exposure. Overall, there was remarkably little consistency of CHD effects observed, including CHD mortality., Conclusions: Although a physiological effect of CS(2) exposure on CHD is plausible, the epidemiological evidence for an association between CS(2) exposure and various cardiac risk indicators is mixed. The only somewhat consistent finding, of CS(2) exposure on total and/or LDL cholesterol level, may be due to residual confounding by other time-dependent risk factors. If real, however, it appears to be of small magnitude and uncertain clinical importance.

Objectives: Following up on two earlier publications showing increased psychological stress and psychosocial effects of travel on the business travellers this study investigated the health of spouses of business travellers., Methods: Medical claims of spouses of Washington DC World Bank staff participating in the medical insurance programme in 1997-8 were reviewed. Only the first of each diagnosis with the ninth revision of the international classification of diseases (ICD-9) recorded for each person was included in this analysis. The claims were grouped into 28 diagnostic categories and subcategories., Results: There were almost twice as many women as men among the 4630 identified spouses. Overall, male and female spouses of travellers filed claims for medical treatment at about a 16% higher rate than spouses of non-travellers. As hypothesised, a higher rate for psychological treatment was found in the spouses of international business travellers compared with non-travellers (men standardised rate ratios (RR)=1.55; women RR=1.37). For stress related psychological disorders the rates tripled for both female and male spouses of frequent travellers (>or= four missions/year) compared with those of non-travelling employees. An increased rate of claims among spouses of travellers versus non-travellers was also found for treatment for certain other diagnostic groups. Of these, diseases of the skin (men RR=2.93; women RR=1.41) and intestinal diseases (men RR=1.31; women RR=1.47) may have some association with the spouses' travel, whereas others, such as malignant neoplasms (men RR=1.97; women RR=0.79) are less likely to have such a relation., Conclusion: The previously identified pattern of increased psychological disorders among business travellers is mirrored among their spouses. This finding underscores the permeable boundary between family relations and working life which earlier studies suggested, and it emphasises the need for concern within institutions and strategies for prevention.

Background: The Cancer Prevention and Control Education (CPACE) program aims to strengthen and coordinate curriculum offerings in cancer prevention and control for medical, graduate nursing and public health students., Methods: Students were surveyed on cancer-related knowledge and confidence as part of needs assessment and evaluation efforts. The students completed self-administered surveys (response rate 78%). Descriptive and stratified analysis and ANOVA were conducted., Results: Knowledge and confidence generally increased with each successive class year, but confidence varied markedly across specific counseling scenarios and by gender. While the students overall reported greater confidence in performing an examination than in interpreting the results, confidence varied significantly across specific types of examinations., Conclusions: Understanding of basic information about common cancers was disappointing. Confidence to perform and interpret examinations could be higher, especially for opposite-gender screening examinations. Implications of the findings for CPACE curriculum development are discussed.

Background: Occupational injuries are responsible for more lost time from work, productivity, and working years of life than any other health condition in either civilian or noncombat military sectors. Injuries, not illnesses, are the leading cause of morbidity and mortality among U.S. Army personnel. We examined the separate and joint roles of gender, race/ethnicity, and age in the odds of discharge from the Army for disabling knee injury., Methods: A total of 860 women and 7868 men were discharged from the Army between 1980 and 1995 for knee-related disability and met all inclusion criteria for this study. All women and a subsample of 1005 men were included in these analyses, along with a simple random sample of three controls per case, stratified by gender, drawn from the population of all active-duty enlisted soldiers in each year from 1980 to 1995. We identified predictors of the occurrence or nonoccurrence of discharge from the Army for disabling knee injury using unconditional multiple logistic regression analyses., Results: We found relations between the risk of knee-related disability and age and race, with marked effect modification by gender. Non-Caucasian men and women were at lower risk than Caucasians at all ages. At most ages, Caucasian women were at higher risk than Caucasian men, and non-Caucasian women were at lower risk than non-Caucasian men. Within race/ethnicity and gender, the risks for men showed an inverted "U" shape with increasing age, and the risks for women showed a "J" shape with increasing age., Conclusions: Age, race/ethnicity, and gender interactions are important in occupational injury. Differences in risk may be related to differences in work assignments, leisure activities, physical or physiological differences, or the ways in which disability compensation is granted.

Background: Previously established predictors of outlet strut fracture in Björk-Shiley convexo-concave (CC) valves include larger valve size, larger opening angle (70 degrees versus 60 degrees), younger age at implant, and date of manufacture. We sought to identify patient characteristics that might be predictive of strut fracture and to refine the estimates associated with previously identified predictors., Methods and Results: We conducted a case-control study of CC60 degrees valves implanted in the United States and Canada and manufactured between January 1, 1979, and March 31, 1984. Cases included all valves with verified outlet strut fractures reported to the manufacturer from January 1979 through January 1992. Up to 10 controls were selected for each case. Control valves were matched according to implanting surgeon and were required to have been functioning at least as long as their matched case valves. Case and control medical records were reviewed for information on patient medical history before the valve implant. There were 96 case and 634 control valves for which clinical data were available. Patient age and valve size and implant position were confirmed as important determinants of fracture. There was a strong inverse gradient of risk with age. The risk of fracture was 42% lower for each 10-year increment of patient age at time of implant. Large mitral valves were at greatest risk of strut fracture, with the largest mitral valves (33 mm) estimated to be 33 times more likely to fracture than the smallest (21 to 25 mm) aortic valves. Date of manufacture was also associated with risk; valves welded from mid-1981 through March 1984 were more likely to fracture than those manufactured in 1979 and 1980. Body surface area < 1.5 m2 was associated with 1/16 the risk of body surface area > or = 2.0 m2. No other patient factor was strongly associated with the risk of strut fracture., Conclusions: Few patient features identifiable in the implant record are predictive of strut fracture. Our analysis supports previous work in identifying valve size, patient age, and date of manufacture as predictors of fracture and adds body surface area. A number of these associations suggest that conditions associated with higher cardiac output may also place patients at increased risk.

Björk-Shiley Convexo-Concave (CC) valves sometimes experience fracture of the outlet strut. Previously implicated valve characteristics that predict strut fracture include larger valve size, larger opening angle (70 degrees vs 60 degrees), remilling, weld date, and implant in the mitral position. While the associations between risk, size, and opening angle suggest that part of the elevated incidence of strut fracture might be due to the design of the Björk-Shiley valves, only a small fraction of implanted valves have experienced strut fracture. In consequence, previously unexamined variations in the manufacturing process have been suggested as possible factors affecting the failure risk of individual valves; materials, manufacturing steps, quality control, and specific workers have all been put forward as potential explanations for valve-to-valve variation in risk. We conducted a case-control study of CC60 degrees valves implanted in the USA and Canada and manufactured between January 1, 1979 and March 31, 1984. Cases included all verified strut fractures reported to the manufacturer from 1979 through January, 1992. up to 10 controls were selected for each case. Controls were matched to cases on implanting surgeon and were required to have been implanted and functioning at least as long as their respective case valves. We reviewed case and control manufacturing records. There were 150 cases and 1095 surgeon-matched controls. Large mitral valves were at greatest risk of strut fracture; 33mm mitral valves were estimated to be 23 times more likely to fracture than 21-25mm aortic valves. Valves welded in 1979 and 1980 were less likely to fracture than those welded in any other time period; however, no specific manufacturing procedures or personnel were uniquely associated with this time period. Valves with more flexible outlet struts, as determined by the hook deflection and load deflection tests during manufacture, appear to have been at higher risk than valves with more rigid outlet struts. There were three welders who had worked on a sufficient number of valves to allow separate estimation of the risk in the valves they welded. One welder's work was associated with about one-third the risk of valves worked on by the other two. Examination of receiver operating characteristic curves revealed, however, that welder identity added little to the discriminating information already available in the form of valve size and implant position. It is concluded that welder identity and strut flexibility appear to contribute to the risk of outlet strut fracture in Björk-Shiley CC60 degrees valves. Neither of these factors, however, is sufficient to account for much of the previously unexplained variation in risk. No other characteristic measurable in existing manufacturing records appears to predict risk of strut fracture in any useful way.

Plasma ascorbic acid (AA) frequently is positively correlated with high-density-lipoprotein (HDL) cholesterol and inversely related to total cholesterol concentration. To determine if vitamin C intake can alter cholesterol concentration, we examined the effect of vitamin C supplementation (1 g/d) on lipoprotein cholesterol and triglyceride levels in 138 subjects, aged 20 to 65 years, who completed an 8-month randomized, double-blinded, placebo-controlled trial. Individuals with higher levels of plasma AA (> 80 mumol/L for men and > 90 mumol/L for women), HDL cholesterol (> 1.4 mmol/L for men and > 1.7 mmol/L for women), and total cholesterol (> 6.7 mmol/L) were excluded from this trial. We observed no overall effect of supplementation on plasma concentrations of HDL, LDL, or total cholesterol, apolipoprotein (apo) B, or triglyceride. We did observe a marginally significant (P < 0.10) increase of 1.9 mumol/L (5.3 mg/dL) in apo A-I concentration with supplementation and a significant (P < 0.05) difference of 0.10 mmol/L (3.8 mg/dL) in HDL cholesterol concentration between vitamin C and placebo treatment in a nonrandomized subgroup of individuals (n = 43) and a baseline plasma AA level less than 55 mumol/L. Although the apo A-I concentration increase was only marginally significant with supplementation, change in plasma AA concentration was significantly (P < 0.05) correlated with change in apo A-I concentration in the entire sample. The overall results of this trial were negative, but our data do not allow us to rule out the possibility that vitamin C supplementation might increase HDL cholesterol or apo A-I concentrations among individuals with lower plasma AA levels.

We examined the association between plasma lipids and total ascorbic acid in 256 men and 221 women age 20-65 years. Among men, we observed that high-density lipoprotein (HDL) cholesterol was 2.1 mg per dl higher, total:HDL cholesterol was 5.4% lower, total cholesterol was 4.8 mg per dl lower, low-density lipoprotein (LDL) cholesterol was 5.6 mg per dl lower, and triglyceride was 5.2% lower for each 0.5 mg per dl increment in ascorbic acid. The association between ascorbic acid and total:HDL cholesterol ratio in men was modified by glucose concentration. Among women, we observed that HDL cholesterol was 14.9 mg per dl higher for women with ascorbic acid levels < or = 1.05 mg per dl and 0.9 mg per dl lower for women with ascorbic acid levels > 1.05 mg per dl for each 0.5 mg per dl increment in ascorbic acid. Total:HDL cholesterol ratio was 10.9% lower for women with ascorbic acid concentrations < or = 1.45 mg per dl and 0.6% higher for women with ascorbic acid concentrations > 1.45 mg per dl for each 0.5 mg per dl increment. The associations among ascorbic acid concentration, total and LDL cholesterol, and triglyceride concentrations were weak or absent among women. These results are consistent with earlier observations relating ascorbic acid and HDL cholesterol and indicate that ascorbic acid might also be related to total and LDL cholesterol concentrations in men.

The relationships between plasma, aqueous humor and lens ascorbic acid levels are examined in 131 samples from 127 patients. Mean ascorbate intake for nonsupplemented individuals was 148 mg/day or over two times the recommended daily allowance. A subset of 44 patients participated in a trial to assess the impact of vitamin C supplementation of 2 grams per day on aqueous and lens ascorbic acid levels. Such supplementation significantly increased both total and reduced ascorbic acid levels in plasma and aqueous and total ascorbic acid in the lens. Correlation coefficients relating total and reduced ascorbic acid levels in the three tissues ranged from 0.42 to 0.19 (p less than 0.05 for all correlation coefficients). Over 60% of the ascorbate was present in the reduced form in plasma and aqueous, and about 50% of the lens ascorbate was in the reduced form.

This paper describes relationships between reported alcohol consumption and selected sociodemographic and health variables. Two hundred and four men and 367 women aged 60-95 years were examined as part of a nutritional status survey of elderly. Fifty-three percent of men and 44% of women reported drinking at least 2 g of alcohol per week. Men were more likely to drink than women, and the level of alcohol consumption decreased with age. Drinking was positively associated with education (p less than 0.01) and negatively associated with recent medical care (p less than 0.01), history of MI (p less than 0.05), and denture use (p less than 0.05). Among drinkers, reported alcohol intake was higher for subjects less than age 70 (p less than 0.01), males (p less than 0.01), the college educated (p less than 0.01), and smokers (p less than 0.05). Level of alcohol intake was lower for those who had received medical care in the year preceding study participation (p less than 0.05). Identical results were observed for alcohol intake expressed as percent of total calories. Intake ranged from 3.8% of total calories among subjects 80+ years old to 6.2% of total calories among 60-69-year-olds.