Special Circumstances and Populations.

Venous thromboembolism is a condition that includes both deep venous thrombosis and pulmonary embolism. Venous thromboembolism disease can result because of a combination of risk factors, including patient-related, treatment-related, and, more specifically, cancer-related factors. It is not disease-specific or a population-specific disorder, but it is more prevalent in certain specialty populations. This article will cover those specialty populations including cancer, pregnancy, and athletes.

History and evolution of warning labels for automotive friction products.

There have been claims over the years that asbestos-containing product manufacturers did not sufficiently warn end users early enough regarding the potential health hazards associated with their products (1930s-1990s). To address this issue, we compared the content of the warnings associated with asbestos-containing friction products (brakes, clutches, and gaskets) manufactured by the US automotive industries to what was expected by regulatory agencies during the time period in which an understanding of asbestos health hazards was being developed. We ended our evaluation around 1990, since asbestos-containing manufacturer supplied automotive products were functionally removed from commerce by 1985 in the United States. We assessed the warnings issued in users' manuals, technical service bulletins, product packaging materials, and labels placed on products themselves. Based on our evaluation, regulatory agencies had no guidelines regarding specific warning language for finished friction products, particularly when a product contained encapsulated asbestos fibers (i.e., modified by a bonding agent). Even today, federal regulations do not require labeling on encapsulated products when, based on professional judgment or sampling, user exposure is not expected to exceed the OSHA PEL. We concluded that, despite limited regulatory guidance, the US automotive industry provided adequate warnings with regards to its friction products.

A randomized placebo-controlled prevention trial of aspirin and/or resistant starch in young people with familial adenomatous polyposis.

Evidence supporting aspirin and resistant starch (RS) for colorectal cancer prevention comes from epidemiologic and laboratory studies (aspirin and RS) and randomized controlled clinical trials (aspirin). Familial adenomatous polyposis (FAP) strikes young people and, untreated, confers virtually a 100% risk of colorectal cancer and early death. We conducted an international, multicenter, randomized, placebo-controlled trial of aspirin (600 mg/d) and/or RS (30 g/d) for from 1 to 12 years to prevent disease progression in FAP patients from 10 to 21 years of age. In a 2 × 2 factorial design, patients were randomly assigned to the following four study arms: aspirin plus RS placebo; RS plus aspirin placebo; aspirin plus RS; RS placebo plus aspirin placebo; they were followed with standard annual clinical examinations including endoscopy. The primary endpoint was polyp number in the rectum and sigmoid colon (at the end of intervention), and the major secondary endpoint was size of the largest polyp. A total of 206 randomized FAP patients commenced intervention, of whom 133 had at least one follow-up endoscopy and were therefore included in the primary analysis. Neither intervention significantly reduced polyp count in the rectum and sigmoid colon: aspirin relative risk = 0.77 (95% CI, 0.54-1.10; versus nonaspirin arms); RS relative risk = 1.05 (95% CI, 0.73-1.49; versus non-RS arms). There was a trend toward a smaller size of largest polyp in patients treated with aspirin versus nonaspirin--mean 3.8 mm versus 5.5 mm for patients treated 1 or more years (adjusted P = 0.09) and mean 3.0 mm versus 6.0 mm for patients treated more than 1 year (P = 0.02); there were similar weaker trends with RS versus non-RS. Exploratory translational endpoints included crypt length (which was significantly shorter in normal-appearing mucosa in the RS group over time) and laboratory measures of proliferation (including Ki67). This clinical trial is the largest ever conducted in the setting of FAP and found a trend of reduced polyp load (number and size) with 600 mg of aspirin daily. RS had no clinical effect on adenomas.

Airborne concentrations of asbestos onboard maritime shipping vessels (1978-1992).

The exposure of shipyard workers to asbestos has been frequently investigated during the installation, repair or removal of asbestos insulation. The same level of attention, however, has not been directed to asbestos exposure of maritime seamen or sailors. In this paper, we assemble and analyze historical industrial hygiene (IH) data quantifying airborne asbestos concentrations onboard maritime shipping vessels between 1978 and 1992. Air monitoring and bulk sampling data were compiled from 52 IH surveys conducted on 84 different vessels, including oil tankers and cargo vessels, that were docked and/or at sea, but these were not collected during times when there was interaction with asbestos-containing materials (ACMs). One thousand and eighteen area air samples, 20 personal air samples and 24 air samples of unknown origin were analyzed by phase contrast microscopy (PCM); 19 area samples and six samples of unknown origin were analyzed by transmission electron microscopy (TEM) and 13 area air samples were analyzed by scanning electron microscopy (SEM). In addition, 482 bulk samples were collected from suspected ACMs, including insulation, ceiling panels, floor tiles, valve packing and gaskets. Fifty-three percent of all PCM and 4% of all TEM samples were above their respective detection limits. The average airborne concentration for the PCM area samples (n = 1018) was 0.008 fibers per cubic centimeter (f cc(-1)) (95th percentile of 0.040 f cc(-1)). Air concentrations in the living and recreational areas of the vessels (e.g. crew quarters, common rooms) averaged 0.004 f cc(-1) (95th percentile of 0.014 f cc(-1)), while air concentrations in the engine rooms and machine shops averaged 0.010 f cc(-1) (95th percentile of 0.068 f cc(-1)). Airborne asbestos concentrations were also classified by vessel type (cargo, tanker or Great Lakes), transport status (docked or underway on active voyage) and confirmed presence of ACM. Approximately 1.3 and 0% of the 1018 area samples analyzed by PCM exceeded 0.1 and 1 f cc(-1), respectively. This data set indicates that historic airborne asbestos concentrations on these maritime shipping vessels, when insulation-handling activities were not actively being performed, were consistently below contemporaneous US occupational standards from 1978 until 1992, and nearly always below the current permissible exposure limit of 0.1 f cc(-1).

A nested case-control study of brain tumors among employees at a petroleum exploration and extraction research facility.

Work-related exposures potentially associated with a cluster of brain tumors at a petroleum exploration and extraction research facility were evaluated in a nested case-control study. Fifteen cases were identified in the original cohort and 150 matched controls were selected. Odds ratios (ORs) for occupational exposure to petroleum, radiation, solvents, magnetic fields, and work activities were near or below 1.0. ORs near 1.5 were observed for: working with computers (OR = 1.47; 95% confidence interval [CI] = 0.30-9.35); work-related travel (OR = 1.48; 95% CI = 0.25-5.95), and travel immunizations (OR = 1.62; 95% CI = 0.23-9.45). Higher ORs were observed for work in administrative and marketing buildings and for achieving a master's or higher degree (OR = 2.0, 95% CI = 0.4-10.7). While some ORs above 1.5 were noted, no work-related chemical and physical exposures were significantly associated with the occurrence of brain tumors among employees at this facility.

Performance of the beryllium blood lymphocyte proliferation test based on a long-term occupational surveillance program.

OBJECTIVE: Data from surveys of the general workforce and new employees at a beryllium manufacturer were used to evaluate the performance of the beryllium blood lymphocyte proliferation test (BeBLPT). METHODS: Over 10,000 results from nearly 2,400 participants collected over 12 years were analyzed using consistent criteria to describe the performance characteristics of the BeBLPT. RESULTS: Approximately 2% of new employees had at least one positive BeBLPT result at the time of hire, and approximately 1% of new employees with no known potential occupational or possible take-home exposures to beryllium were confirmed positive (two positive results) from the time of hire. Positive results were observed in some workers within weeks or months of initial exposure, and the median time to the first positive result in confirmed positive individuals was 5 months. The prevalence of positive BeBLPT results was greatest during the first year of employment with an apparent peak in months 4-8. At least one negative or borderline/negative result was observed in 100% of new workers who underwent follow-up testing after they had been confirmed positive. There was no correlation between time of employment and an increasing prevalence of confirmed positive BeBLPT results in individual surveys; however, the cumulative incidence of confirmed positive results in subsets of workers that participated in multiple surveys increased over time. CONCLUSION: The detection of confirmed positive results in non-occupationally exposed persons, the apparent reversions of previously confirmed positive results, the identification of a positive BeBLPT peak prevalence period, and the variation in intra- and inter-laboratory test methods and interpretation should be considered when interpreting results from studies utilizing the BeBLPT, especially when considering worker-specific interventions. Additional research to refine the BeBLPT or develop a new test is needed to properly characterize the relationship between sensitization and subclinical or clinical indicators of chronic beryllium disease.

Assessment of the beryllium lymphocyte proliferation test using statistical process control.

Despite more than 20 years of surveillance and epidemiologic studies using the beryllium blood lymphocyte proliferation test (BeBLPT) as a measure of beryllium sensitization (BeS) and as an aid for diagnosing subclinical chronic beryllium disease (CBD), improvements in specific understanding of the inhalation toxicology of CBD have been limited. Although epidemiologic data suggest that BeS and CBD risks vary by process/work activity, it has proven difficult to reach specific conclusions regarding the dose-response relationship between workplace beryllium exposure and BeS or subclinical CBD. One possible reason for this uncertainty could be misclassification of BeS resulting from variation in BeBLPT testing performance. The reliability of the BeBLPT, a biological assay that measures beryllium sensitization, is unknown. To assess the performance of four laboratories that conducted this test, we used data from a medical surveillance program that offered testing for beryllium sensitization with the BeBLPT. The study population was workers exposed to beryllium at various facilities over a 10-year period (1992-2001). Workers with abnormal results were offered diagnostic workups for CBD. Our analyses used a standard statistical technique, statistical process control (SPC), to evaluate test reliability. The study design involved a repeated measures analysis of BeBLPT results generated from the company-wide, longitudinal testing. Analytical methods included use of (1) statistical process control charts that examined temporal patterns of variation for the stimulation index, a measure of cell reactivity to beryllium; (2) correlation analysis that compared prior perceptions of BeBLPT instability to the statistical measures of test variation; and (3) assessment of the variation in the proportion of missing test results and how time periods with more missing data influenced SPC findings. During the period of this study, all laboratories displayed variation in test results that were beyond what would be expected due to chance alone. Patterns of test results suggested that variations were systematic. We conclude that laboratories performing the BeBLPT or other similar biological assays of immunological response could benefit from a statistical approach such as SPC to improve quality management.

Biomonitoring for farm families in the farm family exposure study.

OBJECTIVES: The Farm Family Exposure Study was conducted to evaluate real-world pesticide exposure for farmers, spouses, and children. METHODS: Eligible farm families from Minnesota and South Carolina were randomly selected from a roster of licensed private pesticide applicators. Eligibility required that the family include a farmer, spouse, and at least one child between the ages of 4 and 17 years, that the family live on the farm, that the farmer planned to apply one of the target pesticides [glyphosate, chlorpyrifos, 2,4-dichlorophenoxy acetic acid (2,4-D)] to at least 10 acres (4.1 hectares) of land within 1 mile (1.6 kilometers) of the house. For each family member, geometric means were calculated for 24-hour composite urinary samples, with a 1 ppb (part per billion) limit of detection, the day before, the day of, and for 3 days after the application. RESULTS: For the farmers, the peak geometric mean concentrations were 3 ppb for glyphosate, 64 ppb for 2,4-D, and 19 ppb for the primary chlorpyrifos metabolite. For the spouses and children, the percentage with detectable values varied by chemical, although the average values for each chemical did not vary during the study period. The applicators had the highest urine pesticide concentrations, children had much lower values, and spouses had the lowest values. Exposure to family members was largely, though not exclusively, determined by the degree of direct contact with the application process. The exposure profile varied for the three chemicals for each family member. CONCLUSIONS: The data of this study indicate the importance of chemical-specific considerations when exposure assessments are planned in epidemiologic studies.

Occupational magnetic field exposure, cardiovascular disease mortality, and potential confounding by smoking.

PURPOSE: To assess the relationship between occupational magnetic field (MF) exposure and cardiovascular disease (CVD) mortality and to determine whether smoking could confound this relationship. METHODS: Death certificate and proxy respondent information from the US 1986 and 1993 National Mortality Followback Surveys (NMFS) were used to determine whether job titles with potential occupational MF exposure were risk factors for CVD mortality and whether smoking behavior may confound the observed relationship. A qualitative MF exposure matrix was developed based on job titles and published exposure measurements. In a case-control analysis, logistic regression models, adjusting for age, sex, race, working status, level of education, and survey year, were used to examine the associations between estimated MF exposure and death from CVD. To assess the effect of adjustment for smoking, we conducted our analyses with and without including smoking-related variables in the models, and evaluated the change in CVD risk estimates. RESULTS: There was no consistent dose-response relationship between occupational MF exposure estimates and CVD mortality. Adjustment for smoking behavior did not appreciably change the observed MF exposure-CVD mortality relationship. CONCLUSIONS: Although limited by self-reported information on exposure and smoking, our results suggest that CVD mortality was not associated with MF exposure in this study, and smoking behavior was not an apparent confounder of the MF-CVD association.

Farm Family Exposure Study: methods and recruitment practices for a biomonitoring study of pesticide exposure.

PURPOSE: The Farm Family Exposure Study was initiated to characterize pesticide exposure to farm family members around the time of one pesticide application in a manner that will facilitate exposure assessment in epidemiologic studies of pesticides. METHODS: A sample of farm families with children was recruited by randomly selecting farmers from lists of licensed pesticide applicators in Minnesota and South Carolina. Eligible families were selected from among those who planned to apply one of three chemicals, glyphosate, 2,4-D, or chlorpyrifos, as part of their normal operations. The applicator, spouse, and all children in the family ages 4-17 years were included in the study. The applicator and spouse completed self-administered questionnaires addressing demographics, farming practices and potential exposures to them and their children. Field observers documented the application, recorded application practices, equipment, potential exposures, and the presence of children or spouses in the immediate vicinity of pesticide activities. All study participants were asked to collect each urine void for 5 days, 1 day before through 3 days after the application. Pesticides were measured in 24-h composite urine samples with a one part per billion limit of detection. RESULTS: Of 11,164 applicators screened, 994 families met the inclusion criteria. Of these, 95 families were enrolled. Enrollees were similar in most characteristics to their peers who were not participants in the study. In total, there were 106 applications, 10 of which involved more than one chemical. This resulted in urinary data for 48 farmers and spouses and their 79 children for glyphosate, 34 farmers and spouses and their 50 children for chlorpyrifos, and 34 farmers and spouses and their 53 children for 2,4-D. Compliance with the 24-h urine collection was particularly good for the adult participants. There were more missing samples for children than for adults, but overall compliance was high. CONCLUSION: The Farm Family Exposure Study should provide insights about pesticide exposure under real world conditions and thereby facilitate improved exposure assessment in epidemiologic studies of agricultural populations.

Primary brain tumor mortality at a petroleum exploration and extraction research facility.

A cohort mortality study was conducted among 3,779 employees at a petroleum exploration and extraction research facility to evaluate workplace exposures and brain tumor risk. Deaths were identified by searches against the National Death Index, Social Security Administration, and California state mortality files. Work histories were classified by job titles, laboratory activity, and company division. Eleven brain tumor deaths were observed among the cohort (standardized mortality ratio [SMR] 1.8; 95% confidence interval = 0.9-3.2). SMR analyses for scientists, employment in laboratory work, and in the research division were not associated with an increased brain tumor SMR, whereas an increased SMR was observed for administrative and nonresearch employees. Although conclusions are limited by the small study population and lack of specific exposure data, these findings were not consistent with an occupational explanation for the observed brain tumor cluster.

Glyphosate biomonitoring for farmers and their families: results from the Farm Family Exposure Study.

Glyphosate is the active ingredient in Roundup agricultural herbicides and other herbicide formulations that are widely used for agricultural, forestry, and residential weed control. As part of the Farm Family Exposure Study, we evaluated urinary glyphosate concentrations for 48 farmers, their spouses, and their 79 children (4-18 years of age). We evaluated 24-hr composite urine samples for each family member the day before, the day of, and for 3 days after a glyphosate application. Sixty percent of farmers had detectable levels of glyphosate in their urine on the day of application. The geometric mean (GM) concentration was 3 ppb, the maximum value was 233 ppb, and the highest estimated systemic dose was 0.004 mg/kg. Farmers who did not use rubber gloves had higher GM urinary concentrations than did other farmers (10 ppb vs. 2.0 ppb). For spouses, 4% had detectable levels in their urine on the day of application. Their maximum value was 3 ppb. For children, 12% had detectable glyphosate in their urine on the day of application, with a maximum concentration of 29 ppb. All but one of the children with detectable concentrations had helped with the application or were present during herbicide mixing, loading, or application. None of the systemic doses estimated in this study approached the U.S. Environmental Protection Agency reference dose for glyphosate of 2 mg/kg/day. Nonetheless, it is advisable to minimize exposure to pesticides, and this study did identify specific practices that could be modified to reduce the potential for exposure.

Cohort mortality study of employees at the Celanese plant in Pampa, Texas.

BACKGROUND: The mortality experience of chemical workers from the Pampa, Texas Celanese Ltd. plant through 1991 has been previously reported. This study updates that effort and presents an additional seven years of data and follow-up that provided 268 additional cohort members and 71 new deaths. METHODS: Mortality was determined through December 31, 1998, the period for which the National Death Index could provide information on deaths. The mortality experience of Celanese Ltd. employees was compared to that of the general population of the United States. All cause and cause-specific standardized mortality ratios (SMRs) were calculated. RESULTS: For the entire cohort, several causes of death including all causes (SMR = 65.9; 95% confidence interval (CI) = 56.9-76.0), heart disease (SMR = 69.1; 95% CI = 53.6-87.8), and all malignant neoplasms (SMR = 74.2; 95% CI = 56.3-95.9) were significantly less than expected. SMRs were also calculated separately for white men, non-white men, and women. Unlike the initial study, the SMR for prostate cancer among white males was not significantly elevated (SMR=176.1; 95% CI = 76.0-347.0) and was much lower than the prior SMR of 330.4. This suggests that the initial findings, which were based on a small number of deaths, were likely due to chance. CONCLUSIONS: Overall, Celanese Ltd. employees from the Pampa plant have significantly lower than expected SMRs for several causes of death, and no causes of death that are significantly elevated.

The CHEK2 1100delC mutation identifies families with a hereditary breast and colorectal cancer phenotype.

Because of genetic heterogeneity, the identification of breast cancer-susceptibility genes has proven to be exceedingly difficult. Here, we define a new subset of families with breast cancer characterized by the presence of colorectal cancer cases. The 1100delC variant of the cell cycle checkpoint kinase CHEK2 gene was present in 18% of 55 families with hereditary breast and colorectal cancer (HBCC) as compared with 4% of 380 families with non-HBCC (P<.001), thus providing genetic evidence for the HBCC phenotype. The CHEK2 1100delC mutation was, however, not the major predisposing factor for the HBCC phenotype but appeared to act in synergy with another, as-yet-unknown susceptibility gene(s). The unequivocal definition of the HBCC phenotype opens new avenues to search for this putative HBCC-susceptibility gene.