The importance of evaluating specific myeloid malignancies in epidemiological studies of environmental carcinogens.

INTRODUCTION: Although myelodysplastic syndrome (MDS), acute myeloid leukemia (AML), myeloproliferative neoplasms (MPN) - including chronic myeloid leukemia (CML) - and myelodysplastic/myeloproliferative neoplasms (MDS/MPN) are largely clinically distinct myeloid malignancies, epidemiological studies rarely examine them separately and often combine them with lymphoid malignancies, limiting possible etiological interpretations for specific myeloid malignancies. METHODS: We systematically evaluated the epidemiological literature on the four chemical agents (1,3-butadiene, formaldehyde, benzene, and tobacco smoking, excluding pharmaceutical, microbial and radioactive agents, and pesticides) classified by the International Agency for Research on Cancer as having sufficient epidemiological evidence to conclude that each causes "myeloid malignancies." Literature searches of IARC Monographs and PubMed identified 85 studies that we critically assessed, and for appropriate subsets, summarized results using meta-analysis. RESULTS: Only two epidemiological studies on 1,3-butadiene were identified, but reported findings were inadequate to evaluate specific myeloid malignancies. Studies on formaldehyde reported results for AML and CML - and not for MDS or MPN - but reported no increased risks. For benzene, several specific myeloid malignancies were evaluated, with consistent associations reported with AML and MDS and mixed results for CML. Studies of tobacco smoking examined all major myeloid malignancies, demonstrating consistent relationships with AML, MDS and MPN, but not with CML. CONCLUSIONS: Surprisingly few epidemiological studies present results for specific myeloid malignancies, and those identified were inconsistent across studies of the same exposure, as well as across chemical agents. This exercise illustrates that even for agents classified as having sufficient evidence of causing "myeloid malignancies," the epidemiological evidence for specific myeloid malignancies is generally limited and inconsistent. Future epidemiological studies should report findings for the specific myeloid malignancies, as combining them post hoc - where appropriate - always remains possible, whereas disaggregation may not. Furthermore, combining results across possibly discrete diseases reduces the chances of identifying important malignancy-specific causal associations.

An examination of the Environmental Protection Agency risk assessment principles and practices: a brief commentary on section 4.1.3 of the EPA March 2004 Staff Paper.

The US Environmental Protection Agency (EPA) recently issued a Staff Paper that articulates current risk assessment practices. In section 4.1.3, EPA states, "... effects that appear to be adaptive, non-adverse, or beneficial may not be mentioned." This statement may be perceived as precluding risk assessments based on non-default risk models, including the hormetic--or biphasic--dose-response model. This commentary examines several potential interpretations of this statement and the anticipated impact of ignoring hormesis, if present, in light of necessary conservatism for protecting human and environmental health, and the potential for employing alternative risk assessment approaches.

Self-reported wheezing and allergic rhinitis in children and traffic density on street of residence.

A survey of 2050 seventh- and eighth-grade schoolchildren was conducted in Bochum, Germany, in 1991. The prevalence of wheezing and allergic rhinitis was assessed by self-completed written questionnaires and video questionnaires. To estimate the traffic density on the street of residence, children were asked about the frequency of heavy truck traffic on weekdays and to describe the street either as a main road or as a side street. There was a positive correlation between the prevalence of wheezing as well as allergic rhinitis and the indicators of traffic density, controlling for age, sex, nationality, passive smoking, active smoking, parental history of asthma, and so on. The adjusted prevalence odds ratio (ORs) and 95% confidence intervals (CIs) contrasting the "frequent" and "constant" categories for truck traffic with the "never" category were as follows: for wheezing (written questionnaire), OR = 1.53 (CI: 1.06 to 2.20) and OR = 1.67 (CI: 1.05 to 2.66); for wheezing (video questionnaire), OR = 1.58 (CI: 1.13 to 2.20) and OR = 1.94 (CI: 1.26 to 2.99); and for allergic rhinitis, OR = 1.67 (CI: 1.17 to 2.38) and OR = 1.54 (CI: 0.97 to 2.44). In conclusion, a possible role of factors associated with automobile exhausts causing or exacerbating asthma symptoms and allergic rhinitis in children is supported.

Case-control study of discharge from the U.S. Army for disabling occupational knee injury: the role of gender, race/ethnicity, and age.

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.

Gender differences in manifestations of antisocial personality disorder among residential drug abuse treatment clients.

We examined gender differences in manifestations of DSM-III-R antisocial personality disorder in 106 male and 34 female drug abusers enrolled in residential relapse prevention/health education treatment. In childhood, compared to males, females had more often run away but less often used weapons in fights, been cruel to animals, and set fires. Females also reported less vandalism. In adulthood, women had more often been irresponsible as parents and in financial matters, engaged in prostitution, made money finding customers for prostitutes, been physically violent against sex partners and children, failed to plan ahead, and lacked remorse. Our findings suggest that addiction treatment programs need to consider gender differences in antisocial symptomatology in the development of individualized treatment programs for both male and female clients.

Antisocial behavioral syndromes among residential drug abuse treatment clients.

We compared residential addictions treatment clients meeting full criteria for antisocial personality disorder (ASPD+) with those reporting syndromal levels of antisocial behavior only in adulthood (AABS+) on demographics, antisocial symptomatology, drug history, axis I comorbidity and characteristics of index treatment episode. We examined these issues in the sample as a whole, as well as separately in male and female respondents. Among both men and women, ASPD+ initiated their antisocial behavior earlier, met more ASPD criteria and endorsed more violent symptoms, than AABS+. Male ASPD+ also met criteria for more lifetime axis I diagnoses and reported more years of drug involvement than male AABS+. Trends were observed toward poorer retention in treatment among ASPD+ than among AABS+ participants of both genders randomized to a planned duration of 180 days, but retention did not differ between ASPD+ and AABS+ randomized to a planned duration of 90 days. Our findings, which replicate and extend previously published results, carry potential implications for treatment programming and for the nosology of ASPD.

Antisocial behavioral syndromes among residential drug abuse treatment clients.

We compared residential addictions treatment clients meeting full criteria for antisocial personality disorder (ASPD+) with those reporting syndromal levels of antisocial behavior only in adulthood (AABS+) on demographics, antisocial symptomatology, drug history, axis I comorbidity and characteristics of index treatment episode. We examined these issues in the sample as a whole, as well as separately in male and female respondents. Among both men and women, ASPD+ initiated their antisocial behavior earlier, met more ASPD criteria and endorsed more violent symptoms, than AABS+. Male ASPD+ also met criteria for more lifetime axis I diagnoses and reported more years of drug involvement than male AABS+. Trends were observed toward poorer retention in treatment among ASPD+ than among AABS+ participants of both genders randomized to a planned duration of 180 days, but retention did not differ between ASPD+ and AABS+ randomized to a planned duration of 90 days. Our findings, which replicate and extend previously published results, carry potential implications for treatment programming and for the nosology of ASPD.

Video display terminal workstation improvement program: I. Baseline associations between musculoskeletal discomfort and ergonomic features of workstations.

Associations between selected sites of musculoskeletal discomfort and ergonomic characteristics of the video display terminal (VDT) workstation were assessed in analyses controlling for demographic, psychosocial stress, and VDT use factors in 273 VDT users from a large administrative department. Significant associations with wrist/hand discomfort were seen for female gender; working 7+ hours at a VDT; low job satisfaction; poor keyboard position; use of new, adjustable furniture; and layout of the workstation. Significantly increased odds ratios for neck/shoulder discomfort were observed for 7+ hours at a VDT, less than complete job control, older age (40 to 49 years), and never/infrequent breaks. Lower back discomfort was related marginally to working 7+ hours at a VDT. These results demonstrate that some characteristics of VDT workstations, after accounting for psychosocial stress, can be correlated with musculoskeletal discomfort.

Video display terminal workstation improvement program: II. Ergonomic intervention and reduction of musculoskeletal discomfort.

The effects of an ergonomic intervention on musculoskeletal discomfort in 118 video display terminal (VDT) users were assessed 1 year after intervention. The intervention consisted of recommended changes to workstations, which were based on the evaluation of 15 ergonomic characteristics. Compliance with the intervention was at least 75% for most workstation characteristics. Reduction in discomfort was substantial and was highest for the wrist/hand (57%), lower back (43%), and neck/shoulder (41%) severity of discomfort outcomes. Neither compliance with intervention on individual workstation characteristics nor summary intervention scores were associated with reduction in discomfort. Our results demonstrate that although reduction of musculoskeletal discomfort may be observed in the context of an intervention study, it may be difficult to link these benefits to specific interventions.

An occupational cohort mortality study of women in the German rubber industry: 1976 to 1991.

Few previous studies of workers in the rubber industry have focused on women. We examined patterns of mortality among 2871 women employed in one of five German rubber plants for at least 1 year on or after January 1, 1976, and observed through December 31, 1991. All-causes mortality was near that expected (standardized mortality ratio [lsqbSMR], 101; 95% confidence interval [CI], 87 to 118), but cancer mortality was decreased (SMR, 90; 95% CI, 70 to 115). Nevertheless, excesses were observed for mortality from stomach cancer (SMR, 156; 95% CI, 63 to 322), lung cancer (SMR, 140; 95% CI, 56 to 289), and lymphatic system cancers (SMR, 175; 95% CI, 48 to 448). Stronger associations were observed among sub-cohorts defined by time period hired. Despite limited numbers of deaths, modest excesses of mortality due to specific cancers were observed and are consistent with previous studies.

Deep venous thrombosis associated with corporate air travel.

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.

Epidemiological surveillance: a management tool for occupational health.

Epidemiological surveillance represents a practical and intuitive approach to preventing occupational disease and injury, yet it is underutilized in health care management. Through the systematic analysis of employee occupational health data, the epidemiological surveillance approach allows prompt identification of potential workplace hazards, identifies high-risk groups for targeting preventive efforts and provides a mechanism for evaluating interventions. Often, epidemiological surveillance can utilize existing data resources, making it a cost-effective tool. Epidemiological surveillance should be valuable in supporting management decisions relating to health promotion and disease prevention programs, as well as basic clinical needs of employees.

Evaluating worksite health programs.

Worksite health enhancement programs utilize screening and early disease detection or risk reduction as health promotion activities. Objectives for these include improving the health and productivity of employees and reducing health care costs. However, critical questions about the effectiveness of programs should be answered before managers initiate these activities. Issues include accuracy of measurement and subject classification, adequate use of comparisons and follow-up in evaluation studies, and evidence of cost effectiveness.

Measuring ankle systolic blood pressure: validation of the Dinamap 1846 SX.

Clinical and epidemiologic situations requiring repeated measurements of blood pressure in the lower extremity are increasingly incorporating automated measurement devices; however, no device has been validated adequately for ankle blood pressure. This study evaluates the Dinamap 1846 SX against Doppler ultrasound in determining ankle systolic blood pressure (SBP) and compares a parallel with contour wrapping technique for applying the blood pressure cuff. Ankle SBP was measured on 71 adult volunteers by both devices simultaneously, for each cuff wrap. Averages of three readings were compared to evaluate Dinamap versus Doppler SBP estimates and to assess any cuff wrap effect. Multiple linear regression was used to assess potential effect modifiers. Instrument differences (Dinamap minus Doppler) for the parallel wrap (95% confidence intervals in parenthesis) were -1.5 mmHg (-3.1, 0.0) and -3.9 mmHg (-5.6, -2.2) for the contour wrap. Wrap effect differences (contour minus parallel) for the Doppler were -4.9 mmHg (-6.3, -3.5) and -7.2 mmHg (-8.7, -5.8) for the Dinamap. Degree of ankle taper was a strong modifier of cuff effect for the Dinamap but not for the Doppler: adjusted cuff effect with the Dinamap ranged from -3 to -10 mmHg. Measurement precision (within-person reproducibility, measured by within-person standard deviation [sigma 2] and reliability coefficient [R]) was higher for the Dinamap than the Doppler technique, lowest for the parallel wrap and Doppler configuration (sigma 2 = 5.4 mmHg, R = 0.88) and greatest for the contour wrap and Dinamap (sigma 2 = 4.0 mmHg, R = 0.94). In conclusion, cuff-wrapping technique can generate SBP differences of greater magnitude than instrument differences. Conditional on the use of the contour wrap, and by virtue of its high repeatability and ease of operation, the Dinamap is a useful tool for epidemiologic study and the clinical assessment of peripheral arterial disease.

Identification of site of urinary-tract infections by antibody-coated bacteria assay.

Accurate identification of the site of urinary-tract infection (UTI) may be clinically and epidemiologically valuable. A review of the literature on the assessment of the antibody-coated bacteria (ACB) assay, a non-invasive technique introducted five years ago, shows that, compared with acceptable standards (bilateral ureteral catheterization or bladder washout), the overall sensitivity of the ACB assay is 83.1%, the specificity is 76.7%, the predictive value positive is 81.3%, and the predictive value negative is 78.8%. These findings suggest that the ACB assay has at present no role in the management of patients with UTI. Its usefulness as an epidemiological tool remains to be demonstrated.

A retrospective-cohort study of occupational exposure to hexavalent chromium.

A retrospective cohort study was conducted to examine the risk of mortality, cancer, and other adverse health outcomes, at the United States' largest chromate chemicals manufacturing facility in Castle Hayne, North Carolina. This facility, built in 1971, was designed to reduce the high levels of chromium exposure found at most older facilities. Exposure assessment was based on analysis of more than 5,000 personal breathing zone samples collected over a 15-year period. A questionnaire was used to collect relevant occupational, medical, smoking, and other information from current and former employees. Analysis of the cohort's mortality experience found no substantial departures from that expected based on external comparisons, although evidence of a healthy worker effect was observed. Internal cohort analyses were limited by relatively small numbers; however, a subgroup of employees who transferred from older facilities was found to have higher risks of mortality (odds ratio = 1.27 for each 3 years of previous exposure; 90% confidence interval (CI) = 1.07-1.51) and cancer (odds ratio = 1.22 for each 3 years of previous exposure; 90% CI = 1.03-1.45). While this subgroup represented only 11% of the individuals in this study, they accounted for 46% (6/13) of all observed cancers (excluding skin cancers) and 60% (3/5) of lung cancers. There was no increased risk of mortality or cancer among employees who worked only at the newer facility. As an etiologic research study, the results are limited by the relatively small number of subjects and short follow-up; nevertheless, the findings can be used to design and implement a prospective surveillance system for monitoring the health of chromate production workers.

Critical review of the epidemiological literature on the potential cardiovascular effects of occupational carbon disulfide exposure.

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.

Confidence intervals for measures of interaction.

Interaction, defined as departure of disease rates from an additive model, can be measured by the relative excess risk due to interaction, or the attributable proportion due to interaction. Point estimates can be obtained using multiple logistic regression. Using simulated case-control data, we compare several confidence interval estimation techniques for these measures. These include a symmetrical interval based on the delta method estimate of the variance, and three types of bootstrap confidence intervals. One such bootstrap method has coverage closest to the nominal level and is the most evenly balanced with respect to the direction in which intervals miss the true value. The estimation methods are applied to data from an actual case-control study, and the results are interpreted in light of the simulation study.

Medical insurance claims associated with international business travel.

OBJECTIVES: Preliminary investigations of whether 10,884 staff and consultants of the World Bank experience disease due to work related travel. Medical insurance claims filed by 4738 travellers during 1993 were compared with claims of non-travellers. METHODS: Specific diagnoses obtained from claims were analysed overall (one or more v no missions) and by frequency of international mission (1, 2-3, or > or = 4). Standardised rate of claims ratios (SSRs) for each diagnostic category were obtained by dividing the age adjusted rate of claims for travellers by the age adjusted rate of claims for non-travellers, and were calculated for men and women travellers separately. RESULTS: Overall, rates of insurance claims were 80% higher for men and 18% higher for women travellers than their non-travelling counterparts. Several associations with frequency of travel were found. SRRs for infectious disease were 1.28, 1.54, and 1.97 among men who had completed one, two or three, and four or more missions, and 1.16, 1.28, and 1.61, respectively, among women. The greatest excess related to travel was found for psychological disorders. For men SRRs were 2.11, 3.13, and 3.06 and for women, SRRs were 1.47, 1.96, and 2.59. CONCLUSIONS: International business travel may pose health risks beyond exposure to infectious diseases. Because travellers file medical claims at a greater rate than non-travellers, and for many categories of disease, the rate of claims increases with frequency of travel. The reasons for higher rates of claims among travellers are not well understood. Additional research on psychosocial factors, health practices, time zones crossed, and temporal relation between travel and onset of disease is planned.