Mark Cullen

To examine associations between workplace injury and musculoskeletal disorder (MSD) risk and expert ratings of job-level psychosocial demand and job control, adjusting for job-level physical demand. Among a cohort of 9260 aluminium manufacturing workers in jobs for which expert ratings of job-level physical and psychological demand and control were obtained during the 2 years following rating obtainment, multivariate mixed effects models were used to estimate relative risk (RR) of minor injury and minor MSD, serious injury and MSD, minor MSD only and serious MSD only by tertile of demand and control, adjusting for physical demand as well as other recognised risk factors. Compared with workers in jobs rated as having low psychological demand, workers in jobs with high psychological demand had 49% greater risk of serious injury and serious MSD requiring medical treatment, work restrictions or lost work time (RR=1.49; 95% CI 1.10 to 2.01). Workers in jobs rated as having low control di...

Comprehensive and updated throughout, this new edition makes it easy to detect, diagnose, and treat the full spectrum of problems caused by occupational or environmental factors, including physical, chemical, and biologic agents. An international cast of experts offers in-depth, authoritative guidance on clinical problems as well as the legal and regulatory issues impacting the practice of occupational and environmental medicine today. Section 1 is on principles and practice. Section 2 on work sectors and special populations includes a chapter on mining. Section 3 on occupational diseases and injuries includes several chapters of relevance to the coal mining industry, including diseases of the lung and pleura covering silicosis, respiratory diseases of coal miners, and malignancies of the respiratory tract and pleura. Section 4 on hazards in the workplace and the environment includes a chapter on mineral dusts. Section 5 covers policy, regulation and control.

Psychiatrists treating patients with depression or nonspecific somatic complaints seldom think of lead intoxication as a possible cause. Because occupational exposure to lead is so common, these disturbances may often be associated with lead intoxication. To facilitate earlier clinical recognition and proper treatment among the many individuals at risk, the authors describe four cases of organic affective disturbance associated with lead intoxication, review the neuropsychiatric disturbances that have been reported with chronic exposure to lead, and report the results of their experience evaluating the psychiatric aspects of lead intoxication among individuals exposed in their work.

Because many occupationally exposed workers are disabled by medically unexplained symptoms, the authors set out to develop etiologically, prognostically, and therapeutically distinct diagnostic categories for these patients. Rigorous diagnostic criteria were applied to a sample of 21 patients with disproportionate disability: three patients had typical posttraumatic stress disorders (PTSD), seven had atypical PTSD, and the remainder suffered somatoform disorders. Recognition of PTSD is important because, unlike somatoform disorders, PTSD often responds to appropriate treatment. Some of the factors that may lead to PTSD are discussed, based on the case series. Using case examples, the authors discuss the diagnostic criteria for typical and atypical PTSD; differentiate these from somatoform disorders; and discuss the implications of the study for prevention of PTSD and for case management.

Among 31 newly diagnosed cases presented here and in the recent clinical reports reviewed, classic lead intoxication, with colic and anemia, is relatively uncommon. More commonly, manifestations are insidious and range from subtle, often asymptomatic neuropsychiatric and endocrine disturbances to the more classically described neuropathy and arthropathy. Juxtaposing clinical observations and experimental advances, three syndromes of adult inorganic lead intoxication can be discerned. 'Acute' poisoning, usually occurring after brief and intense lead exposure, is often dominated by lead colic, hemolysis and hepatocellular injury are frequently associated. Renal tubular dysfunction and acute encephalopathy may be seen with overwhelming exposure while milder cases may be limited to arthralgia, headache or the like. 'Chronic' intoxication, commonly seen among individuals with ongoing, steady lead exposure, is characterized by nervous system and endocrine impairment, often...

The authors describe a variant of posttraumatic stress disorder that presents as a somatoform disorder. Applying clearly specified diagnostic criteria, they found that seven of 21 patients who were severely disabled by medically unexplained symptoms following occupational exposure to toxic substances had atypical posttraumatic stress disorder, while three patients had typical posttraumatic stress disorder and the remainder suffered from somatoform disorders. Analysis of these cases revealed specific exposure factors and personality characteristics that favor the development of atypical posttraumatic stress disorder. The authors discuss the theoretical, clinical, and therapeutic advantages of this diagnosis.

Weekly oral chloroquine prophylaxis for malaria has been associated with impaired antibody response to intradermal rabies vaccination. Experimental data indicate that chloroquine may inhibit yellow fever virus in vitro, yet there has been no clinical evidence to suggest that antibody response to yellow fever vaccine is impaired by concomitant oral administration of chloroquine. A prospective trial was undertaken to evaluate the antibody response to yellow fever 17D vaccine (Connaught Laboratories) of volunteers who were randomized to taking either chloroquine or no drug. Of fifty subjects, 28 were randomized to taking chloroquine, 22 were randomized to taking no drug. Yellow fever 17D vaccine was administered on day 0 and blood sampled on days 0, 14, 35 and 210. Chloroquine was administered weekly for four weeks. There was no significant difference in peak antibody titer by plaque reduction neutralization testing (PRNT) between the group that took chloroquine (mean log peak of recip...

The clinical characteristics, laboratory results, and liver biopsy findings of seven workers with toxic liver injury associated with exposure to several solvents, including substantial levels of the widely used solvent dimethylformamide, are presented. Three patients had short exposure (less than 3 months), four long exposure (greater than 1 year). Among those with brief exposure, symptoms included anorexia, abdominal pain, and disulfiram-type reaction. Aminotransferases were markedly elevated with the ratio of alanine aminotransferase to aspartate aminotransferase always greater than 1. Liver biopsy showed focal hepatocellular necrosis and microvesicular steatosis with prominence of smooth endoplasmic reticulum, complex lysosomes, and pleomorphic mitochondria with crystalline inclusions. Among workers with long exposure, symptoms were minimal and enzyme elevations modest. Biopsies showed macrovesicular steatosis, pleomorphic mitochondria without crystalloids, and prominent smooth e...

This paper describes a prototype information sources map (ISM), an on-line information source finder, for Occupational and Environmental Medicine (OEM). The OEM ISM was built as part of the Unified Medical Language System (UMLS) project of the National Library of Medicine. It allows a user to identify sources of on-line information appropriate to a specific OEM question, and connect to the sources. In the OEM ISM we explore a domain-specific method of indexing information source contents, and also a domain-specific user interface. The indexing represents a domain expert's opinion of the specificity of an information source in helping to answer specific types of domain questions. For each information source, an index field represents whether a source might provide useful information in an occupational, industrial, or environmental category. Additional fields represent the degree of specificity of a source in individual question types in each category. The paper discusses the deve...

Dr. Cullen: The experience with the new research models, starting with the prototypic experience of the rubber industry studies of the 1970s and expanding to diverse sectors of American industry in the 1980s, has yielded some important lessons for the future. In closing this symposium I shall try to summarize these briefly. Certain strengths of the evolving process seem common to each of the models. Alone and collectively, the new research arrangements have quite apparently served to increase substantially the pool of funds available to the academic sector for the study of occupational health and safety problems. As a consequence, a larger pool of investigators has participated in the research process, greatly strengthening the future academic capability and experience of our fragilely supported teaching centers. Combined with the involvement of the academic centers in the review process, there has been an undeniable broadening and deepening of the nation's research output and l...

To assess the false positive rate of blood lead (BPb) determinations on samples obtained by fingerstick from children screened in an urban clinic. From a single fingerstick (N = 1573), blood was collected in a capillary tube for determining lead concentration (CPb) by graphite furnace and an additional sample was absorbed onto a filter paper for determining lead concentration (FPb) by atomic absorption spectrophotometry with Delves cup. Zinc protoporphyrin (ZPP) was measured immediately and a confirmatory venous lead (VPb) specimen was obtained at the same visit if the ZPP was > or = 35 micrograms/dL (0.6 mumol/L); children with either a CPb or FPb > or = 15 micrograms/dL (0.7 mumol/L) were later recalled for determining VPb. For the 172 children who had a VPb on the same day as the screening tests, the false positive rates (95% confidence intervals) at a lead threshold of 15 micrograms/dL (0.7 mumol/L) were: CPb, 13.5% (6.7-20.3); FPb, 19.1% (11.8-26.4). Analyses using all 67...

This death certificate-based case-control study linked Connecticut Tumor Registry and Connecticut Division of Vital Statistics death data to determine whether machining fluid exposure is associated with laryngeal cancer risk. Laryngeal cancer cases were compared with oral cancer controls and general population controls. Level of exposure to machining fluids was imputed from the usual occupation and industry on the death certificate. Because exposure was infrequent among females, analysis was limited to males. When cases were compared to oral cancer controls, high exposure to machining fluids was associated with laryngeal cancer (odds ratio = 1.48; 95% confidence interval = 1.01-2.16), with a p-value for trend of 0.08. When cases were compared to population controls, no association between machining fluid exposure and laryngeal cancer was observed. A possible reason for the contrasting results, other than chance, is that exposure data quality for the cases and oral cancer controls ma...

The purpose of this investigation was to examine the association between dietary intake of vitamin A in the form of retinol and provitamin A carotenoids and the prevalence of bronchial squamous metaplasia in a sample of asbestos workers from an industrial clinic. Bronchial biopsies were obtained from 49 asbestos workers. Pulmonary function testing was done and in-person interviews were conducted to estimate dietary intake of retinol and provitamin A carotenoids, tobacco exposure, and asbestos exposure. Results indicated that workers with metaplasia reported consuming a significantly lower intake of total vitamin A [2000 retinol equivalents (RE)/d] than did subjects without metaplasia (2710 RE/d, P = 0.02). Logistic regression analyses showed that higher intakes of retinol [odds ratio (OR): 0.31; 95% CI: 0.04, 2.44], provitamin A carotenoids (OR: 0.31; 95% CI: 0.03, 2.84), and total vitamin A (OR: 0.29; 95% CI: 0.03, 2.49) were associated with a nonsignificant reduction in the OR for...

ABSTRACT A systematic search of the peer-reviewed biomedical literature was performed for original studies linking environmental hazards with health effects in wild animal populations. Some 104 original studies were identified in the BIOSIS and Medline databases since 1966 and classified in terms of study design. A marked increase in published studies has occurred over the past decade, examining a wide range of hazards and outcomes. Most analytic studies were ecologic or cross-sectional in nature. All cross-sectional studies sampled subjects on the basis of exposure, using a reference population for the selection of controls. Studies of wild animal populations may hold unique advantages for toxicant hazard identification, yet the current range of study designs appears restricted. Increased use of study approaches such as sampling based on outcome, intra-population comparisons, as well as cohort and case-control designs may improve hazard identification and priority setting for confirmatory toxicologic and human studies of effects seen in wildlife. Copyright © 1999 John Wiley & Sons, Ltd.

Our current understanding of Asian American mortality patterns has been distorted by the historical aggregation of diverse Asian subgroups on death certificates, masking important differences in the leading causes of death across subgroups. In this analysis, we aim to fill an important knowledge gap in Asian American health by reporting leading causes of mortality by disaggregated Asian American subgroups. We examined national mortality records for the six largest Asian subgroups (Asian Indian, Chinese, Filipino, Japanese, Korean, Vietnamese) and non-Hispanic Whites (NHWs) from 2003-2011, and ranked the leading causes of death. We calculated all-cause and cause-specific age-adjusted rates, temporal trends with annual percent changes, and rate ratios by race/ethnicity and sex. Rankings revealed that as an aggregated group, cancer was the leading cause of death for Asian Americans. When disaggregated, there was notable heterogeneity. Among women, cancer was the leading cause of death ...

Investigators across many fields often struggle with how best to capture an individual's overall health status, with options including both subjective and objective measures. With the increasing availability of "big data," researchers can now take advantage of novel metrics of health status. These predictive algorithms were initially developed to forecast and manage expenditures, yet they represent an underutilized tool that could contribute significantly to health research. In this paper, we describe the properties and possible applications of one such "health risk score," the DxCG Intelligence tool. We link claims and administrative datasets on a cohort of U.S. workers during the period 1996-2011 (N = 14,161). We examine the risk score's association with incident diagnoses of five disease conditions, and we link employee data with the National Death Index to characterize its relationship with mortality. We review prior studies documenting the risk score's association with other health and non-health outcomes, including healthcare utilization, early retirement, and occupational injury. We find that the risk score is associated with outcomes across a variety of health and non-health domains. These examples demonstrate the broad applicability of this tool in multiple fields of research and illustrate its utility as a measure of overall health status for epidemiologists and other health researchers.

Workers around the world—despite vast differences in their physical, social, economic, and political environments—face virtually the same kinds of workplace hazards. These hazards are traditionally categorized into four broad types: chemical, biological, physical, and psychosocial. What emerges from our incomplete knowledge of their risk, however, is that the more than 80 percent of the world's workforce that resides in the

Five workers at a precious metal refinery developed granulomatous lung disease between 1972 and 1985. The original diagnosis was sarcoidosis, but 4 of the workers were subsequently proved to have hypersensitivity to beryllium by in vitro proliferative responses of lymphocytes obtained by bronchoalveolar lavage. Review of medical records of coworkers and extensive industrial hygiene surveillance of the plant demonstrated that 4 cases occurred in the furnace area where air concentrations of beryllium fume were consistently below the permissible exposure limit of 2 micrograms/M3. A single case has been recognized from parts of the refinery where exposures to cold beryllium dust often exceeded the standard by as much as 20-fold. These data demonstrate that chronic beryllium disease still occurs and confirm the importance of specific immunologic testing in patients suspected of having sarcoidosis but with potential exposure to beryllium. The data raise concern about the adequacy of moder...

We examined the mental health effects of the Great Recession of 2008 to 2009 on workers who remained continuously employed and insured. We examined utilization trends for mental health services and medications during 2007 to 2012 among a panel of workers in the 25 largest plants, located in 15 states, of a US manufacturing firm. We used piecewise regression to compare trends from 2007 to 2010 in service and medication use before and after 2009, the year of mass layoffs at the firm and the peak of the recession. Our models accounted for changes in county-level unemployment rates and individual-level fixed effects. Mental health inpatient and outpatient visits and the yearly supply of mental health-related medications increased among all workers after 2009. The magnitude of the increase in medication usage was higher for workers at plants with more layoffs. The negative effects of the recession on mental health extend to employed individuals, a group considered at lower risk of psycho...

Aberrations in reproductive fitness may be a harbinger of medical diseases in men. Data suggest a higher risk of testicular cancer in infertile men. However, the relationship between infertility and other cancers remains uncertain. We analyzed subjects from the Truven Health MarketScan® claims database from 2001 to 2009. Infertile men were identified through diagnosis and treatment codes. Comparison groups were created of men who underwent vasectomy and a control cohort of men who were not infertile and had not undergone vasectomy. The incidence of cancer was compared to national U.S. estimates. Infertile men were also compared to men who underwent vasectomy and the control cohort using a Cox regression model. A total of 76,083 infertile men were identified with an average age of 35.1 years. Overall 112,655 men who underwent vasectomy and 760,830 control men were assembled. Compared to age adjusted national averages, infertile, vasectomy and control subjects in the study cohorts had...

This study aimed to examine the associations between acute workplace injury risk, ambient noise exposure, and hearing acuity, adjusting for reported hearing protection use. In a cohort of 9220 aluminum manufacturing workers studied over six years (33 300 person-years, 13 323 person-jobs), multivariate mixed effects models were used to estimate relative risk (RR) of all injuries as well as serious injuries by noise exposure category and hearing threshold level (HTL) adjusting for recognized and potential confounders. Compared to noise <82 dBA, higher exposure was associated with elevated risk in a monotonic and statistically significant exposure-response pattern for all injuries and serious injuries with higher risk estimates observed for serious injuries [82-84.99 dBA: RR 1.26, 95% confidence interval (95% CI) 0.96-1.64; 85-87.99 dBA: RR 1.39, 95% CI 1.05-1.85; ≥88 dBA: RR 2.29, 95% CI 1.52-3.47]. Hearing loss was associated with increased risk for all injuries, but was not a sig...

To evaluate different approaches for including time trends in quantitative exposures to total particulate matter (TPM) in an aluminium smelter for use in epidemiologic evaluation of incident heart disease, we compared the use of regression modelling to discrete modelling of changes in the workplace environment. We used an industrial hygiene database containing results for sampling conducted over 30 years and information on workplace environment (e.g. personal protective equipment policy, ventilation modifications, changes to materials or work organisation). The effects of these changes were tested with an analysis of variance model using log-transformed TPM concentrations. We compared the outcome of this approach to the use of a regression model for TPM concentrations over time. Time trends in 57 jobs in an aluminium smelter were evaluated by using 1123 TPM samples collected from 1984-2012. There was an overall decline in median TPM concentrations (mg/m(3)) at the smelter (3.7% per ...

As part of exposure assessment for an ongoing epidemiologic study of heart disease and fine particle exposures in aluminium manufacturing, area particle samples were collected in smelters and fabrication facilities to assess instrument reliability and particle size distribution at different process areas. Personal Modular Impactors (PMI) and Minimicro-orifice uniform deposition impactors (MiniMOUDI) were used to collect samples. The coefficient of variation (CV) of collocated samples of the same type was used to evaluate the reproducibility of the impactors. PM2.5 measured by PMI was compared to PM2.5 calculated from MiniMOUDI data to assess the validity of using PMI to measure fine particles in personal sampling. Mass median aerodynamic diameter (MMAD) was calculated to characterise particle size distribution at different locations. 62 MiniMOUDI and 71 PMI samples were collected at 44 production areas. Most of CVs were less than 30%. The slope of the liner regression of PMI_PM2.5 v...

Biomarker research has become the predominant theme for study of human dose-host-response relations to environmental chemicals. Increasing interest has been focused on identifying markers for host susceptibility, with mixed results. Efforts to identify markers for host variability in carcinogenic risk, on the basis of theoretical knowledge of carcinogen metabolism, have been disappointing. New work in the area of acquired risk modifiers, such as nutritional status, is theoretically attractive, but results have been limited. Impressive achievements have been made in the area of immunological variability, which may elucidate the molecular basis of as well as provide practical biomarkers for several diseases. The problem of multiple chemical sensitivities, on the other hand, has proved refractory to biomarker research, reflecting inadequate knowledge of the mechanism and inappropriate application of biomarker methods.

ABSTRACT Among 31 newly diagnosed cases presented here and in the recent clinical reports reviewed, classic lead intoxication, with colic and anemia, is relatively uncommon. More commonly, manifestations are insidious and range from subtle, often asymptomatic neuropsychiatric and endocrine disturbances to the more classically described neuropathy and arthropathy. Juxtaposing clinical observations and experimental advances, three syndromes of adult inorganic lead intoxication can be discerned. 'Acute' poisoning, usually occurring after brief and intense lead exposure, is often dominated by lead colic, hemolysis and hepatocellular injury are frequently associated. Renal tubular dysfunction and acute encephalopathy may be seen with overwhelming exposure while milder cases may be limited to arthralgia, headache or the like. 'Chronic' intoxication, commonly seen among individuals with ongoing, steady lead exposure, is characterized by nervous system and endocrine impairment, often subclinical. Musculoskeletal and other nonspecific complaints dominate in symptomatic patients. Hyperuricemia is common but anemia, colic and glomerular dysfunction are rarely profound. Finally, a 'late' syndrome, characterized by gout, chronic renal failure and encephalopathy may occur many years after intense exposure; history usually reveals prior episodes of acute intoxication. Although results of treatment with chelation and removal from exposure have been generally favourable in both acute and chronic poisoning, complete reversal of pathologic effects has been shown only for hematologic and gastrointestinal effects. For this reason, prevention and early detection are the key to management. A strategy for conservative, expectant care is outlined for those clinicians charged with the evaluation and treatment of men and women exposed to inorganic lead.

A fuller understanding of the social epidemiology of disease requires an extended description of the relationships between social factors and health indicators in a systematic manner. In the present study, we investigated the correlations between income and 330 indicators of physiological, biochemical, and environmental health in participants in the US National Health and Nutrition Examination Survey (NHANES) (1999-2006). We combined data from 3 survey waves (n = 249-23,649 for various indicators) to search for linear and nonlinear (quadratic) correlates of income, and we validated significant (P < 0.00015) correlations in an independent testing data set (n = 255-7,855). We validated 66 out of 330 factors, including infectious (e.g., hepatitis A), biochemical (e.g., carotenoids, high-density lipoprotein cholesterol), physiological (e.g., upper leg length), and environmental (e.g., lead, cotinine) measures. We found only a modest amount of association modification by age, race/eth...