Clinical Focus

  • Internal Medicine

Administrative Appointments

  • Director, Stanford Center for Population Health Sciences (2015 - Present)
  • Chief, Division of General Medical Disciplines, Stanford University (2009 - Present)
  • Professor of Medicine and Public Health, Yale University (1993 - 2009)
  • Director, Yale Occupational and Environmental Medicine Program (1980 - 2009)
  • Associate Professor of Medicine and Epidemiology, Yale University (1985 - 1993)
  • Assistant Professor of Medicine, Yale University (1980 - 1985)

Honors & Awards

  • Fifth Place Winner, Westinghouse National Science Talent Search (1967)
  • Faculty scholar in General Internal Medicine, Henry J. Kaiser Family Foundation (1988)
  • Member, Elected, Institute of Medicine (National Academy of Sciences) (1997)
  • Member, Elected, Connecticut Academy of Science & Engineering (2002)

Professional Education

  • Residency:Yale - New Haven Hospital (1980) CT
  • Internship:Yale - New Haven Hospital (1977) CT
  • Medical Education:Yale School of Medicine (1976) CT
  • Board Certification: Occupational Medicine, American Board of Preventive Medicine (1986)
  • Board Certification: Internal Medicine, American Board of Internal Medicine (1979)
  • M.D., Yale University, M.D. (1976)
  • A.B., Harvard College, Philosophy and Physics (1971)

Research & Scholarship

Current Research and Scholarly Interests

Social and environmental determinants of health; role of workplace physical environment and work organization as causes of chronic disease and disability


All Publications

  • Demographic and socio-economic differences between men seeking infertility evaluation and those seeking surgical sterilization: from the National Survey of Family Growth BJU INTERNATIONAL Hotaling, J. M., Patel, D. P., Brant, W. O., Myers, J. B., Cullen, M. R., Eisenberg, M. L. 2015; 116 (2): 288-292


    To identify differences in demographic and socio-economic factors between men seeking infertility evaluation and those undergoing vasectomy, to address disparities in access to these services.Data from Cycle 6 and Cycle 7 (2002 and 2006-2008) of the National Survey of Family Growth (NSFG) were reviewed. The NSFG is a multistage probability survey designed to capture a nationally representative sample of households with men and women aged 15-45 years in the USA. The variables analysed included age, body mass index, self-reported health, alcohol use, race, religious affiliation, marital status, number of offspring, educational attainment, income level, insurance status and metropolitan home designation. Our primary outcome was the correlation of these demographic and socio-economic factors with evaluation for male infertility or vasectomy.Of the 11 067 men identified through the NSFG, 466 men (4.2%) sought infertility evaluation, representing 2 187 455 men nationally, and 326 (2.9%) underwent a vasectomy, representing 1 510 386 men nationally. Those seeking infertility evaluation were more likely to be younger and have fewer children (P = 0.001, 0.001) and less likely to be currently married (78 vs 74%; P = 0.010) or ever married (89 vs 97%; P = 0.002). Men undergoing a vasectomy were more likely to be white (86 vs 70%; P = 0.001). Men seeking infertility evaluation were more likely to have a college or graduate degree compared with men undergoing a vasectomy (68 vs 64%; P = 0.015). There was no difference between the two groups for all other variables.While differences in demographic characteristics such as age, offspring number and marital status were identified, measures of health, socio-economic status, religion and insurance were similar between men undergoing vasectomy and those seeking infertility services. These factors help characterize the utilization of male reproductive health services in the USA and may help address disparities in access to these services and improve public health strategies.

    View details for DOI 10.1111/bju.13012

    View details for Web of Science ID 000358529500024

    View details for PubMedID 25777585

  • Early-Life State-of-Residence Characteristics and Later Life Hypertension, Diabetes, and Ischemic Heart Disease. American journal of public health Rehkopf, D. H., Eisen, E. A., Modrek, S., Mokyr Horner, E., Goldstein, B., Costello, S., Cantley, L. F., Slade, M. D., Cullen, M. R. 2015; 105 (8): 1689-1695


    We examined how state characteristics in early life are associated with individual chronic disease later in life.We assessed early-life state of residence using the first 3 digits of social security numbers from blue- and white-collar workers from a US manufacturing company. Longitudinal data were available from 1997 to 2012, with 305 936 person-years of observation. Disease was assessed using medical claims. We modeled associations using pooled logistic regression with inverse probability of censoring weights.We found small but statistically significant associations between early-state-of-residence characteristics and later life hypertension, diabetes, and ischemic heart disease. The most consistent associations were with income inequality, percentage non-White, and education. These associations were similar after statistically controlling for individual socioeconomic and demographic characteristics and current state characteristics.Characteristics of the state in which an individual lives early in life are associated with prevalence of chronic disease later in life, with a strength of association equivalent to genetic associations found for these same health outcomes.

    View details for DOI 10.2105/AJPH.2014.302547

    View details for PubMedID 26066927

  • Using "Big Data" to Capture Overall Health Status: Properties and Predictive Value of a Claims-Based Health Risk Score PLOS ONE Hamad, R., Modrek, S., Kubo, J., Goldstein, B. A., Cullen, M. R. 2015; 10 (5)


    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.

    View details for DOI 10.1371/journal.pone.0126054

    View details for Web of Science ID 000354214400063

    View details for PubMedID 25951622

  • Increased Risk of Cancer in Infertile Men: Analysis of US Claims Data JOURNAL OF UROLOGY Eisenberg, M. L., Li, S., Brooks, J. D., Cullen, M. R., Baker, L. C. 2015; 193 (5): 1596-1601


    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 higher rates of all cancers and many individual cancers. In time to event analysis, infertile men had a higher risk of cancer than those who underwent vasectomy or controls. Infertile men had a higher risk of testis cancer, nonHodgkin lymphoma and all cancers than the vasectomy and control groups.Consistent with prior reports, we identified an increased risk of testicular cancer in infertile men. The current data also suggest that infertile men are at a mildly increased risk of all cancers in the years after infertility evaluation. Future research should focus on confirming these associations and elucidating pathways between infertility and cancer.

    View details for DOI 10.1016/j.juro.2014.11.080

    View details for Web of Science ID 000353113200052

    View details for PubMedID 25463997

  • Leading Causes of Death among Asian American Subgroups (2003-2011) PLOS ONE Hastings, K. G., Jose, P. O., Kapphahn, K. I., Frank, A. T., Goldstein, B. A., Thompson, C. A., Eggleston, K., Cullen, M. R., Palaniappan, L. P. 2015; 10 (4)


    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 for every group except Asian Indians. In men, cancer was the leading cause of death among Chinese, Korean, and Vietnamese men, while heart disease was the leading cause of death among Asian Indians, Filipino and Japanese men. The proportion of death due to heart disease for Asian Indian males was nearly double that of cancer (31% vs. 18%). Temporal trends showed increased mortality of cancer and diabetes in Asian Indians and Vietnamese; increased stroke mortality in Asian Indians; increased suicide mortality in Koreans; and increased mortality from Alzheimer's disease for all racial/ethnic groups from 2003-2011. All-cause rate ratios revealed that overall mortality is lower in Asian Americans compared to NHWs.Our findings show heterogeneity in the leading causes of death among Asian American subgroups. Additional research should focus on culturally competent and cost-effective approaches to prevent and treat specific diseases among these growing diverse populations.

    View details for DOI 10.1371/journal.pone.0124341

    View details for Web of Science ID 000353659100048

    View details for PubMedID 25915940

  • Bladder Cancer Screening in Aluminum Smelter Workers JOURNAL OF OCCUPATIONAL AND ENVIRONMENTAL MEDICINE Taiwo, O. A., Slade, M. D., Cantley, L. F., Tessier-Sherman, B., Galusha, D., Kirsche, S. R., Donoghue, A. M., Cullen, M. R. 2015; 57 (4): 421-427


    To present results of a bladder cancer screening program conducted in 18 aluminum smelters in the United States from January 2000 to December 2010.Data were collected on a cohort of workers with a history of working in coal tar pitch volatile exposed areas including urine analysis for conventional cytology and ImmunoCyt/uCyt+ assay.ImmunoCyt/uCyt+ and cytology in combination showed a sensitivity of 62.30%, a specificity of 92.60%, a negative predictive value of 99.90%, and a positive predictive value of 2.96%. Fourteen cases of bladder cancer were detected, and the standardized incidence ratio of bladder cancer was 1.18 (95% confidence interval, 0.65 to 1.99). Individuals who tested positive on either test who were later determined to be cancer free had undergone expensive and invasive tests.Evidence to support continued surveillance of this cohort has not been demonstrated.

    View details for DOI 10.1097/JOM.0000000000000377

    View details for Web of Science ID 000352507700016

    View details for PubMedID 25525927

  • Does tinnitus, hearing asymmetry, or hearing loss predispose to occupational injury risk? International journal of audiology Cantley, L. F., Galusha, D., Cullen, M. R., Dixon-Ernst, C., Tessier-Sherman, B., Slade, M. D., Rabinowitz, P. M., Neitzel, R. L. 2015; 54: S30-6


    Abstract Objective: To determine the relative contributions of tinnitus, asymmetrical hearing loss, low frequency hearing loss (pure tone average of 0.5, 1, 2, 3 kHz; PTA.5123), or high frequency hearing loss (pure tone average of 4, 6 kHz; PTA46), to acute injury risk among a cohort of production and maintenance workers at six aluminum manufacturing plants, adjusting for ambient noise exposure and other recognized predictors of injury risk.Retrospective analysis.The study considered 9920 workers employed during 2003 to 2008. The cohort consisted of 8818 workers (89%) whose complete records were available.Adjusting for noise exposure and other recognized injury predictors, a 25% increased acute injury risk was observed among workers with a history of tinnitus in conjunction with high-frequency hearing loss (PTA46). Low frequency hearing loss may be associated with minor, yet less serious, injury risk. We did not find evidence that asymmetry contributes to injury risk.These results provide evidence that tinnitus, combined with high-frequency hearing loss, may pose an important safety threat to workers, especially those who work in high-noise exposed environments. These at risk workers may require careful examination of their communication and hearing protection needs.

    View details for DOI 10.3109/14992027.2014.981305

    View details for PubMedID 25549168

  • Systematic assessment of the correlations of household income with infectious, biochemical, physiological, and environmental factors in the United States, 1999-2006. American journal of epidemiology Patel, C. J., Ioannidis, J. P., Cullen, M. R., Rehkopf, D. H. 2015; 181 (3): 171-179


    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/ethnicity, and gender, and there was no association modification for blacks. The present study is descriptive, not causal. We have shown in our systematic investigation the crucial place income has in relation to health risk factors. Future research can use these correlations to better inform theory and studies of pathways to disease, as well as utilize these findings to understand when confounding by income is most likely to introduce bias.

    View details for DOI 10.1093/aje/kwu277

    View details for PubMedID 25589242

  • Psychological Well-Being During the Great Recession: Changes in Mental Health Care Utilization in an Occupational Cohort AMERICAN JOURNAL OF PUBLIC HEALTH Modrek, S., Hamad, R., Cullen, M. R. 2015; 105 (2): 304-310


    Objectives. We examined the mental health effects of the Great Recession of 2008 to 2009 on workers who remained continuously employed and insured. Methods. 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. Results. 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. Conclusions. The negative effects of the recession on mental health extend to employed individuals, a group considered at lower risk of psychological distress.

    View details for DOI 10.2105/AJPH.2014.302219

    View details for Web of Science ID 000351922500035

    View details for PubMedID 25521885

  • Relationship between semen production and medical comorbidity FERTILITY AND STERILITY Eisenberg, M. L., Li, S., Behr, B., Pera, R. R., Cullen, M. R. 2015; 103 (1): 66-71


    To study the relationship between semen quality and current health status in a cohort of men evaluated for infertility.Cross-sectional study.Fertility clinic.Nine thousand three hundred eighty-seven men evaluated for infertility between 1994 and 2011.None.Charlson comorbidity index, medical diagnoses by organ system.At the time of evaluation, 9,387 men with a mean age of 38 years had semen data available. Of these men, 44% had at least one medical diagnosis unrelated to infertility. When stratifying the cohort by the Charlson comorbidity index (CCI), differences in all measured semen parameters were identified. Men with a higher CCI had lower semen volume, concentration, motility, total sperm count, and morphology scores. In addition, men with diseases of the endocrine, circulatory, genitourinary, and skin diseases all showed significantly higher rates of semen abnormalities. Upon closer examination of diseases of the circulatory system, men with hypertensive disease, peripheral vascular and cerebrovascular disease, and nonischemic heart disease all displayed higher rates of semen abnormalities.The current report identified a relationship between medical comorbidites and male semen production. Although genetics help guide a man's sperm production, his current condition and health play an important role.

    View details for DOI 10.1016/j.fertnstert.2014.10.017

    View details for Web of Science ID 000346911400015

    View details for PubMedID 25497466

  • Association between ambient noise exposure, hearing acuity, and risk of acute occupational injury. Scandinavian journal of work, environment & health Cantley, L. F., Galusha, D., Cullen, M. R., Dixon-Ernst, C., Rabinowitz, P. M., Neitzel, R. L. 2015; 41 (1): 75-83


    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 significant predictor of risk for the subset of more serious injuries. Compared to those without hearing loss, workers with HTL ≥25 dB had 21% increased all injury risk (RR 1.21, 95% CI 1.09-1.33) while those with HTL 10-24.99 dB had 6% increased risk (RR 1.06, 95% CI 1.00-1.13). Reported hearing protection type did not predict injury risk.Noise exposure levels as low as 85 dBA may increase workplace injury risk. HTL was associated with increased risk for all, but not the subset of serious, injuries. Additional study is needed both to confirm the observed associations and explore causal pathways.

    View details for DOI 10.5271/sjweh.3450

    View details for PubMedID 25137556

  • Cardiovascular Disease Mortality in Asian Americans JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY Jose, P. O., Frank, A. T., Kapphahn, K. I., Goldstein, B. A., Eggleston, K., Hastings, K. G., Cullen, M. R., Palaniappan, L. P. 2014; 64 (23): 2486-2494


    Asian Americans are a rapidly growing racial/ethnic group in the United States. Our current understanding of Asian-American cardiovascular disease mortality patterns is distorted by the aggregation of distinct subgroups.The purpose of the study was to examine heart disease and stroke mortality rates in Asian-American subgroups to determine racial/ethnic differences in cardiovascular disease mortality within the United States.We examined heart disease and stroke mortality rates for the 6 largest Asian-American subgroups (Asian Indian, Chinese, Filipino, Japanese, Korean, and Vietnamese) from 2003 to 2010. U.S. death records were used to identify race/ethnicity and cause of death by International Classification of Diseases-10th revision coding. Using both U.S. Census data and death record data, standardized mortality ratios (SMRs), relative SMRs (rSMRs), and proportional mortality ratios were calculated for each sex and ethnic group relative to non-Hispanic whites (NHWs).In this study, 10,442,034 death records were examined. Whereas NHW men and women had the highest overall mortality rates, Asian Indian men and women and Filipino men had greater proportionate mortality burden from ischemic heart disease. The proportionate mortality burden of hypertensive heart disease and cerebrovascular disease, especially hemorrhagic stroke, was higher in every Asian-American subgroup compared with NHWs.The heterogeneity in cardiovascular disease mortality patterns among diverse Asian-American subgroups calls attention to the need for more research to help direct more specific treatment and prevention efforts, in particular with hypertension and stroke, to reduce health disparities for this growing population.

    View details for DOI 10.1016/j.jacc.2014.08.048

    View details for Web of Science ID 000345962400007

    View details for PubMedID 25500233

  • Marginal Structural Models in Occupational Epidemiology: Application in a Study of Ischemic Heart Disease Incidence and PM2.5 in the US Aluminum Industry AMERICAN JOURNAL OF EPIDEMIOLOGY Neophytou, A. M., Costello, S., Brown, D. M., Picciotto, S., Noth, E. M., Hammond, S. K., Cullen, M. R., Eisen, E. A. 2014; 180 (6): 608-615

    View details for DOI 10.1093/aje/kwu175

    View details for Web of Science ID 000343033400008

  • Acoustic neuroma: potential risk factors and audiometric surveillance in the aluminium industry. Occupational and environmental medicine Taiwo, O., Galusha, D., Tessier-Sherman, B., Kirsche, S., Cantley, L., Slade, M. D., Cullen, M. R., Donoghue, A. M. 2014; 71 (9): 624-628


    To look for an association between acoustic neuroma (AN) and participation in a hearing conservation programme (HCP) and also for an association between AN and possible occupational risk factors in the aluminium industry.We conducted a case-control analysis of a population of US aluminium production workers in 8 smelters and 43 other plants. Using insurance claims data, 97 cases of AN were identified between 1996 and 2009. Each was matched with four controls. Covariates included participation in a HCP, working in an aluminium smelter, working in an electrical job and hearing loss.In the bivariate analyses, covariates associated with AN were participation in the HCP (OR=1.72; 95% CI 1.09 to 2.69) and smelter work (OR=1.88; 95% CI 1.06 to 3.36). Electrical work was not significant (OR=1.60; 95% CI 0.65 to 3.94). Owing to high participation in the HCP in smelters, multivariate subanalyses were required. In the multivariate analyses, participation in the HCP was the only statistically significant risk factor for AN. In the multivariate analysis restricted to employees not working in a smelter, the OR was 1.81 (95% CI 1.04 to 3.17). Hearing loss, an indirect measure of in-ear noise dose, was not predictive of AN.Our results suggest the incidental detection of previously undiagnosed tumours in workers who participated in the company-sponsored HCP. The increased medical surveillance among this population of workers most likely introduced detection bias, leading to the identification of AN cases that would have otherwise remained undetected.

    View details for DOI 10.1136/oemed-2014-102094

    View details for PubMedID 25015928

  • Occupational injury risk by sex in a manufacturing cohort. Occupational and environmental medicine Tessier-Sherman, B., Cantley, L. F., Galusha, D., Slade, M. D., Taiwo, O. A., Cullen, M. R. 2014; 71 (9): 605-610


    This study expands previous research comparing injury risk for women and men in a cohort of 24 000 US aluminium manufacturing workers in 15 facilities from 2001 to 2010.We compared injury rates (all injury, first aid, medical treatment, restricted work and lost work time) by sex and by job and sex. Using a mixed effect modelling approach, we calculated ORs and 95% CIs adjusting for age, job tenure, ethnicity and year as fixed effects and person, job and plant as random effects. Additionally, we modelled the data stratified by plant type to examine potential differences in injury risk between smelter (generally recognised as more hazardous) and fabrication production environments.Risk of injury was higher for women in four out of the five injury outcomes: all injuries combined (OR: 1.58, CI 1.48 to 1.67), injuries requiring first aid (OR: 1.61, CI 1.54 to 1.70), injuries requiring medical treatment (OR: 1.18, CI 1.03 to 1.36) and injuries requiring restricted work (OR: 1.65, CI 1.46 to 1.87). No difference in the risk of lost time injury by sex was found in this cohort. Analyses stratified by plant type showed similarly elevated injury risk for women, although the risk estimates were higher in smelters than fabrication plants.To our knowledge, this is the largest single-firm study examining injury risk by sex with sufficient data to appropriately adjust for job. We show a consistently higher injury risk for women compared with men in the smelting and fabrication environments.

    View details for DOI 10.1136/oemed-2014-102083

    View details for PubMedID 24924313

  • Disparities in early exposure to book sharing within immigrant families. Pediatrics Festa, N., Loftus, P. D., Cullen, M. R., Mendoza, F. S. 2014; 134 (1): e162-8


    This study examined the early developmental context of children in immigrant families (CIF), measured by the frequency with which parents share books with their children.Trends in the frequency with which parents report book sharing, defined in this analysis as reading or sharing picture books with their young children, were analyzed across immigrant and nonimmigrant households by using data from the 2005, 2007, and 2009 California Health Interview Survey. Stepwise multivariate logistic regression assessed the likelihood that CIF shared books with parents daily.In this study, 57.5% of parents in immigrant families reported daily book sharing (DBS), compared with 75.8% of native-born parents. The lowest percentage of DBS was seen in Hispanic families with 2 foreign-born parents (47.1%). When controlling for independent variables, CIF with 2 foreign-born parents had the lowest odds of sharing books daily (odds ratio [OR]: 0.61; 95% confidence interval [CI]: 0.54-0.68). When stratified by race/ethnicity, separate multivariate logistic regressions revealed CIF status to be associated with lower odds of DBS for Asian (OR: 0.56; 95% CI: 0.38-0.81) and Hispanic CIF (OR: 0.49; 95% CI: 0.42-0.58).There is an association between the lower odds of DBS and parental immigrant status, especially for Hispanic and Asian children. This relationship holds after controlling for variables thought to explain differences in literacy-related practices, such as parental education and income. Because book sharing is central to children's development of early literacy and language skills, this disparity merits further exploration with the aim of informing future interventions.

    View details for DOI 10.1542/peds.2013-3710

    View details for PubMedID 24918215

  • Semen quality, infertility and mortality in the USA HUMAN REPRODUCTION Eisenberg, M. L., Li, S., Behr, B., Cullen, M. R., Galusha, D., Lamb, D. J., Lipshultz, L. I. 2014; 29 (7): 1567-1574
  • Individual-level and plant-level predictors of acute, traumatic occupational injuries in a manufacturing cohort OCCUPATIONAL AND ENVIRONMENTAL MEDICINE Souza, K., Cantley, L. F., Slade, M. D., Eisen, E. A., Christiani, D., Cullen, M. R. 2014; 71 (7): 477-483


    Workplace and contextual factors that may affect risk for worker injury are not well described. This study used results from an employee job satisfaction survey to construct aggregate indicators of the work environment and estimate the relative contribution of those factors to injury rates in a manufacturing cohort.Principal components analysis was used to construct four plant-level factors from responses to a 32 question survey of the entire workforce, administered in 2006. Multilevel Poisson regression was used to evaluate the relationship between injury rate, individual-level and plant-level risk factors, unionisation and plant type.Plant-level 'work stress' (incident rate ratio (IRR)=0.50, 95% CI 0.28 to 0.90) was significant in the multilevel model, indicating the rate of injury for an average individual in that plant was halved (conditional on plant) when job stress decreased by a tertile. 'Overall satisfaction', 'work environment' and 'perception of supervisor' showed the same trend but were not significant. Unionisation was protective (IRR=0.40, 95% CI 0.17 to 0.95) as was any plant type compared with smelter.We demonstrated utility of data from a human resources survey to construct indicators of the work environment. Our research suggests that aspects of the work environment, particularly work stress and unionisation, may have a significant effect on risk for occupational injury, emphasising the need for further multilevel studies. Our work would suggest monitoring of employee perceptions of job stress and the possible inclusion of stress management as a component of risk reduction programmes.

    View details for DOI 10.1136/oemed-2013-101827

    View details for Web of Science ID 000337918300005

  • 0223 Marginal Structural Models in Occupational Epidemiology: An Application in the US Aluminium industry. Occupational and environmental medicine Neophytou, A., Brown, D., Costello, S., Noth, E., Hammond, K., Cullen, M., Eisen, E. 2014; 71: A30-?


    To apply Marginal Structural Models (MSM) to address healthy workers survivor effect in a cohort study of active workers when time varying variables on health status and exposure are measured.We used Cox MSMs and inverse probability weighting to assess the effect of PM-2.5 exposure on incident ischaemic heart disease (IHD) in an active cohort of 11 966 US aluminium workers. The outcome was assessed using medical claims data from 1998 to 2012. Quantitative exposure metrics of current exposure to PM2.5 were dichotomized using different cutoffs and effects were assessed separately for smelters and fabrication. Risk score based on insurance claims was available as a time varying health status variable.Defining binary PM2.5 exposure by the 10th percentile cut-off, health status was affected by past exposure and predicted subsequent exposure in smelters, but not in fabrication. A Traditional cox model was appropriate for fabricators; the hazard ratio was 1.51(95% CI: 1.12 - 2.06) and was attenuated when considering higher exposure cutoffs. In smelters, Cox MSM Hazard Ratios for IHD comparing the effect of exposure in a population had everyone always been exposed to everyone always unexposed, using the 10(th) percentile exposure cutoff was 1.83 (95% CI: 1.14 - 2.94). Higher exposure cutoffs also resulted in attenuated effects.Marginal Structural Models can be used in active employment occupational cohorts to address time varying confounding. Results from the current study suggest that occupational exposure to PM2.5 in the aluminium industry increases the risk of IHD in both smelters and fabrication.

    View details for DOI 10.1136/oemed-2014-102362.94

    View details for PubMedID 25018317

  • 0060 Particle size distribution in aluminium manufacturing facilities. Occupational and environmental medicine Liu, S., Noth, E. M., Dixon-Ernst, C., Eisen, E. A., Cullen, M. R., Hammond, S. K. 2014; 71: A6-?


    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 versus MiniMOUDI_PM2.5 was 1.12 mg/m(3) per mg/m(3) (± 0.05), with correlation coefficient of 0.97 (± 0.01). MMADs in fabrications were significantly smaller and less variable than those in smelters (p = 0.001). The fraction of PM10 which was PM1.0 or PM0.56 was significantly higher in fabrications than in smelters (p < 0.001).The reproducibility for impactors was moderate to high. PM2.5 measured by PMI can be a valid measure for fine particle exposure in personal sampling. The concentrations of submicron and quasi-ultrafine particles were similar in fabrications and smelters. PM2.5 is not a good surrogate for ultrafine particles in this setting.

    View details for DOI 10.1136/oemed-2014-102362.18

    View details for PubMedID 25018415

  • 0122 Approaches to developing exposure estimates that reflect temporal trends in total particulate matter in aluminium smelters. Occupational and environmental medicine Noth, E., Liu, S., Cullen, M., Eisen, E., Katharine Hammond, S. 2014; 71: A14-?


    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 year). The trend was not observed in the majority individual jobs. The decreasing trend was concentrated in 14% of the jobs. The majority of jobs (61%) had no change over the time period, 19% had no consistent pattern of change, and 5% increased in TPM concentrations.Applying a global trend to worker exposures would result in misclassification error in epidemiologic evaluations. When possible, process changes should be used to define changes in worker exposures rather than using a facility- or industry-wide time trend. Future work will explore regression modelling as a way to explain any remaining time trends in TPM.

    View details for DOI 10.1136/oemed-2014-102362.43

    View details for PubMedID 25018259

  • 0124 PM2.5 and Heart Disease in a Cohort of Aluminium Workers: An Application of Longitudinal Targeted Maximum Likelihood-based Estimation (TMLE). Occupational and environmental medicine Brown, D., Petersen, M., Van der Laan, M., Costello, S., Noth, E., Hammond, K., Cullen, M., Eisen, E. 2014; 71: A14-?


    We estimated the effect of cumulative exposure to PM2.5 on the incidence of ischaemic heart disease (IHD) in aluminium workers followed for 15 years, adjusting for the healthy worker survivor effect. In previous analyses, higher cumulative exposure was found to be associated with lower mortality in this population.We used longitudinal TMLE to estimate the cumulative risk of ischaemic heart disease in the cohort if constantly exposed above an exposure cut-off and compared it to the risk if constantly exposed below. We stratified all analyses by work process because exposures were an order of magnitude higher in smelters than fabrication facilities.We selected cut-offs a priori at the median and 10th percentile exposure within each sub-cohort. Among the smelter workers, we estimated an increase in IHD risk of 2.1% (p = 0.22) after 15 years, comparing the always exposed to never exposed cohort using the median cut-off of 1.77 mg/m(3). The difference was 2.9% (p = 0.01) using the 10th percentile cutoff of 0.10 mg/m(3). For the fabrication workers, the differences were 0.1% (p = 0.47) using the median cut-off of 0.20 mg/m(3) and 2.5% (p < 0.01) for the 10th percentile cut-off of 0.06 mg/m(3). Results are presented as adjusted survival curves, describing the estimated cumulative risk for each cohort under each exposure regimen.The TMLE estimator allows us to observe an association between cumulative PM2.5 exposure and heart disease that was not visible using standard analytical techniques. This work represents the first application of longitudinal TMLE to the field of occupational epidemiology.

    View details for DOI 10.1136/oemed-2014-102362.44

    View details for PubMedID 25018260

  • Population-Level Correlates of Preterm Delivery among Black and White Women in the US PLOS ONE Carmichael, S. L., Cullen, M. R., Mayo, J. A., Gould, J. B., Loftus, P., Stevenson, D. K., Wise, P. H., Shaw, G. M. 2014; 9 (4)
  • Contribution of health status and prevalent chronic disease to individual risk for workplace injury in the manufacturing environment OCCUPATIONAL AND ENVIRONMENTAL MEDICINE Kubo, J., Goldstein, B. A., Cantley, L. F., Tessier-Sherman, B., Galusha, D., Slade, M. D., Chu, I. M., Cullen, M. R. 2014; 71 (3): 159-166


    An 'information gap' has been identified regarding the effects of chronic disease on occupational injury risk. We investigated the association of ischaemic heart disease, hypertension, diabetes, depression and asthma with acute occupational injury in a cohort of manufacturing workers from 1 January 1997 through 31 December 2007.We used administrative data on real-time injury, medical claims, workplace characteristics and demographics to examine this association. We employed a piecewise exponential model within an Andersen-Gill framework with a frailty term at the employee level to account for inclusion of multiple injuries for each employee, random effects at the employee level due to correlation among jobs held by an employee, and experience on the job as a covariate.One-third of employees had at least one of the diseases during the study period. After adjusting for potential confounders, presence of these diseases was associated with increased hazard of injury: heart disease (HR 1.23, 95% CI 1.11 to 1.36), diabetes (HR 1.17, 95% CI 1.08 to 1.27), depression (HR 1.25, 95% CI 1.12 to 1.38) and asthma (HR 1.14, 95% CI 1.02 to 1.287). Hypertension was not significantly associated with hazard of injury. Associations of chronic disease with injury risk were less evident for more serious reportable injuries; only depression and a summary health metric derived from claims remained significantly positive in this subset.Our results suggest that chronic heart disease, diabetes and depression confer an increased risk for acute occupational injury.

    View details for DOI 10.1136/oemed-2013-101653

    View details for Web of Science ID 000330849700003

  • High prevalence of chronic kidney disease in a community survey of urban Bangladeshis: a cross-sectional study GLOBALIZATION AND HEALTH Anand, S., Khanam, M. A., Saquib, J., Saquib, N., Ahmed, T., Alam, D. S., Cullen, M. R., Barry, M., Chertow, G. M. 2014; 10
  • High prevalence of chronic kidney disease in a community survey of urban Bangladeshis: a cross-sectional study. Globalization and health Anand, S., Khanam, M. A., Saquib, J., Saquib, N., Ahmed, T., Alam, D. S., Cullen, M. R., Barry, M., Chertow, G. M. 2014; 10: 9-?


    The burden of chronic kidney disease (CKD) will rise in parallel with the growing prevalence of type two diabetes mellitus in South Asia but is understudied. Using a cross-sectional survey of adults living in a middle-income neighborhood of Dhaka, Bangladesh, we tested the hypothesis that the prevalence of CKD in this group would approach that of the U.S. and would be strongly associated with insulin resistance.We enrolled 402 eligible adults (>30 years old) after performing a multi-stage random selection procedure. We administered a questionnaire, and collected fasting serum samples and urine samples. We used the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation to estimate glomerular filtration rate, and sex-specific cut offs for albuminuria: > 1.9 mg/mmol (17 mg/g) for men, and >2.8 mg/mmol (25 mg/g) for women. We assessed health-related quality of life using the Medical Outcomes Study Short Form-12 (SF-12).A total of 357 (89%) participants with serum samples comprised the analytic cohort. Mean age of was 49.5 (± 12.7) years. Chronic kidney disease was evident in 94 (26%). Of the participants with CKD, 58 (62%) had albuminuria only. A participant with insulin resistance had a 3.6-fold increase in odds of CKD (95% confidence interval 2.1 to 6.4). Participants with stage three or more advanced CKD reported a decrement in the Physical Health Composite score of the SF-12, compared with participants without CKD.We found an alarmingly high prevalence of CKD-particularly CKD associated with insulin resistance-in middle-income, urban Bangladeshis.

    View details for DOI 10.1186/1744-8603-10-9

    View details for PubMedID 24555767

  • Process of care compliance is associated with fewer diabetes complications. American journal of managed care Bayer, F. J., Galusha, D., Slade, M., Chu, I. M., Taiwo, O., Cullen, M. R. 2014; 20 (1): 41-52


    To examine the association between processes measures of diabetes care and time to progression for 4 diabetes complications: coronary artery disease (CAD), stroke, heart failure (HF), and renal disease (RD).This retrospective study followed outcomes from 2003 through 2009 in a cohort of 1797 employees with diabetes who worked for a large US manufacturer and were enrolled in the same health insurance plan.Quality of care was measured by consensus standards for testing glycated hemoglobin, lipids, and microalbuminuria. Employees with diabetes who received all 3 measures of care in the baseline year (2003) were compared with those who received less complete testing. Cox proportional hazard regression models were used to assess potential associations between diabetes care and time to complications, controlling for potential confounders.Observed differences between the 2 groups in time to event were significant for 2 of the 4 complications: HF (hazard ratio [HR] = 0.39, 95% confidence interval [CI], 0.19-0.81; P = .0117) and RD (HR = 0.48, 95% CI, 0.24-0.95; P = .0339) and any of the 4 complications (HR = 0.66, 95% CI, 0.48-0.91; P = .0101). Differences in time to complication for CAD (HR = 0.70, 95% CI, 0.49-1.02; P = .0635) and stroke (HR = 0.63, 95% CI, 0.38-1.07; P = .0891) showed the same trend but were not significant.Employees with diabetes who received all 3 quality measures experienced fewer complications, risk-adjusting for other factors. These results provide support for the importance of care quality.

    View details for PubMedID 24512164

  • Effect of systematic ergonomic hazard identification and control implementation on musculoskeletal disorder and injury risk SCANDINAVIAN JOURNAL OF WORK ENVIRONMENT & HEALTH Cantley, L. F., Taiwo, O. A., Galusha, D., Barbour, R., Slade, M. D., Tessier-Sherman, B., Cullen, M. R. 2014; 40 (1): 57-65


    This study aimed to examine the effect of an ergonomic hazard control (HC) initiative, undertaken as part of a company ergonomics standard, on worker injury risk.Using the company's ergonomic hazards database to identify jobs with and without ergonomic HC implementation and linking to individual job and injury histories, injury risk among person-jobs with HC implementation (the HC group) was compared to those without HC (NoHC group) using random coefficient models. Further analysis of the HC group was conducted to determine the effect of additional ergonomic hazards controlled on injury risk.Among 123 jobs at 17 plant locations, 347 ergonomic hazards were quantitatively identified during the study period. HC were implemented for 204 quantified ergonomic hazards in 84 jobs, impacting 10 385 persons (12 967 person-jobs). No HC were implemented for quantified ergonomic hazards in the remaining 39 jobs affecting 4155 persons (5046 person-jobs). Adjusting for age, sex, plant origin, and year to control for any temporal trend in injury risk, the relative risk (RR) for musculoskeletal disorder (MSD) was 0.85 and the RR for any injury or MSD was 0.92 in the HC compared to NoHC group. Among the HC group, each ergonomic hazard controlled was associated with risk reduction for MSD and acute injury outcomes (RR 0.93).Systematic ergonomic HC through participatory ergonomics, as part of a mandatory company ergonomics standard, is associated with MSD and injury risk reduction among workers in jobs with HC implemented.

    View details for DOI 10.5271/sjweh.3394

    View details for Web of Science ID 000333321400006

    View details for PubMedID 24142048

  • Process of Care Compliance Is Associated With Fewer Diabetes Complications AMERICAN JOURNAL OF MANAGED CARE Bayer, F. J., Galusha, D., Slade, M., Chu, I. M., Taiwo, O., Cullen, M. R. 2014; 20 (1): 41-52
  • Development of a job-exposure matrix for exposure to total and fine particulate matter in the aluminum industry JOURNAL OF EXPOSURE SCIENCE AND ENVIRONMENTAL EPIDEMIOLOGY Noth, E. M., Dixon-Ernst, C., Liu, S., Cantley, L., Tessier-Sherman, B., Eisen, E. A., Cullen, M. R., Hammond, S. K. 2014; 24 (1): 89-99


    Increasing evidence indicates that exposure to particulate matter (PM) at environmental concentrations increases the risk of cardiovascular disease, particularly PM with an aerodynamic diameter of less than 2.5 μm (PM(2.5)). Despite this, the health impacts of higher occupational exposures to PM(2.5) have rarely been evaluated. In part, this research gap derives from the absence of information on PM(2.5) exposures in the workplace. To address this gap, we have developed a job-exposure matrix (JEM) to estimate exposure to two size fractions of PM in the aluminum industry. Measurements of total PM (TPM) and PM(2.5) were used to develop exposure metrics for an epidemiologic study. TPM exposures for distinct exposure groups (DEGs) in the JEM were calculated using 8385 personal TPM samples collected at 11 facilities (1980-2011). For eight of these facilities, simultaneous PM(2.5) and TPM personal monitoring was conducted from 2010 to 2011 to determine the percent of TPM that is composed of PM(2.5) (%PM(2.5)) in each DEG. The mean TPM from the JEM was then multiplied by %PM(2.5) to calculate PM(2.5) exposure concentrations in each DEG. Exposures in the smelters were substantially higher than in fabrication units; mean TPM concentrations in smelters and fabrication facilities were 3.86 and 0.76 mg/m(3), and the corresponding mean PM(2.5) concentrations were 2.03 and 0.40 mg/m(3). Observed occupational exposures in this study generally exceeded environmental PM(2.5) concentrations by an order of magnitude.

    View details for DOI 10.1038/jes.2013.53

    View details for Web of Science ID 000328604900013

  • Incident ischemic heart disease and recent occupational exposure to particulate matter in an aluminum cohort JOURNAL OF EXPOSURE SCIENCE AND ENVIRONMENTAL EPIDEMIOLOGY Costello, S., Brown, D. M., Noth, E. M., Cantley, L., Slade, M. D., Tessier-Sherman, B., Hammond, S. K., Eisen, E. A., Cullen, M. R. 2014; 24 (1): 82-88


    Fine particulate matter (PM(2.5)) in air pollution, primarily from combustion sources, is recognized as an important risk factor for cardiovascular events but studies of workplace PM(2.5) exposure are rare. We conducted a prospective study of exposure to PM(2.5) and incidence of ischemic heart disease (IHD) in a cohort of 11,966 US aluminum workers. Incident IHD was identified from medical claims data from 1998 to 2008. Quantitative metrics were developed for recent exposure (within the last year) and cumulative exposure; however, we emphasize recent exposure in the absence of interpretable work histories before follow-up. IHD was modestly associated with recent PM(2.5) overall. In analysis restricted to recent exposures estimated with the highest confidence, the hazard ratio (HR) increased to 1.78 (95% CI: 1.02, 3.11) in the second quartile and remained elevated. When the analysis was stratified by work process, the HR rose monotonically to 1.5 in both smelter and fabrication facilities, though exposure was almost an order of magnitude higher in smelters. The differential exposure-response may be due to differences in exposure composition or healthy worker survivor effect. These results are consistent with the air pollution and cigarette smoke literature; recent exposure to PM(2.5) in the workplace appears to increase the risk of IHD incidence.

    View details for DOI 10.1038/jes.2013.47

    View details for Web of Science ID 000328604900012

  • Population-level correlates of preterm delivery among black and white women in the U.S. PloS one Carmichael, S. L., Cullen, M. R., Mayo, J. A., Gould, J. B., Loftus, P., Stevenson, D. K., Wise, P. H., Shaw, G. M. 2014; 9 (4)


    This study examined the ability of social, demographic, environmental and health-related factors to explain geographic variability in preterm delivery among black and white women in the US and whether these factors explain black-white disparities in preterm delivery.We examined county-level prevalence of preterm delivery (20-31 or 32-36 weeks gestation) among singletons born 1998-2002. We conducted multivariable linear regression analysis to estimate the association of selected variables with preterm delivery separately for each preterm/race-ethnicity group.The prevalence of preterm delivery varied two- to three-fold across U.S. counties, and the distributions were strikingly distinct for blacks and whites. Among births to blacks, regression models explained 46% of the variability in county-level risk of delivery at 20-31 weeks and 55% for delivery at 32-36 weeks (based on R-squared values). Respective percentages for whites were 67% and 71%. Models included socio-environmental/demographic and health-related variables and explained similar amounts of variability overall.Much of the geographic variability in preterm delivery in the US can be explained by socioeconomic, demographic and health-related characteristics of the population, but less so for blacks than whites.

    View details for DOI 10.1371/journal.pone.0094153

    View details for PubMedID 24740117

  • Systematic evaluation of environmental and behavioural factors associated with all-cause mortality in the United States National Health and Nutrition Examination Survey INTERNATIONAL JOURNAL OF EPIDEMIOLOGY Patel, C. J., Rehkopf, D. H., Leppert, J. T., Bortz, W. M., Cullen, M. R., Chertow, G. M., Ioannidis, J. P. 2013; 42 (6): 1795-1810


    Environmental and behavioural factors are thought to contribute to all-cause mortality. Here, we develop a method to systematically screen and validate the potential independent contributions to all-cause mortality of 249 environmental and behavioural factors in the National Health and Nutrition Examination Survey (NHANES).We used Cox proportional hazards regression to associate 249 factors with all-cause mortality while adjusting for sociodemographic factors on data in the 1999-2000 and 2001-02 surveys (median 5.5 follow-up years). We controlled for multiple comparisons with the false discovery rate (FDR) and validated significant findings in the 2003-04 survey (median 2.8 follow-up years). We selected 249 factors from a set of all possible factors based on their presence in both the 1999-2002 and 2003-04 surveys and linkage with at least 20 deceased participants. We evaluated the correlation pattern of validated factors and built a multivariable model to identify their independent contribution to mortality.We identified seven environmental and behavioural factors associated with all-cause mortality, including serum and urinary cadmium, serum lycopene levels, smoking (3-level factor) and physical activity. In a multivariable model, only physical activity, past smoking, smoking in participant's home and lycopene were independently associated with mortality. These three factors explained 2.1% of the variance of all-cause mortality after adjusting for demographic and socio-economic factors.Our association study suggests that, of the set of 249 factors in NHANES, physical activity, smoking, serum lycopene and serum/urinary cadmium are associated with all-cause mortality as identified in previous studies and after controlling for multiple hypotheses and validation in an independent survey. Whereas other NHANES factors may be associated with mortality, they may require larger cohorts with longer time of follow-up to detect. It is possible to use a systematic association study to prioritize risk factors for further investigation.

    View details for DOI 10.1093/ije/dyt208

    View details for Web of Science ID 000329870400041

    View details for PubMedID 24345851

  • Urinary Triclosan is Associated with Elevated Body Mass Index in NHANES PLOS ONE Lankester, J., Patel, C., Cullen, M. R., Ley, C., Parsonnet, J. 2013; 8 (11)


    Triclosan-a ubiquitous chemical in toothpastes, soaps, and household cleaning supplies-has the potential to alter both gut microbiota and endocrine function and thereby affect body weight.We investigated the relationship between triclosan and body mass index (BMI) using National Health and Nutrition Examination Surveys (NHANES) from 2003-2008. BMI and spot urinary triclosan levels were obtained from adults. Using two different exposure measures-either presence vs. absence or quartiles of triclosan-we assessed the association between triclosan and BMI. We also screened all NHANES serum and urine biomarkers to identify correlated factors that might confound observed associations.Compared with undetectable triclosan, a detectable level was associated with a 0.9-point increase in BMI (p<0.001). In analysis by quartile, compared to the lowest quartile, the 2nd, 3rd and 4th quartiles of urinary triclosan were associated with BMI increases of 1.5 (p<0.001), 1.0 (p = 0.002), and 0.3 (p = 0.33) respectively. The one strong correlate of triclosan identified in NHANES was its metabolite, 2,4-dichlorophenol (ρ = 0.4); its association with BMI, however, was weaker than that of triclosan. No other likely confounder was identified.Triclosan exposure is associated with increased BMI. Stronger effect at moderate than high levels suggests a complex mechanism of action.

    View details for DOI 10.1371/journal.pone.0080057

    View details for Web of Science ID 000327539800048

    View details for PubMedID 24278238

  • Associations between employee and manager gender: impacts on gender-specific risk of acute occupational injury in metal manufacturing BMC PUBLIC HEALTH Kubo, J. T., Cullen, M. R., Desai, M., Modrek, S. 2013; 13
  • High prevalence of type 2 diabetes among the urban middle class in Bangladesh BMC PUBLIC HEALTH Saquib, N., Khanam, M. A., Saquib, J., Anand, S., Chertow, G. M., Barry, M., Ahmed, T., Cullen, M. R. 2013; 13
  • Job insecurity during recessions: effects on survivors' work stress BMC PUBLIC HEALTH Modrek, S., Cullen, M. R. 2013; 13
  • Preference for wine is associated with lower hip fracture incidence in post-menopausal women BMC WOMENS HEALTH Kubo, J. T., Stefanick, M. L., Robbins, J., Wactawski-Wende, J., Cullen, M. R., Freiberg, M., Desai, M. 2013; 13
  • Health consequences of the 'Great Recession' on the employed: Evidence from an industrial cohort in aluminum manufacturing SOCIAL SCIENCE & MEDICINE Modrek, S., Cullen, M. R. 2013; 92: 105-113


    While the negative effects of unemployment have been well studied, the consequences of layoffs and downsizing for those who remain employed are less well understood. This study uses human resources and health claims data from a large multi-site fully insured aluminum company to explore the health consequences of downsizing on the remaining workforce. We exploit the variation in the timing and intensity of layoff to categorize 30 plants as high or low layoff plants. Next, we select a stably employed cohort of workers with history of health insurance going back to 2006 to 1) describe the selection process into layoff and 2) explore the association between the severity of plant level layoffs and the incidence of four chronic conditions in the remaining workforce. We examine four health outcomes: incident hypertension, diabetes, asthma/COPD and depression for a cohort of approximately 13,000 employees. Results suggest that there was an increased risk of developing hypertension for all workers and an increased risk of developing diabetes for salaried workers that remain at the plants with the highest level of layoffs. The hypertension results were robust to a several specification tests. In addition, the study design selected only healthy workers, therefore our estimates are likely to be a lower bound and suggest that adverse health consequences of the 2007-2009 recession may have affected a broader proportion of the population than previously expected.

    View details for DOI 10.1016/j.socscimed.2013.04.027

    View details for Web of Science ID 000322858200012

  • Piecewise exponential models to assess the influence of job-specific experience on the hazard of acute injury for hourly factory workers BMC MEDICAL RESEARCH METHODOLOGY Kubo, J., Cullen, M. R., Cantley, L., Slade, M., Tessier-Sherman, B., Taiwo, O., Desai, M. 2013; 13


    An inverse relationship between experience and risk of injury has been observed in many occupations. Due to statistical challenges, however, it has been difficult to characterize the role of experience on the hazard of injury. In particular, because the time observed up to injury is equivalent to the amount of experience accumulated, the baseline hazard of injury becomes the main parameter of interest, excluding Cox proportional hazards models as applicable methods for consideration.Using a data set of 81,301 hourly production workers of a global aluminum company at 207 US facilities, we compared competing parametric models for the baseline hazard to assess whether experience affected the hazard of injury at hire and after later job changes. Specific models considered included the exponential, Weibull, and two (a hypothesis-driven and a data-driven) two-piece exponential models to formally test the null hypothesis that experience does not impact the hazard of injury.We highlighted the advantages of our comparative approach and the interpretability of our selected model: a two-piece exponential model that allowed the baseline hazard of injury to change with experience. Our findings suggested a 30% increase in the hazard in the first year after job initiation and/or change.Piecewise exponential models may be particularly useful in modeling risk of injury as a function of experience and have the additional benefit of interpretability over other similarly flexible models.

    View details for DOI 10.1186/1471-2288-13-89

    View details for Web of Science ID 000322382600001

    View details for PubMedID 23841648

  • (De)Personalized Medicine SCIENCE Horwitz, R. I., Cullen, M. R., Abell, J., Christian, J. B. 2013; 339 (6124): 1155-1156

    View details for DOI 10.1126/science.1234106

    View details for Web of Science ID 000315709900030

    View details for PubMedID 23471391

  • Selection on Moral Hazard in Health Insurance AMERICAN ECONOMIC REVIEW Einav, L., Finkelstein, A., Ryan, S. P., Schrimpf, P., Cullen, M. R. 2013; 103 (1): 178-219
  • Impact of daily noise exposure monitoring on occupational noise exposures in manufacturing workers INTERNATIONAL JOURNAL OF AUDIOLOGY McTague, M. F., Galusha, D., Dixon-Ernst, C., Kirsche, S. R., Slade, M. D., Cullen, M. R., Rabinowitz, P. M. 2013; 52: S3-S8


    Despite the use of hearing protection devices (HPDs), noise induced hearing loss (NIHL) remains one of the most prevalent occupational conditions. A new technology allows for daily monitoring of noise exposures under HPDs. We report on an intervention employing the voluntary use of this technology in a worksite setting.Volunteers were fitted with a device allowing them to monitor noise exposure under their hearing protection on a daily basis. The trends in noise exposures for individuals who completed at least six months of the intervention were analysed.Recruitment occurred at three manufacturing facilities, with 127 workers enrolling and 66 workers actively using the device during their work shifts.Among volunteers downloading regularly, the percentage of daily exposures in excess of the OSHA action level (85 dBA) decreased from 14% to 8%, while the percentage of daily exposures in excess of 90 dBA decreased from 4% to less than 2%.Initial results from this longitudinal study indicate that volunteers find daily noise exposure monitoring to be feasible, and that workers who monitor daily are able to reduce exposures. The results of subject adherence shed light on the challenges and possibilities of worksite interventions for health and safety.

    View details for DOI 10.3109/14992027.2012.743047

    View details for Web of Science ID 000314532400002

    View details for PubMedID 23373740

  • Further validation that claims data are a useful tool for epidemiologic research on hypertension BMC PUBLIC HEALTH Tessier-Sherman, B., Galusha, D., Taiwo, O. A., Cantley, L., Slade, M. D., Kirsche, S. R., Cullen, M. R. 2013; 13


    The practice of using medical service claims in epidemiologic research on hypertension is becoming increasingly common, and several published studies have attempted to validate the diagnostic data contained therein. However, very few of those studies have had the benefit of using actual measured blood pressure as the gold standard. The goal of this study is to assess the validity of claims data in identifying hypertension cases and thereby clarify the benefits and limitations of using those data in studies of chronic disease etiology.Disease status was assigned to 19,150 employees at a U.S. manufacturing company where regular physical examinations are performed. We compared the presence of hypertension in the occupational medical charts against diagnoses obtained from administrative claims data.After adjusting for potential confounders, those with measured blood pressure indicating stage 1 hypertension were 3.69 times more likely to have a claim than normotensives (95% CI: 3.12, 4.38) and those indicating stage 2 hypertension were 7.70 times more likely to have a claim than normotensives (95% CI: 6.36, 9.35). Comparing measured blood pressure values identified in the medical charts to the algorithms for diagnosis of hypertension from the claims data yielded sensitivity values of 43-61% and specificity values of 86-94%.The medical service claims data were found to be highly specific, while sensitivity values varied by claims algorithm suggesting the possibility of under-ascertainment. Our analysis further demonstrates that such under-ascertainment is strongly skewed toward those cases that would be considered clinically borderline or mild.

    View details for DOI 10.1186/1471-2458-13-51

    View details for Web of Science ID 000314764800001

    View details for PubMedID 23331960

  • Job insecurity during recessions: effects on survivors' work stress. BMC public health Modrek, S., Cullen, M. R. 2013; 13: 929-?


    Previous studies show a variety of negative health consequences for the remaining workforce after downsizing events. This study examined self-reported work stress from 2009-2012 in the context of a large multi-site aluminum manufacturing company that underwent severe downsizing in 2009.This study examined the association between work stress and working at a work site that underwent severe downsizing. We assessed the level of downsizing across thirty plants in 2009 and categorized seven as having undergone severe downsizing. We linked plant-level downsizing information to individual workers' responses to an annual work engagement survey, which included three work stress questions. From 2009 to 2012 over 14, 000 employees were asked about their experience of work stress. Though the surveys were anonymous, the surveys captured employees' demographic and employment characteristic as well as plant location. We used hierarchical logistic regressions to compare responses of workers at severely downsized plants to workers at all other plant while controlling for demographic and plant characteristics. Responses to the work stress questions and one control question were examined.In all yearly surveys salaried workers consistently reported having more work stress than hourly workers. There was no differential in work stress for workers at severely downsized plants in 2009. In 2010 to 2012, salaried workers who remained at severely downsized plants reported significantly higher work stress than salaried workers at all other plants across multiple work stress questions. Examination of the 2006 survey confirmed that there were no pre-existing differences in work stress among salaried employees working at plants that would eventually experience severe downsizing. In addition, there was no difference in responses to the control question at severely downsized plants.Salaried workers at plants with high layoffs experienced more work stress after 2009 than their counterparts at non-high layoff plants. Increased work stress is important to monitor and may be a mediating pathway through which the external economic environment leads to adverse health outcomes.

    View details for DOI 10.1186/1471-2458-13-929

    View details for PubMedID 24093476

  • Preference for wine is associated with lower hip fracture incidence in post-menopausal women. BMC women's health Kubo, J. T., Stefanick, M. L., Robbins, J., Wactawski-Wende, J., Cullen, M. R., Freiberg, M., Desai, M. 2013; 13: 36-?


    Past studies of relationships between alcohol and hip fracture have generally focused on total alcohol consumed and not type of alcohol. Different types of alcohol consist of varying components which may affect risk of hip fracture differentially. This study seeks to examine the relationship between alcohol consumption, with a focus on type of alcohol consumed (e.g. beer, wine, or hard liquor) and hip fracture risk in post-menopausal women.The longitudinal cohort consisted of U.S. post-menopausal women aged 50-79 years enrolled between 1993-1998 in the Women's Health Initiative Clinical Trials and Observational Study (N=115,655).Women were categorized as non-drinkers, past drinkers, infrequent drinkers and drinkers by preference of alcohol type (i.e. those who preferred wine, beer, hard liquor, or who had no strong preference). Mean alcohol consumption among current drinkers was 3.3 servings per week; this was similar among those who preferred wine, beer and liquor. After adjustment for potential confounders, alcohol preference was strongly correlated with hip fracture risk (p = 0.0167); in particular, women who preferred wine were at lower risk than non-drinkers (OR=0.78; 95% CI 0.64-0.95), past drinkers (OR=0.85; 95% CI 0.72-1.00), infrequent drinkers (OR=0.73; 95% CI 0.61-0.88), hard liquor drinkers (OR=0.87; 95% CI 0.71-1.06), beer drinkers (OR=0.72; 95% CI 0.55-0.95) and those with no strong preference (OR=0.89; 95% CI 0.89; 95% CI 0.73-1.10).Preference of alcohol type was associated with hip fracture; women who preferentially consumed wine had a lower risk of hip fracture compared to non-drinkers, past drinkers, and those with other alcohol preferences.

    View details for DOI 10.1186/1472-6874-13-36

    View details for PubMedID 24053784

  • Associations between employee and manager gender: impacts on gender-specific risk of acute occupational injury in metal manufacturing. BMC public health Kubo, J. T., Cullen, M. R., Desai, M., Modrek, S. 2013; 13: 1053-?


    Prior research has shown increased risk of injury for female employees compared to male employees after controlling for job and tasks, but have not explored whether this increased risk might be moderated by manager gender. The gender of one's manager could in theory affect injury rates among male and female employees through their managers' response to an employee's psychosocial stress or through how employees differentially report injuries. Other explanations for the gender disparity in injury experience, such as ergonomic factors or differential training, are unlikely to be impacted by supervisor gender. This study seeks to explore whether an employee's manager's gender modifies the effect of employee gender with regards to risk of acute injury.A cohort of employees and managers were identified using human resources and injury management data between January 1, 2002 and December 31, 2007 for six facilities of a large US aluminum manufacturing company. Cox proportional hazards models were employed to examine the interaction between employee gender and whether the employee had female only manager(s), male only manager(s), or both male and female managers on injury risk. Manager gender category was included as a time varying covariate and reassessed for each employee at the midpoint of each year.The percentage of departments with both female and male managers increased dramatically during the study period due to corporate efforts to increase female representation in management. After adjustment for fixed effects at the facility level and shared frailty by department, manager gender category does not appear to moderate the effect of employee gender (p = 0.717). Manager category was not a significant predictor (p = 0.093) of time to first acute injury. Similarly, having at least one female manager did not modify the hazard of injury for female employees compared to males (p = 0.899) and was not a significant predictor of time to first acute injury (p = 0.601).Prior findings suggest that female manufacturing employees are at higher risk for acute injury compared to males; this analysis suggests that this relationship is not affected by the gender of the employee's manager(s).

    View details for DOI 10.1186/1471-2458-13-1053

    View details for PubMedID 24207014

  • High prevalence of type 2 diabetes among the urban middle class in Bangladesh. BMC public health Saquib, N., Khanam, M. A., Saquib, J., Anand, S., Chertow, G. M., Barry, M., Ahmed, T., Cullen, M. R. 2013; 13: 1032-?


    The prevalence of type-2 diabetes and metabolic syndrome are increasing in the developing world; we assessed their prevalence among the urban middle class in Bangladesh.In this cross-sectional survey (n = 402), we randomly selected consenting adults (≥ 30 years) from a middle-income neighborhood in Dhaka. We assessed demography, lifestyle, and health status, measured physical indices and blood pressure and obtained blood samples. We evaluated two primary outcomes: (1) type-2 diabetes (fasting blood glucose ≥ 7.0 mmol/L or hemoglobin A1C ≥ 6.5% (48 mmol/mol) or diabetes medication use) and (2) insulin resistance (type-2 diabetes or metabolic syndrome using International Diabetes Federation criteria).Mean age and Quételet's (body mass) index were 49.4 ± 12.6 years and 27.0 ± 5.1 kg/m²; 83% were married, 41% had ≥12 years of education, 47% were employed, 47% had a family history of diabetes. Thirty-five percent had type-2 diabetes and 45% had metabolic syndrome. In multivariate models older age and family history of diabetes were significantly associated with type-2 diabetes. Older age, female sex, overweight or obese, high wealth index and positive family history of diabetes were significantly associated with insulin resistance. Participants with type-2 diabetes or insulin resistance had significantly poorer physical health only if they had associated cardiovascular disease.The prevalence of type-2 diabetes and metabolic syndrome among the middle class in Dhaka is alarmingly high. Screening services should be implemented while researchers focus on strategies to lessen the incidence and morbidity associated with these conditions.

    View details for DOI 10.1186/1471-2458-13-1032

    View details for PubMedID 24172217

  • How General Are Risk Preferences? Choices under Uncertainty in Different Domains AMERICAN ECONOMIC REVIEW Einav, L., Finkelstein, A., Pascu, I., Cullen, M. R. 2012; 102 (6): 2606-2638
  • Cardiovascular diseases and Type 2 Diabetes in Bangladesh: A systematic review and meta-analysis of studies between 1995 and 2010 BMC PUBLIC HEALTH Saquib, N., Saquib, J., Ahmed, T., Khanam, M. A., Cullen, M. R. 2012; 12


    Belief is that chronic disease prevalence is rising in Bangladesh since death from them has increased. We reviewed published cardiovascular (CVD) and Type 2 Diabetes Mellitus (T2DM) studies between 1995 and 2010 and conducted a meta-analysis of disease prevalence.A systematic search of CVD and T2DM studies yielded 29 eligible studies (outcome: CVD only = 12, T2DM only = 9, both = 8). Hypertension (HTN) was the primary outcome of CVD studies. HTN and T2DM were defined with objective measures and standard cut-off values. We assessed the study quality based on sampling frame, sample size, and disease evaluation. Random effects models calculated pooled disease prevalence (95% confidence interval) in studies with general population samples (n = 22).The pooled HTN and T2DM prevalence were 13.7% (12.1%-15.3%) and 6.7% (4.9%-8.6%), respectively. Both diseases exhibited a secular trend by 5-year intervals between 1995 and 2010 (HTN = 11.0%, 12.8%, 15.3%, T2DM = 3.8%, 5.3%, 9.0%). HTN was higher in females (M vs. F: 12.8% vs.16.1%) but T2DM was higher in males (M vs. F: 7.0% vs. 6.2%) (non-significant). Both HTN and T2DM were higher in urban areas (urban vs. rural: 22.2% vs. 14.3% and 10.2% vs. 5.1% respectively) (non-significant). HTN was higher among elderly and among working professionals. Both HTN and T2DM were higher in 'high- quality' studies.There is evidence of a rising secular trend of HTN and T2DM prevalence in Bangladesh. Future research should focus on the evolving root causes, incidence, and prognosis of HTN and T2DM.

    View details for DOI 10.1186/1471-2458-12-434

    View details for Web of Science ID 000311081700001

    View details for PubMedID 22694854

  • Systematic evaluation of environmental factors: persistent pollutants and nutrients correlated with serum lipid levels INTERNATIONAL JOURNAL OF EPIDEMIOLOGY Patel, C. J., Cullen, M. R., Ioannidis, J. P., Butte, A. J. 2012; 41 (3): 828-843


    Both genetic and environmental factors contribute to triglyceride, low-density lipoprotein-cholesterol (LDL-C), and high-density lipoprotein-cholesterol (HDL-C) levels. Although genome-wide association studies are currently testing the genetic factors systematically, testing and reporting one or a few factors at a time can lead to fragmented literature for environmental chemical factors. We screened for correlation between environmental factors and lipid levels, utilizing four independent surveys with information on 188 environmental factors from the Centers of Disease Control, National Health and Nutrition Examination Survey, collected between 1999 and 2006.We used linear regression to correlate each environmental chemical factor to triglycerides, LDL-C and HDL-C adjusting for age, age(2), sex, ethnicity, socio-economic status and body mass index. Final estimates were adjusted for waist circumference, diabetes status, blood pressure and survey. Multiple comparisons were controlled for by estimating the false discovery rate and significant findings were tentatively validated in an independent survey.We identified and validated 29, 9 and 17 environmental factors correlated with triglycerides, LDL-C and HDL-C levels, respectively. Findings include hydrocarbons and nicotine associated with lower HDL-C and vitamin E (?-tocopherol) associated with unfavourable lipid levels. Higher triglycerides and lower HDL-C were correlated with higher levels of fat-soluble contaminants (e.g. polychlorinated biphenyls and dibenzofurans). Nutrients and vitamin markers (e.g. vitamins B, D and carotenes), were associated with favourable triglyceride and HDL-C levels.Our systematic association study has enabled us to postulate about broad environmental correlation to lipid levels. Although subject to confounding and reverse causality bias, these findings merit evaluation in additional cohorts.

    View details for DOI 10.1093/ije/dys003

    View details for Web of Science ID 000306417300030

    View details for PubMedID 22421054

  • Geographic and Racial Variation in Premature Mortality in the US: Analyzing the Disparities PLOS ONE Cullen, M. R., Cummins, C., Fuchs, V. R. 2012; 7 (4)


    Life expectancy at birth, estimated from United States period life tables, has been shown to vary systematically and widely by region and race. We use the same tables to estimate the probability of survival from birth to age 70 (S(70)), a measure of mortality more sensitive to disparities and more reliably calculated for small populations, to describe the variation and identify its sources in greater detail to assess the patterns of this variation. Examination of the unadjusted probability of S(70) for each US county with a sufficient population of whites and blacks reveals large geographic differences for each race-sex group. For example, white males born in the ten percent healthiest counties have a 77 percent probability of survival to age 70, but only a 61 percent chance if born in the ten percent least healthy counties. Similar geographical disparities face white women and blacks of each sex. Moreover, within each county, large differences in S(70) prevail between blacks and whites, on average 17 percentage points for men and 12 percentage points for women. In linear regressions for each race-sex group, nearly all of the geographic variation is accounted for by a common set of 22 socio-economic and environmental variables, selected for previously suspected impact on mortality; R(2) ranges from 0.86 for white males to 0.72 for black females. Analysis of black-white survival chances within each county reveals that the same variables account for most of the race gap in S(70) as well. When actual white male values for each explanatory variable are substituted for black in the black male prediction equation to assess the role explanatory variables play in the black-white survival difference, residual black-white differences at the county level shrink markedly to a mean of -2.4% (+/-2.4); for women the mean difference is -3.7% (+/-2.3).

    View details for DOI 10.1371/journal.pone.0032930

    View details for Web of Science ID 000305347400001

    View details for PubMedID 22529892

  • Hearing effects from intermittent and continuous noise exposure in a study of Korean factory workers and firefighters BMC PUBLIC HEALTH Chung, I., Chu, I. M., Cullen, M. R. 2012; 12


    South Korea and surrounding countries in East Asia are believed to have the highest proportion in the world of high frequency hearing loss due to occupational noise exposure, yet there has been limited information published in international journals, and limited information for control of noise in local workplaces beyond strategies from western countries. We exploit medical surveillance information from two worker groups to enhance local knowledge about noise-induced hearing loss and explore the possible importance of shift work to risk.Four-years of hearing data were evaluated for 81 male farm machine factory workers and 371 male firefighters who had successfully completed a health examination and questionnaires for the duration of the study period. The averages of hearing thresholds at 2, 3, and 4 kHz were used as the primary end-point for comparison. Repeat measure analysis adjusted for age, exposure duration and smoking status was used to measure the difference in hearing threshold between the two groups.Noise levels were measured in the factory at a mean of 82 dBA, with a range of 66-97. No concurrent measurements were taken for the firefighters, but historic comparison values showed a wider range but a similar mean of 76-79 dBA. Although losses during follow-up were negligible, the factory workers had significantly (P < 0.0001) more hearing loss at the baseline of the study than the firefighters in both ears at 2, 3, and 4 kHz, adjusted for age, duration of employment and smoking status. Among those with 10 years of employment, mean losses at these frequencies among the factory workers fell into the impairment range (> 25 dB loss). Firefighters also showed increased losses associated with longer exposure duration, but these were significantly less marked. Losses at lower frequencies (< or = 1 kHz) were negligible in both groups.Korean work environments with continuous noise exposure in the measured range should consider implementation of a hearing conservation program. Further evaluation of hearing loss in workers exposed to irregular or intermittent high noise levels, such as firefighters, is also warranted.

    View details for DOI 10.1186/1471-2458-12-87

    View details for Web of Science ID 000300291500001

    View details for PubMedID 22284753

  • Genetic variability in molecular responses to chemical exposure. EXS Patel, C. J., Cullen, M. R. 2012; 101: 437-457


    Individuals differ in their response to environmental exposures. In the following, we describe examples and paradigms of studying heritable differences in response to exposure-commonly known as "gene-environment interaction" or "ecogenetics"-and their relation to disease etiology and susceptibility. Our discussion is framed in three parts. In the first, we describe replicated examples of studies that have typified the field, single genetic variant, and exposure associations to disease. Second, we describe how studies have scaled up search for interaction using genome-wide measurement modalities, bioinformatics, and model organisms. Finally, we discuss a more comprehensive representation of chemical exposures as the "envirome" and how we may use the envirome to examine interplay between genetics and the environment.

    View details for DOI 10.1007/978-3-7643-8340-4_15

    View details for PubMedID 22945578

  • Effect of daily noise exposure monitoring on annual rates of hearing loss in industrial workers OCCUPATIONAL AND ENVIRONMENTAL MEDICINE Rabinowitz, P. M., Galusha, D., Kirsche, S. R., Cullen, M. R., Slade, M. D., Dixon-Ernst, C. 2011; 68 (6): 414-418


    Occupational noise-induced hearing loss (NIHL) is prevalent, yet evidence on the effectiveness of preventive interventions is lacking. The effectiveness of a new technology allowing workers to monitor daily at-ear noise exposure was analysed.Workers in the hearing conservation program of an aluminium smelter were recruited because of accelerated rates of hearing loss. The intervention consisted of daily monitoring of at-ear noise exposure and regular feedback on exposures from supervisors. The annual rate of change in high frequency hearing average at 2, 3 and 4 KHz before intervention (2000-2004) and 4 years after intervention (2006-2009) was determined. Annual rates of loss were compared between 78 intervention subjects and 234 controls in other company smelters matched for age, gender and high frequency hearing threshold level in 2005.Individuals monitoring daily noise exposure experienced on average no further worsening of high frequency hearing (average rate of hearing change at 2, 3 and 4 KHz = -0.5 dB/year). Matched controls also showed decelerating hearing loss, the difference in rates between the two groups being significant (p < 0.0001). Analysis of a subset of intervention subjects matched to controls for initial rate of hearing loss showed a similar trend but the difference was not statistically significant (p = 0.06).Monitoring daily occupational noise exposure inside hearing protection with ongoing administrative feedback apparently reduces the risk of occupational NIHL in industrial workers. Longer follow-up of these workers will help determine the significance of the intervention effect. Intervention studies for the prevention of NIHL need to include appropriate control groups.

    View details for DOI 10.1136/oem.2010.055905

    View details for Web of Science ID 000290516600007

    View details for PubMedID 21193566

  • Aging, Transition, and Estimating the Global Burden of Disease PLOS ONE Seligman, B. J., Cullen, M. R., Horwitz, R. I. 2011; 6 (5)


    The World Health Organization's Global Burden of Disease (GBD) reports are an important tool for global health policy makers, however the accuracy of estimates for countries undergoing an epidemiologic transition is unclear. We attempted to validate the life table model used to generate estimates for all-cause mortality in developing countries.Data were obtained for males and females from the Human Mortality Database for all countries with available data every ten years from 1900 to 2000. These provided inputs for the GBD life table model and served as comparison observed data. Above age sixty model estimates of survival for both sexes differed substantially from those observed. Prior to the year 1960 for males and 1930 for females, estimated survival tended to be greater than observed; following 1960 for both males and females estimated survival tended to be less than observed. Viewing observed and estimated survival separately, observed survival past sixty increased over the years considered. For males, the increase was from a mean (sd) probability of 0.22 (0.06) to 0.46 (0.1). For females, the increase was from 0.26 (0.06) to 0.65 (0.08). By contrast, estimated survival past sixty decreased over the same period. Among males, estimated survival probability declined from 0.54 (0.2) to 0.09 (0.06). Among females, the decline was from 0.36 (0.12) to 0.15 (0.08).These results show that the GBD mortality model did not accurately estimate survival at older ages as developed countries transitioned in the twentieth century and may be similarly flawed in developing countries now undergoing transition. Estimates of the size of older-age populations and their attributable disease burden should be reconsidered.

    View details for DOI 10.1371/journal.pone.0020264

    View details for Web of Science ID 000291005800039

    View details for PubMedID 21629652

  • Gender and sex differences in job status and hypertension OCCUPATIONAL AND ENVIRONMENTAL MEDICINE Clougherty, J. E., Eisen, E. A., Slade, M. D., Kawachi, I., Cullen, M. R. 2011; 68 (1): 16-23


    Studies have shown greater health risks associated with blue-collar manufacturing employment for women than men. It remains challenging, however, to distinguish gendered job status (affected by family composition and other personal characteristics) from sex-linked biological differences influencing physiological response to workplace physical hazards.We examined the effects of hourly (blue-collar) status on incident hypertension among men and women, using health claims data for 14, 618 white- and blue-collar aluminium manufacturing employees in eight US states. To explore gender differences in job status, we developed sex-stratified propensity score models identifying key socioeconomic predictors of hourly status for men and women. To examine the effects of hourly employment on hypertension risk, after adjusting for gender differences in job status, we applied time-weighted logistic regression models, stratified by propensity score, with additional adjustment for socioeconomic confounders.Family structure (partnership, parity) influenced job status for both sexes; single mothers were more likely to hold hourly jobs (OR 2.02; 95% CI 1.37 to 2.97) and partnered men with children less likely (OR 0.68; 95% CI 0.56 to 0.83). Education, age at hire and race influenced job status for both sexes. The effect of hourly status on hypertension was significant only among women predicted to be hourly (OR 1.78; 95% CI 1.34 to 2.35).Our results indicate significant risks of hypertension associated with hourly status for women, possibly exacerbated by sociodemographic factors predicting hourly status (eg, single parenthood, low education). Greater attention to gender differences in job status, and finer exploration of sex-linked biological differences influencing responsivity to workplace exposures, is warranted.

    View details for DOI 10.1136/oem.2009.049908

    View details for Web of Science ID 000285182900005

    View details for PubMedID 20864467

  • Prevalence of beryllium sensitization among aluminium smelter workers OCCUPATIONAL MEDICINE-OXFORD Taiwo, O. A., Slade, M. D., Cantley, L. F., Kirsche, S. R., Wesdock, J. C., Cullen, M. R. 2010; 60 (7): 569-571


    Beryllium exposure occurs in aluminium smelters from natural contamination of bauxite, the principal source of aluminium.To characterize beryllium exposure in aluminium smelters and determine the prevalence rate of beryllium sensitization (BeS) among aluminium smelter workers.A population of 3185 workers from nine aluminium smelters owned by four different aluminium-producing companies were determined to have significant beryllium exposure. Of these, 1932 workers participated in medical surveillance programmes that included the serum beryllium lymphocyte proliferation test (BeLPT), confirmation of sensitization by at least two abnormal BeLPT test results and further evaluation for chronic beryllium disease in workers with BeS.Personal beryllium samples obtained from the nine aluminium smelters showed a range of <0.01-13.00 ?g/m(3) time-weighted average with an arithmetic mean of 0.25 ?g/m(3) and geometric mean of 0.06 ?g/m(3). Nine workers were diagnosed with BeS (prevalence rate of 0.47%, 95% confidence interval = 0.21-0.88%).BeS can occur in aluminium smelter workers through natural beryllium contamination of the bauxite and further concentration during the refining and smelting processes. Exposure levels to beryllium observed in aluminium smelters are similar to those seen in other industries that utilize beryllium. However, compared with beryllium-exposed workers in other industries, the rate of BeS among aluminium smelter workers appears lower. This lower observed rate may be related to a more soluble form of beryllium found in the aluminium smelting work environment as well as the consistent use of respiratory protection.

    View details for DOI 10.1093/occmed/kqq097

    View details for Web of Science ID 000282329000013

    View details for PubMedID 20610489



    We provide a graphical illustration of how standard consumer and producer theory can be used to quantify the welfare loss associated with inefficient pricing in insurance markets with selection. We then show how this welfare loss can be estimated empirically using identifying variation in the price of insurance. Such variation, together with quantity data, allows us to estimate the demand for insurance. The same variation, together with cost data, allows us to estimate how insurer's costs vary as market participants endogenously respond to price. The slope of this estimated cost curve provides a direct test for both the existence and nature of selection, and the combination of demand and cost curves can be used to estimate welfare. We illustrate our approach by applying it to data on employer-provided health insurance from one specific company. We detect adverse selection but estimate that the quantitative welfare implications associated with inefficient pricing in our particular application are small, in both absolute and relative terms.

    View details for Web of Science ID 000281353500001

    View details for PubMedID 21218182

  • Childhood Lead Exposure After the Phaseout of Leaded Gasoline: An Ecological Study of School-Age Children in Kampala, Uganda ENVIRONMENTAL HEALTH PERSPECTIVES Graber, L. K., Asher, D., Anandaraja, N., Bopp, R. F., Merrill, K., Cullen, M. R., Luboga, S., Trasande, L. 2010; 118 (6): 884-889


    Tetraethyl lead was phased out of gasoline in Uganda in 2005. Recent mitigation of an important source of lead exposure suggests examination and re-evaluation of the prevalence of childhood lead poisoning in this country. Ongoing concerns persist about exposure from the Kiteezi landfill in Kampala, the country's capital.We determined blood lead distributions among Kampala schoolchildren and identified risk factors for elevated blood lead levels (EBLLs; >or= 10 microg/dL). Analytical approach: Using a stratified, cross-sectional design, we obtained blood samples, questionnaire data, and soil and dust samples from the homes and schools of 163 4- to 8-year-old children representing communities with different risks of exposure.The mean blood lead level (BLL) was 7.15 microg/dL; 20.5% of the children were found to have EBLL. Multivariable analysis found participants whose families owned fewer household items, ate canned food, or used the community water supply as their primary water source to have higher BLLs and likelihood of EBLLs. Distance < 0.5 mi from the landfill was the factor most strongly associated with increments in BLL (5.51 microg/dL, p < 0.0001) and likelihood of EBLL (OR = 4.71, p = 0.0093). Dust/soil lead was not significantly predictive of BLL/EBLL.Lead poisoning remains highly prevalent among school-age children in Kampala. Confirmatory studies are needed, but further efforts are indicated to limit lead exposure from the landfill, whether through water contamination or through another mechanism. Although African nations are to be lauded for the removal of lead from gasoline, this study serves as a reminder that other sources of exposure to this potent neurotoxicant merit ongoing attention.

    View details for DOI 10.1289/ehp.0901768

    View details for Web of Science ID 000278591300036

    View details for PubMedID 20194080

  • Effects of Externally Rated Job Demand and Control on Depression Diagnosis Claims in an Industrial Cohort AMERICAN JOURNAL OF EPIDEMIOLOGY Iennaco, J. D., Cullen, M. R., Cantley, L., Slade, M. D., Fiellin, M., Kasl, S. V. 2010; 171 (3): 303-311

    View details for DOI 10.1093/aje/kwp359

    View details for Web of Science ID 000273866000006

  • Effects of externally rated job demand and control on depression diagnosis claims in an industrial cohort. American journal of epidemiology DeSanto Iennaco, J., Cullen, M. R., Cantley, L., Slade, M. D., Fiellin, M., Kasl, S. V. 2010; 171 (3): 303-311


    This study examined whether externally rated job demand and control were associated with depression diagnosis claims in a heavy industrial cohort. The retrospective cohort sample consisted of 7,566 hourly workers aged 18-64 years who were actively employed at 11 US plants between January 1, 1996, and December 31, 2003, and free of depression diagnosis claims during an initial 2-year run-in period. Logistic regression analysis was used to model the effect of tertiles of demand and control exposure on depression diagnosis claims. Demand had a significant positive association with depression diagnosis claims in bivariate models and models adjusted for demographic (age, gender, race, education, job grade, tenure) and lifestyle (smoking status, body mass index, cholesterol level) variables (high demand odds ratio = 1.39, 95% confidence interval: 1.04, 1.86). Control was associated with greater risk of depression diagnosis at moderate levels in unadjusted models only (odds ratio = 1.47, 95% confidence interval: 1.12, 1.93), while low control, contrary to expectation, was not associated with depression. The effects of the externally rated demand exposure were lost with adjustment for location. This may reflect differences in measurement or classification of exposure, differences in depression diagnosis by location, or other location-specific factors.

    View details for DOI 10.1093/aje/kwp359

    View details for PubMedID 20035011

  • Reproductive Outcomes Among Male and Female Workers at an Aluminum Smelter JOURNAL OF OCCUPATIONAL AND ENVIRONMENTAL MEDICINE Sakr, C. J., Taiwo, O. A., Galusha, D. H., Slade, M. D., Fiellin, M. G., Bayer, F., Savitz, D. A., Cullen, M. R. 2010; 52 (2): 137-143


    Several adverse pregnancy outcomes were reported among female laboratory workers in a North American aluminum smelter. To determine whether these outcomes were associated with any occupational exposure at the plant, a cross-sectional survey was undertaken.Rates of miscarriage, premature singleton birth, and major congenital anomaly occurring during employment were compared with a reference group comprised of all pregnancies that occurred before employment.Among female workers, the excess of congenital anomalies among female laboratory workers that defined the initial cluster was observed, but no specific pattern was found.On the basis of these analyses, the increase in congenital anomalies could not be attributed to occupational exposures at the smelter nor could potential exposure likely explain the diverse anomalies described.

    View details for DOI 10.1097/JOM.0b013e3181cb59bc

    View details for Web of Science ID 000274491600004

    View details for PubMedID 20134342

  • Long-term follow-up of beryllium sensitized workers from a single employer BMC PUBLIC HEALTH Dugga, M., Deubner, D. C., Curtis, A. M., Cullen, M. R. 2010; 10


    Up to 12% of beryllium-exposed American workers would test positive on beryllium lymphocyte proliferation test (BeLPT) screening, but the implications of sensitization remain uncertain.Seventy two current and former employees of a beryllium manufacturer, including 22 with pathologic changes of chronic beryllium disease (CBD), and 50 without, with a confirmed positive test were followed-up for 7.4 +/-3.1 years.Beyond predicted effects of aging, flow rates and lung volumes changed little from baseline, while DLCO dropped 17.4% of predicted on average. Despite this group decline, only 8 subjects (11.1%) demonstrated physiologic or radiologic abnormalities typical of CBD. Other than baseline status, no clinical or laboratory feature distinguished those who clinically manifested CBD at follow-up from those who did not.The clinical outlook remains favorable for beryllium-sensitized individuals over the first 5-12 years. However, declines in DLCO may presage further and more serious clinical manifestations in the future. These conclusions are tempered by the possibility of selection bias and other study limitations.

    View details for DOI 10.1186/1471-2458-10-5

    View details for Web of Science ID 000274831600003

    View details for PubMedID 20047684

  • Work and its role in shaping the social gradient in health BIOLOGY OF DISADVANTAGE: SOCIOECONOMIC STATUS AND HEALTH Clougherty, J. E., Souza, K., Cullen, M. R. 2010; 1186: 102-124


    Adults with better jobs enjoy better health: job title was, in fact, the social gradient metric first used to study the relationship between social class and chronic disease etiology, a core finding now replicated in most developed countries. What has been less well proved is whether this correlation is causal, and if so, through what mechanisms. During the past decade, much research has been directed at these issues. Best evidence in 2009 suggests that occupation does affect health. Most recent research on the relationship has been directed at disentangling the pathways through which lower-status work leads to adverse health outcomes. This review focuses on six areas of recent progress: (1) the role of status in a hierarchical occupational system; (2) the roles of psychosocial job stressors; (3) effects of workplace physical and chemical hazard exposures; (4) evidence that work organization matters as a contextual factor; (5) implications for the gradient of new forms of nonstandard or "precarious" employment such as contract and shift work; and (6) emerging evidence that women may be impacted differently by adverse working conditions, and possibly more strongly, than men.

    View details for DOI 10.1111/j.1749-6632.2009.05338.x

    View details for Web of Science ID 000277908000007

    View details for PubMedID 20201870

  • Heart disease & the workplace INDIAN JOURNAL OF MEDICAL RESEARCH Cullen, M. R. 2009; 130 (4): 351-353

    View details for Web of Science ID 000272049900001

    View details for PubMedID 19942734

  • Invited Commentary: The Search for Preventable Causes of Cardiovascular Disease-Whither Work? AMERICAN JOURNAL OF EPIDEMIOLOGY Cullen, M. R. 2009; 169 (12): 1422-1425


    The incidence and mortality of the major cardiovascular disorders vary sharply by occupation, but this is usually attributed to broad socioeconomic factors; the contributions of physical and psychosocial stressors at work remain obscure or controversial. Review of the ongoing studies of cardiovascular disease in the United States in this issue of the Journal demonstrates that few have either collected sufficient occupational data or used these data in published analyses to address this issue. There are compelling reasons to study this issue, starting with the sheer magnitude of the occupational gradient and disease prevalence. If only 5%-15% prove causally linked to preventable factors, an enormous disease-control opportunity would present itself. Moreover, the most suspect work factors-job stress, fine particulate dust, heat, noise, and shiftwork-are highly prevalent in the US workforce. Thankfully, there is evidence that many of the large ongoing studies are moving toward enhancing their occupational data and using what they have already collected. However, because of the complexity of studying these relations, the better solution is not retrofitting but designing studies in the future that combine de novo the conceptual frameworks and technical skills of occupational and social epidemiologists with those of more biologically focused investigators.

    View details for DOI 10.1093/aje/kwp078

    View details for Web of Science ID 000266953700002

    View details for PubMedID 19429877

  • Healthcare for Obstructive Lung Disease in an Industrial Spirometry Surveillance Program JOURNAL OF OCCUPATIONAL AND ENVIRONMENTAL MEDICINE Gulati, M., Slade, M. D., Fiellin, M. G., Cullen, M. R. 2009; 51 (3): 336-342


    The efficacy of workplace spirometry surveillance programs is unclear. We examine whether aluminum industry workers with airflow obstruction (AO) received health care for obstructive lung disease.We performed a cross sectional analysis over 7 years of 6821 aluminum production workers. The primary outcome was the association between obstructive lung disease insurance claims and the presence of AO. We also examined whether the presence of claims was associated with increasing AO severity.Although workers with AO more frequently had claims, 60% of workers with AO, most frequently those with mild and borderline obstruction, had no claim.Workers with AO, particularly borderline and mild obstruction, frequently do not receive health care despite respiratory surveillance. Further investigation is needed to determine if workers with undiagnosed AO are symptomatic or have accelerated losses in lung function over time.

    View details for DOI 10.1097/JOM.0b013e3181954ae6

    View details for Web of Science ID 000264140300007

    View details for PubMedID 19225419

  • Sex Differences in Injury Patterns Among Workers in Heavy Manufacturing AMERICAN JOURNAL OF EPIDEMIOLOGY Taiwo, O. A., Cantley, L. F., Slade, M. D., Pollack, K. M., Vegso, S., Fiellin, M. G., Cullen, M. R. 2009; 169 (2): 161-166


    The objective of the study was to determine if female workers in a heavy manufacturing environment have a higher risk of injury compared with males when performing the same job and to evaluate sex differences in type or severity of injury. By use of human resources and incident surveillance data for the hourly population at 6 US aluminum smelters, injuries that occurred from January 1, 1996, through December 21, 2005, were analyzed. Multivariate logistic regression, adjusted for job, tenure, and age category, was used to calculate odds ratios and 95% confidence intervals for female versus male injury risk for all injuries, recordable injuries, and lost work time injuries. The analysis was repeated for acute injuries and musculoskeletal disorder-related injuries separately. Female workers in this industry have a greater risk for sustaining all forms of injury after adjustment for age, tenure, and standardized job category (odds ratio = 1.365, 95% confidence interval: 1.290, 1.445). This excess risk for female workers persisted when injuries were dichotomized into acute injuries (odds ratio = 1.2) and musculoskeletal disorder-related injuries (odds ratio = 1.1). This study provides evidence of a sex disparity in occupational injury with female workers at higher risk compared with their male counterparts in a heavy manufacturing environment.

    View details for DOI 10.1093/aje/kwn304

    View details for Web of Science ID 000262518200006

    View details for PubMedID 18996885

  • Skin Exposure to Aliphatic Polyisocyanates in the Auto Body Repair and Refinishing Industry: III. A Personal Exposure Algorithm ANNALS OF OCCUPATIONAL HYGIENE Liu, Y., Stowe, M. H., Bello, D., Sparer, J., Gore, R. J., Cullen, M. R., Redlich, C. A., Woskie, S. R. 2009; 53 (1): 33-40


    Isocyanate skin exposure may play an important role in sensitization and the development of isocyanate asthma, but such exposures are frequently intermittent and difficult to assess. Exposure metrics are needed to better estimate isocyanate skin exposures. The goal of this study was to develop a semiquantitative algorithm to estimate personal skin exposures in auto body shop workers using task-based skin exposure data and daily work diaries. The relationship between skin and respiratory exposure metrics was also evaluated.The development and results of respiratory exposure metrics were previously reported. Using the task-based data obtained with a colorimetric skin exposure indicator and a daily work diary, we developed a skin exposure algorithm to estimate a skin exposure index (SEI) for each worker. This algorithm considered the type of personal protective equipment (PPE) used, the percentage of skin area covered by PPE and skin exposures without and underneath the PPE. The SEI was summed across the day (daily SEI) and survey week (weekly average SEI) for each worker, compared among the job title categories and also compared with the respiratory exposure metrics.A total of 893 person-days was calculated for 232 workers (49 painters, 118 technicians and 65 office workers) from 33 auto body shops. The median (10th-90th percentile, maximum) daily SEI was 0 (0-0, 1.0), 0 (0-1.9, 4.8) and 1.6 (0-3.5, 6.1) and weekly average SEI was 0 (0-0.0, 0.7), 0.3 (0-1.6, 4.2) and 1.9 (0.4-3.0, 3.6) for office workers, technicians and painters, respectively, which were significantly different (P < 0.0001). The median (10th-90th percentile, maximum) daily SEI was 0 (0-2.4, 6.1) and weekly average SEI was 0.2 (0-2.3, 4.2) for all workers. A relatively weak positive Spearman correlation was found between daily SEI and time-weighted average (TWA) respiratory exposure metrics (microg NCO m(-3)) (r = 0.380, n = 893, P < 0.0001) and between weekly SEI and TWA respiratory exposure metrics (r = 0.482, n = 232, P < 0.0001).The skin exposure algorithm developed in this study provides task-based personal daily and weekly average skin exposure indices that are adjusted for the use of PPE. These skin exposure indices can be used to assess isocyanate exposure-response relationships.

    View details for DOI 10.1093/annhyg/men070

    View details for Web of Science ID 000262329300004

    View details for PubMedID 19011126

  • Workplace status and risk of hypertension among hourly and salaried aluminum manufacturing employees SOCIAL SCIENCE & MEDICINE Clougherty, J. E., Eisen, E. A., Slade, M. D., Kawachi, I., Cullen, M. R. 2009; 68 (2): 304-313


    An inverse relationship between workplace status and morbidity is well established; higher job status has been associated with reduced risks of heart disease, hypertension, and injury. Most research on job status, however, has focused on salaried populations, and it remains unclear whether job status operates similarly among hourly workers. Our objectives were to examine whether hourly status itself influences risk of hypertension after adjustment for socioeconomic confounders, and to explore the role of fine-scale job grade on hypertension incidence within hourly and salaried groups. We examined data for 14,999 aluminum manufacturing employees in 11 plants across the U.S., using logistic regression with adjustment for age, sex, race/ethnicity and other individual characteristics. Propensity score restriction was used to identify comparable groups of hourly and salaried employees, reducing confounding by sociodemographic characteristics. Job grade (coded 1 through 30, within hourly and salaried groups) was examined as a more refined measure of job status. Hourly status was associated with an increased risk of hypertension, after propensity restriction and adjustment for confounders. The observed effect of hourly status was stronger among women, although the propensity-restricted cohort was disproportionately male (96%). Among salaried workers, higher job grade was not consistently associated with decreased risk; among hourly employees, however, there was a significant trend, with higher job grades more protective against hypertension. Increasing the stringency of hypertension case criteria also increased the risk of severe or persistent hypertension for hourly employees.

    View details for DOI 10.1016/j.socscimed.2008.10.014

    View details for Web of Science ID 000263204900014

    View details for PubMedID 19027215

  • MARKETWATCH Who Chooses A Consumer-Directed Health Plan? HEALTH AFFAIRS Barry, C. L., Cullen, M. R., Galusha, D., Slade, M. D., Busch, S. H. 2008; 27 (6): 1671-1679
  • Who chooses a consumer-directed health plan? Health affairs Barry, C. L., Cullen, M. R., Galusha, D., Slade, M. D., Busch, S. H. 2008; 27 (6): 1671-1679


    Consumer-directed health plans (CDHPs) hold the promise of reining in health spending by giving consumers a greater stake in health care purchasing, yet little is known about employers' experience with these products. In examining the characteristics of those selecting a CDHP offered by one large employer, we found stronger evidence of selection than has been identified in prior research. Our findings suggest that in the context of plan choice, CDHPs may offer little opportunity to greatly lower employers' cost burden, and they highlight concerns about the potential for risk segmentation and the value of conferring preferential tax treatment to CDHPs.

    View details for DOI 10.1377/hlthaff.27.6.1671

    View details for PubMedID 18997225

  • The relationships between lost work time and duration of absence spells: Proposal for a payroll driven measure of absenteeism JOURNAL OF OCCUPATIONAL AND ENVIRONMENTAL MEDICINE Hill, J. J., Slade, M. D., Cantley, L., Vegso, S., Fiellin, M., Cullen, M. R. 2008; 50 (7): 840-851


    To propose a standard measure of absenteeism (the work lost rate [WLR]) be included in future research to facilitate understanding and allow for translation of findings between scientific disciplines.Hourly payroll data derived from "punch clock" reports was used to compare various measures of absenteeism used in the literature and the application of the proposed metric (N = 4000 workers).Unpaid hours and full absent days were highly correlated with the WLR (r = 0.896 to 0.898). The highest percentage of unpaid hours (lost work time) is captured by absence spells of 1 and 2 days duration.The proposed WLR metric captures: 1) The range and distribution of the individual WLRs, 2) the percentage of subjects with no unpaid hours, and 3) the population WLR and should be included whenever payroll data is used to measure absenteeism.

    View details for DOI 10.1097/JOM.0b013e31816b44dd

    View details for Web of Science ID 000257723700015

    View details for PubMedID 18617841

  • An examination of cancer epidemiology studies among populations living close to toxic waste sites ENVIRONMENTAL HEALTH Russi, M. B., Borak, J. B., Cullen, M. R. 2008; 7


    Toxic waste sites contain a broad range of suspected or confirmed human carcinogens, and remain a source of concern to many people, particularly those living in the vicinity of a site. Despite years of study, a consensus has not emerged regarding the cancer risk associated with such sites.We examined the published, peer-reviewed literature addressing cancer incidence or mortality in the vicinity of toxic waste sites between 1980 and 2006, and catalogued the methods employed by such studies.Nineteen studies are described with respect to eight methodological criteria. Most were ecological, with minimal utilization of hydrogeological or air pathway modeling. Many did not catalogue whether a potable water supply was contaminated, and very few included contaminant measurements at waste sites or in subjects' homes. Most studies did not appear to be responses to a recognized cancer mortality cluster. Studies were highly variable with respect to handling of competing risk factors and multiple comparisons.We conclude that studies to date have generated hypotheses, but have been of limited utility in determining whether populations living near toxic waste sites are at increased cancer risk.

    View details for DOI 10.1186/1476-069X-7-32

    View details for Web of Science ID 000257560900001

    View details for PubMedID 18578889

  • Organic solvent exposure and hearing loss in a cohort of aluminium workers OCCUPATIONAL AND ENVIRONMENTAL MEDICINE Rabinowitz, P. M., Galusha, D., Slade, M. D., Dixon-Ernst, C., O'Neill, A., Fiellin, M., Cullen, M. R. 2008; 65 (4): 230-235


    Organic solvent exposure has been shown to cause hearing loss in animals and humans. Less is known about the risk of hearing loss due to solvent exposures typically found in US industry. The authors performed a retrospective cohort study to examine the relationship between solvent exposure and hearing loss in US aluminium industry workers.A cohort of 1319 workers aged 35 years or less at inception was followed for 5 years. Linkage of employment, industrial hygiene and audiometric surveillance records allowed for estimation of noise and solvent exposures and hearing loss rates over the study period. Study subjects were classified as "solvent exposed" or not, on the basis of industrial hygiene records linked with individual job histories. High frequency hearing loss was modelled as both a continuous and a dichotomous outcome.Typical solvent exposures involved mixtures of xylene, toluene and/or methyl ethyl ketone (MEK). Recorded solvent exposure levels varied widely both within and between jobs. In a multivariate logistic model, risk factors for high frequency hearing loss included age (OR = 1.06, p = 0.004), hunting or shooting (OR = 1.35, p = 0.049), noisy hobbies (OR = 1.74, p = 0.01), baseline hearing level (OR = 1.04, p<0.001) and solvent exposure (OR = 1.87, p = 0.004). A multivariate linear regression analysis similarly found significant associations between high frequency hearing loss and age (p<0.001), hunting or shooting (p<0.001), noisy hobbies (p = 0.03), solvent exposure (p<0.001) and baseline hearing (p = 0.03).These results suggest that occupational exposure to organic solvent mixtures is a risk factor for high frequency hearing loss, although the data do not allow conclusions about dose-response relationships. Industries with solvent-exposed workers should include such workers in hearing conservation programs.

    View details for DOI 10.1136/oem.2006.031047

    View details for Web of Science ID 000254121000005

    View details for PubMedID 17567727

  • Beryllium sensitization in aluminum smelter workers JOURNAL OF OCCUPATIONAL AND ENVIRONMENTAL MEDICINE Taiwo, O. A., Slade, M. D., Cantley, L. F., Fiellin, M. G., Wesdock, J. C., Bayer, F. J., Cullen, M. R. 2008; 50 (2): 157-162


    To determine whether beryllium-related disease exists among aluminum smelter workers.A total of 1278 employees from four aluminum smelters determined to have significant beryllium exposure based on 5 years of sampling were invited to participate in medical surveillance that included a respiratory symptoms questionnaire, spirometry, and blood beryllium lymphocyte proliferation test.Of these, 734 employees participated in the program. Beryllium exposure from 965 personal samples ranged from 0.002 to 13.00 microg/m time-weighted average, with a median of 0.05 microg/m, geometric mean of 0.05 microg/m, and arithmetic mean of 0.22 microg/m. Only two employees had confirmed beryllium sensitization (0.27%).There is evidence of beryllium sensitization among aluminum smelter workers. When compared with beryllium-exposed workers in other industries, aluminum smelter workers had lower rates of sensitization. The low beryllium sensitization rate observed may be related to work practices and the properties of the beryllium found in this work environment.

    View details for DOI 10.1097/JOM.0b013e318161783f

    View details for Web of Science ID 000253217100008

    View details for PubMedID 18301172

  • Comparison of task-based exposure metrics for an epidemiologic study of isocyanate inhalation exposures among autobody shop workers JOURNAL OF OCCUPATIONAL AND ENVIRONMENTAL HYGIENE Woskie, S. R., Bello, D., Gore, R. J., Stowe, M. H., Eisen, E. A., Liu, Y., Sparer, J. A., Redlich, C. A., Cullen, M. R. 2008; 5 (9): 588-598


    Because many occupational epidemiologic studies use exposure surrogates rather than quantitative exposure metrics, the UMass Lowell and Yale study of autobody shop workers provided an opportunity to evaluate the relative utility of surrogates and quantitative exposure metrics in an exposure response analysis of cross-week change in respiratory function. A task-based exposure assessment was used to develop several metrics of inhalation exposure to isocyanates. The metrics included the surrogates, job title, counts of spray painting events during the day, counts of spray and bystander exposure events, and a quantitative exposure metric that incorporated exposure determinant models based on task sampling and a personal workplace protection factor for respirator use, combined with a daily task checklist. The result of the quantitative exposure algorithm was an estimate of the daily time-weighted average respirator-corrected total NCO exposure (microg/m(3)). In general, these four metrics were found to be variable in agreement using measures such as weighted kappa and Spearman correlation. A logistic model for 10% drop in FEV(1) from Monday morning to Thursday morning was used to evaluate the utility of each exposure metric. The quantitative exposure metric was the most favorable, producing the best model fit, as well as the greatest strength and magnitude of association. This finding supports the reports of others that reducing exposure misclassification can improve risk estimates that otherwise would be biased toward the null. Although detailed and quantitative exposure assessment can be more time consuming and costly, it can improve exposure-disease evaluations and is more useful for risk assessment purposes. The task-based exposure modeling method successfully produced estimates of daily time-weighted average exposures in the complex and changing autobody shop work environment. The ambient TWA exposures of all of the office workers and technicians and 57% of the painters were found to be below the current U.K. Health and Safety Executive occupational exposure limit (OEL) for total NCO of 20 microg/m(3). When respirator use was incorporated, all personal daily exposures were below the U.K. OEL.

    View details for DOI 10.1080/15459620802275429

    View details for Web of Science ID 000259085700003

    View details for PubMedID 18615291

  • A chitinase-like protein in the lung and circulation of patients with severe asthma NEW ENGLAND JOURNAL OF MEDICINE Chupp, G. L., Lee, C. G., Jarjour, N., Shim, Y. M., Holm, C. T., He, S., Dziura, J. D., Reed, J., Coyle, A. J., Kiener, P., Cullen, M., Grandsaigne, M., Dombret, M., Aubier, M., Pretolani, M., Elias, J. A. 2007; 357 (20): 2016-2027


    The evolutionarily conserved 18-glycosyl-hydrolase family contains true chitinases and chitinase-like proteins that lack enzymatic activity. Acidic mammalian chitinase has recently been associated with animal models of asthma. The related chitinase-like protein, YKL-40 (also called human cartilage glycoprotein 39 [HCgp-39] and chitinase 3-like 1), can be readily measured in the serum. However, its relationship to asthma has not been evaluated.We quantified serum YKL-40 levels in three cohorts of patients with asthma--one recruited from the patient population at Yale University, one from the University of Paris, and one from the University of Wisconsin--as well as in controls from the surrounding communities. In the Paris cohort, immunohistochemical analysis and morphometric quantitation were used to evaluate the locus of expression of YKL-40 in the lung. The clinical characteristics of the patients with high serum or lung YKL-40 levels were also evaluated.Serum YKL-40 levels were significantly elevated in patients with asthma as compared with controls. In the Paris cohort, lung YKL-40 levels were elevated and were correlated with circulating YKL-40 levels (r=0.55, P<0.001) and with airway remodeling (measured as the thickness of the subepithelial basement membrane) (r=0.51, P=0.003). In all three cohorts, serum YKL-40 levels correlated positively with the severity of asthma and inversely with the forced expiratory volume in 1 second. Patients with elevated levels of YKL-40 had significantly more frequent rescue-inhaler use, greater oral corticosteroid use, and a greater rate of hospitalization than patients with lower levels.YKL-40 is found in increased quantities in the serum and lungs in a subgroup of patients with asthma, in whom expression of chitinase in both compartments correlates with the severity of asthma. The recovery of YKL-40 from these patients indicates either a causative or a sentinel role for this molecule in asthma.

    View details for Web of Science ID 000250894500004

    View details for PubMedID 18003958

  • Air emissions from wagerup alumina refinery and community symptoms: An environmental case study JOURNAL OF OCCUPATIONAL AND ENVIRONMENTAL MEDICINE Donoghue, A. M., Cullen, M. R. 2007; 49 (9): 1027-1039


    Commissioning of a liquor burner at Wagerup alumina refinery gave rise to complaints of malodor and irritation among employees. Subsequently, community members complained about odor and various health issues. Some employees and community members were diagnosed by general practitioners as having multiple chemical sensitivity. After implementation of emission controls, the situation improved; however, community concerns lingered. This paper describes this experience and summarizes several recent investigations including air dispersion modeling, health risk assessment, ambient air quality monitoring, and complaints analyses. It is concluded that refinery emissions currently present negligible risks of acute or chronic health effects including cancer. Communication of these findings has been generally well received, but modifying the perception of risk among some elements of the community has been difficult. Organizations need to effectively address both technical and perception of risk issues.

    View details for DOI 10.1097/JOM.0b01e31814a5c6f

    View details for Web of Science ID 000249590200011

    View details for PubMedID 17848859

  • Use of employer administrative Databases to identify systematic causes of injury in aluminum manufacturing AMERICAN JOURNAL OF INDUSTRIAL MEDICINE Pollack, K. M., Agnew, J., Slade, M. D., Cantley, L., Taiwo, O., Vegso, S., Sircar, K., Cullen, M. R. 2007; 50 (9): 676-686


    Employer administrative files are an underutilized source of data in epidemiologic studies of occupational injuries.Personnel files, occupational health surveillance data, industrial hygiene data, and a real-time incident and injury management system from a large multi-site aluminum manufacturer were linked deterministically. An ecological-level measure of physical job demand was also linked. This method successfully created a database containing over 100 variables for 9,101 hourly employees from eight geographically dispersed U.S. plants.Between 2002 and 2004, there were 3,563 traumatic injuries to 2,495 employees. The most common injuries were sprain/strains (32%), contusions (24%), and lacerations (14%). A multivariable logistic regression model revealed that physical job demand was the strongest predictor of injury risk, in a dose dependent fashion. Other strong predictors of injury included female gender, young age, short company tenure and short time on current job.Employer administrative files are a useful source of data, as they permit the exploration of risk factors and potential confounders that are not included in many population-based surveys. The ability to link employer administrative files with injury surveillance data is a valuable analysis strategy for comprehensively studying workplace injuries, identifying salient risk factors, and targeting workforce populations disproportionately affected.

    View details for DOI 10.1002/ajim.20493

    View details for Web of Science ID 000249250700005

    View details for PubMedID 17676586

  • Extended work hours and risk of acute occupational injury: A case-crossover study of workers in manufacturing AMERICAN JOURNAL OF INDUSTRIAL MEDICINE Vegso, S., Cantley, L., Slade, M., Taiwo, O., Sircar, K., Rabinowitz, P., Fiellin, M., Russi, M. B., Cullen, M. R. 2007; 50 (8): 597-603


    This study was designed to determine whether injury risk among manufacturing workers was related to hours worked during the previous week.A case-crossover design was utilized to contrast hours worked prior to an injury shift with those worked prior to a non-injury shift for hourly workers. Paired t-tests were used to determine significance of the difference. Conditional logistic regression was used to assess dose-response.Hours worked prior to injury significantly exceeded hours during the control week. Workers who worked more than 64 hr in the week before the shift had an 88% excess risk compared to those who worked 40 hr or fewer, P < 0.05.The study provides evidence that injury risk is related to time worked during the previous week. Control of overtime in manufacturing may reduce risk of worker injury.

    View details for DOI 10.1002/ajim.20486

    View details for Web of Science ID 000248519300006

    View details for PubMedID 17594716

  • Longitudinal study of serum lipids and liver enzymes in workers with occupational exposure to ammonium perfluorooctanoate JOURNAL OF OCCUPATIONAL AND ENVIRONMENTAL MEDICINE Sakr, C. J., Leonard, R. C., Kreckmann, K. H., Slade, M. D., Cullen, M. R. 2007; 49 (8): 872-879


    To examine the relationship between serum perfluorooctanoate (PFOA), a biomarker of ammonium perfluorooctanoate exposure, and lipids and liver enzymes.We conducted a longitudinal study on 454 workers and used mixed models to examine the relationship between serum PFOA and lipids and liver enzymes.One part per million (ppm) increase in serum PFOA was associated with a 1.06 mg/dL increase in total cholesterol, but was not associated with changes in triglycerides or other lipoproteins, after adjusting for potential confounders. Serum PFOA was also associated with total bilirubin (0.008 mg/dL decline/ppm) and serum aspartate aminotransferase (0.35 units increase/ppm) but not with the other liver enzymes.These medical surveillance data collected on workers for up to 25 years contributes useful information on the effects of ammonium perfluorooctanoate exposure on human liver and lipid chemistry.

    View details for DOI 10.1097/JOM.0b013e318124a93f

    View details for Web of Science ID 000248772000008

    View details for PubMedID 17693785

  • Association between body mass index and acute traumatic workplace injury in hourly manufacturing employees AMERICAN JOURNAL OF EPIDEMIOLOGY Pollack, K. M., Sorock, G. S., Slade, M. D., Cantley, L., Sircar, K., Taiwo, O., Cullen, M. R. 2007; 166 (2): 204-211


    In this study, the authors examined the distribution and odds of occupational injury among hourly employees of a US aluminum manufacturing company by body mass index (weight (kg)/height (m)(2)). In 2002, height and weight data on 7,690 workers at eight plants were extracted from medical records from annual physicals, and body mass index was categorized. Information on traumatic injuries recorded between January 1, 2002, and December 31, 2004, was obtained from a company injury surveillance system. Twenty-nine percent of the employees (n = 2,221) sustained at least one injury. Approximately 85 percent of injured workers were classified as overweight or obese. The odds of injury in the highest obesity group as compared with the ideal body mass index group were 2.21 (95% confidence interval: 1.34, 3.53), after adjustment for sex, age, education, smoking, physical demands of the job, plant process and location, time since hire, time in the job, and significant interaction terms. Injuries to the leg or knee were especially prevalent among members of this very obese group. Research findings support an association between body mass index and traumatic workplace injuries among manufacturing employees. Workplace safety personnel might consider adding policies or programs that address weight reduction and maintenance as part of ongoing comprehensive workplace safety strategies.

    View details for DOI 10.1093/aje/kwm058

    View details for Web of Science ID 000247872800011

    View details for PubMedID 17485732

  • Skin exposure to aliphatic Polyisocyanates in the auto body repair and refinishing industry: A qualitative assessment ANNALS OF OCCUPATIONAL HYGIENE Liu, Y., Bell, D., Sparer, J. A., Stowe, M. H., Gore, R. J., Woskii, S. R., Cullen, M. R., Redlich, C. A. 2007; 51 (5): 429-439


    Although respiratory exposures have been the primary concern with isocyanates, skin exposure also can occur and may contribute to sensitization and asthma. Methodologies to assess isocyanate skin exposure in the workplace are limited and skin exposure data scarce. The goals of this study were (i) to evaluate and validate the isocyanate colorimetric indicators against a quantitative assay, (ii) to evaluate the extent of isocyanate surface contamination and skin exposure among auto body shop workers and (iii) to evaluate isocyanate skin exposure determinants.The colorimetric indicators were compared with a high-performance liquid chromatography (HPLC) quantitative assay based on the National Institute for Occupational Safety and Health Method 5525 using paired laboratory sampling. The colorimetric indicators were then used to assess surface contamination and skin exposure to aliphatic isocyanates in 35 auto body shops and 124 workers as part of an epidemiologic study. The positive sample rate was calculated for various surfaces, body parts and tasks. The color intensity of the colorimetric indicators was rated on a scale 0 (yellow color) to 5 (deep red). Side-by-side comparisons of the qualitative method with the quantitative HPLC assay were also performed in the field using paired samples.Laboratory and field evaluation validated use of the colorimetric indicators. The rate of positive surface samples for isocyanates was 46% (n = 145/313). Thirty-four percent (73/216) of samples were positive for unprotected skin and 20% (n = 22/111) for skin under latex gloves. The highest positive rate observed on skin samples was obtained after paint mixing and spraying tasks. The colorimetric indicators were highly specific for isocyanates, but false negatives occurred when compared with the more sensitive HPLC quantitative assay. The presence of surface contamination and the performance of paint-related tasks were the major determinants of isocyanate skin exposure.This study documents extensive surface contamination and skin exposure, including under gloves, to aliphatic polyisocyanates during painting and paint mixing tasks in auto body shop workers. Contaminated surfaces and aerosol deposition during spray painting may both contribute to skin exposure. The colorimetric indicator is a quick, practical and low-cost, but not highly sensitive, industrial hygiene tool to detect isocyanate surface contamination and skin exposures following the use of isocyanate-containing products.

    View details for DOI 10.1093/annhyg/mem021

    View details for Web of Science ID 000249763200001

    View details for PubMedID 17602207

  • Skin exposure to isocyanates: Reasons for concern ENVIRONMENTAL HEALTH PERSPECTIVES Bello, D., Herrick, C. A., Smith, T. J., Woskie, S. R., Streicher, R. P., Cullen, M. R., Liu, Y., Redlich, C. A. 2007; 115 (3): 328-335


    Isocyanates (di- and poly-), important chemicals used worldwide to produce polyurethane products, are a leading cause of occupational asthma. Respiratory exposures have been reduced through improved hygiene controls and the use of less-volatile isocyanates. Yet isocyanate asthma continues to occur, not uncommonly in settings with minimal inhalation exposure but opportunity for skin exposure. In this review we evaluate the potential role of skin exposure in the development of isocyanate asthma.We reviewed the published animal and human literature on isocyanate skin-exposure methods, workplace skin exposure, skin absorption, and the role of skin exposure in isocyanate sensitization and asthma.We selected relevant articles from computerized searches on Medline, U.S. Environmental Protection Agency, Occupational Safety and Health Administration, National Institute for Occupational Safety and Health, and Google databases using the keywords "isocyanate," "asthma," "skin," "sensitization," and other synonymous terms, and our own extensive collection of isocyanate publications.Isocyanate production and use continues to increase as the polyurethane industry expands. There is substantial opportunity for isocyanate skin exposure in many work settings, but such exposure is challenging to quantify and continues to be underappreciated. Isocyanate skin exposure can occur at work, even with the use of personal protective equipment, and may also occur with consumer use of certain isocyanate products. In animals, isocyanate skin exposure is an efficient route to induce sensitization, with subsequent inhalation challenge resulting in asthma-like responses. Several lines of evidence support a similar role for human isocyanate skin exposure, namely, that such exposure occurs and can contribute to the development of isocyanate asthma in certain settings, presumably by inducing systemic sensitization.Integrated animal and human research is needed to better understand the role of skin exposure in human isocyanate asthma and to improve diagnosis and prevention. In spite of substantial research needs, sufficient evidence already exists to justify greater emphasis on the potential risks of isocyanate skin exposure and the importance of preventing such exposures at work and during consumer use of certain isocyanate products.

    View details for DOI 10.1289/ehp.9557

    View details for Web of Science ID 000244651500022

    View details for PubMedID 17431479

  • Do ambient noise exposure levels predict hearing loss in a modern industrial cohort? OCCUPATIONAL AND ENVIRONMENTAL MEDICINE Rabinowitz, P. M., Galusha, D., Dixon-Ernst, C., Slade, M. D., Cullen, M. R. 2007; 64 (1): 53-59


    Much of what is known about the exposure-response relationship between occupational noise exposures and hearing loss comes from cross-sectional studies conducted before the widespread implementation of workplace hearing conservation programmes. Little is known about the current relationship of ambient noise exposure measurements to hearing loss risk.To examine the relationship between rates of high frequency hearing loss and measured levels of noise exposure in a modern industrial workforce.Ten-year hearing loss rates were determined for 6217 employees of an aluminium manufacturing company. Industrial hygiene and human resources records allowed for reconstruction of individual noise exposures. Hearing loss rates were compared to ANSI 3.44 predictions based on age and noise exposure. Associations between hearing loss, noise exposure, and covariate risk factors were assessed using multivariate regression.Workers in higher ambient noise jobs tended to experience less high frequency hearing loss than co-workers exposed at lower noise levels. This trend was also seen in stratified analyses of white males and non-hunters. At higher noise exposure levels, the magnitude of hearing loss was less than predicted by ANSI 3.44 formulae. There was no indication that a healthy worker effect could explain these findings. The majority of 10 dB standard threshold shifts (STS) occurred in workers whose calculated ambient noise exposures were less than or equal to 85 dBA.In this modern industrial cohort, hearing conservation efforts appear to be reducing hearing loss rates, especially at higher ambient noise levels. This could be related to differential use of hearing protection. The greatest burden of preventable occupational hearing loss was found in workers whose noise exposure averaged 85 dBA or less. To further reduce rates of occupational hearing loss, hearing conservation programmes may require innovative approaches targeting workers with noise exposures close to 85 dBA.

    View details for DOI 10.1136/oem.2005.025924

    View details for Web of Science ID 000243043100012

    View details for PubMedID 16973736

  • Effects of a cost-sharing exemption on use of preventive services at one large employer HEALTH AFFAIRS Busch, S. H., Barry, C. L., Vegso, S. J., Sindelar, J. L., Cullen, M. R. 2006; 25 (6): 1529-1536


    In 2004, Alcoa introduced a new health benefit for a portion of its workforce, which eliminated cost sharing for preventive care while increasing cost sharing for many other services. In this era of increased consumerism, Alcoa's benefit redesign constituted an effort to reduce health care costs while preserving use of targeted services. Taking advantage of a unique natural experiment, we find that Alcoa was able to maintain rates of preventive service use. This evidence suggests that differential cost sharing can be used to preserve the use of critical health care services.

    View details for DOI 10.1377/hlthaff.25.6.1529

    View details for Web of Science ID 000242033300011

    View details for PubMedID 17102176

  • Use of medical insurance claims data for occupational health research JOURNAL OF OCCUPATIONAL AND ENVIRONMENTAL MEDICINE Cullen, M. R., Vegso, S., Cantley, L., Galusha, D., Rabinowitz, P., Oyebode, T., Fiellin, M., Wennberg, D., Iennaco, J., Slade, M. D., Sircar, K. 2006; 48 (10): 1054-1061


    The objective of this study was to demonstrate that health claims data, widely available due to the unique nature of the U.S. healthcare system, can be linked to other relevant databases such as personnel files and exposure data maintained by large employers. These data offer great potential for occupational health research.In this article, we describe the process for linking claims data to industrial hygiene exposure data and personnel files of a single large employer to conduct epidemiologic research.Our results demonstrate the ability to replicate previously published findings using commonly maintained data sets and illustrate methodological issues that may arise as newer hypotheses are tested in this way.Health claims files offer potential for epidemiologic research in the United States, although the full extent and guidelines for successful application await further clarification through empiric research.

    View details for DOI 10.1097/01.jom.0000241049.23093.a4

    View details for Web of Science ID 000241301100014

    View details for PubMedID 17033505

  • Trends in the prevalence of hearing loss among young adults entering an industrial workforce 1985 to 2004 EAR AND HEARING Rabinowitz, P. M., Slade, M. D., Galusha, D., Dixon-Ernst, C., Cullen, M. R. 2006; 27 (4): 369-375


    Studies have suggested that hearing loss due to recreational noise exposure may be on the rise among adolescents and young adults. This study examines whether the hearing status of young US adults entering an industrial workforce has worsened over the past 20 yr.The baseline audiograms of 2526 individuals ages 17 to 25 beginning employment at a multisite US corporation between 1985 and 2004 were analyzed to determine the yearly prevalence of hearing loss.Approximately 16% of the young adults in the sample had high frequency hearing loss (defined as hearing thresholds greater than 15 dB in either ear at 3,4, or 6 kHz). In a linear regression model, this prevalence decreased over the 20-yr period (odds ratio (OR) = 0.96, 95% confidence interval (CI): 0.94, 0.99). Almost 20% of subjects had audiometric "notches" consistent with noise exposure; this rate remained constant over the 20 yr, as did the prevalence (5%) of low frequency hearing loss.These results indicate that despite concern about widespread recreational noise exposures, the prevalence of hearing loss among a group of young US adults has not significantly increased over the past two decades.

    View details for Web of Science ID 000238933500005

    View details for PubMedID 16825886

  • Respiratory protection from isocyanate exposure in the autobody repair and refinishing industry JOURNAL OF OCCUPATIONAL AND ENVIRONMENTAL HYGIENE Liu, Y. C., Stowe, M. H., Bello, D., Woskie, S. R., Sparer, J., Gore, R., Youngs, F., Cullen, M. R., Redlich, C. A. 2006; 3 (5): 234-249


    This study, part of the Survey of Painters and Repairers of Auto bodies by Yale (SPRAY), evaluated the effectiveness of respiratory protection against exposure to aliphatic polyisocyanates. A total of 36 shops were assessed for respiratory protection program completeness; 142 workers were measured for respirator fit factor (FF) using PortaCount Plus respirator fit tester. Twenty-two painters from 21 shops were sampled using NIOSH method 5525 to determine the workplace protection factor (WPF) of negative pressure, air-purifying half-facepiece respirators equipped with organic vapor cartridges and paint prefilters during spray-painting and priming activities. Only 11 shops (30%) had written respiratory protection programs. Eighty percent of all fit tested workers passed the test on the first try with FF >or= 100, and 92% passed the second test after respirator use training. Overall geometric mean (GM) FF was 1012 for all fit tested workers. Significant differences on pass rate (92% vs. 72%) and on FF (1990 vs. 736) were found between previously fit tested workers vs. nontested workers. Twenty-nine WPF samples were collected. The outside facepiece GM concentration of total isocyanate group (NCO) was 378.4 micro g NCO/m(3) with 96% concentrations exceeding the U.K. short-term exposure limit, 70 micro g NCO/m(3), but no in-facepiece concentrations exceeded the limit. The GM WPF of total NCO was 319 (GSD 4) and the 5th percentile was 54. WPF of total NCO was positively correlated with the duration of painting task. FF positively correlated with WPF when FF was 450. We conclude that negative pressure, air-purifying half-facepiece respirators equipped with organic vapor cartridges and paint prefilters provide effective protection against isocyanate exposure in spray and priming operations if workers are properly trained and fitted.

    View details for DOI 10.1080/15459620600628704

    View details for Web of Science ID 000237166900003

    View details for PubMedID 16574607

  • Evidence for excess colorectal cancer incidence among asbestos-exposed men in the beta-carotene and retinol efficacy trial AMERICAN JOURNAL OF EPIDEMIOLOGY Aliyu, O. A., Cullen, M. R., Barnett, M. J., Balmes, J. R., Cartmel, B., Redlich, C. A., Brodkin, C. A., Barnhart, S., Rosenstock, L., Israel, L., Goodman, G. E., Thornquist, M. D., Omenn, G. S. 2005; 162 (9): 868-878


    The relation between asbestos exposure and colorectal cancer remains controversial. The authors of this 1984-2004 US study examined the association among 3,897 occupationally exposed participants in the Beta-Carotene and Retinol Efficacy Trial (CARET) for chemoprevention of lung cancer, followed prospectively for 10-18 years. When a Cox stratified proportional hazards model was used, risks of colorectal cancer were elevated among male heavy smokers exposed to asbestos. Their relative risk was 1.36 (95% confidence interval: 0.96, 1.93) when compared with that for CARET heavy smokers not exposed to asbestos, after adjusting for age, smoking history, and intervention arm. The presence of asbestos-induced pleural plaques at baseline was associated with a relative risk of 1.54 (95% confidence interval: 0.99, 2.40); colorectal cancer risk also increased with worsening pulmonary asbestosis (p = 0.03 for trend). A dose-response trend based on years of asbestos exposure was less evident. Nonetheless, these data suggest that colorectal cancer risk is elevated among men occupationally exposed to asbestos, especially those with evidence of nonmalignant asbestos-associated radiographic changes.

    View details for DOI 10.1093/aje/kwi285

    View details for Web of Science ID 000232745900009

    View details for PubMedID 16177148

  • Changes in cholesterol and triglyceride concentrations in the Vanguard population of the Carotene and Retinol Efficacy Trial (CARET) EUROPEAN JOURNAL OF CLINICAL NUTRITION Cartmel, B., Dziura, J., Cullen, M. R., Vegso, S., Omenn, G. S., Goodman, G. E., Redlich, C. A. 2005; 59 (10): 1173-1180


    The Beta-Carotene and Retinol Efficacy Trial (CARET) was terminated 21 months ahead of schedule due to an excess of lung cancers. Deaths from cardiovascular disease also increased (relative risk=1.26 (95% confidence interval (CI) 0.99-1.61)) in the group assigned to a combination of 30 mg beta-carotene and 25 000 IU retinyl palmitate (vitamin A) daily. The basis for increased cardiovascular mortality is unexplained.We analyzed data on serum lipids, available for 1474 CARET Vanguard participants who were enrolled in the two CARET pilot studies and transitioned to the Vanguard study. Total cholesterol and triglycerides were measured 2 months prior to, 4 and 12 months following randomization, and annually thereafter for up to 7 y.In the asbestos-exposed pilot (N = 816), participants were assigned to beta-carotene and retinol or to placebo; in the smokers pilot (N = 1029), participants were assigned to beta-carotene, retinol, a combination, or placebo.Serum cholesterol showed a decline over time in both arms; serum triglycerides had a continuous decline over time in the placebo arm, but an initial increase that persisted in the active arm. Both serum cholesterol concentrations (P < 0.0003) and serum triglycerides (P < 0.0001) were significantly higher in the participants receiving vitamin A and/or a combination of vitamin A and beta-carotene (n = 863) as compared to the placebo group (n = 611). Those in this active intervention group had an average cholesterol concentration 5.3 mg/dl (0.137 mmol/l) higher than those in the placebo arm.The differences in cholesterol and triglyceride concentrations between the groups following randomization may account in part for the unexpected excess in cardiovascular deaths seen in the active intervention arm of CARET.

    View details for DOI 10.1038/sj.ejcn.1602229

    View details for Web of Science ID 000232318200011

    View details for PubMedID 16015255

  • A laboratory investigation of the effectiveness of various skin and surface decontaminants for aliphatic polyisocyanates JOURNAL OF ENVIRONMENTAL MONITORING Bello, D., Woskie, S. R., Streicher, R. P., Stowe, M. H., Sparer, J., Redlich, C. A., Cullen, M. R., Liu, Y. C. 2005; 7 (7): 716-721


    Isocyanates may cause contact dermatitis and respiratory sensitization leading to asthma. Dermal exposure to aliphatic isocyanates in auto body shops is very common. However, little is known about the effectiveness of available commercial products used for decontaminating aliphatic polyisocyanates. This experimental study evaluated the decontamination effectiveness of aliphatic polyisocyanates for several skin and surface decontaminants available for use in the auto body industry. The efficiency of two major decontamination mechanisms, namely (i) consumption of free isocyanate groups via chemical reactions with active hydrogen components of the decontaminant and (ii) physical removal processes such as dissolution were studied separately for each decontaminant. Considerable differences were observed among surface decontaminants in their rate of isocyanate consumption, of which those containing free amine groups performed the best. Overall, Pine-Sol(R) MEA containing monoethanolamine was the most efficient surface decontaminant, operating primarily via chemical reaction with the isocyanate group. Polypropylene glycol (PPG) had the highest physical removal efficiency and the lowest reaction rate with isocyanates. All tested skin decontaminants performed similarly, accomplishing decontamination primarily via physical processes and removing 70-80% of isocyanates in one wiping. Limitations of these skin decontaminants are discussed and alternatives presented. In vitro testing using animal skins and in vivo testing with field workers are being conducted to further assess the efficiency and identify related determinants.

    View details for DOI 10.1039/b503807c

    View details for Web of Science ID 000230893900010

    View details for PubMedID 15986052

  • Predictors of lung cancer among asbestos-exposed men in the beta-carotene and retinol efficacy trial AMERICAN JOURNAL OF EPIDEMIOLOGY Cullen, M. R., Barnett, M. J., Balmes, J. R., Cartmel, B., Redlich, C. A., Brodkin, C. A., Barnhart, S., Rosenstock, L., Goodman, G. E., HAMMAR, S. P., Thornquist, M. D., Omenn, G. S. 2005; 161 (3): 260-270


    Despite numerous published studies, debate continues regarding the risk of developing lung cancer among men exposed occupationally to asbestos, particularly those without radiographic or functional evidence of asbestosis. The beta-Carotene and Retinol Efficacy Trial (CARET), a study of vitamin supplementation for chemoprevention of lung cancer, has followed 4,060 heavily exposed US men for 9-17 years. Lung cancer incidence for 1989-2002 was analyzed using a stratified proportional hazards model. The study confirmed excessive rates of lung cancer among men with radiographic asbestosis. Comparison of study arms revealed a strong, unanticipated synergy between radiographic profusion category and the active intervention. In the large subgroup of men with normal lung parenchyma on chest radiograph at baseline, there was evidence of exposure-related lung cancer risk: Men with more than 40 years' exposure in high-risk trades had a risk approximately fivefold higher than men with 5-10 years, after adjustment for covariates. The effect in these men was independent of study intervention arm, but pleural plaques on the baseline radiograph and abnormal baseline flow rate were strong independent predictors of subsequent lung cancer. Residual confounding by subclinical asbestosis, exposure to unmeasured lung carcinogens, or differences in smoking are unlikely to explain these observations better than a carcinogenic effect of asbestos per se.

    View details for DOI 10.1093/aje/kwi034

    View details for Web of Science ID 000226604900007

    View details for PubMedID 15671258

  • Advancing worker health and safety in the developing world JOURNAL OF OCCUPATIONAL AND ENVIRONMENTAL MEDICINE Rosenstock, L., Cullen, M. R., Fingerhut, M. 2005; 47 (2): 132-136


    Working conditions in the developing world seldom meet the minimum standards required by international agencies. This article addresses some of the major obstacles to occupational and environmental health and suggests methods by which they can be overcome.International agencies such as the World Health Organization (WHO) and the International Labor Organization (ILO) offer a number of programs that address the problem.The results of international efforts to date have been disappointing. There is a need for renewed efforts on the part of international agencies and the developed countries.Occupational health and safety can be advanced in the developing world with modest funding of innovative programs.

    View details for DOI 10.1097/01.jom.0000152919.70232.84

    View details for Web of Science ID 000227078200004

    View details for PubMedID 15706172

  • The beta-carotene and retinol efficacy trial: Incidence of lung cancer and cardiovascular disease mortality during 6-year follow-up after stopping beta-carotene and retinol supplements JOURNAL OF THE NATIONAL CANCER INSTITUTE Goodman, G. E., Thornquist, M. D., Balmes, J., Cullen, M. R., MEYSKENS, F. L., Omenn, G. S., Valanis, B., Williams, J. H. 2004; 96 (23): 1743-1750


    The Beta-Carotene and Retinol Efficacy Trial (CARET) tested the effect of daily beta-carotene (30 mg) and retinyl palmitate (25,000 IU) on the incidence of lung cancer, other cancers, and death in 18,314 participants who were at high risk for lung cancer because of a history of smoking or asbestos exposure. CARET was stopped ahead of schedule in January 1996 because participants who were randomly assigned to receive the active intervention were found to have a 28% increase in incidence of lung cancer, a 17% increase in incidence of death and a higher rate of cardiovascular disease mortality compared with participants in the placebo group.After the intervention ended, CARET participants returned the study vitamins to their study center and provided a final blood sample. They continue to be followed annually by telephone and mail self-report. Self-reported cancer endpoints were confirmed by review of pathology reports, and death endpoints were confirmed by review of death certificates. All statistical tests were two-sided.With follow-up through December 31, 2001, the post-intervention relative risks of lung cancer and all-cause mortality for the active intervention group compared with the placebo group were 1.12 (95% confidence interval [CI] = 0.97 to 1.31) and 1.08 (95% CI = 0.99 to 1.17), respectively. Smoothed relative risk curves for lung cancer incidence and all-cause mortality indicated that relative risks remained above 1.0 throughout the post-intervention follow-up. By contrast, the relative risk of cardiovascular disease mortality decreased rapidly to 1.0 after the intervention was stopped. During the post-intervention phase, females had larger relative risks of lung cancer mortality (1.33 versus 1.14; P = .36), cardiovascular disease mortality (1.44 versus 0.93; P = .03), and all-cause mortality (1.37 versus 0.98; P = .001) than males.The previously reported adverse effects of beta-carotene and retinyl palmitate on lung cancer incidence and all-cause mortality in cigarette smokers and individuals with occupational exposure to asbestos persisted after drug administration was stopped although they are no longer statistically significant. Planned subgroup analyses suggest that the excess risks of lung cancer were restricted primarily to females, and cardiovascular disease mortality primarily to females and to former smokers.

    View details for DOI 10.1093/jnci/djh320

    View details for Web of Science ID 000225480800007

    View details for PubMedID 15572756

  • Variable response to longterm corticosteroid therapy in chronic beryllium disease CHEST Sood, A., Beckett, W. S., Cullen, M. R. 2004; 126 (6): 2000-2007


    Chronic beryllium disease (CBD) shares many of its characteristics with sarcoidosis and is often treated with corticosteroids. There is limited available literature regarding the effect of long-term corticosteroid therapy on the natural history of CBD.We conducted an observational retrospective study of six patients with CBD who received prolonged corticosteroid treatment with a mean pulmonary function test follow-up period of 10.1 years. Five of the six patients were exposed to beryllium at the same workplace. The diagnosis in four of the six cases was confirmed by a positive beryllium lymphocyte proliferation test result on blood or BAL fluid. Periodic pulmonary function tests were analyzed in relation to removal from beryllium exposure and treatment with corticosteroids.Two broad patterns of response were noted in these patients. The first pattern seen in two patients showed no improvement in FVC or diffusion capacity of the lung for carbon monoxide (Dlco) with corticosteroids. However, a significant improvement in these parameters was noted on cessation of beryllium exposure in one of the two patients. The second pattern showed an initial improvement in FVC and Dlco with corticosteroids, which was not sustained. An improvement was noted on stopping beryllium exposure.The response to long-term corticosteroids in CBD, quite like that in sarcoidosis, is variable. Significant lung function improvement may be seen following cessation of beryllium exposure.

    View details for Web of Science ID 000225754900047

    View details for PubMedID 15596705

  • Polyisocyanates in occupational environments: A critical review of exposure limits and metrics AMERICAN JOURNAL OF INDUSTRIAL MEDICINE Bello, D., Woskie, S. R., Streicher, R. P., Liu, Y. C., Stowe, M. H., Eisen, E. A., Ellenbecker, M. J., Sparer, J., Youngs, F., Cullen, M. R., Redlich, C. A. 2004; 46 (5): 480-491


    Determination of polyisocyanates is important because they are a major contributor of exposure to the isocyanate functional group in many workplace environments and are capable of inducing sensitization and asthma. However, with multiple different measurement metrics in use, comparison of isocyanate exposure data between studies and development of occupational exposure limits (OELs) for polyisocyanates is difficult.An analysis of existing problems in the measurement and regulation of isocyanates is presented based on the published analytical, toxicological, and regulatory literature, and the authors' own analytical data and experience with isocyanates.This analysis supports a need for standardization of isocyanate measurement metrics and provides a framework for the development of an OEL for polyisocyanates.The total isocyanate group (microg NCO/m(3)) is recommended as the most feasible and practical metric (unit) by which to express polyisocyanate exposures for research, control, and regulatory purposes. The establishment of a comprehensive isocyanate OEL that simplifies the current agent-by-agent approach and expands coverage to polyisocyanates is also recommended.

    View details for DOI 10.1002/ajim.20076

    View details for Web of Science ID 000225076900007

    View details for PubMedID 15490474

  • Isocyanate exposures in autobody shop work: The SPRAY study JOURNAL OF OCCUPATIONAL AND ENVIRONMENTAL HYGIENE Sparer, J., Stowe, M. H., Bello, D., Liu, Y. C., Gore, R. J., Youngs, F., Cullen, M. R., Redlich, C. A., Woskie, S. R. 2004; 1 (9): 570-581


    Isocyanates, known to cause respiratory sensitization and asthma, are widely used in automotive refinishing where exposures to aliphatic polyisocyanates occur by both inhalation and skin contact. The work reported here, the characterization of isocyanate exposure in the autobody industry, was part of an epidemiologic study of workers in 37 autobody shops in Connecticut. This article describes workplaces, tasks, and controls, and outlines the frequency, duration, and intensity of isocyanate exposures. Personal air samples taken outside of respirators had median concentrations of 66.5 microg NCO/m3 for primer, 134.4 microg (NCO)/m3 for sealer, and 358.5 microg NCO/m3 for clearcoat. Forty-eight percent of primer, 66% of sealer, and 92% of clearcoat samples exceeded the United Kingdom Health and Safety Executive guideline for isocyanate, though none exceeded the National Institute for Occupational Safety and Health (NIOSH) recommended exposure limit for monomer. Nonisocyanate-containing primers and sealers are used in more than half the shops, but nonisocyanate clearcoats are rare. Eighty-two percent of personal samples taken within a spray booth exceeded the U.K. guideline: 81% of those in downdraft spray booths, 74% in semidowndraft booths, and 92% in crossdraft booths. Only 8% of shops reported that spraying is done exclusively in spray booths. All painters wore some type of respirator. In 30% of shops, painters used supplied air respirators; the rest relied on half face organic vapor cartridge respirators with N95 overspray pads. All shops provided some type of gloves, usually latex, not recommended for isocyanate protection. Despite improvements in autobody shop materials, practices, and controls, there are still opportunities for substantial exposures to isocyanates.

    View details for DOI 10.1080/15459620490485909

    View details for Web of Science ID 000223691500004

    View details for PubMedID 15559329

  • Determinants of isocyanate exposures in auto body repair and refinishing shops ANNALS OF OCCUPATIONAL HYGIENE Woskie, S. R., Sparer, J., Gore, R. J., Stowe, M., Bello, D., Liu, Y., Youngs, F., Redlich, C., Eisen, E., Cullen, M. 2004; 48 (5): 393-403


    As part of the Survey of Painters and Repairers of Auto bodies by Yale (SPRAY), the determinants of isocyanate exposure in auto body repair shops were evaluated. Measurements (n = 380) of hexamethylene diisocyanate-based monomer and polyisocyanate and isophorone diisocyanate-based polyisocyanate were collected from 33 auto body shops. The median total reactive isocyanate concentrations expressed as mass concentration of the NCO functional group were: 206 microg NCO/m3 for spray operations; 0.93 microg NCO/m3 for samples collected in the vicinity of spray operations done on the shop floor (near spray); 0.05 microg NCO/m3 for office or other shop areas adjacent to spray areas (workplace background); 0.17 microg NCO/m3 for paint mixing and gun cleaning operations (mixing); 0.27 microg NCO/m3 for sanding operations. Exposure determinants for the sample NCO mass load were identified using linear regression, tobit regression and logistic regression models. For spray samples in a spray booth the significant determinants were the number of milliliters of NCO applied, the gallons of clear coat used by the shop each month and the type of spray booth used (custom built crossdraft, prefabricated crossdraft or downdraft/semi-downdraft). For near spray (bystander) samples, outdoor temperature >65 degrees F (18 degrees C) and shop size >5000 feet2 (465 m2) were significant determinants of exposure levels. For workplace background samples the shop annual income was the most important determinant. For sanding samples, the shop annual income and outdoor temperature >65 degrees F (18 degrees C) were the most significant determinants. Identification of these key exposure determinants will be useful in targeting exposure evaluation and control efforts to reduce isocyanate exposures.

    View details for DOI 10.1093/annhyg/meh021

    View details for Web of Science ID 000223051300002

    View details for PubMedID 15148052

  • Impact of OSHA final rule - Recording hearing loss: An analysis of an industrial audiometric dataset JOURNAL OF OCCUPATIONAL AND ENVIRONMENTAL MEDICINE Rabinowitz, P. M., Slade, M., Dixon-Ernst, C., Sircar, K., Cullen, M. 2003; 45 (12): 1274-1280


    The 2003 Occupational Safety and Health Administration (OSHA) Occupational Injury and Illness Recording and Reporting Final Rule changed the definition of recordable work-related hearing loss. We performed a study of the Alcoa Inc. audiometric database to evaluate the impact of this new rule. The 2003 rule increased the rate of potentially recordable hearing loss events from 0.2% to 1.6% per year. A total of 68.6% of potentially recordable cases had American Academy of Audiology/American Medical Association (AAO/AMA) hearing impairment at the time of recordability. On average, recordable loss occurred after onset of impairment, whereas the non-age-corrected 10-dB standard threshold shift (STS) usually preceded impairment. The OSHA Final Rule will significantly increase recordable cases of occupational hearing loss. The new case definition is usually accompanied by AAO/AMA hearing impairment. Other, more sensitive metrics should therefore be used for early detection and prevention of hearing loss.

    View details for DOI 10.1097/01.jom.0000100040.45929.42

    View details for Web of Science ID 000187227300008

    View details for PubMedID 14665813

  • Truncating the dose range for methacholine challenge tests: Three occupational studies JOURNAL OF OCCUPATIONAL AND ENVIRONMENTAL MEDICINE Agalliu, I., Eisen, E. A., Hauser, R., Redlich, C. A., Stowe, M. H., Cullen, M. R., Wegman, D. H., CHRISTIANI, D. C., Kennedy, S. M. 2003; 45 (8): 841-847


    The methacholine challenge test protocol was assessed in the reanalysis of three occupational studies. We evaluated the impact of truncating the range of methacholine on responsiveness, as defined by slope and PC(20). In original analysis, reactivity was similar for apprentices and auto body shop workers, whereas boilermakers were more responsive. Truncating high concentrations did not change the classification of subjects with PC(20) <8 or 16 in any population. However, when responsiveness was measured by slope, the mean responsiveness increased, from -7.9 to -15.3 for apprentices and -7.2 to -10.0 for auto-body shop workers. Results support the American Thoracic Society's recommended maximum of 16 mg/ml and provide evidence that extending the dose range beyond that does not increase sensitivity, whereas stopping before 16 may exaggerate response. Furthermore, to ensure validity, neither slope nor PC(20) should be extrapolated beyond data.

    View details for DOI 10.1097/01.jom.0000083031.56116.53

    View details for Web of Science ID 000184777400009

    View details for PubMedID 12915785

  • Diisocyanate-exposed auto body shop workers: A one-year follow-up AMERICAN JOURNAL OF INDUSTRIAL MEDICINE Redlich, C. A., Stowe, M. H., Coren, B. A., Wisnewski, A. V., Holm, C. T., Cullen, M. R. 2002; 42 (6): 511-518


    Diisocyanates currently are the most commonly identified cause of occupational asthma in industrialized countries. Auto body shops, a common hexamethylene diisocyanate (HDI) exposure setting, are difficult to study due to their small size and episodic exposures.A 1-year follow-up was undertaken as an adjunct to the cross-sectional SPRAY study (Survey of Painters & Repairers of Auto bodies by Yale) to investigate the effects of HDI on auto body shop workers over time and whether or not the healthy worker effect may exist in this industry.Forty-eight workers from seven shops were re-contacted. Thirty-four subjects who stayed at the same shop and 11 who left their original shop participated. No statistically significant changes in physiology, symptoms, and immunologic responses from baseline to follow-up were noted. However, significant differences between those who left the shops and those who stayed were noted. Those who left were younger, less experienced in the industry, and more likely to have a history of asthma (23 vs. 3%; P < 0.05), bronchial hyper-responsiveness (23 vs. 9%), HDI-specific IgG (64 vs. 29%; P < 0.05), and HDI-specific proliferation (S.I. 2.0 vs. 1.3; P < 0.05).The differences in workers who stayed at their shop compared to those who left, combined with the low asthma prevalence and high job turnover rate, all suggest that a healthy worker effect may exist in the auto body industry, and may in part account for the low prevalence of asthma noted in SPRAY and other cross-sectional studies of diisocyante workers.

    View details for DOI 10.1002/ajim.10143

    View details for Web of Science ID 000179506400006

    View details for PubMedID 12439874

  • Subclinical immunologic and physiologic responses in hexamethylene diisocyanate-exposed auto body shop workers AMERICAN JOURNAL OF INDUSTRIAL MEDICINE Redlich, C. A., Stowe, M. H., Wisnewski, A. V., Eisen, E. A., Karol, M. H., Lemus, R., Holm, C. T., Chung, J. S., Sparer, J., Liu, Y. C., Woskie, S. R., Appiah-Pippim, J., Gore, R., Cullen, M. R. 2001; 39 (6): 587-597


    Diisocyanates are potent sensitizing agents and currently the most commonly identified cause of occupational asthma in industrialized countries. However, diisocyanate asthma is difficult to diagnose and exposure and host risk factors are unclear. Auto body shops, one of the most common hexamethylene diisocyanate (HDI) exposure settings, are particularly difficult to study due to their small size and episodic exposures. Surveillance studies of such workers are limited.We have initiated a cross-sectional field epidemiologic study, Survey of Painters and Repairers of Auto bodies by Yale (SPRAY), to characterize the effects of diisocyanate exposures on actively employed auto body shop workers. Methods and Results We present here questionnaire, physiologic, immunologic, and exposure data on 75 subjects enrolled in the study. No overt cases of clinically apparent diisocyanate asthma were identified based on spirometry, methacholine challenge, peak flows, and symptoms. HDI-specific lymphocyte proliferation was present in 30% of HDI-exposed workers and HDI-specific IgG in 34% of HDI-exposed workers, but they were not associated. HDI-specific IgE was detected in two workers. HDI-specific lymphocyte proliferation, increased methacholine responsiveness, and symptoms of chest tightness and shortness of breath were more common in the most heavily HDI-exposed workers, the painters. More long-term follow-up of this cohort should clarify the significance of these HDI-specific immunologic responses, physiologic changes, and symptoms.These findings demonstrate the presence of HDI-specific immune responses in a large proportion of healthy HDI-exposed workers.

    View details for Web of Science ID 000169037900007

    View details for PubMedID 11385643

  • Prevention of lead poisoning in construction workers: A new public health approach AMERICAN JOURNAL OF INDUSTRIAL MEDICINE Vork, K. L., Hammond, S. K., Sparer, J., Cullen, M. R. 2001; 39 (3): 243-253


    In 1990, Yale University, the Connecticut Departments of Health Services and of Transportation, the Connecticut Construction Industries Association, and the state's construction trade unions created the Connecticut Road Industry Surveillance Project (CRISP).Data from 90 bridge projects from 1991 to 1995 and approximately 2,000 workers were evaluated. The distribution of peak lead concentrations in the blood for CRISP workers classified into five groups were compared to that from workers outside of Connecticut.This demonstration project was instrumental in lowering bridge worker blood lead levels. After 1992, only the painting contract employees experienced peak blood lead levels with < or = 2% exceeding 50 microg/dl. Compared to similar workers in other states, Connecticut workers had significantly lower peak blood lead levels.Two thousand workers and over 120 contractors benefited directly from CRISP. Two key features of the CRISP model differed from the 1993 OSHA standard: a contract-specified lead health protection program and a centralized system of medical monitoring. These differences may account for the improved protection observed between the CRISP and non-Connecticut cohorts.

    View details for Web of Science ID 000167217300001

    View details for PubMedID 11241557

  • Qualitative assessment of isocyanate skin exposure in auto body shops: A pilot study AMERICAN JOURNAL OF INDUSTRIAL MEDICINE Liu, Y. C., Sparer, J., Woskie, S. R., Cullen, M. R., Chung, J. S., Holm, C. T., Redlich, C. A. 2000; 37 (3): 265-274


    Little is known about the extent of human isocyanate skin exposure in auto body shops and the effectiveness of personal protective equipment. Animal studies have suggested that skin exposure to isocyanates may be an important risk factor for respiratory sensitization leading to asthma. This study provides initial data on hexamethylene diisocyanate skin exposure in three auto body shops.Three auto body shops of different size which use different paint systems were examined for the presence of aliphatic isocyanates on environmental surfaces and workers' skin and for breakthrough of personal protective equipment. Qualitative detection of contamination by isocyanates was conducted using a wipe-sampling technique. Assessment focused on the painters and their tasks, although other auto body repairers were also evaluated.Environmental surfaces such as painters' workbenches, spray equipment, and cleaning tools were found contaminated with isocyanates. Painters had frequent contact with contaminated surfaces, often without wearing gloves. Moderate to heavy contamination of some skin surfaces was found with painters from two of the three auto body shops. Latex gloves used for skin protection showed significant penetrations by isocyanates even after a single painting session.Contaminated environmental surfaces and skin exposure to isocyanates were documented in several auto body shops. Latex gloves were not adequate protection for workers using isocyanate paints. Further research which would better quantify skin exposure, and its potential relationship to respiratory sensitization and asthma is warranted.

    View details for Web of Science ID 000085133900004

    View details for PubMedID 10642416

  • Effect of long-term beta-carotene and vitamin A on serum cholesterol and triglyceride levels among participants in the Carotene and Retinol Efficacy Trial (CARET) Atherosclerosis Redlich, C. A., Chung, J. S., Cullen, M. R., Blaner, W. S., Van Bennekum, A. M., Berglund, L. 1999; 145 (2): 425-432


    The Carotene and Retinol Efficacy Lung Cancer Chemoprevention Trial (CARET) ended prematurely due to the unexpected findings that the active treatment group on the combination of 30 mg beta-carotene and 25,000 IU retinyl palmitate had a 46% increased lung cancer mortality and a 26% increased cardiovascular mortality compared with placebo. This study was designed when the CARET intervention was halted to evaluate the effects of long-term supplementation with beta-carotene and retinol on serum triglyceride and cholesterol levels, in an attempt to explore possible explanations for the CARET result.Serum triglyceride levels, and total, high-density lipoprotein (HDL), and low-density lipoprotein (LDL) cholesterol levels were determined in a subgroup of 52 CARET participants. Baseline and mid-trial levels were available on 23 participants on placebo and 29 on active treatment who were then serially followed for 10 months after trial termination.Triglyceride, and total, HDL and LDL cholesterol levels were similar in the two groups at baseline. After a mean of 5 years on the intervention there was a small nonsignificant increase in serum triglyceride levels in the active group, but no difference in total, HDL, or LDL cholesterol levels. After stopping the intervention there was a decrease in triglyceride levels in the active intervention group, and no change in the other parameters.Based on a small convenience sample, CARET participants in the active treatment arm had a small nonsignificant increase in serum triglyceride levels while on the intervention, and a decrease in serum triglyceride levels after the intervention was discontinued. No significant changes in total or HDL cholesterol were noted. These results argue against a major contribution of treatment-induced changes in serum lipid and lipoprotein levels to the increased cardiovascular mortality in the active treatment group.

    View details for PubMedID 10488974

  • Effect of long-term beta-carotene and vitamin A on serum cholesterol and triglyceride levels among participants in the Carotene and Retinol Efficacy Trial (CARET) ATHEROSCLEROSIS Redlich, C. A., Chung, J. S., Cullen, M. R., Blaner, W. S., Van Bennekum, A. M., Berglund, L. 1999; 143 (2): 427-?


    The Carotene and Retinol Efficacy Lung Cancer Chemoprevention Trial (CARET) ended prematurely due to the unexpected findings that the active treatment group on the combination of 30 mg beta-carotene and 25,000 IU retinyl palmitate had a 46% increased lung cancer mortality and a 26% increased cardiovascular mortality compared with placebo. This study was designed when the CARET intervention was halted to evaluate the effects of long-term supplementation with beta-carotene and retinol on serum triglyceride and cholesterol levels, in an attempt to explore possible explanations for the CARET result.Serum triglyceride levels, and total, high-density lipoprotein (HDL), and low-density lipoprotein (LDL) cholesterol levels were determined in a subgroup of 52 CARET participants. Baseline and mid-trial levels were available on 23 participants on placebo and 29 on active treatment who were then serially followed for 10 months after trial termination.Triglyceride, and total, HDL and LDL cholesterol levels were similar in the two groups at baseline. After a mean of 5 years on the intervention there was a small nonsignificant increase in serum triglyceride levels in the active group, but no difference in total, HDL, or LDL cholesterol levels. After stopping the intervention there was a decrease in triglyceride levels in the active intervention group, and no change in the other parameters.Based on a small convenience sample, CARET participants in the active treatment arm had a small nonsignificant increase in serum triglyceride levels while on the intervention, and a decrease in serum triglyceride levels after the intervention was discontinued. No significant changes in total or HDL cholesterol were noted. These results argue against a major contribution of treatment-induced changes in serum lipid and lipoprotein levels to the increased cardiovascular mortality in the active treatment group.

    View details for Web of Science ID 000079595800023

    View details for PubMedID 10217373

  • Thyroid function in lead smelter workers: absence of subacute or cumulative effects with moderate lead burdens INTERNATIONAL ARCHIVES OF OCCUPATIONAL AND ENVIRONMENTAL HEALTH Schumacher, C., Brodkin, C. A., Alexander, B., Cullen, M., Rainey, P. M., van Netten, C., Faustman, E., Checkoway, H. 1998; 71 (7): 453-458


    To evaluate the effect of low to moderate occupational lead exposure on thyroid function we conducted a cross-sectional study of 151 male lead smelter workers.Parameters of thyroid function were assessed in relation to both subacute and cumulative lead exposure over a 10-year employment period. Blood lead levels, obtained from plant surveillance records, were used to establish four ordinal levels of current and cumulative exposure (< 15, 15-24, 25-39, and > or =40 microg/dl).Mean values for the lowest as compared with the highest current exposure group were similar for thyroxine (T4: 6.8 versus 6.1 microg/dl), estimated free thyroxine (EFT4: 1.6 ng/dl in both groups), and thyroid-stimulating hormone (TSH: 1.8 versus 1.7 mIU/l); there was no evidence of a significant trend for diminished thyroid function associated with increasing current lead exposure. Similarly, no significant difference was observed for T4, EFT4, or TSH in relation to the 10-year cumulative exposure or for adjusted analyses controlling for potential confounders, including age and alcohol use.In contrast to studies observing thyroid dysfunction in the setting of high lead exposure and related clinical poisoning, our findings weigh against a significant physiologic effect on thyroid function at lower levels (< 60 microg/dl) of occupational lead exposure.

    View details for Web of Science ID 000076552900003

    View details for PubMedID 9826077

  • Dietary vitamin A and prevalence of bronchial metaplasia in asbestos-exposed workers AMERICAN JOURNAL OF CLINICAL NUTRITION Mayne, S. T., Redlich, C. A., Cullen, M. R. 1998; 68 (3): 630-635


    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 metaplasia (highest quartile compared with lowest quartile, adjusted ORs). Current smoking (OR: 5.25; 95% CI: 0.50, 55.1) and former smoking (OR: 2.95; 95% CI: 0.31, 28.1) were associated with a nonsignificant increase in the OR for bronchial metaplasia compared with never smoking. Greater airway obstruction [decreased forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC)] was associated with an increased OR for metaplasia (OR: 2.86; 95% CI: 1.09, 7.69). These results suggest that a higher (ie, above the median) intake of vitamin A from foods decreases the risk of bronchial metaplasia in workers occupationally exposed to asbestos.

    View details for Web of Science ID 000075646100019

    View details for PubMedID 9734740

  • Effect of supplementation with beta-carotene and vitamin A on lung nutrient levels CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION Redlich, C. A., Blaner, W. S., Van Bennekum, A. M., Chung, J. S., Clever, S. L., Holm, C. T., Cullen, M. R. 1998; 7 (3): 211-214


    The Carotene and Retinol Efficacy Trial (CARET), a randomized, placebo-controlled lung cancer chemoprevention trial of 30 mg of beta-carotene and 25,000 IU of retinyl palmitate, was prematurely terminated when a 46% excess lung cancer mortality was found in subjects on the active arm. Before the CARET intervention ended, 21 men were recruited to participate in a 6-month biomarker study using the same intervention as CARET that determined the effect of this supplementation on lung nutrient levels. Plasma and bronchoalveolar lavage (BAL) cell nutrient levels were measured before and after the intervention. The group in the active arm (n = 10) had plasma carotene level increases of over 10-fold, with a small increase in plasma retinol levels BAL cell levels of beta-carotene in the active group also increased 10-fold, from 4.5 to 46.3 pmol/10(6) cells (P = 0.0008), with no change in BAL cell retinol levels. Surgically obtained lung tissue from three CARET subjects in the active arm showed elevated carotene lung tissue levels but no increase in lung retinol levels compared to a group of surgical controls. Combined with our previous work showing a strong correlation between BAL and lung tissue nutrient levels, these findings suggest that supplementation with beta-carotene and vitamin A results in increased lung tissue as well as BAL cell levels of beta-carotene, with little change in lung retinol.

    View details for Web of Science ID 000072384000007

    View details for PubMedID 9521435

  • The CARET asbestos-exposed cohort: Baseline characteristics and comparison to other asbestos-exposed cohorts AMERICAN JOURNAL OF INDUSTRIAL MEDICINE Barnhart, S., Keogh, J., Cullen, M. R., Brodkin, C., Liu, D., Goodman, G., Valanis, B., Glass, A., Thornquist, M., Rosenstock, L., Omenn, G., Balmes, J. 1997; 32 (6): 573-581


    The Carotene and Retinol Efficacy Trial (CARET) was a double-blind, placebo-controlled trial of the daily administration of 25,000 IU vitamin A and 30 mg beta-carotene for the prevention of lung cancer. Of close to 18,500 participants, more than 4,000 were asbestos-exposed men recruited from shipyard and construction trades at five study centers in the United States. While the primary endpoint of the trial was the incidence of lung cancer, a number of questions about the natural history of asbestos-related disease will also be addressed. The mean age at entry into the trial was 57 years and the mean duration of follow-up on active intervention was 4 years. With the exception of 133 never-smoker pilot participants (3%), all subjects recruited were by intention current (38%) or ex-smokers (58%), with a mean cumulative smoking exposure at entry of 43 pack-years. Mean years from first asbestos exposure were 35, and mean duration of asbestos exposure in a high-risk trade was 19 years. The distribution of radiographic abnormalities was as follows: normal, 34%; parenchymal opacities (ILO profusion score > 1/0) alone, 18%; pleural thickening alone, 27%; both parenchymal opacities and pleural thickening, 21%. The CARET cohort, when compared to previously reported asbestos-exposed cohorts, is characterized by substantial asbestos exposure and high proportion of asbestos-related radiographic findings. The active intervention was halted in 1996, after a mean duration of 40 years. Passive follow-up of the cohort will continue until the year 2000.

    View details for Web of Science ID A1997YE13800001

    View details for PubMedID 9358912

  • Airway isocyanate-adducts in asthma induced by exposure to hexamethylene diisocyanate SCANDINAVIAN JOURNAL OF WORK ENVIRONMENT & HEALTH Redlich, C. A., Karol, M. H., Graham, C., Homer, R. J., Holm, C. T., Wirth, J. A., Cullen, M. R. 1997; 23 (3): 227-231


    The clinical features, airway histology, and detection of hexamethylene diisocyanate (HDI) protein adducts in endobronchial biopsies from a patient with HDI asthma are described.Isocyanate asthma was diagnosed by history, methacholine challenge, and workplace HDI challenge. Bronchoscopy was performed 24 h after challenge and immunohistochemical staining was performed.Airway biopsies obtained at bronchoscopy demonstrated inflammatory changes typical for asthma, including increased airway eosinophils and T cells. Immunohistochemical staining with specific anti-HDI antibodies demonstrated the presence and localization of HDI adducts in human bronchial biopsies.These studies confirm epithelial exposure to HDI following workplace challenge and demonstrate the feasibility of detecting and localizing isocyanate adducts in human lung tissue. Identifying and characterizing the airway macromolecules to which isocyanates bind in vivo are probably crucial to the understanding of how isocyanates cause sensitization and asthma. The ability to detect isocyanate adducts may also help characterize isocyanate exposure patterns and exposure-disease relationships.

    View details for Web of Science ID A1997XJ31700010

    View details for PubMedID 9243734

  • Sick-building syndrome LANCET Redlich, C. A., Sparer, J., Cullen, M. R. 1997; 349 (9057): 1013-1016


    Sick-building syndrome (SBS) is an increasingly common problem. Although objective physiological abnormalities are not generally found and permanent sequelae are rare, the symptoms of SBS can be uncomfortable, even disabling, and whole workplaces can be rendered non-functional. In assessment of patients with SBS complaints, specific building-related illnesses suggested by history or physical examination should be ruled out. On-site assessment of buildings is extremely useful. Treatment involves both the patient and the building. Whenever possible, changes such as ventilation improvements and reduction of sources of environmental contamination should be initiated even if specific aetiological agents have not been identified.

    View details for Web of Science ID A1997WR62100042

    View details for PubMedID 9100639

  • The protective effect of beta-carotene and retinol on ventilatory function in an asbestos-exposed cohort AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE CHUWERS, P., Barnhart, S., Blanc, P., Brodkin, C. A., Cullen, M., Kelly, T., Keogh, J., Omenn, G., Williams, J., Balmes, J. R. 1997; 155 (3): 1066-1071


    The association between serum beta-carotene or retinol concentration and level of ventilatory function was investigated in a population of asbestos-exposed men with a high rate of current and former cigarette smoking. The study population consisted of 816 subjects enrolled in the pilot component of the Carotene and Retinol Efficacy Trial (CARET), a placebo-controlled trial of supplemental beta-carotene and retinyl palmitate for the chemoprevention of lung cancer. Data available for analysis included baseline questionnaire, spirometry, chest X-ray, food frequency questionnaire, and serum beta-carotene and retinol concentrations. Serum beta-carotene concentration was associated with FEV1 (p < 0.05) and FVC (p < 0.05), with an approximately 100-ml increase over predicted values associated with raising the serum concentration from the 25th to the 75th percentile of the distribution in the study population (absolute difference = 155 ng/ml), even after adjustment for the confounding effects of asbestos exposure and cigarette smoking. Raising the serum retinol concentration from the 25th to the 75th percentile (absolute difference = 211 ng/ml) was associated with an approximately 70 ml increase in FVC (p < 0.05) over the predicted value. These results provide support for the hypothesis that beta-carotene and retinol have a protective effect on loss of ventilatory function.

    View details for Web of Science ID A1997WN85700044

    View details for PubMedID 9116988

  • Occupational exposure to machining fluids and laryngeal cancer risk: Contrasting results using two separate control groups AMERICAN JOURNAL OF INDUSTRIAL MEDICINE Russi, M., Dubrow, R., FLANNERY, J. T., Cullen, M. R., Mayne, S. T. 1997; 31 (2): 166-171


    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 may have differed from that of the population controls.

    View details for Web of Science ID A1997WF87900005

    View details for PubMedID 9028432

  • Risk factors for lung cancer and for intervention effects in CARET, the beta-carotene and retinol efficacy trial JOURNAL OF THE NATIONAL CANCER INSTITUTE Omenn, G. S., Goodman, G. E., Thornquist, M. D., Balmes, J., Cullen, M. R., Glass, A., Keogh, J. P., MEYSKENS, F. L., Valanis, B., Williams, J. H., Barnhart, S., CHERNIACK, M. G., Brodkin, C. A., Hammar, S. 1996; 88 (21): 1550-1559


    Evidence has accumulated from observational studies that people eating more fruits and vegetables, which are rich in beta-carotene (a violet to yellow plant pigment that acts as an antioxidant and can be converted to vitamin A by enzymes in the intestinal wall and liver) and retinol (an alcohol chemical form of vitamin A), and people having higher serum beta-carotene concentrations had lower rates of lung cancer. The Beta-Carotene and Retinol Efficacy Trial (CARET) tested the combination of 30 mg beta-carotene and 25,000 IU retinyl palmitate (vitamin A) taken daily against placebo in 18314 men and women at high risk of developing lung cancer. The CARET intervention was stopped 21 months early because of clear evidence of no benefit and substantial evidence of possible harm; there were 28% more lung cancers and 17% more deaths in the active intervention group (active = the daily combination of 30 mg beta-carotene and 25,000 IU retinyl palmitate). Promptly after the January 18, 1996, announcement that the CARET active intervention had been stopped, we published preliminary findings from CARET regarding cancer, heart disease, and total mortality.We present for the first time results based on the pre-specified analytic method, details about risk factors for lung cancer, and analyses of subgroups and of factors that possibly influence response to the intervention.CARET was a randomized, double-blinded, placebo-controlled chemoprevention trial, initiated with a pilot phase and then expanded 10-fold at six study centers. Cigarette smoking history and status and alcohol intake were assessed through participant self-report. Serum was collected from the participants at base line and periodically after randomization and was analyzed for beta-carotene concentration. An Endpoints Review Committee evaluated endpoint reports, including pathologic review of tissue specimens. The primary analysis is a stratified logrank test for intervention arm differences in lung cancer incidence, with weighting linearly to hypothesized full effect at 24 months after randomization. Relative risks (RRs) were estimated by use of Cox regression models; tests were performed for quantitative and qualitative interactions between the intervention and smoking status or alcohol intake. O'Brien-Fleming boundaries were used for stopping criteria at interim analyses. Statistical significance was set at the .05 alpha value, and all P values were derived from two-sided statistical tests.According to CARET's pre-specified analysis, there was an RR of 1.36 (95% confidence interval [CI] = 1.07-1.73; P = .01) for weighted lung cancer incidence for the active intervention group compared with the placebo group, and RR = 1.59 (95% CI = 1.13-2.23; P = .01) for weighted lung cancer mortality. All subgroups, except former smokers, had a point estimate of RR of 1.10 or greater for lung cancer. There are suggestions of associations of the excess lung cancer incidence with the highest quartile of alcohol intake (RR = 1.99; 95% CI = 1.28-3.09; test for heterogeneity of RR among quartiles of alcohol intake has P = .01, unadjusted for multiple comparisons) and with large-cell histology (RR = 1.89; 95% CI = 1.09-3.26; test for heterogeneity among histologic categories has P = .35), but not with base-line serum beta-carotene concentrations.CARET participants receiving the combination of beta-carotene and vitamin A had no chemopreventive benefit and had excess lung cancer incidence and mortality. The results are highly consistent with those found for beta-carotene in the Alpha-Tocopherol Beta-Carotene Cancer Prevention Study in 29133 male smokers in Finland.

    View details for Web of Science ID A1996VQ46500012

    View details for PubMedID 8901853

  • Investigation of a cluster of pituitary adenomas in workers in the aluminum industry OCCUPATIONAL AND ENVIRONMENTAL MEDICINE Cullen, M. R., Checkoway, H., Alexander, B. H. 1996; 53 (11): 782-786


    Four cases of pituitary adenoma among employees at a primary aluminum production factory were identified over a five year period by a community physician. The objective of this investigation was to determine whether there has been a comparable high incidence in other aluminum factories, and if particular jobs, departments, or activities in the industry are associated with higher rates of the disease.Pituitary adenoma in employees at all United States factories of the company for the years 1989-94 was assessed by a search of a health data information bank and an insurance data base covering present and past employees of the corporation. The incidence in the aluminum workers was estimated and compared with the workers in the index plant. A nested case control study was conducted to compare employment histories of identified cases with those of age and sex matched controls selected from the health information data base.25 cases, including the index cases, were identified which had been diagnosed during the period 1989-94. The resulting rate of 10.4/100,000 person-years was much lower than that at the index plant. Case-control analysis showed no coherent pattern of location, department, or job significantly associated with risk. In particular, jobs and departments associated with exposures common to aluminum smelting-such as coal tar pitch volatiles and fluorides-were shown to be uncommon among cases compared with age and sex matched controls.Overall, despite the unprecedented cluster at a single plant, no strong evidence was found that the rate of pituitary adenoma is increased in aluminum workers generally. We found no association with any work activity or location in the industry to suggest a work related or exposure related cause for the disease.

    View details for Web of Science ID A1996VR52200012

    View details for PubMedID 9038804

  • Feasibility study of respiratory questionnaire and peak flow recordings in autobody shop workers exposed to isocyanate-containing spray paint: Observations and limitations OCCUPATIONAL MEDICINE-OXFORD Cullen, M. R., Redlich, C. A., Beckett, W. S., Weltmann, B., Sparer, J., Jackson, G., Ruff, T., Rubinstein, E., Holden, W. 1996; 46 (3): 197-204


    Diisocyanates, highly reactive monomers which cross-link polyurethane, are the most widely recognized causes of occupational asthma. Many exposed workers are end-users, including autobody spray painters who form a large population at risk. Neither the factors which determine incidence rate nor strategies for control have been adequately studied in this setting. We have conducted a cross-sectional survey of 23 (about one in five) autobody shops in the New Haven area to determine the feasibility of clinical epidemiological studies in this population. Among 102 workers, there was a high rate of airway symptoms consistent with occupational asthma (19.6%). Symptoms were most prevalent among those with the greatest opportunity for exposure (dedicated spray painters) and least among office workers; part-time painters had intermediate rates. Atopy was not associated with risk while smoking seemed to correlate with symptoms. Regular use of air-supplied respirators appeared to be associated with lower risk among workers who painted part- or full-time. We were unable to validate the questionnaire responses with peak expiratory flow record data attempted on a 1/3 sample of the workers. Despite intensive training and effort, subject compliance was limited. Among those who provided adequate data (24 of 38), only two demonstrated unequivocal evidence of labile airways; two others demonstrated lesser changes consistent with an occupational effect on flow rates. There was no clear association between these findings and either questionnaire responses or exposure classification. Overall, the survey suggests that there is a high prevalence of airway symptoms among workers in autobody shops, at least in part due to work-related asthma. However, there is need for both methodological and substantive research in this setting to document rates of occupational asthma and to develop a scientific basis for its effective control.

    View details for Web of Science ID A1996UW12200004

    View details for PubMedID 8695771

  • Effects of a combination of beta carotene and vitamin A on lung cancer and cardiovascular disease NEW ENGLAND JOURNAL OF MEDICINE Omenn, G. S., Goodman, G. E., Thornquist, M. D., Balmes, J., Cullen, M. R., Glass, A., Keogh, J. P., MEYSKENS, F. L., Valanis, B., Williams, J. H., Barnhart, S., Hammar, S. 1996; 334 (18): 1150-1155


    Lung cancer and cardiovascular disease are major causes of death in the United States. It has been proposed that carotenoids and retinoids are agents that may prevent these disorders.We conducted a multicenter, randomized, double-blind, placebo-controlled primary prevention trial -- the Beta Carotene and Retinol Efficacy Trial -- involving a total of 18,314 smokers, former smokers, and workers exposed to asbestos. The effects of a combination of 30 mg of beta carotene per day and 25,000 IU of retinol (vitamin A) in the form of retinyl palmitate per day on the primary end point, the incidence of lung cancer, were compared with those of placebo.A total of 388 new cases of lung cancer were diagnosed during the 73,135 person-years of follow-up (mean length of follow-up, 4.0 years). The active-treatment group had a relative risk of lung cancer of 1.28 (95 percent confidence interval, 1.04 to 1.57; P=0.02), as compared with the placebo group. There were no statistically significant differences in the risks of other types of cancer. In the active-treatment group, the relative risk of death from any cause was 1.17 (95 percent confidence interval, 1.03 to 1.33); of death from lung cancer, 1.46 (95 percent confidence interval, 1.07 to 2.00); and of death from cardiovascular disease, 1.26 (95 percent confidence interval, 0.99 to 1.61). On the basis of these findings, the randomized trial was stopped 21 months earlier than planned; follow-up will continue for another 5 years.After an average of four years of supplementation, the combination of beta carotene and vitamin A had no benefit and may have had an adverse effect on the incidence of lung cancer and on the risk of death from lung cancer, cardiovascular disease, and any cause in smokers and workers exposed to asbestos.

    View details for Web of Science ID A1996UG83100002

    View details for PubMedID 8602180

  • Immunologic responses to isocyanates in sensitized asthmatic subjects CHEST Redlich, C. A., Homer, R. J., Smith, B. R., Wirth, J. A., Cullen, M. R. 1996; 109 (3): S6-S8
  • Immunologic responses to isocyanates in sensitized asthmatic subjects. Chest Redlich, C. A., Homer, R. J., Smith, B. R., Wirth, J. A., Cullen, M. R. 1996; 109 (3): 6S-8S

    View details for PubMedID 8598159

  • Chemoprevention of lung cancer: The beta-Carotene and Retinol Efficacy Trial (CARET) in high-risk smokers and asbestos-exposed workers CHEMOPREVENTION IN CANCER CONTROL Omenn, G. S., Goodman, G., Thornquist, M., Barnhart, S., Balmes, J., Cherniack, M., Cullen, M., Glass, A., Keogh, J., Liu, D., Meyskens, F., Perloff, M., Valanis, B., Williams, J. 1996: 67-85

    View details for Web of Science ID A1996BH72G00010

    View details for PubMedID 8791118

  • Significance of individual sensitivity to chemicals: elucidation of host susceptibility by use of biomarkers in environmental health research. Clinical chemistry Cullen, M. R., Redlich, C. A. 1995; 41 (12): 1809-1813


    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.

    View details for PubMedID 7497637



    To assess the false-positive rate of blood lead determinations on samples obtained by fingerstick from children screened in private suburban and rural practices.Screening capillary lead samples were obtained by fingerstick; children with capillary lead levels of 0.7 mumol/L (15 micrograms/dL) or greater were recalled for a confirmatory venous lead test that served as the criterion standard. Parents completed a five-question risk assessment questionnaire at the time of initial screening.Four private suburban to rural practices that serve predominantly white, middle-class populations.Children seen for routine care between August 1992 and February 1993 (N = 1085; 98% between 6 months and 6 years of age).Capillary lead level was 0.7 mumol/L (15 micrograms/dL) or greater in 35 children (3% of total sample); venous lead samples were obtained in 30 patients. Nine of the elevated capillary lead results were true-positives (venous lead = 0.7, 0.8, 0.8, 0.9, 0.9, 0.9, 1.1, 1.1, and 1.7 mumol/L [15, 17, 17, 18, 18, 18, 22, 22, and 35 micrograms/dL]); parents of only two of these children answered yes to any question on the risk assessment questionnaire. Although the false-positive rate of the capillary lead screening test was 70% (21/30) in this setting, only 2% of the total sample had a false-positive screening test (an average of fewer than one false-positive per month per practice). Screening by fingerstick allowed phlebotomy to be avoided for 97% of the children.Fingerstick screening for lead poisoning is a reasonable alternative to direct venous testing within private suburban and rural practices, provided that care is taken to avoid specimen contamination, that appropriate caution is used in the interpretation of screening test results, and that medical and environmental interventions are based on the results of confirmatory venous testing.

    View details for Web of Science ID A1995QR55800015

    View details for PubMedID 7704175

  • Vitamin A chemoprevention of lung cancer - A short-term biomarker study DIET AND CANCER Redlich, C. A., VANBENNEKUM, A. M., Wirth, J. A., Blaner, W. S., Carter, D., Tanoue, L. T., Holm, C. T., Cullen, M. R. 1995; 375: 17-29

    View details for Web of Science ID A1995BD36X00002

    View details for PubMedID 7645426

  • SCREENING FOR LEAD-POISONING IN AN URBAN PEDIATRIC-CLINIC USING SAMPLES OBTAINED BY FINGERSTICK PEDIATRICS Schonfeld, D. J., Cullen, M. R., Rainey, P. M., Berg, A. T., Brown, D. R., HOGAN, J. C., TURK, D. S., RUDE, C. S., Cicchetti, D. V. 1994; 94 (2): 174-179


    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 679 screens with a paired venous specimen (mean delay between screen and venous testing = 30 days) yielded much higher false positive rates (CPb, 31.3%; FPb, 46.0%).Screening for lead poisoning is feasible within an urban pediatric clinic by direct measurement of lead concentration in blood samples obtained by fingerstick. The false positive rate that can be obtained is acceptable given the precision of measuring BPb concentration. Practitioners using a staged screening protocol may incorrectly attribute a higher false positive rate to the screening tests, when much of the error may be due to the temporal variability of BPb resulting from both biologic variability in BPb concentration and intermittent exposures.

    View details for Web of Science ID A1994NY95600007

    View details for PubMedID 8036069

  • THE NATIONAL SHEET-METAL WORKER ASBESTOS DISEASE SCREENING-PROGRAM - RADIOLOGIC FINDINGS AMERICAN JOURNAL OF INDUSTRIAL MEDICINE Welch, L. S., Michaels, D., ZOLOTH, S. R., Alexander, V., Balmes, J., Barnhart, S., Bresnitz, E., BONHAM, D., CASTEN, P., Christiani, D., Cook, R., Cooper, K., Cullen, M., DeHart, D., Demers, R., Fagan, K., Frumkin, H., Frank, A., Friedman, G., Garman, R., Gibson, M., Hake, J., Herbert, R., HESSL, S., HINCAMP, D., Hodgson, M., HOLSTEIN, E., Johns, R. E., KALAMOTO, M., Kern, D., Kay, K., Lang, E., LANGWORTHY, J. R., Lockey, J., MERCHANT, J., Miller, K., Morse, L., MULLOY, K., Oliver, C., Rosenstock, L., ROUNDTREE, P., Schenker, M., Sharpe, I., Schwartz, D., Simmons, J., Sliwinski, J., Stein, C., TENCZA, A., Wallerstein, N., Wagner, G. 1994; 25 (5): 635-648
  • THE BETA-CAROTENE AND RETINOL EFFICACY TRIAL (CARET) FOR CHEMOPREVENTION OF LUNG-CANCER IN HIGH-RISK POPULATIONS - SMOKERS AND ASBESTOS-EXPOSED WORKERS CANCER RESEARCH Omenn, G. S., Goodman, G., Thornquist, M., Grizzle, J., Rosenstock, L., Barnhart, S., Balmes, J., CHERNIACK, M. G., Cullen, M. R., Glass, A., Keogh, J., Meyskens, F., Valanis, B., Williams, J. 1994; 54 (7): S2038-S2043
  • The beta-carotene and retinol efficacy trial (CARET) for chemoprevention of lung cancer in high risk populations: smokers and asbestos-exposed workers. Cancer research Omenn, G. S., Goodman, G., Thornquist, M., Grizzle, J., Rosenstock, L., Barnhart, S., Balmes, J., CHERNIACK, M. G., Cullen, M. R., Glass, A. 1994; 54 (7): 2038s-2043s


    CARET is a multicenter, two-armed, double-masked randomized chemoprevention trial in Seattle, Portland, San Francisco, Baltimore, Connecticut, and Irvine, to test whether oral administration of beta-carotene (30 mg/day) plus retinyl palmitate (25,000 IU/day) can decrease the incidence of lung cancer in high risk populations, namely, heavy smokers and asbestos-exposed workers. The intervention combines the antioxidant action of beta-carotene and the tumor suppressor mechanism of vitamin A. As of April 30, 1993, CARET had randomized 1,845 participants in the 1985-1988 pilot phase plus 13,260 "efficacy" participants since 1989; of these, 4,000 are asbestos-exposed males and 11,105 are smokers and former smokers (44% female). Accrual is complete everywhere except Irvine, which was the last center added (1991), and the safety profile of the regimen to date has been excellent. With 14,420 smokers, 4,010 asbestos-exposed participants, and 114,100 person-years through February 1998, we expect CARET to be capable of detecting a 23% reduction in lung cancer incidence in the two populations combined and 27, 49, 32, and 35% reductions in the smokers, female smokers, male smokers, and asbestos-exposed subgroups, respectively. CARET is highly complementary to the alpha-tocopherol-beta-carotene study in Finland and the Harvard Physicians Health Study (beta-carotene alone) in the National Cancer Institute portfolio of major cancer chemoprevention trials.

    View details for PubMedID 8137335

  • STATISTICAL DESIGN AND MONITORING OF THE CAROTENE AND RETINOL EFFICACY TRIAL (CARET) CONTROLLED CLINICAL TRIALS Thornquist, M. D., Omenn, G. S., Goodman, G. E., Grizzle, J. E., Rosenstock, L., Barnhart, S., Anderson, G. L., Hammar, S., Balmes, J., Cherniack, M., Cone, J., Cullen, M. R., Glass, A., Keogh, J. P., Meyskens, F., Valanis, B., Williams, J. H. 1993; 14 (4): 308-324


    CARET is a chemoprevention trial of beta-carotene and vitamin A with lung cancer as the primary outcome. Participants at high risk for lung cancer are drawn from two populations: asbestos-exposed workers and heavy smokers. The intervention is a daily combination of 30 mg beta-carotene and 25,000 IU vitamin A as retinyl palmitate. Nearly 18,000 participants will be followed for a mean 6 years, yielding over 100,000 person-years of follow-up. We project that this sample size will have 80% power to detect a 23% decrease in the incidence of lung cancer cases. The purpose of this paper is to present the values of the key sample size parameters of CARET; our schemes for monitoring CARET for sample size adequacy, incidence of side effects, and efficacy of the study vitamins; an overview of the data collected; and plans for the primary, secondary, and ancillary analyses to be performed at the end of the trial. These approaches to the design, monitoring, and analysis of CARET are applicable for many other prevention trials.

    View details for Web of Science ID A1993LQ02000006

    View details for PubMedID 8365195



    In a previous cross-sectional survey, up to 15% of shipyard painters were found to have mild anemia or granulocytopenia, mostly acquired since employment. Environmental studies had suggested a possible etiologic role for ethylene glycol ethers, solvents to which the men were heavily exposed and which have established myelotoxic potential. To exclude alternative hypotheses, examine possible common patterns of injury, and identify potential risk factors and markers for such an effect, the affected painters were further studied. The painters were matched with two groups of controls: exposed painters without evidence of hematologic abnormality on the previous survey and unexposed controls. Altogether 25 subjects were studied by histopathologic examination of bone marrow, cytogenetic studies of marrow cells, and peripheral lymphocytes and peripheral red cell studies of membrane and metabolic function. Except for an unexpected finding of a race-associated effect on marrow histology, insignificant differences were seen among the groups in terms of marrow morphology and cellularity, stem cell growth kinetics, and marrow or peripheral cytogenetics. Two metabolic abnormalities of peripheral red cells related to exposure or clinical status of the subjects were found. Pyruvate kinase, an established marker of acquired myelodysplasia, was significantly depressed in the subjects with previously abnormal counts. Although reduced glutathione levels and holoenzyme activities of glutathione reductase (GSHR) did not differ among groups, exposed subjects had decreased saturation of GSHR with flavin adenine dinucleotide which could be restored in vitro, suggesting riboflavin deficiency or impaired riboflavin metabolism. Thus, although a unique pattern of bone marrow injury by histologic or genetic assay attributable to ethylene glycol ethers was not defined, biochemical effects of possible mechanistic importance were identified. The relevance of these findings as subclinical disease markers remains to be established.

    View details for Web of Science ID A1992KC12900023

    View details for PubMedID 1425515



    In epidemiologic studies, airway disease and parenchymal injury are known morbid outcomes of occupational exposure to asbestos. However, the relationship of inflammatory events considered to be responsible for parenchymal injury to the subsequent development of airway injury is unknown. To assess this we performed bronchoalveolar lavage (BAL) and airway biopsies on a population of subjects with exposure to asbestos in the workplace. As an index of airway injury, we employed histologic metaplasia seen in mucosal biopsy specimens. Lung BAL fluid was analyzed for two potentially relevant protein markers and for inflammatory cells recovered from the lower respiratory tract. We related metaplasia to demographic features of this study population (eg, smoking history and asbestos exposure data) and also to the protein and cellular markers recovered by BAL. We studied 50 workers and detected keratinizing metaplasia in 15 and varying lesser abnormalities in the other 28. Cigarette smoking was not associated with the presence of metaplasia (p less than 0.2). Smoking status was associated with an increase in BAL cells (p less than 0.02); however, neither the percent nor concentration of acute inflammatory cells was significantly increased. Acute inflammatory cells (percent and cells per milliliter of BAL fluid) were significantly increased among the subjects with severe metaplasia compared with other study subjects. This increase was true of both neutrophils and eosinophils and the sum of these two (p less than 0.02). Stratification of subjects by smoking status demonstrated a persistent association of inflammatory cells with metaplasia. By logistic regression analysis, polymorphonuclear leukocytes per milliliter and eosinophils per milliliter were significantly related to the presence of metaplasia in two independent models (odds ratios, 9.9 and 7.6, respectively). Cigarette smoking and other demographic or BAL variables were not significantly associated with metaplasia in these models.

    View details for Web of Science ID A1992JL85700008

    View details for PubMedID 1516388



    It has been observed widely that some individuals exposed to asbestos will experience continued losses of lung function after asbestos exposure ceases. Unfortunately, there are few data on factors that determine clinical course, limiting the clinician's ability to determine prognosis in an individual case and restricting the possibility for testing or targeting any potential intervention to alter the course among the millions at risk. In an attempt to address this question, we studied a volunteer population of 50 such men from among a stable, heterogeneous population of asbestos-exposed workers who had been continuously followed in our occupational medicine clinics for up to 12 years (mean, 6.3 years); most had some clinical or roentgenographic sign of asbestos effect, pleural or parenchymal. Each subject was reexamined clinically, functionally, and roentgenographically. Asbestos and tobacco exposure histories were carefully reviewed with the subjects and quantified based on these reports and available data regarding the various work environments from which they came. Subsequently, each underwent a bronchoalveolar lavage to assess cellularity and levels of various proteins. The levels of risk factors, clinical findings, and biologic parameters from lavage were examined for their relationship to serial changes in lung function during the period over which they had been previously followed. Results of the study demonstrate that serial changes in lung function were not closely related to level or length of prior exposure, smoking behavior, chest roentgenographic findings, or lung volumes. Progressive loss of diffusing capacity for carbon monoxide (Dco) was significantly associated with two factors: level of neutrophil concentration in lavage fluid (0.043 +/- 0.016 ml/min/mm Hg/yr drop for each 0.1 x 10(4) neutrophils per milliliter, p = 0.02) and the level of Dco itself (0.17 +/- 0.07 ml/min/mm Hg/yr drop for each 10 percent decrease in percent Dco predicted, p = 0.01). The relationship with neutrophil concentration was statistically independent of the association with Dco itself and stronger; it persisted when loss of Dco was adjusted for baseline value. Lung volume changes were not associated with any predictor variables, alone or in combination. We conclude that the presence of neutrophils in bronchoalveolar lavage fluid is associated with recent disease progression that may have implications in studies of the mechanisms of asbestos-associated disease and in clinical treatment of patients at risk.

    View details for Web of Science ID A1992JL85700007

    View details for PubMedID 1516387


    View details for Web of Science ID A1992JJ33800003

    View details for PubMedID 1412482

  • RECRUITMENT FOR THE BETA-CAROTENE AND RETINOL EFFICACY TRIAL (CARET) TO PREVENT LUNG-CANCER IN SMOKERS AND ASBESTOS-EXPOSED WORKERS WESTERN JOURNAL OF MEDICINE Omenn, G. S., Goodman, G., Grizzle, J., Thornquist, M., Rosenstock, L., Barnhart, S., Anderson, G., Balmes, J., Cone, J., Cherniack, M., Cullen, M., Glass, A., Valanis, B., Keogh, J., Meyskens, F., Williams, J. 1992; 156 (5): 540-544

    View details for Web of Science ID A1992HU80900013

    View details for PubMedID 1595284



    Bronchoscopy and bronchoalveolar lavage (BAL) yield important information about the lower respiratory tract of subjects who have been exposed to asbestos. Evidence of metaplasia is easily detected with random biopsies in large airways and a relationship with smoking status can be found. A significant finding, however, is that inflammatory cells recovered by late BAL aliquots which presumably reflect alveolar space inflammation are also importantly associated with the presence of metaplasia. Asbestos provides an important stimulus for recruitment of inflammatory cells. These cells release oxidants which can be responsible for direct or indirect mutagenesis. Our data suggest that this inflammatory cell recruitment may be an important additional factor predictive of airway metaplasia and perhaps subsequent carcinogenesis.

    View details for Web of Science ID A1992HP72200013

    View details for PubMedID 1579733

  • OCCUPATIONAL AND ENVIRONMENTAL MEDICINE - MEETING THE GROWING NEED FOR CLINICAL SERVICES NEW ENGLAND JOURNAL OF MEDICINE Rosenstock, L., Rest, K. M., Benson, J. A., CANNELLA, J. M., Cohen, J., Cullen, M. R., Davidoff, F., Landrigan, P. J., Reynolds, R. C., Clever, L. H., Ellis, G. B., Goldstein, B. D. 1991; 325 (13): 924-927

    View details for Web of Science ID A1991GF85600005

    View details for PubMedID 1815547



    To assess the role of acute inflammatory cells in large airways in the pathogenesis of metaplasia, we performed BAL (divided into aliquots) and mucosal biopsies on asbestos workers. They had evidence of asbestos-related lung injury. We found that acute inflammatory cells were significantly increased in the first aliquot. Ex-smokers had a greater percentage of PMN compared with nonsmokers and current smokers. The subjects were subgrouped with respect to biopsy-detected metaplasia. There was no difference between these groups for percentage or total number of PMN in the first aliquot. However, subjects with metaplasia had significant reduction in FEV1/FVC compared with those without. We conclude that there are significant differences in cells between the first and subsequent aliquots. Although inflammatory stimuli may be important in the pathogenesis of metaplasia, PMN present in the first aliquot could not be related to the severity of the metaplastic changes in these workers.

    View details for Web of Science ID A1991FV61000028

    View details for PubMedID 2060332

  • CARET, THE BETA-CAROTENE AND RETINOL EFFICACY TRIAL TO PREVENT LUNG-CANCER IN ASBESTOS-EXPOSED WORKERS AND IN SMOKERS ANTI-CANCER DRUGS Omenn, G. S., Goodman, G., Grizzle, J., Thornquist, M., Rosenstock, L., Barnhart, S., Anderson, G., Balmes, J., Cherniack, M., Cone, J., Cullen, M., Glass, A., Keogh, J., Meyskens, F., Valanis, B. 1991; 2 (1): 79-86


    CARET is a two-armed, double-blind, randomized chemo-prevention trial to test the hypothesis that oral administration of beta-carotene 30 mg/day plus retinyl palmitate 25,000 IU/day will decrease the incidence of lung cancer in high-risk populations: heavy smokers and asbestos-exposed workers who have smoked. The agents combine anti-oxidant and nuclear tumor suppressor mechanisms. Fastidious monitoring for possible side effects is facilitated by inclusion of a Vanguard population. As of 31 December 1990, 6,105 participants of the 18,000 needed have been randomized in the trial. Efficacy results are expected in 1999.

    View details for Web of Science ID A1991FY07400011

    View details for PubMedID 1958856



    Data on the health effects caused by locally mined chrysotile asbestos in Zimbabwe have been very limited. The prevailing local view has been that risk is minimal. In this report we critically reassess the cases of 51 individuals with asbestos exposure who have been compensated by the Central Pneumoconiosis Bureau since independence in 1980. Results demonstrate that the major health risks of exposure reported elsewhere--morbid asbestosis, nonmalignant pleural disease, malignant mesothelioma, and lung cancer--all occur in Zimbabwe, at least among workers in the asbestos mines and mills. It is concluded that further investigation and control measures in the industry are warranted.

    View details for Web of Science ID A1991EP47500003

    View details for PubMedID 1847001



    As part of the effort to establish industrial practice and public policy regarding asbestos in Zimbabwe, we have conducted a cross-sectional study of the chrysotile mines and mills. A stratified random sample of workers with greater than 10 years of exposure has been evaluated by spirometry, chest radiographs, and employment history. The latter was converted to quantitative estimates of exposure dose, using a matrix based on measured and reconstructed fiber levels for each job and facility during the years of work. Based on these data, a clear dose-response between asbestos exposure and functional loss has been demonstrated, with mean losses from predicted of about 400-600 cc in vital capacity in the 10% of the population with heaviest exposures. Low-grade parenchymal radiographic abnormalities (ILO grade greater than or equal to 1/0) were evident in 8.7% of the total study group and were almost 10 times more common in those with more than 100 fibers/cc.years cumulative exposure than in those with 16 fibers/cc.years or less. Pleural disease was relatively rare, occurring in just under 10% of the study group, and was unrelated to exposure dose. Overall, these findings are compatible with results of similar studies in Quebec and Swaziland and suggest that similar control strategies are probably indicated.

    View details for Web of Science ID A1991EP47500004

    View details for PubMedID 1847002



    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 reciprocal titer 1.43 +/- SD 0.60) with vaccine subcutaneously compared to vaccine-only group (mean log peak of reciprocal titer = 1.21 +/- 0.55). All fifty subjects seroconverted to yellow fever vaccine by day 210. ELISA testing was also performed on all subjects. The two tests showed good correlation (Spearman r = 0.675), although ELISA readings were positive by day 14 in significantly more subjects (p = .01). We conclude that routine anti-malarial doses of chloroquine do not affect antibody response to yellow fever 17D vaccine. ELISA testing, a less complex and less time-consuming test, correlates well with PRNT and is proposed for additional trials to measure yellow fever 17D vaccine response in flavivirus non-immune subjects.

    View details for Web of Science ID A1991EY65900011

    View details for PubMedID 1996743



    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 endoplasmic reticulum, but no evidence of persisting acute injury or fibrosis. Abnormal aminotransferases in both groups may persist for months after removal from exposure, but progression to cirrhosis in continually exposed workers was not observed. We conclude that exposure of these workers to solvents, chiefly dimethylformamide, may result in two variants of toxic liver injury with subtle clinical, laboratory, and morphological features. This may be readily overlooked if occupational history and biopsy histology are not carefully evaluated.

    View details for Web of Science ID A1990DU07700020

    View details for PubMedID 2379779

  • OCCUPATIONAL-MEDICINE .2. NEW ENGLAND JOURNAL OF MEDICINE Cullen, M. R., CHERNIACK, M. G., Rosenstock, L. 1990; 322 (10): 675-683

    View details for Web of Science ID A1990CR78100007

    View details for PubMedID 2406599

  • OCCUPATIONAL-MEDICINE .1. NEW ENGLAND JOURNAL OF MEDICINE Cullen, M. R., CHERNIACK, M. G., Rosenstock, L. 1990; 322 (9): 594-601

    View details for Web of Science ID A1990CQ30800005

    View details for PubMedID 2406603



    No prevalence data on pneumonoconiosis among Zimbabwe's 30,000 miners have been available. Passage of a 1984 law requiring examination of all miners has provided a data base to assess this, but the records had not been previously evaluated or stored in a manner to facilitate this. In 1988 we developed a strategy to utilize the existing records to estimate cross-sectional rates rapidly. In this report, we describe the approach and demonstrate high rates of simple pneumonoconiosis among long-term workers in the coal, nickel, copper, and gold mines. These data, though limited, provide a rationale for more detailed investigations in these workforces and an impetus to establish an ongoing surveillance plan for the nation's miners.

    View details for Web of Science ID A1990DE00900003

    View details for PubMedID 2343873



    The inability to characterize the extent of occupational disease in the United States limits clinical diagnosis and public health interventions. We present an 8-year (1979 to 1987) experience with clinic-based reporting in Connecticut. Altogether, 3566 cases were sequentially coded for demographics, diagnoses, workplace identification, and exposures at two academic occupational medicine clinics. The lungs were the principal organs of diagnosed effect, with asbestos-related disorders predominating, whereas the urinary tract, endocrine organs, and cardiovascular systems were rarely involved. Of all diseases, 64.8% were diagnosed as chronic and irreversible. Three common disorders, lead intoxication (acute and chronic), asbestosis, and occupational asthma were selected for illustration. Patients with lead poisoning and asbestosis, although collectively numerous (40 and 504, respectively), came from a small number of worksites and industries. Occupational asthma was more variable: 141 diagnosed cases came from 56 different trades and industries and were caused by 28 recognized agents. While we recognize that clinic-based reporting suffers from obvious problems with referral bias and misclassification, our experience shows that it provides an important index of disease burden. Our data document the effects of legislation and litigation on lead poisoning and asbestosis, and correspondingly helps characterize diseases that will respond to broad intervention. On the other hand, occupational asthma is more pervasive and would require a more specialized, partially clinical approach.

    View details for Web of Science ID A1989AE81300021

    View details for PubMedID 2742436



    Using a mailed survey questionnaire directed toward division chiefs of general internal medicine, we have confirmed that despite increased interest among faculty, few medical residents currently receive required or elective training in occupational medicine. However, recent changes in societal perceptions about environmental risks, corporate health care practices, and medical reimbursement patterns favoring provision by hospitals of contractual outpatient services to healthy workers all portend expanded involvement of residents in certain occupational medicine activities in the future, in response to economic pressures on both consumers and providers. These same forces may, unfortunately, undermine the scientific and ethical quality of such training experiences, compared with emerging, more academically motivated approaches. The implications of these prospects are analyzed in the hope that a proper balance can ultimately be struck between economic and academic imperatives.

    View details for Web of Science ID A1988Q934000011

    View details for PubMedID 3190373

  • LIVER-DISEASE ASSOCIATED WITH OCCUPATIONAL EXPOSURE TO THE SOLVENT DIMETHYLFORMAMIDE ANNALS OF INTERNAL MEDICINE Redlich, C. A., Beckett, W. S., Sparer, J., BARWICK, K. W., Riely, C. A., Miller, H., SIGAL, S. L., Shalat, S. L., Cullen, M. R. 1988; 108 (5): 680-686


    to characterize an outbreak of liver disease among workers in a fabric coating factory; and to determine the outbreak's cause and natural history and strategies for clinical recognition, treatment, and prevention.clinical-epidemiological investigation.academic medical center, Occupational Medicine Clinic, and worksite.fifty-eight of sixty-six workers participated in the study. All had standard liver function tests at least once. Forty-six workers completed a questionnaire; 27 had more extensive clinical evaluation for recognized liver abnormalities.a plant-wide outbreak of liver disease was recognized after a new employee presented with signs and symptoms of hepatitis. Evaluation of the worksite showed that dimethylformamide, a widely used industrial solvent and known hepatotoxin, was being used to coat fabric in poorly ventilated areas without appropriate skin protection. No other major hepatotoxic exposure was identified. Overall, 36 of 58 (62%) workers tested had elevations of either aspartate aminotransferase (AST) or alanine aminotransferase (ALT) levels. Enzyme abnormalities occurred almost exclusively in production workers (35 of 46 were abnormal), whereas only 1 of 12 nonproduction workers showed any elevations in enzyme levels (P less than 0.0001). Serologic tests excluded known infectious causes of hepatitis in all but 2 workers and changes characteristic of toxic liver injury were confirmed by histologic examinations of biopsy specimens from 4 workers. The ratio of AST to ALT levels was one or less in all but 1 worker. After modification of work practices and removal of workers most severely affected from exposure, improvement in liver enzyme abnormalities and symptoms in most patients were seen, although some patients showed persistent elevations of enzyme outbreak of toxic liver disease has been associated with exposure to dimethylformamide in the workplace. The diagnosis of toxic liver disease was established by the clinical histories, negative viral serologies, an enzyme pattern of ALT levels being greater than AST levels, epidemiologic data on coworkers, and liver biopsy specimens. The high prevalence of unsuspected liver enzyme abnormalities in these workers suggests that occupational liver disease may occur more frequently than is generally recognized.

    View details for Web of Science ID A1988N345000006

    View details for PubMedID 3358569



    to ascertain whether measuring the proliferative response of bronchoalveolar lymphocytes to beryllium salts is useful for diagnosing chronic beryllium disease.prospective case series compared to normal volunteers and patients with referral center.twenty-three consecutive beryllium workers were evaluated. Fourteen had chronic beryllium disease diagnosed on the basis of histologic evidence of a progressive pulmonary granulomatosis. Four had biopsy evidence of non-beryllium disease. Three had probable chronic beryllium disease but did not have lung biopsies. Two did not have biopsies and had basilar fibrosis on chest roentgenogram suggestive of non-beryllium lung disease. These patients were compared with 6 normal volunteers and 16 patients with sarcoidosis.bronchoalveolar lavage was done and the proliferative response of the lung cells to two beryllium salts was tested. A positive proliferative test was defined as a stimulation index of more than five on two determinations. The sensitivity of this test was 100% in the 14 patients with definite chronic beryllium disease. The specificity of the test was also 100% among the normal volunteers and the 16 patients with sarcoidosis. The test was positive in none of the four patients with biopsy evidence of non-beryllium disease, none out of two patients with lower lobe fibrosis suggestive of non-beryllium disease, and all of three patients with probable chronic beryllium lung disease.the proliferative response of bronchoalveolar lymphocytes to beryllium appears to be a useful test for chronic beryllium disease.

    View details for Web of Science ID A1988N345000007

    View details for PubMedID 3282464



    Hemoglobin, hematocrit, red cell indices, total and differential white blood cell counts, and platelet count were measured in shipyard painters and control subjects as part of a cross-sectional, observational study of the effects of ethylene glycol ethers. Although the means of all variables were comparable between the groups, a significant proportion of painters were anemic (10%) and granulocytopenic (5%); none of the controls were affected. Review of company records documented that most of these abnormalities were acquired during employment; preexisting disease and other exposure could not explain the findings. These findings are consistent with prior animal studies and human case reports. Potential biases and confounding of the data are discussed.

    View details for Web of Science ID A1988Q620600003

    View details for PubMedID 3265857



    To determine whether 2-ethoxyethanol (2-EE) and 2-methoxyethanol (2-ME) affected the reproductive potential of exposed men, we examined the semen of 73 painters and 40 controls who work in a large shipyard. An industrial hygiene survey was performed to characterize the work environment. The men supplied information on demographic characteristics, medical conditions, personal habits, and reproductive history; underwent a physical examination; and provided a semen sample. Semen samples were analyzed for pH, volume, turbidity, liquidity, viability by stain exclusion and hypo-osmotic stress, sperm density and count per ejaculate, motility using a videotape technique, morphology, and morphometry. Serum was analyzed for testosterone, FSH, and LH. The industrial hygiene survey revealed that the painters were exposed to 2-EE at a time-weighted average (TWA) of 0-80.5 mg/m3 with a mean of 9.9 mg/m3, and to 2-ME at a TWA of 0-17.7 mg/m3 with a mean of 2.6 mg/m3. Painters had an increased prevalence of oligospermia and azoospermia and an increased odds ratio for a lower sperm count per ejaculate, while smoking was controlled. This finding is consistent with prior animal studies and with one human study. Potential biases and confounding of the data are discussed.

    View details for Web of Science ID A1988Q620600002

    View details for PubMedID 3228067



    An industrial hygiene survey was performed to characterize exposure of shipyard painters to 2-ethoxyethanol (2-EE) and 2-methoxyethanol (2-ME). One hundred and two samples were taken over six workshifts. Overall results showed that the time-weighted average (TWA) of airborne exposure to 2-EE ranged from 0-80.5 mg/m3 with a mean of 9.9 mg/m3 and a median of 4.4 mg/m3. Samples for 2-ME TWA ranged from 0-17.7 mg/m3 with a mean of 2.6 mg/m3 and a median of 1.6 mg/m3. Limitations of the sampling and a few prior measurements suggest that these data may underestimate usual or previous exposure. These data are discussed in the context of available data on airborne exposure to ethylene glycol ethers from other workplaces.

    View details for Web of Science ID A1988Q620600001

    View details for PubMedID 3228066

  • Chronic beryllium disease in a precious metal refinery. Clinical epidemiologic and immunologic evidence for continuing risk from exposure to low level beryllium fume. American review of respiratory disease Cullen, M. R., Kominsky, J. R., Rossman, M. D., CHERNIACK, M. G., Rankin, J. A., Balmes, J. R., Kern, J. A., DANIELE, R. P., Palmer, L., NAEGEL, G. P. 1987; 135 (1): 201-208


    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 modern industrial controls, especially in the setting of exposure to highly respirable beryllium fume.

    View details for PubMedID 3492158



    Prompted by referral of a printer with aplastic anemia, a study of possible marrow toxicity of workplace substances was undertaken. Dermal and respiratory exposures to dipropylene glycol monomethyl ether, ethylene glycol monoethyl ether, and a range of aliphatic, aromatic and halogenated hydrocarbons used for offset and ultraviolet cured multicolor printing were documented. Evaluation of seven co-workers revealed normal peripheral blood pictures, but bone marrow specimens demonstrated clear patterns of injury in three while the others had nonspecific signs of marrow effect. These changes could not be explained by known risk factors. The authors conclude that further evaluation of possible bone marrow toxicity resulting from exposure to glycol ethers and ultraviolet curing printing processes is warranted. More generally, we have provided data demonstrating that peripheral blood counts may be an insensitive tool for the study of hematologic toxins acting at the bone marrow level.

    View details for Web of Science ID A1983SC87800005

    View details for PubMedID 6667035


    View details for Web of Science ID A1982PG52900009

    View details for PubMedID 7140288


    View details for Web of Science ID A1981LB36500011

    View details for PubMedID 7030593


    View details for Web of Science ID A1980KP07700013

    View details for PubMedID 7408550

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