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Purpose: Lead is a known neurotoxicant. Several studies have suggested that occupational exposure to lead may lead to depression, anxiety and other psychiatric illness, but few studies have examined environmental lead exposure and depression. We evaluated the relationship between blood lead levels (BLL) and depression in a sample representative of the US population., Methods: We analyzed data from 4,159 adults ages ≥20 who participated in the 2005-2006 cycle of the National Health and Nutrition Examination Survey (NHANES). Depression was assessed by the Patient Health Questionnaire-9 (PHQ-9). Relative risks were calculated using Poisson regression, and odds ratios were calculated with ordinal logistic regression using SUDAAN, controlling for pertinent covariates., Results: The risk of depression was only slightly elevated with increasing blood lead levels when lead was modeled as a categorical variable, with adjusted relative risks of 1.16 (95% confidence interval (CI) = 0.99-1.36), 1.20 (CI = 1.07-1.36) and 1.16 (CI = 0.87-1.54) for 0.89-1.40 μg/dL, 1.41-2.17 μg/dL and >2.17 μg/dL, respectively, when compared to 0-0.88 μg/dL using Poisson regression. Similar results were obtained with ordinal logistic regression. Analyses using BLL as a continuous variable did not show a significant relationship with depression., Conclusions: This cross-sectional study did not provide consistent evidence for an association between environmental lead exposure and depression within the investigated blood lead levels.

Studies of neurodevelopmental outcomes in offspring exposed to MeHg from maternal consumption of fish have primarily measured cognitive abilities. Reported associations have been subtle and in both adverse and beneficial directions. Changes in functional outcomes such as school achievement and behavior in exposed children and adolescents have not been examined. We undertook an assessment of school success of children in the Seychelles Child Development Study (SCDS) main cohort to determine if there were any associations with either prenatal or recent postnatal MeHg exposure. The primary endpoints were Seychelles nationally standardized end-of-year examinations given when the cohort children were 9 and 17 years of age. A subgroup (n=215) from the main cohort was also examined at 9 years of age using a regional achievement test called SACMEQ. Prenatal MeHg exposure was 6.8 ppm in maternal hair; recent postnatal exposure was 6.09 ppm at 9 years and 8.0 ppm at 17 years, measured in child hair. Multiple linear regression analyses showed no pattern of associations between prenatal or postnatal exposure, and either the 9- or 17-year end-of-year examination scores. For the subgroup of 215 subjects who participated in the SACMEQ test, there were significant adverse associations between examination scores and postnatal exposure, but only for males. The average postnatal exposure level in child hair for this subgroup was significantly higher than for the overall cohort. These results are consistent with our earlier studies and support the interpretation that prenatal MeHg exposure at dosages achieved by mothers consuming a diet high in fish are not associated with adverse educational measures of scholastic achievement. The adverse association of educational measures with postnatal exposure in males is intriguing, but will need to be confirmed by further studies examining factors that influence scholastic achievement., (Copyright © 2010 Elsevier Inc. All rights reserved.)

Recent research suggests that ultraviolet radiation exposure (UVRE), our major source of vitamin D, is associated with reduced lymphoma risk. Animal and human studies support an association between vitamin D (vitD) insufficiency and increased risk of some malignancies. We conducted a clinic-based case-control study (140 lymphoma cases, 139 controls; 2002-2005, Rochester, NY) to evaluate UVRE and vitD insufficiency in relation to lymphoma risk. Subjects completed a survey and provided a blood sample. We used multivariable logistic regression to estimate lymphoma risk in relation to past (5-10 years prior) UVRE and current vitD insufficiency (determined by serum 25(OH)D). Possible differences in effect by lymphoma subtype were explored, but statistical power was limited. We confirmed the previously reported decrease in lymphoma risk with past UVRE, specifically sunbathing (>once/week versus never); adjusted odds ratio (OR(adj)), = 0.28, 95% confidence interval (CI): 0.10-0.79. Current vitD insufficiency was not associated with lymphoma risk (OR(adj) = 0.89, 95% CI: 0.47-1.72). However, current sunbathing frequency was correlated with measured serum 25(OH)D values. Therefore, while our data do not support an association with current vitD status, development of accurate methods for past vitD assessment to further investigate its role in the association between past UVRE and lymphoma risk is warranted.

Background: Some experimental and observational research suggests that inflammation may be an important mediator of lead toxicity. However, lead-induced inflammation has not been well-studied in non-occupationally exposed populations., Methods: Using data for 9,145 individuals >or=40 years of age from the National Health and Nutrition Examination Survey 1999-2004, we assessed the association between blood lead levels (BLLs) and C-reactive protein (CRP), fibrinogen, and white blood cell (WBC) count via ordinal logistic regression. We also examined the interaction between BLL and gender in relation to the inflammatory markers., Results: No evidence for an association between lead exposure and inflammatory markers was observed with odds ratios around or below the null. Although men but not women appeared to be at increased risk of lead-induced inflammation, no consistent dose-response patterns were observed across BLL quintiles., Conclusion: Inflammation does not appear to be an important mediator of lead toxicity., ((c) 2010 Elsevier Inc. All rights reserved.)

Previous studies have demonstrated increased levels of serum markers of systemic inflammation and immune system function among individuals with depressive symptoms. Despite these observations, the biological mechanisms behind this association remain elusive. The objective of the present analysis was to examine the individual and joint associations of white blood cell counts, platelet counts, and C-reactive protein with depression severity and to determine whether oxidative stress might mediate these associations. We conducted an analysis of 3867 subjects from the 2005-2006 National Health and Nutritional Examination Survey. Ordinal logistic regression was used to assess associations between three levels of depression symptom severity (as measured by the nine-item Patient Health Questionnaire) and serum C-reactive protein, white blood cell counts, platelet counts, and four surrogate markers of oxidative stress. Covariates included sex, age, smoking status, physical activity, education, poverty to income ratio, as well as medication use and medical conditions influencing inflammation levels. In separate models, the risk of moderate to severe depression was significantly greater in the highest quartiles of CRP (OR=1.84. 95 percent confidence interval (CI)=1.35-2.52), WBC (OR=1.70, CI=1.31-2.19), and platelet counts (OR=1.41, CI=1.13-1.76) after adjusting for basic sociodemographic and behavioral factors. After additional adjustment for medication use and oxidative stress surrogate measures, the highest quartile of WBC counts remained associated with depression (OR=1.60, CI=1.23-2.09). Adjustment for oxidative stress measures did not substantially affect estimated associations of inflammation/immunologic markers. In summary, we observed significantly elevated white blood cell counts among subjects with moderate and severe depression, and oxidative stress and a medical history of inflammatory diseases do not appear to mediate this association. Although limited through its use of cross-sectional data, this is the first analysis to simultaneously consider immunologic and oxidative stress markers. Further research is needed to identify the biological basis for this persistent association., (2009 Elsevier Inc. All rights reserved.)

Animal and human studies support a protective effect of vitamin D sufficiency related to malignancy by uncovering paracrine and autocrine effects of extra-renal 25-hydroxyvitamin D (25(OH)D) activation including regulation of cell cycle proliferation, apoptosis induction, and increased cell differentiation signaling. Recent epidemiologic studies demonstrate a reduction in non-Hodgkin lymphoma (NHL) risk with increased sunlight exposure. As sunlight is a major vitamin D source, it has been suggested that vitamin D status may mediate this observed association. This review provides a comprehensive discussion of the current epidemiologic evidence with regard to the investigation of an association between vitamin D status and NHL risk.

Purpose: The potential for ill-informed causal inference is a major concern in published longitudinal studies evaluating impaired neurological function in children prenatally exposed to background levels of methyl mercury (MeHg). These studies evaluate a large number of developmental tests. We propose an alternative analysis strategy that reduces the number of comparisons tested in these studies., Methods: Using data from the 9-year follow-up of 643 children in the Seychelles child development study, we grouped 18 individual endpoints into one overall ordinal outcome variable as well as by developmental domains. Subsequently, ordinal logistic regression analyses were performed., Results: We did not find an association between prenatal MeHg exposure and developmental outcomes at 9 years of age., Conclusion: Our proposed framework is more likely to result in a balanced interpretation of a posteriori associations. In addition, this new strategy should facilitate the use of complex epidemiological data in quantitative risk assessment.

Accumulating evidence suggests a link between lead exposure and memory impairment but assessments based on predictive and validated measures are lacking. We conducted a pilot study of 47 healthy subjects 55-67 years of age to examine associations between bone lead levels and 4 tests sensitive to the natural history of Mild Cognitive Impairment (MCI) and Alzheimer's disease (AD). These include three subtests of the Cambridge Neuropsychological Test Automated Battery (delayed match-to-sample, paired associates learning and spatial recognition memory) and the Montreal Cognitive Assessment Test. Bone lead concentrations were measured at the mid-shaft of the tibia and the calcaneus with K X-ray fluorescence. Higher tibial and calcaneal bone lead values were significantly (p<0.05) associated with lower performance levels on delayed match-to-sample and paired associates learning in unadjusted analyses with Spearman rank correlation coefficients of about 0.4. Multiple linear regression analyses (i.e., least-squares means of cognitive test scores across tertiles of lead exposure) adjusted for age, education and smoking status continued to show an association of higher calcaneal lead levels with increasing memory impairments on delayed match-to-sample (p=0.07). As might be expected, additional adjustment for history of hypertension reduced the strength of this association (p=0.19). Given the demonstrated impact of lead exposure on hypertension and the vascular etiology of certain dementias, we speculate that hypertension could play a mediating role in the association between lead exposure and memory impairment.

Objective: To explore the relationship between sleep-disordered breathing (SDB) and behavioral problems among inner-city children with asthma., Methods: We examined data for 194 children (aged 4-10 years) who were enrolled in a school-based asthma intervention program (response rate: 72%). SDB was assessed by using the Sleep-Related Breathing Disorder Questionnaire that contains 3 subscales: snoring, sleepiness, and attention/hyperactivity. For the current study, we modified the Sleep-Related Breathing Disorder Questionnaire by removing the 6 attention/hyperactivity items. A sleep score of >0.33 was considered indicative of SDB. To assess behavior, caregivers completed the Behavior Problem Index (BPI), which includes 8 behavioral subdomains. We conducted bivariate analyses and multiple linear regression to determine the association of SDB with BPI scores., Results: The majority of children (mean age: 8.2 years) were male (56%), black (66%), and insured by Medicaid (73%). Overall, 33% of the children experienced SDB. In bivariate analyses, children with SDB had significantly higher (worse) behavior scores compared with children without SDB on total BPI (13.7 vs 8.8) and the subdomains externalizing (9.4 vs 6.3), internalizing (4.4 vs 2.5), anxious/depressed (2.4 vs 1.3), headstrong (3.2 vs 2.1), antisocial (2.3 vs 1.7), hyperactive (3.0 vs 1.8), peer conflict (0.74 vs 0.43), and immature (2.0 vs 1.5). In multiple regression models adjusting for several important covariates, SDB remained significantly associated with total BPI scores and externalizing, internalizing, anxious/depressed, headstrong, and hyperactive behaviors. Results were consistent across SDB subscales (snoring, sleepiness)., Conclusions: We found that poor sleep was independently associated with behavior problems in a large proportion of urban children with asthma. Systematic screening for SDB in this high-risk population might help to identify children who would benefit from additional intervention.

Background: The etiology of childhood brain cancer remains largely unknown. However, previous studies have yielded suggestive associations with parental pesticide use., Objectives: We aimed to evaluate parental exposure to pesticides at home and on the job in relation to the occurrence of brain cancer in children., Methods: We included 526 one-to-one-matched case-control pairs. Brain cancer cases were diagnosed at < 10 years of age, and were identified from statewide cancer registries of four U.S. Atlantic Coast states. We selected controls by random digit dialing. We conducted computer-assisted telephone interviews with mothers. Using information on residential pesticide use and jobs held by fathers during the 2-year period before the child's birth, we assessed potential exposure to insecticides, herbicides, and fungicides. For each job, two raters independently classified the probability and intensity of exposure; 421 pairs were available for final analysis. We calculated odds ratios (ORs) and 95% confidence intervals (CIs) using conditional logistic regression, after adjustment for maternal education., Results: A significant risk of astrocytoma was associated with exposures to herbicides from residential use (OR = 1.9; 95% CI, 1.2-3.0). Combining parental exposures to herbicides from both residential and occupational sources, the elevated risk remained significant (OR = 1.8; 95% CI, 1.1-3.1). We observed little association with primitive neuroectodermal tumors (PNET) for any of the pesticide classes or exposure sources considered., Conclusions: Our observation is consistent with a previous literature reporting suggestive associations between parental exposure to pesticides and risk of astrocytoma in offspring but not PNET. However, these findings should be viewed in light of limitations in exposure assessment and effective sample size.

Objectives: The goal of the study was to test the hypothesis that infants with known congenital diaphragmatic hernias born at early term gestation (37-38 weeks) rather than later (39-41 weeks) had greater survival rates and less extracorporeal membrane oxygenation use. Primary outcomes were survival to hospital discharge or transfer and extracorporeal membrane oxygenation use. METHODS; A retrospective cohort study of term infants with prenatal diagnoses of congenital diaphragmatic hernia was performed with the Congenital Diaphragmatic Hernia Study Group Registry of patients with congenital diaphragmatic hernias who were treated between January 1995 and December 2006., Results: Among 628 term infants at 37 to 41 weeks of gestation who had prenatal diagnoses of congenital diaphragmatic hernia and were free of major associated anomalies, early term birth (37 vs 39-41 weeks) and greater birth weight were associated independently with survival, whereas black race was related inversely to survival. Infants born at early term with birth weights at or above the group mean (3.1 kg) had the greatest survival rate (80%). Among infants born through elective cesarean delivery, infants born at 37 to 38 weeks of gestation, compared with 39 to 41 weeks, had less use of extracorporeal membrane oxygenation (22.0% vs 35.5%) and a trend toward a greater survival rate (75.0% vs 65.8%)., Conclusions: The timing of delivery is an independent, potentially important factor in the consideration of elective delivery for infants diagnosed prenatally as having congenital diaphragmatic hernias. Among fetuses with prenatally diagnosed congenital diaphragmatic hernias and without major associated anomalies, early term delivery may confer advantage.

Purpose: This cohort study aims to examine cardiovascular disease (CVD) mortality risks among workers in occupations potentially exposed to magnetic fields (MF)., Methods: Risks for major CVD mortality by potential job-related MF exposure were examined in a sample of U.S. workers from the National Longitudinal Mortality Study using multivariate proportional hazards models., Results: After adjustment for demographic factors, there were no significant excess risks between individuals with medium (0.15 to <0.20 microT), high (0.20 to < 0.30 microT), or very high (>/= 0.30 microT) exposure levels as compared with individuals with background exposure levels of MF (<0.15 microT) for the CVD mortality outcomes. Indirect adjustment for potential confounding by current smoking prevalence did not change the pattern of these results., Conclusion: Our study does not provide evidence for an association between occupational MF exposure and CVD mortality risk.

Background: Inflammation has been implicated in prostate carcinogenesis; therefore, the use of nonsteroidal anti-inflammatory drugs (NSAIDs) has the potential of decreasing the risk of prostate cancer. However, to the authors' knowledge the precise correlation between oral NSAID use, serum prostate-specific antigen (PSA), and prostate cancer risk is unknown. To further characterize this association, the authors evaluated serum PSA levels with regard to NSAID and acetaminophen consumption in a large cross-sectional study of men in the US., Methods: PSA levels were determined in 1319 men aged >40 years in the 2001-2002 National Health and Nutrition Examination Survey (NHANES). Linear regressions were performed on log-transformed PSA levels, accounting for the complex survey design, to evaluate the relations between PSA and the use of NSAIDs and acetaminophen after adjusting for the effects of age, race, educational level, smoking status, body mass index, coexisting inflammatory conditions, and heart disease., Results: NSAID and acetaminophen consumption displayed a negative association with PSA levels, namely, individuals who reported using NSAIDs (19.8%) or acetaminophen (1.3%) regularly had lower PSA levels than individuals who did not take these drugs, although the impact of acetaminophen was not statistically significant. PSA levels among NSAID users were 0.9 times the levels among nondrug takers (P = .038), whereas PSA levels among acetaminophen users were 0.76 times the levels in nondrug takers (P = .14). Individuals who stated they took both NSAIDs and acetaminophen (0.99%) on a regular basis had higher PSA levels (1.8 times greater), although not statistically significantly so (P = .24), than individuals who stated they did not take either of these drugs regularly., Conclusions: The findings of the current study suggest that regular NSAID consumption may reduce serum PSA levels. Whether this is indicative of a protective effect on prostate cancer risk or masks possible prostate injury resulting in reduced detection of prostate cancer is unclear. Given the widespread consumption of NSAIDs and the regular use of PSA for the assessment of prostate cancer risk, the potential implications of the current study's findings may be substantial and warrant further investigation., ((c) 2008 American Cancer Society.)

Background: Cadmium exposure has been suggested as a risk factor for prostate cancer, and experimental literature suggests that the carcinogenic effect of cadmium is modified by the presence of zinc. We evaluated total prostate-specific antigen (PSA) levels in relation to urinary cadmium concentrations and dietary zinc intake., Methods: PSA levels were determined in 1,320 men over the age of 40 in the 2001-2002 National Health and Nutrition Examination Survey (NHANES). Urinary cadmium concentrations were measured in about one-third of the sample population, whereas dietary zinc intake was based on participants' 24-hr recall. Information on all three variables was available for 422 men in the 2001-2002 NHANES survey. We performed linear regressions to evaluate the relationships these factors after accounting for age and other covariates., Results: Little evidence for an association between cadmium and elevated PSA level was observed. However, the data provide suggestive evidence for an interaction between zinc intake and cadmium exposure (P for interaction=0.09). Among men with zinc intake less than the median level of 12.67 mg/day, an increase in 1 microg/g creatinine cadmium exposure was associated with a 35% increase in PSA level. In contrast, among men with greater than median zinc intake, little evidence for an association between cadmium and PSA was found., Conclusions: These findings suggest a protective effect of zinc intake on cadmium-induced prostatic injury, and may provide further rationale for investigating the impact of these factors individually and jointly on the etiology of prostate cancer.

A database of benzene, toluene, and xylene measurements was compiled from an extensive literature review that contained information on several exposure determinants, including job type, operation, mechanism of release, process type, ventilation, temperature, distance from the source, quantity, and location. The database was used to develop statistical models for benzene, toluene, and xylene exposure as a function of operation and other workplace determinants. These models can be used to predict exposure levels for subjects enrolled in community-based case-control studies. This article presents the derived parameter estimates for specific operations and additional workplace exposure determinants and describes a number of statistical and data limitation issues that are inherent in determinants modeling of historical published data. [Supplementary materials are available for this article. Go to the publisher's online edition of Journal of Occupational and Environmental Hygiene for the following free supplemental resource(s): a PDF file of QQ plots and a Word file with references used in the benzene/toluene/xylene exposure database].

This review assesses the epidemiological literature describing dentist mortality and cancer incidence risk. In the dental workplace a variety of hazards may have been historically present or currently exist which can impact dentists' long-term health, including their mortality and cancer incidence. The epidemiological literature of dentistry's health outcomes was reviewed with a focus on all cancers combined and cancers of the brain, lung, reproductive organs and skin. Relevant studies were identified using MEDLINE and NIOSHTIC through early 2006 and from references cited in the articles obtained from these databases. Dentist cancer mortality and incidence generally showed a favourable risk pattern for lung cancer and overall cancer occurrence. Nevertheless, several studies reported an increased risk for certain cancers, such as those of the skin and, to a lesser extent, the brain and female breast. These elevated risks may be related to social status or education level, or may alternatively represent the impact of hazards in the workplace. The evidence for an increased mortality or cancer incidence risk among dentists must be interpreted in light of methodological limitations of published studies. Future studies of dentists would benefit from the assessment of specific occupational exposures rather than relying on job title alone.

Background: Phthalates impair rodent testicular function and have been associated with anti-androgenic effects in humans, including decreased testosterone levels. Low testosterone in adult human males has been associated with increased prevalence of obesity, insulin resistance, and diabetes., Objectives: Our objective in this study was to investigate phthalate exposure and its associations with abdominal obesity and insulin resistance., Methods: Subjects were adult U.S. male participants in the National Health and Nutrition Examination Survey (NHANES) 1999-2002. We modeled six phthalate metabolites with prevalent exposure and known or suspected antiandrogenic activity as predictors of waist circumference and log-transformed homeostatic model assessment (HOMA; a measure of insulin resistance) using multiple linear regression, adjusted for age, race/ethnicity, fat and total calorie consumption, physical activity level, serum cotinine, and urine creatinine (model 1); and adjusted for model 1 covariates plus measures of renal and hepatic function (model 2). Metabolites were mono-butyl phthalates (MBP), mono-ethyl phthalate (MEP), mono-(2-ethyl)-hexyl phthalate (MEHP), mono-benzyl phthalate (MBzP), mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), and mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP)., Results: In model 1, four metabolites were associated with increased waist circumference (MBzP, MEHHP, MEOHP, and MEP; p-values

Objective: This pilot study was undertaken to determine whether cine organ imaging (COI) of the entire kidney yields a quicker and equally diagnostic study compared with traditional 2-dimensional (2D) scanning., Methods: Fifty-seven adult patients referred for diagnostic renal sonography underwent 2D sonography followed by COI performed by a second sonographer, who was blinded to the results of the first examination. Images were interpreted blindly by 2 independent readers in 2 separate reading sessions divided into 2D or COI image sets for each patient. The acquisition time and interpretation time of each protocol were recorded. Images were scored for the percentage of kidney visualized and for the presence or absence of hydronephrosis, stones, cysts, and renal lesions (non-simple cysts and solid masses)., Results: The average acquisition time decreased from 13.3 to 10.5 minutes between 2D and COI studies, respectively (P = .02). The average image interpretation time increased 37 seconds (P < .0001). A greater percentage of parenchymal visualization was achieved with COI versus 2D imaging. There was no significant difference in detection of renal abnormalities (hydronephrosis, stones, renal cysts, and masses) between the 2 modes, although the detection of cysts on COI was equal to or greater than that on 2D imaging on a per-patient basis., Conclusions: Cine organ imaging decreased the acquisition time significantly while retaining and possibly improving diagnostic quality. The minimally increased interpretation time may be decreased in the future by fewer volume acquisitions per patient. Further investigations will be needed to assess the impact of color Doppler imaging in volumetric protocols as well as to compare renal lesion detection versus computed tomography and magnetic resonance imaging.

Methyl mercury (MeHg) is highly toxic to the developing nervous system. Human exposure is mainly from fish consumption since small amounts are present in all fish. Findings of developmental neurotoxicity following high-level prenatal exposure to MeHg raised the question of whether children whose mothers consumed fish contaminated with background levels during pregnancy are at an increased risk of impaired neurological function. Benchmark doses determined from studies in New Zealand, and the Faroese and Seychelles Islands indicate that a level of 4-25 parts per million (ppm) measured in maternal hair may carry a risk to the infant. However, there are numerous sources of uncertainty that could affect the derivation of benchmark doses, and it is crucial to continue to investigate the most appropriate derivation of safe consumption levels. Earlier, we published the findings from benchmark analyses applied to the data collected on the Seychelles main cohort at the 66-month follow-up period. Here, we expand on the main cohort analyses by determining the benchmark doses (BMD) of MeHg level in maternal hair based on 643 Seychellois children for whom 26 different neurobehavioral endpoints were measured at 9 years of age. Dose-response models applied to these continuous endpoints incorporated a variety of covariates and included the k-power model, the Weibull model, and the logistic model. The average 95% lower confidence limit of the BMD (BMDL) across all 26 endpoints varied from 20.1 ppm (range=17.2-22.5) for the logistic model to 20.4 ppm (range=17.9-23.0) for the k-power model. These estimates are somewhat lower than those obtained after 66 months of follow-up. The Seychelles Child Development Study continues to provide a firm scientific basis for the derivation of safe levels of MeHg consumption.

We evaluated the association between potential occupational lead exposure and the risk of brain cancer mortality in the National Longitudinal Mortality Study (NLMS), which is a prospective census-based cohort study of mortality among the noninstitutionalized United States population (1979-1989). The present study was limited to individuals for whom occupation and industry were available (n = 317,968). Estimates of probability and intensity of lead exposure were assigned using a job-exposure matrix (JEM). Risk estimates for the impact of lead on brain cancer mortality were computed using standardized mortality ratio (SMR) and proportional hazards and Poisson regression techniques, adjusting for the effects of age, gender and several other covariates. Brain cancer mortality rates were greater among individuals in jobs potentially involving lead exposure as compared to those unexposed (age- and gender-adjusted hazard ratio (HR) = 1.5; 95% confidence interval (CI) = 0.9-2.3) with indications of an exposure-response trend (probability: low HR = 0.7 (95% CI = 0.2-2.2), medium HR = 1.4 (95% CI = 0.8-2.5), high HR = 2.2 (95% CI = 1.2-4.0); intensity: low HR = 1.2 (95% CI = 0.7-2.1), medium/high HR = 1.9 (95% CI = 1.0-3.4)). Brain cancer risk was greatest among individuals with the highest levels of probability and intensity (HR = 2.3; 95% CI = 1.3-4.2). These findings provide further support for an association between occupational lead exposure and brain cancer mortality, but need to be interpreted cautiously due to the consideration of brain cancer as one disease entity and the absence of biological measures of lead exposure., (Copyright 2006 Wiley-Liss, Inc.)

Objective: The goal of this pilot study was primarily to explore the safety and, secondarily, the efficacy of the use of "prn" quetiapine for treatment of moderate agitation accompanied by psychosis in an emergency department setting., Methods: This was an open-label study in which 20 patients with psychotic agitation were treated in the emergency department with 100, 150, or 200 mg of quetiapine. Physicians who were unaffiliated with the study established the diagnoses and selected the doses to be used for each patient. A rater who was blinded to the dose performed the assessments. The primary safety measure was the onset of orthostatic hypotension. The primary efficacy measure was a 40% reduction in scores on the Positive and Negative Syndrome Scale-Excited Component (PANSS-EC) over 120 minutes. The secondary efficacy measure was a reduction of 2 points or more on the Behavioral Activity Rating Scale (BARS) at 120 minutes post-dose. All subjects provided written informed consent., Results: With regard to safety outcomes, 40% of subjects exhibited orthostasis by 120 minutes, although only 25% of these patients described clinically significant symptoms. In terms of efficacy, 50% of subjects experienced at least a 40% reduction in PANSS-EC scores at 2 hours, while 68.8% showed reductions of 2 points or more in scores on the BARS over the same time period., Conclusion: Quetiapine demonstrated some efficacy as a sedative agent in the emergency setting, although no clear dose-response pattern emerged over the narrow dose range tested. Orthostasis was common and did not correlate with dosing. This small study did not support the use of quetiapine to treat acute agitation in potentially volume-depleted patients.

In occupational epidemiology, exposure-response analyses play an important role in the evaluation of the etiologic relevance of chemical and physical exposures. The standardized mortality or morbidity ratio (SMR) has been commonly used in occupational cohort studies. Statistical approaches to evaluate exposure-response patterns using SMRs have mostly been limited to analyses in which the exposure under investigation is categorized. Here, a graphical method for evaluating exposure-response patterns is presented based on SMR estimates across moving exposure windows. This method is demonstrated using the results of two hypothetical cohort studies. The proposed approach may be useful for graphical exploration of exposure-response trends in situations where the number of observed cases is small.

Quantitative risk assessment provides formalized scientific input for setting occupational and environmental standards for potentially toxic exposures. We describe the methods to perform quantitative cancer risk assessment based on published epidemiological literature using a hand calculator or spreadsheet. These methods are illustrated for some suspected or known human carcinogens, including perchloroethylene, formaldehyde, benzene and nickel. The approach to cancer risk assessment presented here may prove useful for those without access to original data from epidemiologic studies. The methods described should facilitate the use of published epidemiological data in the estimation of cancer risk in the general or working population.

Some have suggested a threshold mechanism for the carcinogenicity of exposure to hexavalent chromium, Cr(VI). We evaluated the nature of the exposure-response relationship between occupational exposure to Cr(VI) and respiratory cancer based on results of two recently published epidemiological cohort studies. The combined cohort comprised a total of 2,849 workers employed at two U.S. chromate production plants between 1940 and 1974. Standardized mortality ratios (SMRs) for lung cancer in relation to cumulative Cr(VI) exposure categories were reported using regional mortality rates. Linear additive and multiplicative relative risk regression models were fit to the SMRs of the individual and combined studies. Both models fit the data from the individual studies reasonably well; however, the fit was somewhat less adequate for the pooled data. Meta-analysis of the slope estimates obtained from the multiplicative relative risk model showed substantial heterogeneity between the two epidemiological studies. In conclusion, these data indicate that a linear dose response describes the relationship between Cr(VI) and lung cancer reasonably well, and therefore these analyses do not necessarily support the threshold hypothesis for the lung carcinogenicity of Cr(VI). However, these results must be interpreted with recognition of the limitations of the use of epidemiological data in the evaluation of nonlinear exposure-response patterns.

This article presents the results of an extensive literature review identifying the uses or occurrences of, and exposures to, benzene in a variety of industries for a community-based case-control study of childhood brain cancer in the United States and Canada. We focused on industries for which quantitative exposure data were identified in studies conducted in North America in the 1980s. Each industry was coded according to the 1987 Standard Industrial Classification (SIC) system. For each industry, information relevant to exposure assessment, including process descriptions, job titles, tasks, and work practices, was summarized when available. Estimates of probability and intensity of exposure, and our confidence in these estimates are presented. Arithmetic means (AMs), weighted for the number of measurements for each industry, were calculated based on measurement data from long-term (i.e., 60+ minutes) personal sampling; short-term or area samples were only used when no other data were available for a given industry. Industries for which no quantitative exposure levels were identified in the North American literature but for which information was found on benzene use are briefly described. Published exposure data indicate that workers in most industries in the 1980s experienced exposure levels below the current standard of 1 part per million (ppm), with a weighted AM of 0.33 ppm across all industries. Despite the longtime recognition of the hematological effects of benzene, little information was available on exposure levels and determinants for many industries with potential exposure. Nevertheless, this review may clarify some of the procedures involved in assessing occupational exposures in community-based studies and may aid in the interpretation of previous occupational studies that relied on job title or industry.

The authors examined the risk of childhood brain cancer in relation to parental exposure to classes of pesticides among 154 children diagnosed with astrocytoma and 158 children diagnosed with primitive neuroectodermal tumors (PNET) in the United States and Canada between 1986 and 1989. Controls were selected by random digit dialing and were individually matched to cases by race, age, and geographic area. Each job in the fathers' work history and the usual occupation of mothers were assigned a probability, intensity, and frequency of exposure to insecticides, herbicides, and agricultural and nonagricultural fungicides. Elevated risks of astrocytoma were found for paternal exposure (ever vs. never) to all four classes of pesticides (odds ratio (OR) = 1.4-1.6). An increased risk of PNET was observed for only herbicides (OR = 1.5). For mothers, odds ratios for astrocytoma were elevated for insecticides, herbicides, and nonagricultural fungicides (OR = 1.3-1.6) but not agricultural fungicides (OR = 1.0). No indication was found of an increased risk for PNET. There was little indication for an association with cumulative and average parental exposure. Most risk estimates were around unity, and exposure-response patterns were absent. Overall, it seems unlikely that parental exposure to pesticides plays an important role in the etiology of childhood brain cancer.

Some studies have suggested a role of pesticide exposure in the development of neurobehavioral disorders. This case-control study examined the association between mortality from mental disorders and occupational exposure to pesticides. The study population consisted of 7756 deaths and 330,452 eligible controls identified from US death certificate files for the years 1988 through 1992. Exposure assignment was based on job title reported on the death certificates. Employment in jobs potentially involving pesticide exposure was weakly associated with the risk of death from mental disorders (odds ratio [OR] = 1.46; 95% confidence interval (95% CI) = 1.33-1.60). This association was stronger among women (OR = 2.65; 95% CI = 1.89-3.71), in particular for deaths from neurotic disorders (OR = 4.32; 95% CI = 2.44-7.64). These results must be interpreted with caution, however, because the impact of social and work-related factors other than pesticide exposure is not known.

This exploratory study evaluated the association between suicide and occupational exposure to electromagnetic fields, pesticides, and hydrocarbon solvents. The study population comprised 11,707 suicide deaths and 132,771 eligible controls identified from United States death certificate files for the years 1991 and 1992. Exposure assignment was based on job title reported on the death certificates. Exposure to electromagnetic fields and pesticides was weakly associated with suicide risk, while little evidence for an increased risk was seen for hydrocarbon solvents. The association for electromagnetic field exposure was highest for suicide between the ages 20 and 35 (odds ratio; OR = 1.5), while the highest risk of suicide for pesticide exposure was seen between the ages of 35 and 49 years (OR = 1.5). Further investigation to replicate these findings seems warranted, using higher quality occupational data.