Tsuji J.S.,Exponent, Inc. |
Perez V.,Exponent, Inc. |
Garry M.R.,Exponent, Inc. |
Alexander D.D.,EpidStat Institute
Toxicology | Year: 2014
The U.S. Environmental Protection Agency (EPA) is developing an integrated assessment of non-cancer and cancer risk assessment of inorganic arsenic (iAs). Cardiovascular disease (CVD) in association with iAs exposure has been examined in a number of studies and provides a basis for evaluating a reference dose (RfD) for assessing potential non-cancer health risks of arsenic exposure. In this systematic review of low-level iAs exposure (i.e., <100-150. μg/L arsenic water concentration) and CVD in human populations, 13 cohort and case-control studies from the United States, Taiwan, Bangladesh, and China were identified and critically examined for evidence for derivation of a RfD. Eight cross-sectional and ecological studies from the United States were also examined for additional information. Prospective cohort data from Bangladesh provided the strongest evidence for determining the point of departure in establishing a candidate RfD based on a combined endpoint of mortality from "ischemic heart disease and other heart diseases." This study as well as the overall literature supported a no-observed-adverse-effect level of 100. μg/L for arsenic in water, which was equivalent to an iAs dose of 0.009. mg/kg-day (based on population-specific water consumption rates and dietary iAs intake). The study population was likely sensitive to arsenic toxicity because of nutritional deficiencies affecting arsenic methylation and one-carbon metabolism, as well as increasing CVD risk. Evidence is less clear on the interaction of CVD risk factors in the United States (e.g., diabetes, obesity, and hypertension) with arsenic at low doses. Potential uncertainty factors up to 3 resulted in a RfD for CVD in the range of 0.003-0.009. mg/kg-day. Although caution should be exercised in extrapolating these results to the U.S. general population, these doses allow a margin of exposure that is 10-30 times the current RfD derived by EPA (based on skin lesions in Southwest Taiwan). These findings suggest that the current EPA RfD is protective of CVD. © 2014.
Berent S.,University of Michigan |
Giordani B.,University of Michigan |
Albers J.W.,University of Michigan |
Garabrant D.H.,University of Michigan |
And 3 more authors.
NeuroToxicology | Year: 2014
Background: Exposure to chlorpyrifos (CPF), an organophosphorus (OP) anticholinesterase insecticide, occurs typically in settings where multiple agents are present (e.g., agriculture) and quantitative dose measures may be absent (e.g., pesticide application). Such exposures allow few opportunities to study potential neurobehavioral effects of CPF alone. We studied the relationship between CPF exposure and behavioral function among CPF manufacturing workers, which allowed identification, measurement, and estimation of exposure and important non-exposure variables that potentially could affect study findings. Methods: A prospective longitudinal study design was used to compare neurobehavioral function over a one-year period among 53 CPF workers and 60 referent workers. Quantitative and qualitative measures were used, and potential confounders were identified and tested for possible inclusion in our statistical models. Neurobehavioral function was assessed by neuropsychological tests covering various behavioral domains that may be adversely affected by exposure to CPF in sufficient amount. Results: CPF workers had significantly greater CPF exposures during the study period than did referents at levels where physiologic effects on plasma butyrylcholinesterase (BuChE) activity were apparent and with higher 3,5,6-trichloro-2-pyridinol (TCPy/Cr) urinary excretion (p<. 0.0001) and lower average BuChE activity (p<. 0.01). No evidence for impaired neurobehavioral domains by either group of workers was observed at baseline, on repeat examination, or between examinations. CPF workers scored higher than referent workers on the verbal memory domain score (p= 0.03) at baseline, but there were no significant changes in verbal memory over time and no significant group-by-time interactions. Conclusions: The study provides important information about CPF exposure in the workplace by not supporting our working hypothesis that CPF exposure associated with various aspects of the manufacturing process would be accompanied by adverse neurobehavioral effects detectable by quantitative neurobehavioral testing. Some aspects making this workplace site attractive for study and also present limitations for the generalization of results to other situations that might have exposures that vary widely between and within different facilities and locations. For example, these results might not apply to occupations such as applicators with higher exposure or to workers with low educational levels. © 2014 Elsevier Inc.
Matthews C.E.,U.S. National Cancer Institute |
Cohen S.S.,EpidStat Institute |
Fowke J.H.,Vanderbilt University |
Han X.,International Epidemiology Institute |
And 6 more authors.
American Journal of Epidemiology | Year: 2014
There is limited evidence demonstrating the benefits of physical activity with regard to mortality risk or the harms associated with sedentary behavior in black adults, so we examined the relationships between these health behaviors and cause-specific mortality in a prospective study that had a large proportion of black adults. Participants (40-79 years of age) enrolled in the Southern Community Cohort Study between 2002 and 2009 (n = 63,308) were prospectively followed over 6.4 years, and 3,613 and 1,394 deaths occurred in blacks and whites, respectively. Black adults who reported the highest overall physical activity level (≥32.3 metabolic equivalent-hours/day vs. <9.7 metabolic equivalent-hours/day) had lower risks of death from all causes (hazard ratio (HR) = 0.76. 95% confidence interval (CI): 0.69, 0.85), cardiovascular disease (HR = 0.81, 95% CI: 0.67, 0.98), and cancer (HR = 0.76, 95% CI: 0.62, 0.94). In whites, a higher physical activity level was associated with a lower risk of death from all causes (HR = 0.76, 95% CI: 0.64, 0.90) and cardiovascular disease (HR = 0.69, 95% CI: 0.49, 0.99) but not cancer (HR = 0.95, 95% CI: 0.67, 1.34). Spending more time being sedentary (>12 hours/day vs. <5.76 hours/day) was associated with a 20%-25% increased risk of all-cause mortality in blacks and whites. Blacks who reported the most time spent being sedentary (≥10.5 hours/day) and lowest level of physical activity (<12.6 metabolic equivalent-hours/day) had a greater risk of death (HR = 1.47, 95% CI: 1.25, 1.71). Our study provides evidence that suggests that health promotion efforts to increase physical activity level and decrease sedentary time could help reduce mortality risk in black adults. © The Author 2014.
Moulard O.,Oncology Global Evidence and Value Development |
Mehta J.,Sanofi S.A. |
Fryzek J.,EpidStat Institute |
Olivares R.,Oncology Global Evidence and Value Development |
And 2 more authors.
European Journal of Haematology | Year: 2014
Background: Primary myelofibrosis (PMF), essential thrombocythemia (ET), and polycythemia vera (PV) are BCR ABL-negative myeloproliferative neoplasms (MPN). Published epidemiology data are scarce, and multiple sources are needed to assess the disease burden. Methods: We assembled the most recent information available on the incidence and prevalence of myelofibrosis (MF), ET, and PV by conducting a structured and exhaustive literature review of the published peer-reviewed literature in EMBASE and by reviewing online documentation from disease registries and relevant health registries in European countries. The search was restricted to human studies written in English or French and published between January 1, 2000, and December 6, 2012. Results: Eleven articles identified from EMBASE, three online hematology or oncology registries, and two Web-based databases or reports were used to summarize epidemiological estimates for MF, PV, and ET. The incidence rate of MF ranged from 0.1 per 100 000 per year to 1 per 100 000 per year. Among the various registries, the incidence of PV ranged from 0.4 per 100 000 per year to 2.8 per 100 000 per year, while the literature estimated the range of PV incidence to be 0.68 per 100 000 to 2.6 per 100 000 per year. The estimated incidence of ET was between 0.38 per 100 000 per year and 1.7 per 100 000 per year. While a few studies reported on the MPNs' prevalences, it is difficult to compare them as various types of prevalence were calculated (point prevalence vs. period prevalence) and standardization was made according to different populations (e.g., the world population and the European population). Conclusion: There is a wide variation in both prevalence and incidence estimates observed across European data sources. Carefully designed studies, with standardized definitions of MPNs and complete ascertainment of patients including both primary and secondary MFs, should be conducted so that estimates of the population aimed to receive novel treatments for these neoplasms are better understood assist public health planning and provide valuable information about the burden of illness to policy makers, funding agencies, resource planners, healthcare insurers, and pharmaceutical manufacturers. © 2013 John Wiley & Sons A/S.
News Article | November 1, 2016
Park Ridge, Ill. (November 1, 2016) - On the heels of the 2015 Dietary Guidelines for Americans that placed no daily limit on dietary cholesterol and noted eggs are an affordable, accessible, nutrient-rich source of high quality protein, new research shows eggs are associated with a 12 percent reduction in the risk of stroke, the 5th leading cause of death in the United States. The study is published in the Journal of the American College of Nutrition (1). Researchers report that consumption of up to one egg per day had no association with coronary heart disease (CHD) and a 12 percent reduction of stroke risk. These findings come from a systematic review and meta-analysis of studies dating back between 1982 and 2015, which evaluated relationships between egg intake and coronary heart disease (total of 276,000 subjects) and stroke (total of 308,000 subjects). Principal Investigator on this study, Dr. Dominik Alexander of the EpidStat Institute, Ann Arbor, MI, notes that mechanistic work is needed to understand the connection between egg consumption and stroke risk. However, he theorizes that, "Eggs do have many positive nutritional attributes, including antioxidants, which have been shown to reduce oxidative stress and inflammation. They are also an excellent source of protein, which has been related to lower blood pressure." One large egg boasts 6 grams of high-quality protein and antioxidants lutein and zeaxanthin, found within the egg yolk, as well as vitamins E, D, and A. Alexander's research lends further support to changes in the recently-released 2015 Dietary Guidelines for Americans, which have eliminated dietary cholesterol limits, and now include regular consumption of eggs among lean protein choices (2). It also builds on a 2015 meta-analysis in which dietary cholesterol was shown to have no association with cardiovascular diseases, including coronary artery disease and stroke (3). "This systematic review and meta-analysis underscores prior research, showing the lack of a relationship between eggs and heart disease and now suggests a possible beneficial effect of eating eggs on risk of stroke," Tia M. Rains, PhD, Interim Executive Director of the Egg Nutrition Center, the scientific research arm of the American Egg Board. More information on the nutritional benefits of eggs can be found at The Egg Nutrition Center http://www. . ENC is dedicated to providing accurate information on eggs, nutrition, and health, and sponsors scientific research on these topics. Research grants are openly solicited and reviewed by experts in nutrition research to ensure scientific rigor. Independent scientists guide many of the research projects and provide analysis and interpretation of scientific literature. The ENC is the scientific research arm of the American Egg Board, which uses funds from egg farmers for promotion and research. The U.S. Department of Agriculture provides oversight of its activities. ENC is located in Park Ridge, Ill. Visit http://www. for more information. Through AEB, U.S. egg producers come together, in accordance with statutory authority, to establish, finance and execute coordinated programs, on research, education and promotion--all geared to drive demand for eggs and egg products. AEB and all program activities are funded by U.S. egg producers, subject to USDA approval. Visit http://www. for more information. (1) Alexander DD, Miller PE, Vargas AJ, Weed DL, Cohen SS. Meta-analysis of egg consumption and risk of coronary heart disease and stroke. J Am Coll Nutr. 2016 Oct 6:1-13. (2) U.S. Department of Health and Human Services and U.S. Department of Agriculture. 2015-2020 Dietary Guidelines for Americans. 8th Edition. December 2015. Pages 23-25. Available at http://health. . (3) Berger S, Raman G, Vishwanathan R, Jacques PF, Johnson EJ. Dietary cholesterol and cardiovascular disease: a systematic review and meta-analysis. Am J Clin Nutr. 2015;102(2):276-94.
News Article | November 2, 2016
A systematic review and meta-analysis of studies going back more than three decades linked eating eggs with a 12 percent decrease in the risk of stroke. The findings were published in the Journal of the American College of Nutrition. For the study researchers, led by Dr. Dominik Alexander of the EpidStat Institute analyzed the link between eating eggs and stroke in 308,000 people, as well as coronary heart disease in 276,000 people. They found a daily intake of eggs had no link to coronary heart disease and had benefits related to risk of stroke. More research is needed to understand the mechanism at work behind the consumption of eggs and reduced risk of stroke, but Alexander proposed a possible theory. “Eggs do have many positive nutritional attributes, including antioxidants, which have been shown to reduce oxidative stress and inflammation,” Alexander said in a prepared statement. “They are also an excellent source of protein which has been related to lower blood pressure.” In addition to antioxidants, one egg contains 6 grams of good protein, along with vitamins A, D, and E. The U.S. Department of Health and Human Services and the U.S. Department of Agriculture’s 2015 Dietary Guidelines for Americans recently added eggs to its recommended sources of protein and also removed dietary cholesterol limits.
Hirko K.A.,Harvard University |
Kantor E.D.,Harvard University |
Cohen S.S.,EpidStat Institute |
Blot W.J.,International Epidemiology Institute |
And 3 more authors.
American Journal of Epidemiology | Year: 2015
Although much research has been conducted on the role adult body mass index (BMI) plays in mortality, there have been fewer studies that evaluated the associations of BMI in young adulthood and adult weight trajectory with mortality, and it remains uncertain whether associations differ by race or sex. We prospectively examined the relationships of BMI in young adulthood (21 years of age) and adult obesity trajectory with later-life mortality rates among 75,881 men and women in the Southern Community Cohort Study. Study participants were enrolled between 2002 and 2009 at ages 40-79 years and were followed through December, 2011. Multivariable Cox proportional hazards models were used to estimate hazard ratios and 95% confidence intervals. There were 7,301 deaths in the 474,970 person-years of follow-up. Participants who reported being overweight or obese as young adults had mortality rates that were 19% (95% confidence interval: 12, 27) and 64% (95% confidence interval: 52, 78) higher, respectively, than those of their normal weight counterparts. The results did not significantly differ by race or sex. Participants who reported being obese in young adulthood only or in both young and middle adulthood experienced mortality rates that were 40%-90% higher than those of participants who were nonobese at either time. These results suggest that obesity in young adulthood is associated with higher mortality risk regardless of race, sex, and obesity status in later life. © The Author 2015. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health.
Fryzek J.,EpidStat Institute |
Pastula S.,PLLC PLLC |
Jiang X.,PLLC PLLC |
Garabrant D.H.,EpidStat Institute |
Garabrant D.H.,PLLC PLLC
Journal of Occupational and Environmental Medicine | Year: 2013
Objective: Evaluate whether childhood cancer incidence is associated with counties with hydraulic fracturing (HF). Methods: We compared cancer incidence in children in Pennsylvania counties before and after HF drilling began, using standardized incidence ratios (SIRs) and 95% confidence intervals (CIs). Results: The total number of cancers observed was close to expected both before drilling began (SIR = 0.94; 95% CI, 0.90 to 0.99) and after drilling (SIR = 1.02; 95% CI, 0.98 to 1.07) for counties with oil and natural gas wells. Analyses for childhood leukemia were also unremarkable (SIR for leukemia before drilling = 0.97 [95% CI, 0.88 to 1.06]; SIR for leukemia after drilling = 1.01 [95% CI, 0.92 to 1.11]). A slightly elevated SIR was found for central nervous system tumors after drilling (SIR = 1.13; 95% CI, 1.02 to 1.25). This was because of a slight excess in those counties with the fewest number of wells. Conclusions: This study offers comfort concerning health effects of HF on childhood cancers. Copyright © 2013 by American College of Occupational and Environmental Medicine.
Alexander D.D.,EpidStat Institute |
Weed D.L.,DLW Consulting Services |
Miller P.E.,EpidStat Institute |
Mohamed M.A.,Doctors Without Borders
Journal of the American College of Nutrition | Year: 2015
The potential relationship between red meat consumption and colorectal cancer (CRC) has been the subject of scientific debate. Given the high degree of resulting uncertainty, our objective was to update the state of the science by conducting a systematic quantitative assessment of the epidemiologic literature. Specifically, we updated and expanded our previous meta-analysis by integrating data from new prospective cohort studies and conducting a broader evaluation of the relative risk estimates by specific intake categories. Data from 27 independent prospective cohort studies were meta-analyzed using random-effects models, and sources of potential heterogeneity were examined through subgroup and sensitivity analyses. In addition, a comprehensive evaluation of potential dose-response patterns was conducted. In the meta-analysis of all cohorts, a weakly elevated summary relative risk was observed (1.11, 95% CI: 1.03–1.19); however, statistically significant heterogeneity was present. In general, summary associations were attenuated (closer to the null and less heterogeneous) in models that isolated fresh red meat (from processed meat), adjusted for more relevant factors, analyzed women only, and were conducted in countries outside of the United States. Furthermore, no clear patterns of dose-response were apparent. In conclusion, the state of the epidemiologic science on red meat consumption and CRC is best described in terms of weak associations, heterogeneity, an inability to disentangle effects from other dietary and lifestyle factors, lack of a clear dose-response effect, and weakening evidence over time. Key Teaching Points: •The role of red meat consumption in colorectal cancer risk has been widely contested among the scientific community.•In the current meta-analysis of red meat intake and colorectal cancer, we comprehensively examined associations by creating numerous sub-group stratifications, conducting extensive sensitivity analyses, and evaluating dose-response using several different methods.•Overall, all summary associations were weak in magnitude with no clear dose-response patterns.•Interpretation of findings from epidemiologic studies investigating diet and health outcomes involves numerous methodological considerations, such as accurately measuring food intake, dietary pattern differences across populations, food definitions, outcome classifications, bias and confounding, multicollinearity, biological mechanisms, genetic variation in metabolizing enzymes, and differences in analytical metrics and statistical testing parameters. © 2015 The Author(s). Published with license by Taylor & Francis Group, LLC.
Yurko-Mauro K.,Clinical Research |
Alexander D.D.,EpidStat Institute
PLoS ONE | Year: 2015
Introduction: Subjective memory complaints are common with aging. Docosahexaenoic acid (DHA; 22:6 n-3) is a long-chain polyunsaturated fatty acid (LCPUFA) and an integral part of neural membrane phospholipids that impacts brain structure and function. Past research demonstrates a positive association between DHA plasma status/dietary intake and cognitive function. Objectives: The current meta-analysis was designed to determine the effect of DHA intake, alone or combined with eicosapentaenoic acid (EPA; 20:5 n-3), on specific memory domains: episodic, working, and semantic in healthy adults aged 18 years and older. A secondary objective was to systematically review/summarize the related observational epidemiologic literature. Methods: A systematic literature search of clinical trials and observational studies that examined the relationship between n-3 LCPUFA on memory outcomes in healthy adults was conducted in Ovid MEDLINE and EMBASE databases. Studies of subjects free of neurologic disease at baseline, with or without mild memory complaints (MMC), were included. Random effects meta-analyses were conducted to generate weighted group mean differences, standardized weighted group mean differences (Hedge's g), z-scores, and p-values for heterogeneity comparing DHA/EPA to a placebo. A priorisub-group analyses were conducted to evaluate the effect of age at enrollment, dose level, and memory type tested. Results: Episodic memory outcomes of adults with MMC were significantly (P<.004) improved with DHA/EPA supplementation. Regardless of cognitive status at baseline, > 1 g/day DHA/EPA improved episodic memory (P<.04). Semantic and working memory changes from baseline were significant with DHA but no between group differences were detected. Observational studies support a beneficial association between intake/blood levels of DHA/EPA and memory function in older adults. Conclusion: DHA, alone or combined with EPA, contributes to improved memory function in older adults with mild memory complaints. © 2015 Yurko-Mauro et al.