MEDI 604

HEAVY METALS III: EPIDEMIOLOGY & PUBLIC HEALTH – 1999

This course can be taken as a stand-alone course but is also Part III of the three course graduate series on Heavy Metals which is offered in conjunction with Part I (Bio 125: Occurrence, Analysis and Ecological Impact) and Part II (Pharmacology 133: Chemistry, Biochemistry and Pharmacology), Part III will focus on the principles and methods of epidemiology, the study of the distribution and determinants of disease in human populations. There will be an emphasis on environmental exposures, and metals in particular. The course will provide an overview of epidemiological study designs, measures of disease frequency and association, and causal inference. It will cover exposure assessment and other methodological considerations and concepts in the design, conduct and analysis of epidemiological studies. Specific topics will be covered though student presentations.

OBJECTIVES:

To enable students from varying disciplines to understand, evaluate and synthesize the epidemiological literature and participate in collaborative research.

EVALUATION:

Students will be evaluated based on their classroom participation and presentations.

REQUIRED READINGS:

There will be required readings for each class. Please do the readings before class. Three copies of each reading packet will be available on reserve at Dana Library. They are filed at Dana by class date.

RECOMMENDED TEXT:

There will be recommended readings from this text listed for each class. The problems at the end of each chapter are also suggested. This book is available for purchase at the DMS Bookstore, 8th floor Vail:

  • Medical Epidemiology, Second Edition (Appleton and Lang, 1996) by Raymond S. Greenberg, Stephen R. Daniels, W. Dana Flanders, J. William Eley and John R. Boring

    The following are recommended texts on specific topics. These may be useful for supplementary reading.

    The following books are on reserve at Dana:

  • Research Methods in Occupational Epidemiology by Harvey Checkoway, Neil E. Pearce, and Douglas J. Crawford-Brown

  • Introduction to the Cellular and Molecular Biology of Cancer, Second Edition Edited by L.M. Franks and N.M. Teich

  • Biological Markers in Epidemiology by Barbara S. Hulka, Timothy C. Wilcosky, and Jack D. Griffith

  • IARC Monographs on the Evaluation of Carcinogenic Risks to Humans

  • ATSDR, Toxicological Profiles

    The following books are located in Margaret’s office, DHMC, 4th floor Rubin Building, Suite 3:

  • Principles of Exposure Measurement in Epidemiology by Bruce K. Armstrong, Emily White, and Rodolfo Saracci

  • Environmental Epidemiology; Public Health and Hazardous Wastes by National Reasearch Council

  • Topics in Environmental Epidemiology Edited by Kyle Steenland and David A. Savitz

  • Molecular Epidemiology; Principles and Practices Edited by Paul A. Schulte and Frederica P. Perera

  • Nutritional Epidemiology by Walter C. Willett

    COURSE FACULTY:

    Course Director:

    Margaret Karagas, PhD, Department of Community and Family Medicine

    Instructors:

  • Amy Warren, Visiting Assistant Professor, Departments of Pharmacology and Toxicology and Chemistry

  • Tor Tosteson, ScD, Associate Professor of Community and Family Medicine

  • John Baron, MD, Professor of Community and Family Medicine

  • Kim Perez, BA, Department of Community and Family Medicine

  • Virginia Stannard, RN, MEd, Research Associate, Department of Community and Family Medicine

    Guest Instructors:

  • Karl Kelsey, MD, MPH, Professor, Harvard School of Public Health

  • Peter Shields, MD, Section Chief, Molecular Epidemiology, National Cancer Institute

    TA:

  • Jennifer Miglionico, MS, Department of Community and Family Medicine

    (Blitz with questions or to set up an appointment)

     

    COURSE LOCATION AND TIMES:

    Tuesdays and Thursdays, 2-4 PM 615 Vail, except April 13th will be held in room 311/312 in Dana Library and May 6th will be in Remsen 619.

     

    COURSE WEBSITE:

    http://www.dartmouth.edu/~medi604

    (Syllabus, bibliographies for each of the Superfund metals, and WWW links will be placed on this site).

     

    SYLLABUS:

    March 30 Introduction to the Course and Epidemiology

    Margaret Karagas

    Read article packet for today’s class, on reserve at Dana

    Suggested: Chapter 1 in Medical Epidemiology

    April 1 Study Designs

    Margaret Karagas

    Read Chapters 3, 7-9 in Medical Epidemiology

    Suggested: article packet for today’s class, on reserve at Dana

    April 6 Risk Estimation/Causal Inference

    Margaret Karagas

    Read suggested article packet for today’s class, on reserve at Dana

    Suggested: Chapters 2 and 4 in Medical Epidemiology

    April 8 Effect Modification/Confounding

    Margaret Karagas

    Read article packet for today’s class, on reserve at Dana

    Suggested: Pages 141-142 in Medical Epidemiology

    April 13 Resources in Epidemiology

    Jennifer Miglionico

    April 15 Measurement of Exposure & Outcome

    Margaret Karagas

    Suggested: Chapters 6 and 10 in Medical Epidemiology

    April 20 DNA adducts and other Biomarkers

    Amy Warren

    April 22 Measurement Error

    Tor Tosteson

    Read article packet for today’s class, on reserve at Dana

    April 27 Cancers in Women and Endocrine Disruption

    John Baron

    Read article packet for today’s class, on reserve at Dana

    April 29 Evaluating Epidemiology

    John Baron

    Read article packet for today’s class, handed out

    Suggested: Chapter 13 in Medical Epidemiology

    May 4 Student Presentations

    Exposure Measurement

    Students scheduled: Angeline (Nickel), Kristin (Zinc) and Ron (Arsenic)

    May 6 Student Presentations

    Exposure Measurement

    Students scheduled: Paul (Mercury), Ronnie (Chromium)

    May 11 Meta-Analysis/Risk Assessment

    Tor Tosteson

    Read article packet for today’s class, on reserve at Dana

    May 13 Molecular Epidemiology

    Karl Kelsey

    May 18 Reproductive and Perinatal epidemiology

    Kim Perez

    Read article packet for today’s class, on reserve at Dana

    May 20 Peter Shields

    May 25 Student Presentations

    Journal Club

    Students scheduled: Angeline, Ron

    May 27 Student Presentations

    Journal Club

    Students scheduled: Paul, Ronnie, Kristin

    June 1 Practical Issues in the Conduct of Epidemiologic Studies

    Virginia Stannard

    PROJECTS:

    You will be expected to make two presentations during the course (1) on exposure assessment and (2) a journal club presentation about an epidemiologic article related to heavy metals. As part of the presentation, you will need to provide a handout outlining the material you will cover. The handout may simply be your overheads for your presentation and possibly copies of some key articles or materials. Please also provide a complete bibliography of the references you consulted for your presentation. A half hour will be allotted to each presentation (about 20 minutes of presentation and 10 minutes for questions).

    You should pick topics of interest to you. For example, if your dissertation work is on the biochemical effects of chromium exposure, you may want to choose chromium for both your exposure measurement topic and your epidemiology review topic. But this is entirely up to you and what others choose. Topics will be taken on a first come, first serve basis. You will need to decide on your topics by the end of class on April 13th.

    Exposure Measurement:

    1. Choose a metal and describe:

  • how humans are exposed

  • how to measure exposure

    consider issues relating to:

  • measuring the recent past vs the distant past

  • validity, reliability

  • prevalence of the exposure

    OR

    2. Choose a genotype/phenotype involved in susceptibility to metal carcinogenesis and describe:

  • the trait

  • how it is measured

  • studies involving the genotype/phenotype and metal exposure (not outcome)

    Epidemiologic Review:

  • 1.Review the epidemiology of a metal and a specific outcome (e.g., arsenic and reproductive outcomes, chromium and lung cancer).

  • 2. Review studies of a specific design i.e., using GIS or intervention/prevention studies.

  • 3. Review the epidemiologic studies of a genotype/phenotype involved in metal susceptibility

    Readings for Session 1, March 30, 1999 on Reserve at Dana Library

    *Feinstein AR. Scientific standard in epidemiologic studies of the menace of daily life. Science 242:1257-1263, 1988.

    *Savitz DA, Greenland S, Stolley PD, Kelsey JL. Scientific standards of criticism: a reaction to "Scientific standards in epidemiologic studies of the menace of daily life," by AR Feinstein. Epidemiology 1:78-83, 1990.

    Taubes, G. Epidemiology faces its limits. Science 269:164-169, 1995.

    Various authors. The discipline of epidemiology. Science 269:1325-1328, 1995.

    Feinstein AR. Scientific news and epidemiologic editorials: reply to the critics. Epidemiology 1:170-180, 1990.

    Savitz DA, Kelsey JL. Response to Feinstein. Epidemiology 2:61-63, 1991.

    Greenland S. Science versus advocacy: the challenge of Dr. Feinstein. Epidemiology 2:64-72.

    Feinstein AR. Reprise and lyrics for another chorus. Epidemiology 2:72-76, 1991.


    * denotes mandatory reading for discussion, rest are optional


    Suggested Readings for Session 2, April 1, 1999 on Reserve at Dana Library

    Karagas MR. When subjects are not randomly assigned: the cohort approach. Journal of Cutaneous Medicine and Surgery 2:90-94, 1997.

    Heacock HJ, Rivers JK. Assessing scientific data: the case-control study as it applies to dermatology. Part 1: The case-control method. Journal of Cutaneous Medicine and Surgery 1:151-154, 1997.

    Heacock HJ, Rivers JK. Assessing scientific data: the case-control study as it applies to dermatology. Part II: Interpreting the results. Journal of Cutaneous Medicine and Surgery 2:35-40, 1997.

    Yusuf S, Collins R, Peto R. Why do we need some large, simple randomized trials? Statistics in Medicine 3:409-420, 1984.

    Morgenstern H. Use of ecologic analysis in epidemiologic research. Am J Pub Health 72:1336-1344, 1982.

    Newspaper clip and New Yorker article on disease clusters.


    Suggested Readings for Session 3, April 6, 1999 on Reserve at Dana Library

    Mueller BA, Daling JR, Moore DE, Weiss NS, Spadoni LR, Stadel BV, Soules MR. Appendectomy and the Risk of Tubal Infertility. New England Journal of Medicine 35:1506-8, 1986.

    Ahlbom A, Axelson O, Hansen ES, Hogstedt C, Jensen UJ, Olsen J. Interpretation of "negative" studies in occupational epidemiology. Scand J Work Environ Health 16:153-7, 1990.

    Savitz D. In defense of black box epidemiology. Epidemiology 5:550-552, 1994.

    Milham, S. Increased mortality in amateur radio operators due to lymphatic and hematopoietic malignancies. American Journal of Epidemiology 127:50-54, 1988.

    Rothman KJ. Causes. American Journal of Epidemiology 104:587-592, 1976.

    Weiss NS. Inferring causal relationships: elaboration of the criterion of "dose-response". American Journal of Epidemiology 113:487-490, 1981.

    Weiss NS, Liff JM. Accounting for the multicausal nature of disease in the design and analysis of epidemiologic studies. American Journal of Epidemiology


    Readings for Session 4, April 8, 1999 on Reserve at Dana Library

    Excerpts from: Rothman KJ. Modern Epidemiology (First Edition). Little Brown, 1986.

    Dales LG, Ury HK. An improper use of statistical significance testing in studying covariables. Int J Epidemiology 7:373-375, 1978.

    Schlesselman JJ. Assessing effects of confounding variables. Am J Epidemiology 108:3-8, 1978.

    Weed DL. Kramer BS. Induced abortion, bias, and breast cancer: why epidemiology has not reached its limit. Journal of the National Cancer Institute 88:1698-1700, 1996.

    *Rookus MA, van Leeuwen FE. Induced abortion and risk for breast cancer: reporting (recall) bias in a Dutch case-control study. Journal of the National Cancer Institute 88:1759-1764, 1996.

    *Andrieu N, Goldstein AM. Epidemiologic and genetic approaches in the study of gene-environment interaction: an overview of available methods. Epidemiologic Reviews 20:137-147, 1998.

    *optional


    Readings for Session 8 - Tor Tosteson, April 22, 1999 on Reserve at Dana Library

    Knuiman MW, Divitini ML, Buzas JS, Fitzgerald PEB. Adjustment for regression dilution in epidemiological regression analyses. Ann Epidemiol 8:56-63, 1998.

    *Prentice RL. Measurement error and results from analytic epidemiology: dietary fat and breast cancer. JNCI 88:1738-47, 1996.

    *Spiegelman D, Valanis B. Correcting for bias in relative risk estimates due to exposure measurement error: A case study of occupational exposure to antineoplastics in pharmacists. Am J Pub Health 88:406-412, 1998.

    *McKeown-Eyssen GE, Tibshirani R. Implications of measurement error in exposure for the sample sizes of case-control studies. Am J Epidemiol 139:415-21, 1994.

    *Wu AH, Pike MC, Stram DO. Meta-analysis: Dietary fat intake, serum estrogen levels, and the risk of breast cancer. JNCI 91:529-534, 1999.

    *Carroll RJ, Freedman L, Pee D. Design aspects of calibration studies in nutrition, with analysis of missing data in linear measurement error. Biometrics 53:1440-1457, 1997.

    *optional

    Also suggested:

    Chapters 3-5 in Principles of Exposure Measurement in Epidemiology by Bruce Armstrong, Emily White and Rodolfo Saracci

    Nutritional Epidemiology by Walter C. Willett


    Readings for Session 9 - John Baron, April 27, 1999 on Reserve at Dana Library

    Required (for discussion - think about the epidemiologic concepts we have learned as well as study design):

    Sturgeon SR, Brock JW, Potischman N, Needham LL, Rothman N, Brinton LA, Hoover RN. Serum concentrations of organochlorine compounds and endometrial cancer risk (United States). Cancer Causes and Control 9:417-424, 1998.

    Hunter DJ, Hankinson SE, Laden F, Colditz GA, Manson JE, Willett WC, Speizer FE, Wolff MS. Plasma organochlorine levels and the risk of breast cancer. NEJM 377:1253-1258, 1997.

    Required (for background):

    Lewin DI. Is it science? EPA's dioxin reassessment stirs debate. The Journal of NIH Research 7:34-38, 1995.

    Grisso JA. Making comparisons. The Lancet 342:157-160, 1993.

    Required (just read the abstracts):

    Arnold SF, Klotz DM, Collins BM, Vonier PM, Guillette LJ, McLachlan JA. Synergistic activation of estrogen receptor with combinations of environmental chemicals. Science 272: 1489-1492, 1996.

    Kelce WR, Stone CR, Laws SC, Gray LE, Kemppainen JA, Wilson EM. Persistent DDT metabolite p,p'-DDE is a potent androgen receptor antagonist. Nature 375:581-585, 1995.

    Optional (but good review articles for your collection):

    Adami H, Lipworth L, Titus-Ernstoff L, Hsieh C, Hanberg A, Ahlborg U, Baron J, Trichopoulos D. Organochlorine compounds and estrogen-related cancers in women. Cancer Causes and Control 6:551-566, 1995.

    Ahlborg UG, Lipworth L, Titus-Ernstoff L, Hsieh C, Hanberg A, Baron J, Trichopoulos D, Adami H. Organochlorine compounds in relation to breast cancer, endometrial cancer, and endometriosis: an assessment of the biological and epidemiological evidence. Critical Reviews in Toxicology 25:463-531, 1995.


    Readings for Session 10 - John Baron, April 29, 1999

    Hopenhayn-Rich C, Biggs ML, Fuchs A, Bergoglio R, Tello RE, Nicolli H, Smith AH. Bladder cancer mortality associated with arsenic in drinking water in Argentina. Epidemiology 7:117-124, 1996.

    Bates MN, Smith AH, Cantor KP. Case-control study of bladder cancer and arsenic in drinking water. American Journal of Epidemiology 141:523-30, 1995.

    Handout, "Research Design: Assessing the Medical Literature".

    Chapter 13, in course text, Medical Epidemiology, is suggested but optional.


    Readings for Session 13 ­ Tor Tosteson, May 11 on Reserve at Dana Library

    He J, Vupputuri S, Allen K, Prerost MR, Hughes J, Whelton PK. Passive Smoking and the risk of coronary heart disease: A meta-analysis of epidemiologic studies. NEJM 340:920-6, 1999.

    Kheifets LI. Afifi AA. Buffler PA. Zhang ZW. Occupational electric and magnetic field exposure and brain cancer: a meta-analysis [see comments]. Journal of Occupational & Environmental Medicine 37:1327-41, 1995

    Kawachi I, Colditz GA. Invited commentary: Confounding, measurement error and publication bias in studies of passive smoking. Am J Epidemiol. 144, 1996.

    Brown KG. Assessing risk of inorganic arsenic in drinking water in the United States. Human and Ecological Risk Assessment 4:1061-1070, 1998.

    National Research Council. Report on Arsenic in Drinking Water. Prepubulication Release, 1999. (Read chapters on 1988 Risk Asssessment and Statistical Issues).

    Piegorsch WW, Cox LH. Combining environmental information. Environmental Epidemiology and Toxicology. Environmetrics 7:309-324, 1996.

    Jones DR. Meta-Analysis ­ Weighing the evidence. Statistics in Medicine 14:137-149, 1996.

    Morris RD. Meta-Analysis in cancer epidemiology. Environmental Health Perspectives 102:61-661, 1994.


    Readings for Session 15 - Kim Perez, May 18 on Reserve at Dana Library

    Required

    Selevan SG, Lemasters GK. The dose-response fallacy in human reproductive studies of toxic exposures. J Occupational Med 29:451454, 1987.

    Zelikoff JT, Bertin JE, Burbacher TM, Hunter ES, Miller RK, Silbergeld EK, Tabacova S, Rogers JM. Health risks associated with prenatal metal exposure. Fundamental and Applied Toxicology 25:161-70, 1995.

    Recommended

    Sever LE. Epidemiologic evidence for toxic effects of occupational and environmental chemicals on the testes. In Thomas JA, Colby HD (editors). Endocrine Toxicology, 2nd Edition. Taylor and Francis, 1997.

    Myers GJ, Davidson PW, Shamlaye CF. A review of methylmercury and child development. NeuroToxicology 19:313-328, 1998.

    Golub MS, Macintosh MS, Baumrind N. Developmental and reproductive toxicity of inorganic arsenic: animal studies and human concerns. J Toxicol and Environ Health, Part B 1:199-241, 1998.

    DeSesso JM, Jacobson CF, Scialli AR, Farr CH, Holson JF. An assessment of the developmental toxicity of inorganic arsenic. Reproductive Toxicology Review 12:385-433, 1998.


    Readings for Session 17 - Student Journal Club, May 25 handed out in class

    Angeline

    Dockery DW, Pope CA, Xu X, Spengler JD, Ware JH, Fay ME, Ferris BG, Speizer FE. An association between air pollution and mortality in six US cities. New England Journal of Medicine 329:1753-9, 1993.

    Ron

    Steenland K, Beaumont J, Elliot L. Lung cancer in mild steel welders. American Journal of Epidemiology 133:220-9, 1991.


    Readings for Session 18 - Student Journal Club, May 27 handed out in class

    Paul

    MacIntosh DL, Williams PL, Hunter DJ, Sampson LA, Morris SC, Willett WC, Rimm EB. Evaluation of a food frequency questionnaire-food composition approach for estimating dietary intake of inorganic arsenic and methymercury. Cancer Epidemiology, Biomarkers & Prevention 6:1043-50, 1997.

    Ronnie

    Sorahan T, Burges DC, Hamilton L, Harrington JM. Lung cancer mortality in nickel/chromium platers, 1946-95. Occup Environ Med 55:236-42, 1998.



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