Department of Epidemiology & Community Medicine, EPI 5240: Introduction to Epidemiology Course Overview; Case studies & historical background September 14, 2009 Dr. N. Birkett, Department of Epidemiology & Community Medicine, University of Ottawa 8/2009

The Government is extremely fond of amassing great quantities of statistics. These are raised to the nth degree, the cube roots are extracted, and the results are arranged into elaborate and impressive displays. What must be kept ever in mind, however, is that in every case, the figures are first put down by a village watchman, and he puts down anything he damn well pleases! Sir Josiah Stamp (1880-1941), Her Majesty’s Collector of Internal Revenue. 8/2009

Pneumonia relapse after therapy with Bohbymycetin (synopsis) A 47-year old male physician was diagnosed with acute pneumonia 8 days prior to admission. Initial treatment involved bohbymycetin in standard dose p.o. q4hrs. Defervescence occurred in 36 hrs. and a chest x-ray film taken 5 days prior to admission was entirely normal. Because he felt better, he declined to complete the prescribed 10-day course of Bohbymycetin. He was well for a few days and then, the night before admission, got nauseous. He flew to Cleveland the next morning arrived is severe respiratory distress. He was transferred to a local hospital where tests confirmed a recurrence of his pneumonia with a marked impairment of oxygenation. Gram stain of the sputum showed swarming diplococci and multiple cultures of sputum and blood subsequently grew out type 4 Pneumococcus. 3 8/2009

Pneumonia (Cnt’d) Bohbymycetin being unavailable, the patient was started on one million units q 6 hrs of intravenous penicillin. Failure to progress led to the performance of a right thoracotomy on day 12. Thereafter, he made an uneventful recovery and was discharged on the 25th day after admission. 8/2009

Discussion of Bohbymycetin article Pneumonia (Cnt’d) Discussion of Bohbymycetin article The therapeutic efficacy of Bohbymycetin was first discovered several thousand years ago when an epidemic highly fatal to young Egyptian males seemed not to affect an ethnic minority residing in the same area. Contemporary epidemiologic inquiry revealed that the diet of the group not afflicted by the epidemic contained large amounts of a preparation made by boiling chicken with various vegetables. It is notable in this regard that the dietary injunctions given to Moses on Mount Sinai, while restricting consumption of no less than 19 types of fowl, exempted chicken from prohibition. Chicken soup was widely used in Europe for many centuries, but disappeared from commercial production after the Inquisition. 8/2009

Pneumonia (Cnt’d) It remained as a popular therapy among certain Eastern European groups, however, and was introduced into the United States in the early part of this century. While chicken soup is now widely employed against a variety of organic and functional disorders, its manufacture remains largely in the hands of private individuals, and standardization has proved nearly impossible. 8/2009

Pneumonia (Cnt’d) Preliminary investigation into the pharmacology of chicken soup (Bohbymycetin) has shown that it is readily absorbed after oral administration, achieving peak serum levels in two hours and persisting in detectable levels for up to 24 hrs. Intravenous administration is not recommended. The metabolic fate of the agent is not well understood, although varying proportions are excreted by the kidneys, and dosage should be appropriately adjusted in patients with renal failure. Untoward side-effects are minimal, consisting primarily of mild euphoria which rapidly remits on discontinuation of the agent. 8/2009

Pneumonia (Cnt’d) The present case illustrates a potential hazard of abrupt chicken soup withdrawal. It was not possible to determine whether the relapse was caused by resistant organisms, as chicken soup was unavailable at the time treatment had to be restarted and a synthetic product of lesser potency was used instead. Pending further study of the optimal therapeutic regimen, it would be prudent to give a full 10-day course with gradual tapering thereafter and immediate resumption of therapy at the first sign of relapse. CHEST. 1975;67:215-216. 8/2009

Consider a precise number: the normal body temperature of 98. 6EF Consider a precise number: the normal body temperature of 98.6EF. Recent investigations involving millions of measurements have shown that this number is wrong: normal body temperature is actually 98.2EF. The fault lies not with the original measurements - they were averaged and sensibly rounded to the nearest degree: 37EC. When this was converted to Fahrenheit, however, the rounding was forgotten and 98.6 was taken as accurate to the nearest tenth of a degree. 8/2009

St. Christopher medal and cancer 8/2009

Laboratory and anecdotal clinical evidence suggest that some common non-antineoplastic drugs may affect the course of cancer. The authors present two cases that appear to be consistent with such a possibility: that of a 63-year-old woman in whom a high-grade angiosarcoma of the forehead improved after discontinuation of lithium therapy and then progressed rapidly when treatment with carbamezepine was started and that of a 74-year-old woman with metastatic adenocarcinoma of the colon which regressed when self-treatment with a non-prescription decongestant preparation containing antihistamine was discontinued. The authors suggest ...... ‘that consideration be given to discontinuing all nonessential medications for patients with cancer.’. 8/2009

Two priests, a Dominican and a Jesuit met for their regular Monday morning walk. They got into a discussion about whether it was a sin to smoke and pray at the same time. The Jesuit was sure that it wasn’t a sin while the Dominican was sure that it was. Unable to resolve it, they decided to ask their superiors. 8/2009

The next week, they met again. Dominican: What did your superior say? Jesuit: He said that it definitely was not a sin. Dominican: That’s strange because mine said that it was a sin. Jesuit: What did you ask him? Dominican: Whether it was a sin to smoke while praying. Jesuit: I asked if it was a sin to pray while smoking. 8/2009

DISCUSS COURSE OUTLINE 8/2009

Course Overview (2) Class sessions (lectures): ‘office hours’ Monday, 1300-1600, room 3248 ‘office hours’ Priority access on Tuesday mornings Otherwise, whenever I’m around (call ahead) Room 3230B (RGN) and 315 (1 Stewart St) 8/2009

Course Overview (3) Web site: http://cancer-epidemiology.org/epi_5240 Contains Full course outline Copies of all assignments, class objectives, readings Copies of the PPT files Copies of the audio recordings I will make of each class Discussion forum Can be accessed from Web page. Everyone has been added with an account. Participation provides 5% of final mark – activity not ‘quality’ Quick overview of how to use it. 8/2009

Course Overview (4) Optional activities Two NOVA videos on epidemiology (Ebola virus outbreak and esophageal cancer etiology/prevention). Will be shown from 1600-1700 on Sept 14 and 21. Small group discussion classes Wednesday afternoons (1300-1500) Room 3233 Maximum of 14 participants Topics Journal club Research ethics Outbreak investigation 8/2009

Course Overview (5) Class format: Interactive lecture Assumes that you have read the background material Lectures will attempt to address main points but will concentrate on special issues which people bring to class arising from the readings. I won’t necessarily cover ALL material during the lectures! 8/2009

Course Overview (6) OBJECTIVES To develop the attitude that data drives conclusions, not the other way around; To be able to tell good from bad research; To be aware of sources of data about the health status of Canadians, as well as the strengths and weaknesses of this data; 8/2009

Course Overview (7) OBJECTIVES (cont) To understand the basic approaches to epidemiological research and be able to describe the advantages and disadvantages of the various design options; To understand the major threats to the validity of epidemiologic research and to be able to apply basic strategies to preventing and adjusting for these problems. To be able to define and use the main measures of mortality, morbidity and study group comparison. 8/2009

Course Overview (8) We will follow the outline of the Aschengrau text, with some re-ordering. 1st two months of course generally provide an overview of the field and key concepts Focus is on the ‘big picture’ not on details. Last 6 weeks delve into some core areas in more depth Explains why things are done More quantitative in approach. 8/2009

Course Overview (9) Reading Materials No single book covers all of this material Some material must come from other sources Primary textbook: Aschengrau A, Seage GR III. Essentials of Epidemiology in Public Health, 2nd Edition. Jones and Bartlett Publishers Inc, Sudbury, MA, 2007 Recommended second level textbook: Szklo M, Nieto FJ. Epidemiology: Beyond the Basics, 2nd Edition. Jones and Bartlett Publishers Inc, Sudbury, MA, 2007 8/2009

Course Overview (10) Reading Materials (cont) A ‘course notes’ pack has been produced which contains core readings not in these two textbooks. Can be purchased from the Reprography department in the second floor of RGN. A copy of supplemental readings is available in room 3105 (in black binders). These provide: Enrichment Alternate approaches to the core material I encourage you to read through the following book on risk perception: Gardner, A. Risk: The Science and Politics of Fear. McClelland & Stewart, 2008 8/2009

Course Overview (11) Evaluation Methods Assignment #1 (due: October 5) 10% Assignment #2 (due: November 9) 25% Assignment #3 (due: December 7) 25% Participation in on-line discussion forum 5% Final examination (December 17) 35% 8/2009

Course Overview (12) Three course assignments. Can work in groups but you MUST hand-on your own assignment (not a copy). Assignments designed so knowledge of core material will give 75-80% mark. Remainder is awarded for more advanced concepts, insights, etc. Assignment #2 is longer than #1 and #3 is longer than #2. They also get harder. Some questions are meant to be hard! 8/2009

Course Overview (13) Evaluation (cont) Final exam 35% of final mark Semi-open book. You can bring the primary course text (Aschengrau) and a list of formulae I will give you. But, no other books. Will probably include a mixture of multiple-choice, matching categories, and short-answer questions. Less quantitative than assignments. More later. 8/2009

(http://pre.ethics.gc.ca/francais/tutorial/ ) Course Overview (14) Research ethics Most REBs are expecting that applicants will have completed recognized study in research ethics. EPI 5240 gives a good opportunity to complete your first certification The Ottawa Hospital REB is recommending an on-line course (http://www.pre.ethics.gc.ca/english/tutorial ) OR (http://pre.ethics.gc.ca/francais/tutorial/ ) Takes about two hours to complete Provides you with a certificate which the OHREB accepts for all applications 8/2009

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11 BLUE MEN EXAMPLE 8/2009

ELEVEN BLUE MEN Time # of men 0800 1 1025 1105 3 1120 2 1125 1135 1845 1* * Became ill at 1000 8/2009

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5 were stricken at the Globe Hotel, a sunless, upstairs flop house. 2 were stricken at the Star Hotel, a similar place 1 was found in a third similar hotel (the Lion Hotel) 1 was found in a doorway of a condemned building 1 was found on the street in front of the Eclipse café. 8/2009

All impoverished, street people All had eaten breakfast at the Eclipse Café between 7 and 10 o'clock. 8/2009

INITIAL IMPRESSION: Carbon Monoxide Poisoning SOURCE: Gas inhalation. PROBLEM: 125 People ate food in restaurant over 3 hours but only 10 got sick. 8/2009

All got sick within 30 minutes of eating breakfast with abrupt onset. 9/10 had eaten oatmeal, rolls and coffee. 1/10 had eaten only oatmeal. 8/2009

IMPRESSION: FOOD POISONING DRUG INDUCED 8/2009

blood test positive for methaemoglobin -----> drug poisoning CONCLUSIONS blood test positive for methaemoglobin -----> drug poisoning Analysis showed that the large can supposedly containing sodium nitrate actually contained sodium nitrite. Blood tests in the subjects were positive for sodium nitrite Can be/Has been used for curing meats as long as final concentration is < 1 part in 5,000. Most of this will be destroyed by cooking. Here, the before-cooking concentration was around 1 part in 80. 8/2009

Main action ---> relax smooth muscles Cardiovascular vasodilator Sodium nitrite Main action ---> relax smooth muscles Cardiovascular vasodilator side effects include headache, postural hypotension and METHEMOGLOBINAEMIA. 8/2009

Oxidation of Fe2+ to Fe3+ in haemoglobin Methaemoglobinaemia Oxidation of Fe2+ to Fe3+ in haemoglobin Decreases oxygen carrying capacity of blood 30% level - fatigue, headache, tachycardia 55% level - dyspnea, seizures, coma >70% level - death due to hypoxia Useful in treating cyanide poisoning! Methaemoglobin binds with cyanide in competition with cytochrome oxidase (also an Fe3+ compound) 8/2009

125 people ate breakfast at the café on the morning in question 125 people ate breakfast at the café on the morning in question. Only 10 got ill. WHY?? 8/2009

THE REASON a regular serving of oatmeal contained 5/6 of the toxic dose of sodium nitrite. one of 17 salt shakers at the café tables contained sodium nitrite enriched salt. some people add salt to their oatmeal rather than sugar. These were the people who got ill! 8/2009

DEFINITION OF EPIDEMIOLOGY The study of the distribution and determinants of health-related states or events in specified populations, and the application of this study to control health problems. 8/2009

Traditional Epidemiology Questions Who gets disease ‘X’? Why did someone get disease ‘X’? What is going to happen to someone who has disease ‘X’? What can we do to prevent someone getting disease ‘X’? What can we do to help someone with disease ‘X’? Why are more (or fewer) people getting disease ‘X’ now than before? Why do people living in ‘Y’ get more (or less) of disease ‘X’ than people living in ‘Z’? 8/2009

‘Modern’ Epidemiology Questions How can we help someone be healthier? Why did this person get ill while that person didn’t when they both smoked, etc.? What is the role of government policies on health? What is the role of research in directing policy? How can we improve the health care system? When is a community ‘healthy’? How can we empower people to make informed decisions about their health? How do we make sense of conflicting research results? 8/2009

USES OF EPIDEMIOLOGY Historical Study Community Diagnosis Working of Health Services Individual Risks and Chances Completing the Clinical Picture Identification of Syndromes Search for Causes Evaluation of Therapy ‘Scientific Knowledge’ 8/2009

‘Types’ of Epidemiology Clinical Epidemiology Public Health Epidemiology Scientific Epidemiology Nutritional Epidemiology Genetic Epidemiology Injury Epidemiology Environmental Epidemiology Social Epidemiology Molecular Epidemiology Psychiatric Epidemiology Population Health Epidemiology as social action vs. science 8/2009

CLINICAL EPIDEMIOLOGY The application of epidemiologic principles and methods to problems encountered in clinical medicine. (Fletcher, Fletcher and Wagner) The application, by a physician who provides direct patient care, of epidemiologic and biometric methods to the study of diagnostic and therapeutic processes in order to effect an improvement in health. (Sackett) 8/2009

Definitions of Health A state of complete physical, mental and social well-being and not merely the absence of disease or infirmity. [The WHO, 1948] A joyful attitude toward life and a cheerful acceptance of the responsibility that life puts upon the individual [Sigerist, 1941] The ability to identify and to realize aspirations, to satisfy needs, and to change or cope with the environment. Health is therefore a resource for everyday life, not the objective of living. Health is a positive concept emphasizing social and personal resources, as well as physical capacities. (WHO Europe, 1986] 8/2009

The healthiest people is not that which possesses the best or the greatest number of hospitals, but rather that which needs the fewest. Chief ‘gesundheitfuhren’, Germany around 1935 8/2009

Some Key Dates in Epidemiology 400BC Hippocrates 1660's John Graunt (birth of vital statistics) 1660's Thomas Sydenham (Classification of fevers) 1753 James Lind (Studies on Scurvy) 1774 Jenner and Jesty (smallpox immunization) 1830’s James Farr (concept of rates, population health) 1840's Semmelweis (childbirth infections) 1850's John Snow (studies on cholera) 1880's Germ theory of Disease 1900's Mosquitoes and malaria 1950's Smoking and health 1930-70 Tuskegee Syphilis study 8/2009

Hippocrates (400BC) Died at age 97! Proposed a misguided theory of medicine which led to 2500 years of problems. But, he was first epidemiologist and developed insights into public health. Was concerned with finding causes in order to prevent disease. Emphasized need for clear observation 8/2009

Hippocrates (400BC) [2] Published three books on epidemiology. Need to consider place, time, season, environmental circumstances Role of water, diet, physical activity Doctors need to know local disease in order to treat patients. 8/2009

Some Key Dates in Epidemiology 400BC Hippocrates 1660's John Graunt (birth of vital statistics) 1660's Thomas Sydenham (Classification of fevers) 1753 James Lind (Studies on Scurvy) 1774 Jenner and Jesty (smallpox immunization) 1830’s James Farr (concept of rates, population health) 1840's Semmelweis (childbirth infections) 1850's John Snow (studies on cholera) 1880's Germ theory of Disease 1900's Mosquitoes and malaria 1950's Smoking and health 1930-70 Tuskegee Syphilis study 8/2009

John Graunt (1662) Initial work on vital statistics registration. When anyone dies, then, either by tolling or ringing a bell, or by bespeaking of a Grave of the Sexton, the same is known to the Searchers, corresponding to the said Sexton. The Searchers hereupon (who are ancient matrons, sworn to their office) repair to the place where the dead corpse lies, and by view of the same, and by other enquiries, they examine by what disease or causality the corpse did die. 8/2009

Graunt (2) Hereupon they make their Report to the Parish-Clerk and he, every Tuesday night, carries in an Account of all the Burials and Christenings happening that Week, to the Clerk of the Hall. On Wednesday the general account is made up and printed and on Thursdays published and dispersed to the several Families, who pay four shillings per Annum for them. 8/2009

Graunt (3) 75% mortality by age 25 Estimated errors in data (20% under-count) Men have higher mortality rate than women Most ‘greatly feared’ causes of death (e.g. starvation, leprosy) were uncommon. Common causes: old age, consumption, smallpox, plague, diseases of teeth, worms Fall is ‘most unhealthy season’ Distinguished between epidemic and endemic diseases. 8/2009

Some Key Dates in Epidemiology 400BC Hippocrates 1660's John Graunt (birth of vital statistics) 1660's Thomas Sydenham (Classification of fevers) 1753 James Lind (Studies on Scurvy) 1774 Jenner and Jesty (smallpox immunization) 1830’s James Farr (concept of rates, population health) 1840's Semmelweis (childbirth infections) 1850's John Snow (studies on cholera) 1880's Germ theory of Disease 1900's Mosquitoes and malaria 1950's Smoking and health 1930-70 Tuskegee Syphilis study 8/2009

James Farr MD and mathematician Oversaw the General Registry Office,1839-1880 Recognized need for denominators. Developed the SMR to adjust for age differences. Developed disease classification system (precursor of ICD system) 8/2009

Farr (2) Living in densely populated areas gives increased mortality. Living at lower elevations was associated with higher cholera mortality than higher elevations Mortality decreased following improvements to sanitation Widowers had a higher marriage rate than bachelors 8/2009

Some Key Dates in Epidemiology 400BC Hippocrates 1660's John Graunt (birth of vital statistics) 1660's Thomas Sydenham (Classification of fevers) 1753 James Lind (Studies on Scurvy) 1774 Jenner and Jesty (smallpox immunization) 1830’s James Farr (concept of rates, population health) 1840's Semmelweis (childbirth infections) 1850's John Snow (studies on cholera) 1880's Germ theory of Disease 1900's Mosquitoes and malaria 1950's Smoking and health 1930-70 Tuskegee Syphilis study 8/2009

Examples (1):Streptomycin & TB First modern RCT (1946). Designed by Sir Bradford Hill Four key features: Random allocation to 2 treatment groups Clear eligibility criteria Precise endpoints (death) and blinding of MD’s reading x-rays (treatment arm unknown) Addressed ethical issues. Introduced concept that not doing RCT would be unethical 8/2009

Examples(2):Smoking & lung cancer Doll & Hill (1950) Marked lung cancer mortality post WW1 Unclear why: Better diagnosis Environmental cause. Doll and Hill’s work moved Epi from infectious diseases to chronic diseases. 8/2009

Examples(2):Smoking & lung cancer Invented case-control design. 709 cases and 709 controls. Used personal interview to recall smoking and other behaviours. 99.7% of male cases smoked; 95.8% of male controls smoked OR=16 British Doctor’s study Cohort 20 years of follow-up 8/2009

Examples (3):Framingham study ‘Prototypical cohort study’ (1947) Recruited 5,000 men living in Framingham Followed up every two years for 50 years Interview Physical exams Various lab tests Study is now following the off-spring. Shows power of long-term follow-up with physical measures. 8/2009

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Diabetes Time Prevalence Prevalence = Incidence * Duration 1924 8/2009

CHD Mortality Trends Time Predicted 800 Case deficit 700 600 Observed Deaths (in 1,000s) 1968 1977 Time 8/2009

MORTALITY IN CANADA # of Deaths, Canada (Dec 31, 1980-June 30,1995) Ratio AIDS 7,111 1.0 (ref) CHD 841,000 118 Cancer (any) 667,000 94 Falls 27,500 4 “Smoking related” 725,000 102 In Canada, more people die from smoking every two months than died from AIDS in the first 15 years of the epidemic. 8/2009

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Rice and health: A warning!(1) Rice will kill you! Every kernel of rice you eat brings you nearer to death. Amazingly, ‘the thinking man’ has failed to grasp the terrifying significance of rice. Although leading horticulturists have long known that oryza sativa possesses indehiscent pepo, the rice market continues to expand. 8/2009

Rice and health: A warning! (2) Rice is associated with all major diseases of the body. Eating it breeds war and social unrest. It can be related to most airline tragedies. Traffic accidents are caused by rice. There exists a positive relationship between crime waves and the consumption of this member of the grass family. For example: 8/2009

Rice and health: A warning!(3) Nearly all sick people have eaten rice. The effects are obviously cumulative. 99.9% of people who die from cancer have eaten rice. 100% of all soldiers have eaten rice 96.8% of all politicians have eaten rice. 99.7% of the people involved in air and auto accidents have eaten rice in the 14 days preceding their accident 93.1% of people in jails come from homes where rice is served frequently. 8/2009

Rice and health: A warning!(4) Evidence points to the long term effects of rice eating: Of the people born in 1865 who later ate rice, there has been a 100% mortality. All rice eaters born between 1895 and 1905 have wrinkled skin, have lost most of their teeth, have brittle bones and failing eye sight – if the ills of eating rice haven’t already caused their death! 8/2009

Rice and health: A warning!(6) Even more convincing is the report of a noted team of medical specialists Rats force fed 10 kg of rice per day for 30 days developed a bulging abdomen. Their appetite for wholesome food was destroyed. The only way to avoid the deleterious effects of rice eating is to change eating habits. Eat orchid petal soup. Practically no one has any problems from eating orchid petal soup. After all, do you know anyone who has died from eating orchid petal soup?? 8/2009

Summary Epidemiology has a long history but most active in past 50 years Many successes smoking and lung cancer, infectious disease outbreak control Must be careful that bias doesn’t affect your judgment. 8/2009