8/20091 EPI 5240: Introduction to Epidemiology Course Overview; Case studies & historical background September 14, 2009 Dr. N. Birkett, Department of Epidemiology.

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EPI 5240:Introduction to Epidemiology

Course Overview; Case studies & historical backgroundSeptember 14, 2009

Dr. N. Birkett,Department of Epidemiology & Community

Medicine,University of Ottawa

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The Government is extremely fond of amassinggreat 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.

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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.

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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.

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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.

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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.

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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.

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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.

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Consider a precise number: the normal body temperature of 98.6F. Recent investigations involving millions of measurements have shown that this number is wrong: normal body temperature is actually 98.2F. The fault lies not with the original measurements - they were averaged and sensibly rounded to the nearest degree: 37C. 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.

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St. Christopher medal and cancer

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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.’.

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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.

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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.

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DISCUSS COURSE OUTLINE

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Course Overview (2)

• Class sessions (lectures):– 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)

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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.

http://cancer-epidemiology.org/epi_5240

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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

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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!

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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;

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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.

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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.

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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

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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

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• 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%

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– 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!

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• 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.

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• 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

http://www.pre.ethics.gc.ca/english/tutorial

http://pre.ethics.gc.ca/francais/tutorial/

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11 BLUE MEN EXAMPLE

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ELEVEN BLUE MEN

Time # of men

0800 1

1025 1

1105 3

1120 2

1125 1

1135 1

1845 1*

* Became ill at 1000

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11 Blue Men ExampleEpidemic Curve

Time (07:00 to 12:00)

600 700 800 900 1000 1100 1200

# ca

ses

0

1

2

3

4

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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.

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• All impoverished, street people• All had eaten breakfast at the

Eclipse Café between 7 and 10 o'clock.

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INITIAL IMPRESSION:Carbon Monoxide Poisoning

SOURCE: Gas inhalation.PROBLEM:125 People ate food in restaurant over 3

hours but only 10 got sick.

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• 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.

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DRUG INDUCED

IMPRESSION:FOOD POISONING

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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.

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Sodium nitrite

•Main action ---> relax smooth muscles

•Cardiovascular vasodilator• side effects include

headache, postural hypotension and METHEMOGLOBINAEMIA.

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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)

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125 people ate breakfast at the café on the

morning in question. Only 10 got ill. WHY??

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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!

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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.

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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’?

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‘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?

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USES OF EPIDEMIOLOGY

Historical StudyCommunity Diagnosis

Working of Health ServicesIndividual Risks and Chances

Completing the Clinical PictureIdentification of Syndromes

Search for CausesEvaluation of Therapy‘Scientific Knowledge’

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‘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

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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)

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Definitions of Health1. A state of complete physical, mental and social well-

being and not merely the absence of disease or infirmity. [The WHO, 1948]

2. A joyful attitude toward life and a cheerful acceptance of the responsibility that life puts upon the individual [Sigerist, 1941]

3. 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]

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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

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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

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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

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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.

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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.

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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.

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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.

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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)

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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

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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

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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.

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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

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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.

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AIDS Epidemic# of cases, Ontario

Year

1985 1986 1987 1988 1989

# o

f ca

se

s

0

100

200

300

400

Cummulative (prevalence)

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AIDS Epidemic# of cases, Ontario

Year

1985 1986 1987 1988 1989

# of

ca

ses

0

100

200

300

400

Actual (incident)

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Time

Pre

vale

nc

e

Diabetes

1924

Prevalence = Incidence * Duration

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Time

Deaths (in 1,000s)

1968 1977

800

700

600

CHD Mortality Trends

Predicted

Observed

Case deficit

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# 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

MORTALITY IN CANADA

In Canada, more people die from smoking every two months than died from AIDS in the first 15 years of the epidemic.

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Mortality for Men, 1990-1997Canada, age-standardized

Year

1990 1992 1994 1996

Mo

rta

lity

art

e (

/10

0,0

00)

0

50

100

150

200

250

IHDLung cancerStrokeSuicideColon CancerCOPDCirrhosisMVAProstate cancerPneumonia

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Ratio of 1992 to 1991 mortality ratesMen, age-standardized (1991 vs 1971)

Cause of death

IHD Lung CaStroke COPD SuicideColon CaCirrhosis MVAProstate CaPneumonia

Rat

io

0.0

0.2

0.4

0.6

0.8

1.0

1.2

1.4

1.6

1.8

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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.

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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:

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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.

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• 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!

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• 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??

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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.

8/20091 EPI 5240: Introduction to Epidemiology Course Overview; Case studies & historical background September 14, 2009 Dr. N. Birkett, Department of Epidemiology.

Documents

pneumonia cntd bohbymycetin

cancer slide

pneumonia relapse

day course of bohbymycetin

acute pneumonia

university of ottawa

bohbymycetin synopsis

boiling chicken