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  1. Medical Council of CanadaCertifying Exam Review April 16, 2007 Jeffrey P Schaefer MSc MD FRCPC

  2. Epidemiology

  3. Clinical Epidemiology

  4. Commonest Clinical Questions • Harm • Diagnosis • Therapy • Prognosis • Prevention

  5. Measures of Disease

  6. Measures of Disease Frequency • Disease Incidence • refers to new cases of disease among a population at risk for that disease over a specified period of time.

  7. Measures of Disease Frequency • Cumulative Incidence (CI) CI = new cases / population at risk / time interval 1 yr Population at risk 100 New cases 25 Population 120 Population not at risk 20 CI = 25/100/yr

  8. Measures of Disease Frequency • Incidence Density ID = new cases . person-time population at risk per time period Useful when there is losses to follow-up among the population under observation

  9. Measures of Disease Frequency • A study plans to observe 20,000 people for 1 years but 10,000 left town after 6 mo. 15 cases of disease were observed among the population. 10,000 observed x 1 yr = 10,000 p-yr 10,000 observed x 0.5 yr = 5,000 p-yr Total persons years = 15,000 p-yr

  10. Measures of Disease Frequency 15 cases / 15,000 person years 1 cases / 1,000 person-years 10 cases / 10,000 persons per year

  11. Incidence of Cancer of the Lung, Trachea, and Bronchus, Both Sexes Combined, All Ages, 1998 from Statistics Canada by Province or Territory.

  12. Incidence Data • Challenge • ensure the denominator is truly at risk.

  13. Measures of Disease Frequency • Disease Prevalence • refers to the proportion of individuals who have the disease at a specific time among a given population. (not a rate) Prevalence = existing cases at a point in time total population

  14. Measures of Disease Frequency • Point Prevalence • ‘snapshot’ in calendar time or event related time • number of cases of diabetes on June 30, 2002 in Calgary • number of people with infected incision on post-operative day 3 on General Surgery unit at Foothills Hospital

  15. Measures of Disease Frequency • Period Prevalence • longer duration under consideration • number of people with diabetes between Jan 1 and Dec 31, 2002 in Calgary • number of people with infected incision between surgery and post-operative day 90 on General Surgery unit at Foothills Hospital

  16. Period Prevalence of Diabetes Canada 1996-97

  17. Global Cigarette Consumption

  18. Special Measures of Disease Frequency • Mortality Rate • incidence of death (cause specific vs all cause mortality) • Infant Mortality Rate • death of a live born infant within the 1st year of life • Neonatal Death • death of an infant under 28 days of age • Post-neonatal Death • death of an infant between 4 weeks and 1 year of age

  19. Infant Mortality Rates Selected Countries, 1995

  20. Infant Mortality Rates by Income Quintile, Urban Canada, 1991

  21. Prevention primary prevention secondary prevention tertiary prevention risk factors only subclinical disease clinical disease complicated disease time

  22. Harm

  23. Harm • Exposures that cause disease = Harm • Harmful exposures are Risk Factors • Risk Factors may be etiologies of disease.

  24. Harm A harmful exposure is a RISK FACTOR EXPOSURE DISEASE

  25. Robert Koch • Dec 11, 1843 - May 27, 1910 • Nobel Prize - 1905 • Anthrax • Tuberculosis • Cholera

  26. Harm • Koch’s Postulates (1882) • Criteria for Causation • the organism must be present in every case of disease, • the organism be isolated from the diseased animal and grown in pure culture, • the organism causes the same disease when inoculated into a healthy animal, • the organism must be recovered from that animal (step 3) and identified.

  27. Harm • Limitations of Koch’s Postulates • not all diseases are infectious • one risk factor may cause > 1 diseases • one disease may have > 1 risk factors

  28. Harm Emphysema Chronic Bronchitis Smoking Lung Cancer Bladder Cancer Lip Cancer Coronary dx Stroke Ischemic Limb

  29. Harm Hypertension Myocardial Infarction Hyper- cholesterolemia Smoking Male Sex Family History

  30. Causality for the Modern Era • Austin Bradford Hill • July 8, 1897 - April 18, 1991 • English epidemiologist and statistician • pioneered the randomized clinical trial • published criteria for causality

  31. Harm • Austin Bradford Hill’s criteria for causality. • Temporality • exposure precedes onset of disease • Strength of Association • exposure strongly associated with disease frequency

  32. Harm • Dose – Response • more exposure associates with higher disease frequency or severity • Reversibility • reduction in exposure associates with lower rates of disease • Consistency • association between exposure and disease is observed by difference persons in different places during different circumstances

  33. Harm • Specificity • one cause leads to one effect • Analogy • cause and effect relationship already established for similar risk factor or disease • Biological Plausibility • is the association biologically plausible (keeping in mind that plausibility changes with time)

  34. Measures of Risk for Disease • 1964 cohort study data Lung Cancer Death Population Smokers RF+ Not Lung Cancer Death Not Smoker RF- Lung Cancer Death Not Lung Cancer Death Stratify on Smoking Status Observe for several years

  35. Measures of Risk for Disease lung cancer mortality cigarette smokers 0.96 / 1000 / year non-smokers 0.07 / 1000 / year all subjects 0.56 / 1000 / year prevalence of cigarette smoking = 56%

  36. Measures of Risk for Disease • Q: What is the additional risk (incidence) of disease following exposure, over and above that experienced by people who are not exposed? • Attributable Risk

  37. Measures of Risk for Disease AR = Attributable Risk IEXP = disease incidence among exposed IUNEXP = disease incidence among not exposed AR = IEXP – IUNEXP

  38. Measures of Risk for Disease lung cancer mortality cigarette smokers 0.96 / 1000 / year non-smokers 0.07 / 1000 / year 0.96 - 0.07 = 0.89 Attributable Risk = 0.89 deaths / 1000 / yr For every 10,000 smokers compared to 10,000 non-smokers there were 9 more deaths each year.

  39. Measures of Risk for Disease • Q: How many times are exposed persons more likely to get the disease relative to nonexposed persons? • Relative Risk

  40. Measures of Risk for Disease RR = Relative Risk IEXP = disease incidence among exposed IUNEXP = disease incidence among not exposed IEXP RR = ----------------- IUNEXP

  41. Measures of Risk for Disease lung cancer mortality cigarette smokers 0.96 / 1000 / year non-smokers 0.07 / 1000 / year 0.96 / 0.07 = 13.7 Relative Risk = 13.7 Smokers are 13.7 times more likely to die from lung cancer than non-smokers.

  42. Measures of Risk for Disease • Q: How much does a risk factor contribute to the overall rates of disease in groups of people, rather than individuals? • Population Attributable Risk

  43. Measures of Risk for Disease • PAR = Population Attributable Risk • AR = attributable risk • P = prevalence of exposure PAR = AR x P

  44. Measures of Risk for Disease lung cancer mortality cigarette smokers 0.96 / 1000 / year non-smokers 0.07 / 1000 / year smokers 56% of the population (0.96-0.07) x 0.56 = 0.4984 ~ 0.5 Population Attributable Risk = 0.5 / 1000 / yr Annually, smoking accounts for 1 lung cancer death per every 2000 people in the population.

  45. Measures of Risk for Disease • Example of utility of Pop. Attributable Risk • Hypertension (high blood pressure) is a risk factor for stroke. What would be more effective in lowering the incidence of stroke in a population? Treating mild hypertension Treating severe hypertension Surprise! Treating Mild Hypertension The prevalence of mild hypertension far exceeds the prevalence of severe hypertension.

  46. Measures of Risk for Disease • What fraction of disease in a population is attributable to exposure to a risk factor? • Population Attributable Fraction

  47. Measures of Risk for Disease • PAF = Population Attributable Fraction • PAR = population attributable risk • ITotal = disease incidence in total population PAR PAF = ---------- ITotal

  48. Measures of Risk for Disease lung cancer mortality all subjects 0.56 / 1000 / year PAR 0.4984 / 1000 / year 0.4984 / 0.56 = 0.89 Population Attributable Fraction = 0.89 Eighty-nine (89)% of the lung cancer deaths were accounted for by cigarette smoking.