1 Chapter 1 The History and Scope of Epidemiology

2 Tap Water Increases MiscarriagesSwan et al. (1998) released results on total trihalomethanes (TTHMs) in drinking water. Human exposure to TTHMs may be related to adverse pregnancy outcomes.

3 Bioterrorism-Associated Anthrax CasesIndex case reported in Florida. Additional cases, including fatal cases, reported in New York, New Jersey, Connecticut. Contaminated mail linked to some of the cases.

4 Epidemiology Defined Epidemiology derives from "epidemic," a term which provides an immediate clue to its subject matter. Epidemiology originates from the Greek words, epi (upon) + demos (people) + logy (study of). 3

5 Definition of EpidemiologyEpidemiology is concerned with the distribution and determinants of health and diseases, morbidity, injuries, disability, and mortality in populations. 4

6 Key Aspects of This DefinitionDeterminants Distribution Population Health phenomena Morbidity and mortality 5

7 Determinants Factors or events that are capable of bringing about a change in health. 6

8 Examples of DeterminantsBiologic agents--bacteria Chemical agents--carcinogens Less specific factors--stress, drinking, sedentary lifestyle, or high-fat diet

9 The Search for DeterminantsOutbreak of Fear--Ebola virus in Kikwit, Zaire Fear on Seventh Ave.--Legionnaires’ disease in New York City Red Spots on Airline Flight Attendants--dye from life vests 7

10 Distribution Frequency of disease occurrence may vary from one population group to another. 8

11 Disease Distribution ExamplesHypertension more common among young black men than among young white men. Coronary heart disease occurrence differs between Hispanics and non-Hispanics.

12 Population Epidemiology examines disease occurrence among population groups, not individuals. Epidemiology is often referred to as population medicine. The epidemiologic description indicates variation by age groups, time, geographic location, and other variables. 9

13 Health Phenomena Epidemiology investigates many different kinds of health outcomes: Infectious diseases Chronic diseases Disability, injury, limitation of activity Mortality Active life expectancy Mental illness, suicide, drug addiction 10

14 Morbidity and MortalityMorbidity--designates illness. Mortality--refers to deaths that occur in a population or other group. Note that most measures of morbidity and mortality are defined for specific types of morbidity or causes of death. 11

15 Aims and Levels To describe the health status of populations.To explain the etiology of disease. To predict the occurrence of disease. To control the occurrence of disease. 12

16 Foundations of EpidemiologyInterdisciplinary Methods and procedures--quantification Use of special vocabulary Epidemic frequency of disease 13

17 Epidemiology Is InterdisciplinaryEpidemiology is an interdisciplinary field that draws from biostatistics and the social and behavioral sciences, as well as from the medically related fields of toxicology, pathology, virology, genetics, microbiology, and clinical medicine. 14

18 Quantification Quantification is a central activity of epidemiology.Epidemiologic measures often require counting the number of cases of disease. Disease distributions are examined according to demographic variables such as age, sex, and race. 15

19 Epidemic “The occurrence in a community or region of cases of an illness (or an outbreak) clearly in excess of expectancy…” Relative to usual frequency of the disease. 17

20 Infectious Disease EpidemicsA single case of a long absent communicable disease. First invasion of a communicable disease. Two cases of such a disease associated in time and place are sufficient evidence of transmission to be considered an epidemic. 18

21 Concept of Epidemic and Non-infectious DiseasesSome examples that use the concept of an epidemic are: Love Canal Brown lung disease Asbestosis among shipyard workers Diseases associated with lifestyle

22 Pandemic “ an epidemic on a worldwide scale; during a pandemic, large numbers of persons may be affected and a disease may cross international borders.” An example is a flu pandemic.

23 Ascertainment of EpidemicsSurveillance Epidemic threshold 19

24 Surveillance The systematic collection of data pertaining to the occurrence of specific diseases. Analysis and interpretation of these data. Dissemination of disease-related information.

25 Epidemic Threshold The minimum number of cases (or deaths) that would support the conclusion than an epidemic was underway.

26 Historical AntecedentsEnvironment and disease Use of mortality counts Use of natural experiments Identification of specific agents of disease 20

27 The Environment Hippocrates wrote On Airs, Waters, and Places in 400 BC. He suggested that disease might be associated with the physical environment. This represented a movement away from supernatural explanations of disease causation. 22

28 Use of Mortality CountsJohn Graunt, in 1662, published Natural and Political Observations Made upon the Bills of Mortality. 23

29 John Graunt’s ContributionsRecorded seasonal variations in births and deaths. Showed excess male over female differences in mortality. Known as the “Columbus” of biostatistics.

30 Use of Natural ExperimentsJohn Snow was an English physician and anesthesiologist. He investigated a cholera outbreak that occurred during the mid-19th century in Broad Street, Golden Square, London. 24

31 Snow’s Contributions Linked the cholera epidemic to contaminated water supplies. Used a spot map of cases and tabulation of fatal attacks and deaths.

32 Snow’s Natural ExperimentTwo different water companies supplied water from the Thames River to houses in the same area. The Lambeth Company moved its source of water to a less polluted portion of the river. Snow noted that during the next cholera outbreak those served by the Lambeth Company had fewer cases of cholera.

33 Natural Experiment Definition: The epidemiologist does not manipulate a risk factor but rather observes the changes in an outcome as the result of a naturally occurring situation.

34 Contemporary Natural ExperimentsCurrently, natural experiments may be the result of legislation, policy changes or environmental interventions.

35 Examples of Contemporary Natural ExperimentsSeat Belt Law--Did seat belt use reduce fatalities from motor vehicle accidents? Tobacco Tax--Did the increase in cigarette price decrease the sale of cigarettes? Helmet Law--Did requiring the use of helmets by motorcyclists reduce the number of head injuries sustained?

36 William Farr Appointed compiler of abstracts in England, 1839.Provided foundation for classification of diseases (ICD system). Examined linkage between mortality rates and population density.

37 Koch's Postulates Microorganism must be observed in every case of the disease. Microorganism must be isolated and grown in pure culture. Pure culture must, when inoculated into a susceptible animal, reproduce the disease. Microorganism must be observed in, and recovered from, diseased animal. 28

38 Other Historical DevelopmentsAlexander Langmuir established CDC’s Epidemiologic Intelligence Service. Wade Hampton Frost was the first professor of epidemiology in the U.S. Joseph Goldberger discovered the cure for pellagra.

39 Recent Applications of EpidemiologyFramingham Heart Study (since 1949) investigates coronary heart disease risk factors. Smoking and lung cancer; e.g., Doll and Peto’s study of British doctors’ smoking. AIDS, chemical spills, breast cancer screening, secondhand smoke. 30

40 Additional Applications of EpidemiologyInfectious diseases Environmental health Chronic diseases Lifestyle and health promotion Psychiatric and social epidemiology Molecular and genetic epidemiology 31

41 Practical Applications of EpidemiologyChapter 2 Practical Applications of Epidemiology

42 Seven Uses of EpidemiologyTo study the history of the health of populations. To diagnose the health of the community. To study the working of health services-operations research. To estimate the individual risks of disease and other conditions.

43 Uses, continued... To identify syndromes.To complete the clinical picture of chronic diseases. To search for causes of health and disease.

44 Historical Use of EpidemiologyRefers to the study of past and future trends in health and illness. Secular trends--changes in disease frequency over time.

45 Examples of Trends Chronic diseases have replaced acute infectious diseases as the major causes of morbidity and mortality. Leading causes of U.S. deaths are heart disease, cancer, and stroke.

46 Factors Affecting Reliability of Observed ChangesLack of comparability over time due to altered diagnostic criteria. Aging of the general population. Changes in the fatal course of the condition.

47 Four Trends in DisordersDisappearing Residual Persisting New epidemic

48 Disappearing DisordersThis category refers to conditions that were once common but are no longer present in epidemic form; an example is smallpox.

49 Residual Disorders Conditions for which the key contributing factors are largely known. Methods of control not implemented effectively. Examples: STDs, alcohol abuse, tobacco use.

50 Persisting Disorders Diseases for which there is no effective method of prevention or no known cure. Examples: certain types of cancer.

51 New Epidemic DisordersDiseases that are increasing in frequency. Examples: lung cancer, HIV.

52 Predictions About the FutureAbout 20 percent of the U.S. population in 2030 will be age 65 and older. The need for health- and aging-related services will grow.

53 Population Dynamics Three factors that affect the size of populations are births, deaths, and migration. When these factors do not contribute to net increases or decreases, the population is in equilibrium.

54 Population Terms Fixed population--adds no new members and, as a result, decreases in size due to deaths only. Dynamic population--adds new members through migration and births or loses members through emigration and deaths.

55 Demographic TransitionShift from high birth and death rates found in agrarian societies to lower birth and death rates found in developed countries.

56 Steady Population A population is in steady state when the number of members exiting equals the number entering.

57 Epidemiology and the Health of the CommunityProvides a key to the types of problems requiring attention. Determines the need for specific health services.

58 Demographic and Social VariablesAge and sex distribution Socioeconomic status Family structure Racial, ethnic, and religious composition

59 Variables Related to Community InfrastructureAvailability of social and health services Quality of housing stock Social stability (residential mobility)

60 Health-Related Outcome VariablesHomicide and suicide rates Infant mortality rate Selected mortality rates Drug and alcohol abuse rates Teen pregnancy rates Birth rate

61 Healthy People 2010, Goal 2 “ To eliminate health disparities among segments of the population, including differences that occur by gender, race, or ethnicity, . . .”

62 Epidemiology and Policy EvaluationUsing epidemiologic methodologies to evaluate public health policies Examples: tobacco control policies, drug treatment systems, food sold to schoolchildren

63 Operations Research (OR)The study of the placement and optimum utilization of health services in a community.

64 Epidemiology and OR Methods for selecting target populationsData analysis techniques Research designs Measurement procedures

65 Program Evaluation Uses epidemiologic tools to determine how well a health program meets certain stated goals.

66 Examples of OR Coordination of programs for the developmentally disabled Studies of health care utilization Minority access to health insurance

67 Epidemiology and Disease EtiologyApplications include: Search for causes Individual risks Specific clinical concerns

68 Modern Concepts of CausalityFive criteria for causality (source: 1964 Surgeon General’s Report): Strength of association Time sequence Consistency upon repetition Specificity Coherence of explanation

69 Further Consideration of CausalitySir Austin Bradford Hill expanded the list of criteria to include: Biologic gradient Plausibility Experiment Analogy

70 Risk Factors Due to the uncertainty of “causal” factors the term risk factor is used. Definition: exposure that is associated with a disease. Example of a risk factor: smoking.

71 Three Criteria for Risk FactorsThe frequency of the disease varies by category or value of the factor, e.g., light smokers vs. heavy smokers. The risk factor precedes onset of the disease. The observation must not be due to error.

72 Etiologic Study DesignsCase control Cohort

73 Case Control Design A type of design that compares persons who have a disease (cases) with those who are free from the disease (controls). This design explores whether differences between cases and controls result from exposures to risk factors.

74 Cohort Design A group of people free from a disease is assembled according to a variety of exposures. The group (cohort) is followed over a period of time for development of disease.

75 How Results Impact Clinical DecisionsThe following considerations determine a study’s influence: Criteria of causality Relevance to each patient Size of the risk Public health implications Individual vs. population

76 Natural History of DiseasePrepathogenesis--before agent reacts with host. Pathogenesis--after agent reacts with host. Later stages include development of active signs and symptoms. Clinical end points are: recovery, disability, or death.

77 Primary Prevention Occurs during prepathogenesis phase.Designed to reduce the occurrence of disease. Examples are education and immunization.

78 Secondary Prevention Occurs during pathogenesis phase.Designed to reduce the progress of disease. Examples are screening programs for cancer and diabetes.

79 Tertiary Prevention Designed to limit disability from disease.Also directed at restoring optimal functioning. An example is physical therapy for stroke patients.

80 Measures of Morbidity and Mortality Used in EpidemiologyChapter 3 Measures of Morbidity and Mortality Used in Epidemiology

81 Copyright 2004 Jones and Bartlett PublishersLearning Objectives Define and distinguish among proportions, rates, and ratios Explain the term population at risk Identify and calculate commonly used rates for morbidity, mortality, and natality State the meanings and applications of incidence rates and prevalence Copyright 2004 Jones and Bartlett Publishers

82 Learning Objectives (cont’d)Discuss limitations of crude rates and alternative measures for crude rates Apply direct and indirect methods to adjust rates List situations where direct and indirect adjustment should be used Copyright 2004 Jones and Bartlett Publishers

83 Copyright 2004 Jones and Bartlett PublishersCount The simplest and most frequently performed quantitative measure in epidemiology. Refers to the number of cases of a disease or other health phenomenon being studied. Significant for rare diseases or symptom presentations (e.g., case of Ebola virus). Copyright 2004 Jones and Bartlett Publishers

84 Copyright 2004 Jones and Bartlett PublishersExamples of Counts traffic fatalities in Manhattan in a 24-hour time period college dorm students who had hepatitis foreign-born stomach cancer patients Copyright 2004 Jones and Bartlett Publishers

85 Definition of ProportionA measure that states a count relative to the size of the group. A ratio in which the numerator is part of the denominator. May be expressed as a percentage. Copyright 2004 Jones and Bartlett Publishers

86 Copyright 2004 Jones and Bartlett PublishersUses of Proportions Can demonstrate the magnitude of a problem. Example: 10 dormitory students develop hepatitis. How important is this problem? If only 20 students live in the dorm, 50% are ill. If 500 students live in the dorm, 2% are ill. Copyright 2004 Jones and Bartlett Publishers

87 Example of a ProportionCalculate the proportion of African-American male deaths among African-American and white males aged 5 to 14 years. A B Total (A + B) Number of deaths among Total African-American males white males 1,150 3,810 4,960 Proportion = A/(A + B) x 100 = (1,150/4,960) x100 = 23.2% Copyright 2004 Jones and Bartlett Publishers

88 Copyright 2004 Jones and Bartlett PublishersRatio Fraction (consists of both numerator and denominator) No specified relationship between numerator and denominator Number of male cases Number of female cases 19:1 male to female = Copyright 2004 Jones and Bartlett Publishers

89 Copyright 2004 Jones and Bartlett PublishersRate Definition: a ratio that consists of a numerator and a denominator and in which time forms part of the denominator. Contains the following elements: disease frequency unit size of population time period during which an event occurs Copyright 2004 Jones and Bartlett Publishers

90 Copyright 2004 Jones and Bartlett PublishersExample of Rate Number of deaths in a given year Reference Population (during midpoint of the year) Crude Death Rate = x 100,000 Example: Number of deaths in the United States during 1990 = 2,148,463 Population of the U.S. as of June 30, 1990 = 248,709,873 2,148,463 248,709,873 Crude Death Rate = = per 100,000 Copyright 2004 Jones and Bartlett Publishers

91 Definition of PrevalenceThe number of existing cases of a disease or health condition in a population at some designated time. Copyright 2004 Jones and Bartlett Publishers

92 Interpretation of PrevalenceProvides an indication of the extent of a health problem. Example 1: prevalence of diarrhea in a children’s camp on July 13 was 33% (point prevalence). Example 2: prevalence of cancer in women during a specified time period (period prevalence) Copyright 2004 Jones and Bartlett Publishers

93 Copyright 2004 Jones and Bartlett PublishersUses of Prevalence Describing the burden of a health problem in a population. Estimating the frequency of an exposure. Determining allocation of health resources such as facilities and personnel. Copyright 2004 Jones and Bartlett Publishers

94 Copyright 2004 Jones and Bartlett PublishersPoint Prevalence Point Prevalence = Number of persons ill Total number in the group at point in time Example: Total number of smokers in the group = ,234 Total number in the group ,837 or 14.9% = per 1,000 Copyright 2004 Jones and Bartlett Publishers

95 Copyright 2004 Jones and Bartlett PublishersPeriod Prevalence Period Prevalence = during a time period Number of persons ill Average population Example: Persons ever diagnosed with cancer = ,293 Average Population ,837 = 5.5% Copyright 2004 Jones and Bartlett Publishers

96 Incidence Rate (Cumulative Incidence)Describes the rate of development of a disease in a group over a certain time period. Contains three elements: Numerator = the number of new cases. Denominator = the population at risk. Time = the period during which the cases occur. Copyright 2004 Jones and Bartlett Publishers

97 Applications of Incidence DataHelps in research on the etiology/causality of disease. Estimates the risk of developing a disease. Used to estimate the effects of exposure to a hypothesized factor of interest. Copyright 2004 Jones and Bartlett Publishers

98 Incidence Rate CalculationNumber of new cases over a time period x Total population at risk multiplier Number of new cases = 1,085 Population at risk = 37,105 1,085 37,105 = cases per 100,000 women per year Incidence Rate = = /8 = x 100,000 Copyright 2004 Jones and Bartlett Publishers

99 Copyright 2004 Jones and Bartlett PublishersAttack Rate Alternative form of incidence rate. Used for diseases observed in a population for a short time period. Example: Salmonella gastroenteritis outbreak Formula: Ill___ Ill + Well AR = x 100 (during a time period) Copyright 2004 Jones and Bartlett Publishers

100 Copyright 2004 Jones and Bartlett PublishersIncidence Density An incidence measure used when members of a population or study group are under observation for different lengths of time. Copyright 2004 Jones and Bartlett Publishers

101 Formulas for Incidence DensityNumber of new cases during the time period Total person-time of observation If period of observation is measured in years, formula becomes: Total person-years of observation Incidence Density = Copyright 2004 Jones and Bartlett Publishers

102 Incidence Density, exampleCopyright 2004 Jones and Bartlett Publishers

103 Interrelationship Between Prevalence and IncidenceInterrelationship: P ID = ~ The prevalence (P) of a disease is proportional to the incidence rate (I) times the duration (D) of a disease. Copyright 2004 Jones and Bartlett Publishers

104 Prevalence and Incidence (cont’d)If duration of disease is short and incidence is high, prevalence becomes similar to incidence. Short duration--cases recover rapidly or are fatal Example: common cold Copyright 2004 Jones and Bartlett Publishers

105 Prevalence and Incidence (cont’d)If duration of disease is long and incidence is low, prevalence increases greatly relative to incidence. Example: many chronic diseases Copyright 2004 Jones and Bartlett Publishers

106 Copyright 2004 Jones and Bartlett PublishersOutbreak of Meningococcal Infections in a Summer School Class of 10 Students Copyright 2004 Jones and Bartlett Publishers

107 Crude Rates, Measures of NatalityCrude birth rate Fertility rate Infant mortality rate Fetal death rate Neonatal mortality rate Postneonatal mortality rate Perinatal mortality rate Maternal mortality rate Copyright 2004 Jones and Bartlett Publishers

108 Copyright 2004 Jones and Bartlett PublishersCrude Birth Rate Used to project population changes; it is affected by the number and age composition of women of childbearing age Number of live births within a given period Crude Birth Rate = X 1,000 population Population size at the middle of that period Sample calculation: 4,111,000 babies were born in the U.S. during 1991, when the U.S. population was 252,688,000. The birth rate was 4,111,000/252,688,000 = 16.3 per 1,000. Copyright 2004 Jones and Bartlett Publishers

109 General Fertility RateUsed for comparisons of fertility among age, racial, and socioeconomic groups. # of live births within a year General fertility rate 1,000 women aged 15-44 = X # of women aged yrs. during the midpoint of the year Copyright 2004 Jones and Bartlett Publishers

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111 Infant Mortality Rate Used for international comparisons; a high rate indicates unmet health needs and poor environmental conditions. Number of infant deaths among infants aged days during the year 1,000 live births Infant Mortality = X Number of live births during the year Copyright 2004 Jones and Bartlett Publishers

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113 Fetal Death Rate Used to estimate the risk of death of the fetus associated with the stages of gestation. Fetal Death Rate (per 1,000 live births plus fetal deaths) = Number of fetal deaths after 20 weeks or more gestation Number of live births + number of fetal deaths after 20 weeks or more gestation X 1,000 Late fetal death rate (per 1,000 live births plus late fetal deaths) = Number of fetal deaths after 28 weeks or more gestation Number of live births + number of fetal deaths after 28 weeks or more gestation X 1,000 Copyright 2004 Jones and Bartlett Publishers

114 Fetal Death Ratio Provides a measure of fetal wastage (loss) relative to the number of live births. Number of fetal deaths after 20 weeks or more gestation Number of live births X 1,000 (during a year) Fetal Death Ratio = Copyright 2004 Jones and Bartlett Publishers

115 Neonatal Mortality RateReflects events happening after birth, primarily: congenital malformations prematurity (birth before gestation week 28) low birth weight (birth weight less than 2,500 g) Copyright 2004 Jones and Bartlett Publishers

116 Neonatal Mortality Rate FormulaNumber of infant deaths under 28 days of age Number of live births X 1,000 live births (during a year) Copyright 2004 Jones and Bartlett Publishers

117 Postneonatal Mortality RateReflects environmental events, control of infectious diseases, and improvement in nutrition. Postneonatal Mortality Rate = Number of infant deaths from 28 days to 365 days after birth Number of live births - neonatal deaths X 1,000 live births Copyright 2004 Jones and Bartlett Publishers

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119 Perinatal Mortality RateReflects environmental events that occur during pregnancy and after birth; it combines mortality during the prenatal and postnatal periods. Perinatal Mortality Rate = Number of late fetal deaths after 28 weeks or more gestation plus infant deaths within 7 days of birth X 1,000 live births and fetal deaths Number of live births + number of late fetal deaths Copyright 2004 Jones and Bartlett Publishers

120 Perinatal Mortality RatioNumber of late fetal deaths after 28 weeks or more gestation plus infant deaths within 7 days of birth Perinatal Mortality Ratio = X 1,000 live births Number of live births Copyright 2004 Jones and Bartlett Publishers

121 Maternal Mortality RateReflects health care access and socioeconomic factors; it includes maternal deaths resulting from causes associated with pregnancy and puerperium (during and after childbirth). Maternal Mortality Rate (per 100,000 live births, includes multiple births) = Number of deaths assigned to causes related to childbirth Number of live births X 100,000 live births (during a year) Copyright 2004 Jones and Bartlett Publishers

122 Copyright 2004 Jones and Bartlett PublishersCrude Rates Use crude rates with caution when comparing disease frequencies between populations. Observed differences in crude rates may be the result of systematic factors (e.g., sex or age distributions) within the population rather than true variation in rates. Copyright 2004 Jones and Bartlett Publishers

123 Copyright 2004 Jones and Bartlett PublishersSpecific Rates Specific rates refer to a particular subgroup of the population defined in terms of race, age, sex, or single cause of death or illness. Copyright 2004 Jones and Bartlett Publishers

124 Copyright 2004 Jones and Bartlett PublishersCause-Specific Rate Cause-Specific Rate = Mortality (or frequency of a given disease) X 100,000 Population size at midpoint of time period Example: Cause-specific mortality rate due to HIV in 1996 = 22,795/83,761,000 = 27.2 per 100,000 Copyright 2004 Jones and Bartlett Publishers

125 Proportional Mortality Ratio (PMR)Mortality due to a specific cause during a time period X 100 Mortality due to all causes during the same time period Example: PMR (%) for HIV among the 25- to 44-year-old group = 22,795/148,904 = 15.3% Indicates relative importance of a specific cause of death; not a measure of the risk of dying of a particular cause. Copyright 2004 Jones and Bartlett Publishers

126 Copyright 2004 Jones and Bartlett PublishersThe 10 Leading Causes of Death, Years, All Races, Both Sexes, U.S., 1996 Copyright 2004 Jones and Bartlett Publishers

127 Age-Specific Rate The number of cases per age group of population (during a specified time period). Example: Number of deaths among those aged 5-14 years Number of persons who are 5-14 years (during time period) X 100,000 Sample calculation: In the U.S. during 1991, there were 1,106 deaths due to malignant neoplasms among the age group 5 to 14 years, and there were 35,904,000 persons in the same age group. The age-specific malignant neoplasm death rate in this age group is (1,106/35,904,000) = 3.1 per 100,000. Copyright 2004 Jones and Bartlett Publishers

128 Method for Calculation of Age-Specific Death Rates

129 Copyright 2004 Jones and Bartlett PublishersAdjusted Rates Summary measures of the rate of morbidity and mortality in a population in which statistical procedures have been applied to remove the effect of differences in composition of various populations. Copyright 2004 Jones and Bartlett Publishers

130 Copyright 2004 Jones and Bartlett PublishersDirect Method Direct method may be used if age-specific death rates in a population to be standardized are known and a suitable standard population is available. Copyright 2004 Jones and Bartlett Publishers

131 Copyright 2004 Jones and Bartlett PublishersIndirect Method Indirect method may be used if age-specific death rates of the population for standardization are unknown or unstable, for example, because the population is small. Copyright 2004 Jones and Bartlett Publishers

132 Direct Method for Adjustment of Death Rates

133 New Standard PopulationYear 2000 population Replaces the standard based on 1940 population. Results in age-adjusted death rates that are much larger. Affects trends in age-adjusted rates for certain causes of death. Narrows race differentials in age-adjusted death rates. Reduces the three different standards into one acceptable standard. Copyright 2004 Jones and Bartlett Publishers

134 Standardized Mortality Ratio (SMR)Observed deaths Expected deaths x 100 Sample calculation: The number of observed deaths due to heart disease is 600 in a certain county during year The expected number of deaths is 1,000. The SMR = (600/1,000 x 100) = 60% (0.6). Copyright 2004 Jones and Bartlett Publishers

135 Copyright 2004 Jones and Bartlett PublishersInterpretation of SMR If the observed and expected numbers are the same, the SMR would be 1.0, indicating that observed mortality is not unusual. An SMR of 2.0 means that the death rate in the study population is two times greater than expected. Copyright 2004 Jones and Bartlett Publishers

136 Copyright 2004 Jones and Bartlett PublishersIllustration of Indirect Age Adjustment: Mortality Rate Calculation for a Fictitious Population of 230,109 Persons Copyright 2004 Jones and Bartlett Publishers

137 Indirect Age Adjustment (cont’d)From previous table, SMR is (502/423) X 100 = 118.7% Copyright 2004 Jones and Bartlett Publishers

138 Copyright 2004 Jones and Bartlett PublishersChapter 4 Descriptive Epidemiology: Person, Place, Time Copyright 2004 Jones and Bartlett Publishers

139 Descriptive vs. Analytic EpidemiologyDescriptive studies--used to identify a health problem that may exist. Characterize the amount and distribution of disease. Analytic studies--follow descriptive studies, and are used to identify the cause of the health problem. Copyright 2004 Jones and Bartlett Publishers 2

140 Objectives of Descriptive EpidemiologyTo evaluate and compare trends in health and disease. To provide a basis for planning, provision, and evaluation of health services. To identify problems for analytic studies (creation of hypothesis). Copyright 2004 Jones and Bartlett Publishers 3

141 Descriptive Studies and Epidemiologic HypothesesHypotheses--theories tested by gathering facts that lead to their acceptance or rejection. Three types: Positive declaration (research hypothesis) Negative declaration (null hypothesis) Implicit question Copyright 2004 Jones and Bartlett Publishers 4

142 Mill’s Canons of Inductive ReasoningThe method of difference--all the factors in two or more places are the same except for a single factor. The method of agreement--a single factor is common to a variety of settings. Example: air pollution. Copyright 2004 Jones and Bartlett Publishers 5

143 Mill’s Canons (cont’d)The method of concomitant variation--the frequency of disease varies according to the potency of a factor. The method of residues--involves subtracting potential causal factors to determine which factor(s) has the greatest impact. Copyright 2004 Jones and Bartlett Publishers 6

144 Copyright 2004 Jones and Bartlett PublishersMethod of Analogy The mode of transmission and symptoms of a disease of unknown etiology bear a pattern similar to that of a known disease. This information suggests similar etiologies for both diseases. Copyright 2004 Jones and Bartlett Publishers

145 Categories of Descriptive EpidemiologyCase reports (counts)--simplest category. Case series--summarize characteristics of patients from major clinical settings. Cross-sectional studies--surveys of the population to estimate the prevalence of a disease or exposure. Copyright 2004 Jones and Bartlett Publishers 7

146 Characteristics of PersonsAge Sex Marital Status Race and ethnicity Nativity and migration Religion Socioeconomic status Copyright 2004 Jones and Bartlett Publishers

147 Copyright 2004 Jones and Bartlett PublishersAge One of the most important factors to consider when describing the occurrence of any disease or illness. Age-specific distributions can be linear (e.g., cancer), or multimodal (e.g., tuberculosis). Age-specific incidence rates among elderly often inaccurate. Copyright 2004 Jones and Bartlett Publishers 8

148 Age Effects on MortalityBiologic clock phenomenon--waning of the immune system may result in increased susceptibility to disease, or aging may trigger appearance of conditions believed to have genetic basis. Example: Alzheimer’s disease. Copyright 2004 Jones and Bartlett Publishers 9

149 Copyright 2004 Jones and Bartlett PublishersAge Effects (cont’d) Latency period—Age effects on mortality may reflect the long latency period between environmental exposures and subsequent development of disease. Copyright 2004 Jones and Bartlett Publishers

150 Copyright 2004 Jones and Bartlett Publishers

151 Copyright 2004 Jones and Bartlett PublishersSex--Males Mortality rate higher for men than for women. May be due to social factors. May have biological basis. Example: With risk status being equal, men still have higher mortality from CHD. Copyright 2004 Jones and Bartlett Publishers 10

152 Copyright 2004 Jones and Bartlett PublishersSex--Females Females have greater morbidity rates than males for acute and chronic conditions. Generally, death rates for both sexes are declining. Copyright 2004 Jones and Bartlett Publishers

153 Copyright 2004 Jones and Bartlett PublishersMarital Status In general, married people have lower rates of morbidity and mortality. Examples: chronic and infectious diseases, suicides, and accidents. Copyright 2004 Jones and Bartlett Publishers 11

154 Marital Status (cont’d)Marriage may operate as a protective or selective factor. Protective: may provide an environment conducive to health. Selective: people who marry may be healthier to begin with. Copyright 2004 Jones and Bartlett Publishers

155 Copyright 2004 Jones and Bartlett PublishersMeasurement of Race Census 2000 changed the race category by allowing respondents to choose one or more race categories. Census 2000 used five categories of race (Exhibit 4-1). Copyright 2004 Jones and Bartlett Publishers

156 Race/Ethnicity Categories Discussed in Chapter 4African American American Indian Asian Hispanic/Latino Copyright 2004 Jones and Bartlett Publishers

157 Copyright 2004 Jones and Bartlett PublishersAfrican Americans In a study of differential mortality in U.S., had the highest rate of mortality of all groups studied. Higher blood pressure levels Possible influence of stress or diet. Higher rates of hypertensive heart disease. Copyright 2004 Jones and Bartlett Publishers 12

158 Copyright 2004 Jones and Bartlett Publishers

159 Copyright 2004 Jones and Bartlett PublishersAmerican Indians For Pima Indians: Age- and sex-adjusted mortality rate many times that for all races in U.S. for: accidents, cirrhosis, homicide, suicide, and diabetes. Infectious disease is the 10th leading cause of death. For males ages 25 to 34, the death rate is 6.6 times that for all races in U.S. Copyright 2004 Jones and Bartlett Publishers 13

160 Copyright 2004 Jones and Bartlett PublishersAsians--Japanese Comparatively lower mortality rates. Lower rates of CHD and cancer. Low CHD rates attributed to low-fat diet and institutionalized stress-reducing strategies. Copyright 2004 Jones and Bartlett Publishers 14

161 Copyright 2004 Jones and Bartlett PublishersAcculturation Defined as modifications that individuals or groups undergo when they come in contact with another country. Provide evidence of the influence of environmental and behavioral factors on chronic disease. Example: Japanese migrants experience a shift in rates of chronic disease toward those of the host country. Copyright 2004 Jones and Bartlett Publishers 15

162 Copyright 2004 Jones and Bartlett PublishersHispanics/Latinos Hispanic Health and Nutrition Examination Survey (HHANES). Examined health and nutrition status of major Hispanic/Latino populations in the U.S. San Antonio Heart Study Found high rates of obesity and diabetes among Mexican Americans. Copyright 2004 Jones and Bartlett Publishers 16

163 Nativity and MigrationNativity--Place of origin of the individual. Categories are foreign born and native born. Nativity and migration are related. Copyright 2004 Jones and Bartlett Publishers 17

164 Copyright 2004 Jones and Bartlett PublishersImpact of Migration Importation of “Third World” disease by immigrants from developing countries. Programmatic needs resulting from migration: Specialized screening programs (tuberculosis and nutrition). Familiarization with formerly uncommon (in U.S.) tropical diseases. Copyright 2004 Jones and Bartlett Publishers

165 Healthy Migrant EffectObservation that healthier, younger persons usually form the majority of migrants. Often difficult to separate environmental influences in the host country from selective factors operative among those who choose to migrate. Copyright 2004 Jones and Bartlett Publishers

166 Copyright 2004 Jones and Bartlett PublishersReligion Certain religions prescribe lifestyles that may influence rates of morbidity and mortality. Example: Seventh Day Adventists Follow vegetarian diet and abstain from alcohol and tobacco use. Have lower rates of CHD, reduced cancer risk, and lower blood pressure. Similar findings for Mormons. Copyright 2004 Jones and Bartlett Publishers 18

167 Copyright 2004 Jones and Bartlett PublishersSocioeconomic Status Low social class is related to excess mortality, morbidity, and disability rates. Factors include: Poor housing Crowded conditions Racial disadvantage Low income Poor education Unemployment Copyright 2004 Jones and Bartlett Publishers 19

168 Measurement of Social ClassVariables include: Prestige of occupation or social position Educational attainment Income Combined indices of two or more of the above variables Copyright 2004 Jones and Bartlett Publishers 20

169 Hollingshead and RedlichStudied association of socioeconomic status and mental illness. Classified New Haven, Connecticut, into five social classes based on occupational prestige, education, and address. Copyright 2004 Jones and Bartlett Publishers 23

170 Hollingshead and Redlich FindingsStrong inverse association between social class and likelihood of being a mental patient under treatment. As social class increased, severity of mental illness decreased. Type of treatment varied by social class. Copyright 2004 Jones and Bartlett Publishers 24

171 Mental Health and Social ClassIn the U.S., the highest incidence of severe mental illness occurs among the lowest social classes. Copyright 2004 Jones and Bartlett Publishers

172 Mental Health and Social Class: Two HypothesesSocial causation explanation (breeder hypothesis)--conditions associated with lower social class produce mental illness. Downward drift hypothesis—Persons with severe mental disorders move to impoverished areas. Copyright 2004 Jones and Bartlett Publishers 21

173 Other Correlates of Low Social ClassHigher rate of infectious disease. Higher infant mortality rate and overall mortality rates. Lower life expectancy. Larger proportion of cancers with poor prognosis. May be due to delay in seeking health care. Copyright 2004 Jones and Bartlett Publishers 22

174 Characteristics of PlaceTypes of place comparisons: International Geographic (within-country) variations Urban/rural differences Localized occurrence of disease Copyright 2004 Jones and Bartlett Publishers 25

175 International Comparisons of Disease FrequencyWorld Health Organization (WHO) tracks international variations in rates of disease. Infectious diseases account for 44% of deaths in less developed nations (4% in developed nations). Variation attributable to climate, cultural factors and dietary habits. Copyright 2004 Jones and Bartlett Publishers 26

176 Within-Country Variations in Rates of DiseaseDue to variations in climate, geology, latitude, pollution, and ethnic and racial concentrations. In U.S., comparisons can be made by region, state, and/or county. Examples include: higher rates of leukemia in Midwest; state by state variations in intestinal parasites. Copyright 2004 Jones and Bartlett Publishers 27

177 Urban/Rural Differences in Disease RatesUrban diseases and mortality are associated with crowding, pollution, and poverty. Example: lead poisoning in inner cities. Copyright 2004 Jones and Bartlett Publishers 28

178 Standard Metropolitan Statistical Areas (SMSAs)Established by the U.S. Bureau of the Census to make regional and urban/rural comparisons in disease rates. Copyright 2004 Jones and Bartlett Publishers

179 Localized Place ComparisonsDisease patterns are due to unique environmental or social conditions found in particular areas of interest. Examples include: Fluorosis: associated with naturally occurring fluoride deposits in water. Goiter: iodine deficiency formerly found in land-locked areas of U.S. Copyright 2004 Jones and Bartlett Publishers 29

180 Geographic Information Systems (GIS)A method to provide a spatial perspective on the geographic distribution of health conditions. A GIS produces a choroplath map that shows variations in disease rates by different degrees of shading. Copyright 2004 Jones and Bartlett Publishers

181 Reasons for Place Variation in DiseaseGene/environment interaction Examples: sickle-cell gene; Tay-Sachs disease. Influence of climate Examples: yaws, Hansen’s disease Environmental factors Example: chemical agents linked to cancer Copyright 2004 Jones and Bartlett Publishers 30

182 Characteristics of TimeCyclic fluctuations Point epidemics Secular time trends Clustering Temporal Spatial Copyright 2004 Jones and Bartlett Publishers 31

183 Copyright 2004 Jones and Bartlett PublishersCyclic Fluctuations Periodic changes in the frequency of diseases and health conditions over time. Related to changes in lifestyle of the host, seasonal climatic changes, and virulence of the infectious agent. Examples: higher heart disease mortality in winter; more accidents in summer. Copyright 2004 Jones and Bartlett Publishers

184 Copyright 2004 Jones and Bartlett Publishers

185 Copyright 2004 Jones and Bartlett PublishersPoint Epidemics The response of a group of people circumscribed in place and time to a common source of infection, contamination, or other etiologic factor to which they were exposed almost simultaneously. Examples: foodborne illness; responses to toxic substances; infectious disease. Copyright 2004 Jones and Bartlett Publishers 32

186 Copyright 2004 Jones and Bartlett PublishersSecular Time Trends Refer to gradual changes in the frequency of a disease over long time periods. Example is the decline of heart disease mortality in the U.S. May reflect impact of public health programs, dietary improvements, better treatment, or unknown factors. Copyright 2004 Jones and Bartlett Publishers 33

187 Copyright 2004 Jones and Bartlett PublishersClustering Case clustering--refers to an unusual aggregation of health events grouped together in space and time. Temporal clustering: e.g., post-vaccination reactions, postpartum depression. Spatial clustering: concentration of disease in a specific geographic area, e.g., Hodgkin’s disease. Copyright 2004 Jones and Bartlett Publishers 35

188 Chapter 5 Sources of Data for Use in Epidemiology

189 Criteria for the Quality and Utility of Epidemiologic DataNature of the data Availability of the data Completeness of population coverage Representativeness (external validity) Thoroughness Value and limitations Copyright 2004 Jones and Bartlett Publishers 2

190 Copyright 2004 Jones and Bartlett PublishersNature of the Data Refers to the source of data, e.g., vital statistics, case registries, physicians’ records, surveys of the general population, or hospital and clinic cases. Will affect the types of statistical analyses and inferences that are possible. Copyright 2004 Jones and Bartlett Publishers 3

191 Availability of the DataRefers to investigator’s access to data. For example, medical records and other data with personal identifiers may not be used without patients’ consent. Copyright 2004 Jones and Bartlett Publishers 4

192 Representativeness and ThoroughnessRepresentativeness (external validity)--generalizability of findings to the population from which the data have been taken. Thoroughness--the extent to which all cases of a health phenomenon have been identified. Copyright 2004 Jones and Bartlett Publishers 5

193 Copyright 2004 Jones and Bartlett PublishersValue and Limitations The utility of the data for various types of epidemiologic research. Factors inherent in the data may limit their usefulness. Incomplete diagnostic information. Case duplication. Copyright 2004 Jones and Bartlett Publishers 6

194 Computerized Bibliographic DatabasesFacts related to the distribution of diseases can be obtained through such sources as: Index Medicus, Psychological Abstracts, Sociological Abstracts, Education Index. On-line databases include Medline, Toxline, and DIALOG. Internet, including World Wide Web. Copyright 2004 Jones and Bartlett Publishers 7

195 Copyright 2004 Jones and Bartlett PublishersConfidentiality Privacy Act of 1974 Prohibits the release of confidential data without the consent of the individual. Freedom of Information Act Mandates the release of government information to the public, except for personal and medical files. The Public Health Service Act Protects confidentiality of information collected by some federal agencies, e.g., NCHS. Copyright 2004 Jones and Bartlett Publishers 8

196 Copyright 2004 Jones and Bartlett PublishersData Sharing Refers to the voluntary release of information by one investigator or institution to another for the purpose of scientific research. Key issue is the primary investigator’s potential loss of control over information. Copyright 2004 Jones and Bartlett Publishers 9

197 Copyright 2004 Jones and Bartlett PublishersRecord Linkage Joining data from two or more sources, e.g., employment records and mortality data. Applications include genetic research, planning of health services, and chronic disease tracking. Copyright 2004 Jones and Bartlett Publishers 10

198 Statistics Derived from the Vital Registration SystemMortality statistics Birth statistics: certificates of birth and fetal death. Copyright 2004 Jones and Bartlett Publishers 11

199 Copyright 2004 Jones and Bartlett PublishersMortality Statistics Mortality data are nearly complete, since most deaths in the U.S. and other developed countries are unlikely to be unreported. Death certificates include demographic information about the deceased and cause of death (immediate cause and contributing factors). Copyright 2004 Jones and Bartlett Publishers 12

200 Limitations of Mortality DataCertification of cause of death. For example, in an elderly person with chronic illness, exact cause of death may be unclear. Lack of standardization of diagnostic criteria. Stigma associated with certain diseases, e.g., AIDS, may lead to inaccurate reporting. Copyright 2004 Jones and Bartlett Publishers 13

201 Limitations of Mortality Data (Cont’d)Errors in coding by nosologist. Changes in coding. Revisions in the (ICD) International Classification of Disease. Sudden increases or decreases in a particular cause of death may be due to changes in coding. Copyright 2004 Jones and Bartlett Publishers 14

202 Birth Statistics: Certificates of Birth and of Fetal DeathBirth certificate includes information that may affect the neonate, such as congenital malformations, birth weight, and length of gestation. Sources of unreliability: Mothers’ recall of events during pregnancy may be inaccurate. Conditions which affect neonate may not be present at birth. Copyright 2004 Jones and Bartlett Publishers 15

203 Birth Statistics (Cont’d)Varying state requirements for fetal death certificates. Both types of certificates have been used in studies of environmental influences upon congenital malformations. Both provide nearly complete data. Copyright 2004 Jones and Bartlett Publishers 16

204 Reportable Disease StatisticsFederal and state statutes require health care providers to report those cases of diseases classified as reportable and notifiable. Include infectious and communicable diseases that endanger a population, e.g., STDs, measles, foodborne illness. Copyright 2004 Jones and Bartlett Publishers 17

205 Limitations of Reportable Disease StatisticsPossible incompleteness of population coverage. For example, asymptomatic persons would not seek treatment. Failure of physician to fill out required forms. Unwillingness to report cases that carry a social stigma. Copyright 2004 Jones and Bartlett Publishers 18

206 Copyright 2004 Jones and Bartlett PublishersScreening Surveys Conducted on an ad-hoc basis to identify individuals who may have infectious or chronic diseases. Examples: breast cancer screenings, health fairs. Clientele are highly selected. Individuals who participate are concerned about the particular health issue. Copyright 2004 Jones and Bartlett Publishers 19

207 Multiphasic Screening ProgramsOngoing screening programs often are carried out at worksites. Data can be useful for research on occupational health problems. Biases of data due to worker attrition and turnover. Data may not contain etiologic information. Copyright 2004 Jones and Bartlett Publishers 20

208 Copyright 2004 Jones and Bartlett PublishersDisease Registries Registry--a centralized database for collection of data about a disease. Coding algorithms are used to maintain patient confidentiality. Applications of registries: Patient tracking Identification of trends in rates of disease Case control studies Example: SEER program Copyright 2004 Jones and Bartlett Publishers 21

209 Surveillance, Epidemiology, and End Results (SEER) ProgramConducted by the National Cancer Institute (NCI). Collects cancer data from different cancer registries across the U.S. Provides information about trends in cancer incidence, mortality, and survival. Copyright 2004 Jones and Bartlett Publishers 22

210 Morbidity Surveys of the General PopulationCollect data on the health status of a population group. Obtain more comprehensive information than would be available from routinely collected data. Example: National Health Survey Copyright 2004 Jones and Bartlett Publishers 23

211 National Health SurveyAuthorized under the National Health Survey Act of 1956 to obtain information about the health of the U.S. population. Conducted by the NCHS; consists of three programs: National Health Interview Survey (HIS, a household health interview survey) Health Examination Survey (HES) Surveys of health resources Copyright 2004 Jones and Bartlett Publishers 24

212 Household Interview Survey (HIS)General household health survey of the U.S. civilian noninstitutionalized population. Studies a comprehensive range of conditions such as diseases, injuries, disabilities, and impairments. Copyright 2004 Jones and Bartlett Publishers 25

213 Health Examination Survey (HES)Provides direct information about morbidity through examinations, measurements, and clinical tests. Identifies conditions previously unreported or undiagnosed. Provides information not previously available for a defined population. Now known as the Health and Nutrition Examination Survey (HANES). Copyright 2004 Jones and Bartlett Publishers 26

214 Copyright 2004 Jones and Bartlett PublishersInsurance Data Sources include: Social Security--provides data on disability benefits and Medicare. Health insurance--provides data on those who receive care through a prepaid medical program. Life insurance--provides information on causes of mortality; also provides results of physical examinations. Copyright 2004 Jones and Bartlett Publishers 27

215 Limitations of Insurance DataData may not be representative of entire population, as the uninsured are excluded. Copyright 2004 Jones and Bartlett Publishers

216 Copyright 2004 Jones and Bartlett PublishersHospital Data Consists of both inpatient and outpatient data. Deficiencies of data: Not representative of any specific population. Different information collected on each patient. Settings may differ according to social class of patients; e.g., specialized clinics, emergency rooms. Copyright 2004 Jones and Bartlett Publishers 28

217 Diseases Treated in Special Clinics and HospitalsData cannot be generalized because patients are a highly selected group. Case control studies can be done with unusual and rare diseases. However, it is not possible to determine incidence and prevalence rates without knowing the size of the denominator. Copyright 2004 Jones and Bartlett Publishers 29

218 Data from Physicians’ PracticesLimited application due to: Confidentiality of patient data. Highly selected group of patients. Lack of standardization of information collected. Useful for the purposes of: Verification of self-reports. Source of exposure data. Copyright 2004 Jones and Bartlett Publishers 30

219 Copyright 2004 Jones and Bartlett PublishersAbsenteeism Data Records of absenteeism from work or school. Possible deficiencies: Data omit people who neither work nor attend school. Not all people who are ill take time off. Those absent are not necessarily ill. Useful for the study of rapidly spreading conditions. Copyright 2004 Jones and Bartlett Publishers 31

220 School Health ProgramsProvide information about immunizations, physical exams, and self-reports of illness. Have been used in studies of intelligence, mental retardation, and disease etiology. Paffenbarger, et al. used information from health records of college students to track causes of chronic diseases. Copyright 2004 Jones and Bartlett Publishers 32

221 Morbidity Data from the Armed ForcesReports from physicals, hospitalizations, and selective service examinations. Data have been used for: Studies of disease etiology. Study of twins serving in Korean War or WWII to determine influence of “nature and nurture” on cause of disease. Studies investigating genetic factors in obesity. Copyright 2004 Jones and Bartlett Publishers 33

222 Other Data Sources Relevant to Epidemiologic StudiesU.S. Bureau of the Census publications: Statistical Abstract of the U.S. County and City Data Book Decennial Censuses of Population and Housing Historical Statistics of the U.S., Colonial Time to 1957 Copyright 2004 Jones and Bartlett Publishers 34

223 Copyright 2004 Jones and Bartlett PublishersU.S. Bureau of the Census Provides information on the general, social, and economic characteristics of the U.S. population. U.S. Census administered every 10 years. Attempts to account for every person and his or her residence. Characterizes population according to sex, age, family relationships, and other demographic variables. Copyright 2004 Jones and Bartlett Publishers 37

224 Metropolitan Statistical Areas (MSAs)Provide a distinction between metropolitan and nonmetropolitan areas by type of residence, industrial concentration, and population concentration. Copyright 2004 Jones and Bartlett Publishers 35

225 Copyright 2004 Jones and Bartlett PublishersDefinition of MSA To be defined as an MSA, an area must include one of the following: One city with a population of 50,000 or more. An area defined as urbanized (total MSA population of at least 100,000). Copyright 2004 Jones and Bartlett Publishers

226 Copyright 2004 Jones and Bartlett PublishersCensus Tracts Small geographic subdivisions of cities, counties, and adjacent areas. Each tract contains about 4,000 residents. Are designed to provide a degree of uniformity of population economic status and living conditions in each tract. Copyright 2004 Jones and Bartlett Publishers 36

227 Study Designs: Ecologic, Cross-sectional, Case- ControlChapter 6 Study Designs: Ecologic, Cross-sectional, Case- Control

228 Lecture Outline Review epidemiologic conceptsA typology of study designs The cross-sectional study The ecologic study The case-control study Conclusions

229 What is Epidemiology? Epidemiology is concerned with the distribution and determinants of health and diseases, morbidity, injuries, disability and mortality in populations.

230 Review of Definitions Prevalence (point)--refers to all cases of a disease in a population of interest at a specified point in time. Incidence--refers to new cases of a disease that occur among a population at risk during a specified period of time.

231 How Study Designs DifferNumber of observations made Directionality of exposure Data collection methods Timing of data collection Unit of observation Availability of subjects

232 Observational Vs. Experimental ApproachesManipulation of study factor Was exposure of interest controlled by investigator? Randomization of study subjects Was there use of a random process to determine exposure of study subjects?

233 Typology of Epidemiologic Research

234 Overview of Study DesignsExperimental studies Quasi-experimental studies Observational studies Descriptive studies: cross-sectional surveys Analytic studies: many ecologic studies, case-control studies, cohort studies

235 Ecologic Studies The unit of analysis is the group, not the individual. Correlations are obtained between exposure rates and disease rates among different groups or populations.

236 Types of Ecologic StudiesEcologic comparison study—examines exposure rates and disease rates among different groups over the same time period. Ecologic trend study—examines changes in exposure and changes in disease within the same community, country, or other aggregate unit.

237 Example of an Ecologic StudyThe association between breast cancer and dietary fat for 39 countries. High intakes of dietary fats associated with high rates of breast cancer mortality.

238 Additional Examples of Ecologic StudiesChildhood lead poisoning in communities in Massachusetts. Mean systolic blood pressure levels and stroke mortality rates in the Seven Countries Study.

239 The Ecologic Fallacy: DefinitionObservations made at the group level may not represent the exposure-disease relationship at the individual level. The ecologic fallacy occurs when incorrect inferences about the individual are made from group level data.

240 The Ecologic Study: ExampleAn ecologic study finds that 70% of men have sunburned heads although 60% wore hats. The media report that wearing hats will not protect you from sunburn.

241 What the Individual Data Show

242 The Ecologic Fallacy (cont’d)From the ecologic data, one would conclude that wearing hats affords little protection from sunburn. From the individual data, one observes that 100% of men (4) who did not wear hats were sunburned. Among men who wore hats (6), only 50% were sunburned

243 Ecologic Studies: Advantages and DisadvantagesQuick, simple, inexpensive Good approach for generating hypotheses when a disease is of unknown etiology Disadvantages Ecological fallacy Imprecise measurement of exposure and disease

244 Cross-Sectional StudyA type of prevalence study. Exposure and disease measures obtained at the individual level. Single period of observation. Exposure and disease histories collected simultaneously. Both probability and non-probability sampling used.

245 Cross-Sectional Study: ExamplesSurveys of smokeless tobacco use among high school students. Prevalence surveys of the number of vasectomies performed. Prevalence of congenital malformations across maternal age groups.

246 Uses of Cross-Sectional StudiesHypothesis generation Intervention planning Estimation of the magnitude and distribution of a health problem

247 Limitations of Cross-Sectional StudiesDo not provide incidence data. Cannot study low prevalence diseases. Cannot determine temporality of exposure and disease.

248 Overview of Case-Control StudiesIn a case-control study with two groups, one group has the disease of interest (cases) and a comparable group is free from the disease (controls). The case-control study identifies possible causes of disease by finding out how the two groups differ with respect to exposure to some factor.

249 Characteristics of the Case-Control StudyA single point of observation. Defined by presence or absence of the outcome. Exposure is determined retrospectively. Does not directly provide incidence data.

250 Sources of Cases Need to define a case conceptually.Ideally, identify and enroll all incident cases in a defined population in a specified time period. A tumor registry or vital statistics bureau may provide a complete listing of all cases. Medical facilities also may be a source of cases, but not always incident cases.

251 Sources of Controls Population-based controlsPatients from the same hospital as the cases Relatives of cases Friends of cases--SES control

252 Measures of Association

253 Case-Control Studies Sample CalculationOn the association between chili pepper consumption and gastric cancer risk: a case-control study conducted in Mexico City. Source: Lopez-Carillo, et al. Am J Epidemiol. 1994;139:

254 Sample Calculation (cont’d)

255 Interpretation of an Odds Ratio (OR)OR=1 implies no association. Assuming statistical significance: OR = 2 suggests cases were twice as likely as controls to be exposed. OR<1 suggests a protective factor.

256 Odds Ratio (cont’d) An OR provides a good approximation of risk when:Controls are representative of a target population. Cases are representative of all cases. The frequency of disease in the population is small.

257 Examples of Case-Control StudiesGreen tea consumption and lung cancer Maternal anesthesia and development of fetal birth defects Passive smoking at home and risk of acute myocardial infarction

258 Advantages of Case-Control StudiesTend to use smaller sample sizes than surveys or prospective studies. Quick and easy to complete. Cost effective. Useful for studies of rare diseases.

259 Limitations of Case-Control StudiesProvide indirect estimate of risk. Timing of exposure-disease relationship difficult to determine. Representativeness of cases and controls often unknown.

260 Key Points to Remember Descriptive studies: cross-sectional surveys (hypothesis generation) Analytic studies: ecologic, case-control, and cohort (hypothesis testing)

261 Conclusion Study designs differ in a number of key respects, including: the unit of observation the unit of analysis the timing of exposure data in relation to occurrence of disease endpoint complexity rigor amount of resources required.

262 Study Designs: Cohort StudiesChapter 7 Study Designs: Cohort Studies

263 Copyright 2004 Jones and Bartlett PublishersLearning Objectives Differentiate cohort studies from other study designs. List main characteristics, advantages, and disadvantages of cohort studies. Describe three research questions that lend themselves to cohort studies. Calculate and interpret a relative risk. Copyright 2004 Jones and Bartlett Publishers

264 Copyright 2004 Jones and Bartlett PublishersTemporality Temporality refers to the timing of information about cause and effect. Did the information about cause and effect refer to the same point in time? Or, was the information about the cause garnered before or after the information about the effect? Copyright 2004 Jones and Bartlett Publishers

265 Limitations of Other Study DesignsDemonstrating temporality is a difficulty of most observational studies. Copyright 2004 Jones and Bartlett Publishers

266 Limitations of Other Study Designs (cont’d)Cross-sectional and case-control study designs are based on exposure and disease information that is collected at the same time. Advantage: Efficient for generating and testing hypotheses. Disadvantage: Leads to challenges regarding interpretation of results. Copyright 2004 Jones and Bartlett Publishers

267 Limitations of Other Study Designs (cont’d)Cross-sectional studies: Present difficulties in distinguishing the exposures from the outcomes of the disease, especially if the outcome marker is a biological or physiological parameter. Copyright 2004 Jones and Bartlett Publishers

268 Limitations of Other Study Designs (cont’d)Case-control studies: Raise concerns that recall of past exposures differs between cases and controls. Copyright 2004 Jones and Bartlett Publishers

269 Limitations of Other Study Designs (cont’d)There has been no actual lapse of time between measurement of exposure and disease. None of the previous study designs is well-suited for uncommon exposures. Copyright 2004 Jones and Bartlett Publishers

270 Copyright 2004 Jones and Bartlett PublishersWhat is a cohort? A cohort is defined as a population group, or subset thereof, that is followed over a period of time. The term cohort is said to originate from the Latin cohors, which referred to one of ten divisions of an ancient Roman legion. Copyright 2004 Jones and Bartlett Publishers

271 What is a cohort? (cont’d)Cohort group members experience a common exposure associated with a specific setting (e.g., an occupational cohort or a school cohort) or they share a non-specific exposure associated with a general classification (e.g., a birth cohort—being born in the same year or era). Copyright 2004 Jones and Bartlett Publishers

272 Copyright 2004 Jones and Bartlett PublishersCohort Effect The influence of membership in a particular cohort. Example: Tobacco use in the U.S. Less than 5% of population smoked around 1900. Free cigarettes for WWI troops increased prevalence of smoking in the population. During WWI, age of onset varied greatly; then people began smoking earlier in life. One net effect: a shift in the distribution of the age of onset of lung cancer. Copyright 2004 Jones and Bartlett Publishers

273 Copyright 2004 Jones and Bartlett PublishersCohort Analysis The tabulation and analysis of morbidity or mortality rates in relationship to the ages of a specific group of people (cohort) identified at a particular period of time and followed as they pass through different ages during part or all of their life span. Copyright 2004 Jones and Bartlett Publishers

274 Copyright 2004 Jones and Bartlett PublishersWade Hampton Frost Popularized cohort analysis method. Arranged tuberculosis mortality rates in a table with age on one axis and year of death on the other. One can quickly see the age-specific mortality for each of the available years on one axis and the time trend for each age group on the other. Copyright 2004 Jones and Bartlett Publishers

275 Copyright 2004 Jones and Bartlett PublishersWade Hampton Frost Copyright 2004 Jones and Bartlett Publishers

276 Copyright 2004 Jones and Bartlett PublishersLife Table Methods Give estimates for survival during time intervals and present the cumulative survival probability at the end of the interval. Example: Life tables can be constructed to portray the survival times of patients in clinical trials. Copyright 2004 Jones and Bartlett Publishers

277 Life Table Methods (cont’d)There are two life table methods: Cohort Life Table Period (Current) Life Table Copyright 2004 Jones and Bartlett Publishers

278 Life Table Methods (cont’d)Cohort life table: Shows the mortality experience of all persons born during a particular year. Period life table: Enables us to project the future life expectancy of persons born during the year as well as the remaining life expectancy of persons who have attained a certain age. Copyright 2004 Jones and Bartlett Publishers

279 Survival Curves A method for portraying survival timesTo construct a survival curve, the following information is required: Time of entry into the study Time of death or other outcome Status of patient at time of outcome, e.g., dead or censored (patient is lost to follow-up) Copyright 2004 Jones and Bartlett Publishers

280 Survival Curves: Example15 subjects followed over 36 months; all entered the study at the same time. Nine died at different points of the study. Deaths of two patients caused a steep drop at 19 months. Each step indicates the death(s) of one or more patients. Copyright 2004 Jones and Bartlett Publishers

281 Copyright 2004 Jones and Bartlett PublishersCohort Studies Start with a group of subjects who lack a positive history of the outcome of interest and are at risk for the outcome. Include at least two observation points: one to determine exposure status and eligibility and a second (or more) to determine the number of incident cases. Copyright 2004 Jones and Bartlett Publishers

282 Cohort Studies (cont’d)Permit the calculation of incidence rates. Can be thought of as going from cause to effect. Involve the collection of primary data. Copyright 2004 Jones and Bartlett Publishers

283 Cohort Studies Timing of Data CollectionCopyright 2004 Jones and Bartlett Publishers

284 Sampling and Cohort Formation OptionsCohort studies differ according to sampling strategy used. The two strategies are population-based samples and exposure-based samples. Copyright 2004 Jones and Bartlett Publishers

285 Population-based Cohort StudiesThe cohort includes either an entire population or a representative sample of the population. Population-based cohorts have been used in studies of coronary heart disease. Copyright 2004 Jones and Bartlett Publishers

286 Copyright 2004 Jones and Bartlett PublishersFramingham Study Conducted in Framingham, Massachusetts. Ongoing study of CHD initiated in 1949. Used a random sample of 6,500 from targeted age range of 30 to 59 years. Copyright 2004 Jones and Bartlett Publishers

287 Copyright 2004 Jones and Bartlett PublishersTecumseh Study Conducted in Tecumseh, Michigan. A total community cohort study. Examined the contribution of environmental and constitutional factors to the maintenance of health and origins of illness. Started in and enrolled 8,641 (88% of the community). Copyright 2004 Jones and Bartlett Publishers

288 Population-based Cohort Studies (cont’d)Exposures unknown until the first period of observation when exposure information is collected. There can be two or more levels of exposure. Copyright 2004 Jones and Bartlett Publishers

289 Exposure-based Cohort StudiesThese studies overcome limitations of population-based cohort studies, which are not efficient for rare exposures. Certain groups, such as occupational groups, may have higher exposures than the general population to specific hazards. Copyright 2004 Jones and Bartlett Publishers

290 Definition of Exposure-based CohortAn exposure-based cohort is made up of subjects with a common exposure, for example, workers exposed to lead during battery production. Copyright 2004 Jones and Bartlett Publishers

291 Comparison (Non-exposed Group)Cohort studies involve the comparison of disease rates between exposed and non-exposed groups. The comparison group is similar in demographics and geography to the exposed group, but lacks the exposure. In an occupational setting, several categories of exposure may exist. Copyright 2004 Jones and Bartlett Publishers

292 Temporal Differences in Cohort DesignsThere are several variations in cohort designs that depend on the timing of data collection. These variations are: prospective cohort studies retrospective cohort studies historical prospective cohort studies Copyright 2004 Jones and Bartlett Publishers

293 Prospective Cohort StudyPurely prospective in nature; characterized by determination of exposure levels at baseline (the present), and follow-up for occurrence of disease at some time in the future. Copyright 2004 Jones and Bartlett Publishers

294 Advantages of Prospective Cohort StudiesEnable the investigator to collect data on exposures; the most direct and specific test of the study hypothesis. The size of the cohort is under greater control by the investigators. Copyright 2004 Jones and Bartlett Publishers

295 Advantages of Prospective Cohort Studies (cont’d)Biological and physiological assays can be performed with decreased concern that the outcome will be affected by the underlying disease process. Direct measures of the environment (e.g., indoor radon levels, electromagnetic field radiation, cigarette smoke concentration) can be made. Copyright 2004 Jones and Bartlett Publishers

296 Retrospective Cohort StudyDespite substantial benefits of prospective cohort studies, investigators have to wait for cases to accrue. Retrospective cohort studies make use of historical data to determine exposure level at some baseline in the past. Copyright 2004 Jones and Bartlett Publishers

297 Advantages of Retrospective Cohort StudiesA significant amount of follow-up may be accrued in a relatively short period of time. The amount of exposure data collected can be quite extensive and available to the investigator at minimal cost. Copyright 2004 Jones and Bartlett Publishers

298 Practical Considerations Regarding Cohort StudiesAvailability of exposure data Size and cost of the cohort used Data collection and data management Follow-up issues Sufficiency of scientific justification Copyright 2004 Jones and Bartlett Publishers

299 Availability of Exposure DataHigh quality historical exposure data are absolutely essential for retrospective cohort studies. Need to trade off between a retrospective study design (with the benefits of more immediate follow-up time) and collection of primary exposure data in a prospective cohort design. Copyright 2004 Jones and Bartlett Publishers

300 Size and Cost of the CohortThe larger the size of the cohort, the greater the opportunity to obtain findings in a timely manner. Resource constraints typically influence design decisions. Copyright 2004 Jones and Bartlett Publishers

301 Data Collection and Data ManagementLarger studies are more demanding than smaller ones; challenges due to data collection and data management. Explicit protocols for quality control (e.g., double entry of data and scannable forms) should be considered in the design and implementation stage. Copyright 2004 Jones and Bartlett Publishers

302 Data Collection and Data Management (cont’d)Organizational and administrative burdens are increased when there are multiple levels of data collection (such as phone interviews, mailed questionnaires, consent forms to access medical records). Copyright 2004 Jones and Bartlett Publishers

303 Copyright 2004 Jones and Bartlett PublishersFollow-up Issues There are two types of follow-up: Active follow-up Passive follow-up Copyright 2004 Jones and Bartlett Publishers

304 Copyright 2004 Jones and Bartlett PublishersActive Follow-up The investigator, through direct contact with the cohort, must obtain data on subsequent incidence of the outcome (disease, change in risk factor, change in biological marker). Accomplished through follow-up mailings, phone calls, or written invitations to return to study sites/centers. Copyright 2004 Jones and Bartlett Publishers

305 Active Follow-up (cont’d)Example: Minnesota Breast Cancer Family Study Mailed survey A reminder postcard 30 days later A second survey A telephone call to non-responders Copyright 2004 Jones and Bartlett Publishers

306 Copyright 2004 Jones and Bartlett PublishersPassive Follow-up Does not require direct contact with cohort members. Possible when databases containing the outcomes of interest are collected and maintained by organizations outside the investigative team. Example: Used in the Iowa Women’s Health Study. Copyright 2004 Jones and Bartlett Publishers

307 Sufficiency of Scientific JustificationThere should be considerable scientific rationale for a cohort study. Additional justification for cohort studies may come from laboratory experiments or animal studies. Cohort studies are the only observational study design that permits examination of multiple outcomes. Copyright 2004 Jones and Bartlett Publishers

308 Cohort Studies: Measures of AssociationRelative risk provides a direct measure of association between exposure and outcome. Relative risk is the ratio of the incidence of disease in the exposed group to the incidence in the non-exposed group. Copyright 2004 Jones and Bartlett Publishers

309 Copyright 2004 Jones and Bartlett PublishersRelative Risk Relative risk = Incidence rate in the exposed Incidence rate in the non-exposed Copyright 2004 Jones and Bartlett Publishers

310 Measures of Association (cont’d)Disease Status Incidence Exposure Yes No Totals Rate Status Yes A B A+B A/(A+B) No C D C+D C/(C+D) Relative Risk [A/A+B]/[C/C+D] Attributable Risk [A/A+B]-[C/C+D] Copyright 2004 Jones and Bartlett Publishers

311 Cohort Studies: Sample CalculationIs there an association between child abuse and suicide attempts among chemically dependent adolescents? Source: Deykin EY, Buka SL. Am J Public Health. 1994;84: Copyright 2004 Jones and Bartlett Publishers

312 Sample Calculation (cont’d)History of Sexual Abuse Suicide Attempt No Suicide Attempt Totals Yes A = 14 B = 9 A + B = 23 No C = 49 D = 149 C + D = 198 Relative Risk = (14/23) ÷ (49/198) = 2.46 Copyright 2004 Jones and Bartlett Publishers

313 Examples of Major Cohort StudiesThe Alameda County Study Studied factors associated with health and mortality. Involved residents of Alameda County, CA, ages years. Data collected through mailed questionnaires; telephone interviews or home interviews of non-respondents. Follow-up with same procedures at years 9, 18, and 29. Copyright 2004 Jones and Bartlett Publishers

314 Examples of Major Cohort Studies (cont’d)Honolulu Heart Program Studied coronary heart disease and stroke in men of Japanese ancestry. Involved men of Japanese ancestry living on Oahu, HI, ages years. Data collected through mailed questionnaires, interviews, and clinic examinations. Copyright 2004 Jones and Bartlett Publishers

315 Examples of Major Cohort Studies (cont’d)Nurses’ Health Study Originally studied oral contraceptive use; expanded to women’s health. Married female R.N.s ages years. Data collected through mailed questionnaires. Follow-up every 2 years; toenail sample at year 6 and blood sample at year 13. Copyright 2004 Jones and Bartlett Publishers

316 Nested Case-Control StudiesDefined as a type of case-control study in which cases and controls are drawn from the population in a cohort study. The population of the cohort study comprises both exposed and non-exposed persons. Copyright 2004 Jones and Bartlett Publishers

317 Advantages of Nested Case-Control StudiesProvide a degree of control over confounding factors. Reduce cost because exposure information is collected from a subset of the cohort only. An example is an investigation of suicide among electric utility workers. Copyright 2004 Jones and Bartlett Publishers

318 Strengths of Cohort StudiesPermit direct determination of risk. Time sequencing of exposure and outcome. Can study multiple outcomes. Can study rare exposures. Copyright 2004 Jones and Bartlett Publishers

319 Limitations of Cohort StudiesTake a long time Costly Subjects lost to follow-up Copyright 2004 Jones and Bartlett Publishers

320 Experimental Study DesignsChapter 8 Experimental Study Designs

321 Learning Objectives (abridged)State how study designs compare with respect to validity of causal inference. Define the term controlled clinical trials. Define what is meant by community trials. Copyright 2004 Jones and Bartlett Publishers

322 Copyright 2004 Jones and Bartlett PublishersExperimental Studies Most rigorous design: greatest control over the research setting. Manipulation of study factor and random assignment. Copyright 2004 Jones and Bartlett Publishers

323 Copyright 2004 Jones and Bartlett PublishersExperimental Studies An example is a randomized clinical trial. Typically implemented as intervention studies (controlled or quasi-experimental). Copyright 2004 Jones and Bartlett Publishers

324 Quasi-Experiment/Community TrialRanked immediately below controlled experiments in rigor. Investigator is unable to randomly allocate subjects to the conditions. There may be contamination across the conditions of the study. Copyright 2004 Jones and Bartlett Publishers

325 Copyright 2004 Jones and Bartlett PublishersIntervention Studies Used to test efficacy of preventive or therapeutic measures. Two categories: Controlled clinical trials Community interventions Multicenter trials--results from several researchers are pooled. Copyright 2004 Jones and Bartlett Publishers

326 History of Clinical TrialsIn 1537, Ambroise Paré applied experimental treatment for battlefield wounds. East India Shipping Company (1600) found that lemon juice protected against scurvy. James Lind (1747) used the concurrently treated control group method. Copyright 2004 Jones and Bartlett Publishers

327 Clinical Trials DefinitionA planned experiment that assesses the efficacy of a treatment in man. Outcomes in treated group are compared with outcomes in an equivalent control group. Participants in both groups are enrolled, treated, and followed over the same time period. Copyright 2004 Jones and Bartlett Publishers

328 Copyright 2004 Jones and Bartlett PublishersClinical Trials Assess the efficacy of a treatment. Carefully designed and rigidly enforced protocol. Random assignment of subjects to study groups (intervention and control). Placebo given to control group. Copyright 2004 Jones and Bartlett Publishers

329 Clinical Trials (cont’d)Eligibility rules carefully defined and rigidly enforced. Subjects are randomly assigned to one of the study groups, e.g., intervention or control (placebo). More than one experimental intervention can be run in parallel. Copyright 2004 Jones and Bartlett Publishers

330 Prophylactic and Therapeutic TrialsA prophylactic trial evaluates the effectiveness of a substance that is used to prevent disease; it can also involve a prevention program. A therapeutic trial involves the study of curative drugs or a new surgical procedure to improve the patient’s health. Copyright 2004 Jones and Bartlett Publishers

331 Outcomes of Clinical TrialsReferred to as clinical end points. May include rates of disease, death, or recovery. Outcomes must be measured in a comparable manner in the intervention and control conditions. Copyright 2004 Jones and Bartlett Publishers

332 Examples of Clinical TrialsMedical Research Council Vitamin Study—studied role of folic acid in preventing neural tube defects. South Bronx, NY, STD Program—evaluated effectiveness of education efforts to prevent spread of sexually transmitted diseases (STDs). Copyright 2004 Jones and Bartlett Publishers

333 Copyright 2004 Jones and Bartlett PublishersBlinding (Masking) To maintain the integrity of a study and reduce the potential for bias, the investigator may utilize one of two popular approaches: Single-blind design: subject unaware of group assignment. Double-blind design: Neither subject nor experimenter is aware of group assignment. Copyright 2004 Jones and Bartlett Publishers

334 Phases of Clinical TrialsBefore a vaccine, drug, or treatment can be licensed for general use, it must go through several stages of development. This lengthy process helps to protect the public, yet at the same time delays access to needed pharmaceutical agents for critically ill patients, such as those afflicted with AIDS or cancer. Copyright 2004 Jones and Bartlett Publishers

335 Phases of Clinical Trials for New VaccinesPhase I--tests a new vaccine in adult volunteers (fewer than 100 volunteers). Phase II--expands testing to a group of 100 to 200 subjects (from the targeted population). Phase III (the main test)--assesses the efficacy of the vaccine in the target population. Copyright 2004 Jones and Bartlett Publishers

336 Copyright 2004 Jones and Bartlett PublishersRandomization Method of choice for assigning subjects to the treatment or control conditions of a clinical trial. Non-random assignment may cause mixing of the effects of the intervention with differences (e.g., demographic) among the participants of the trial. Copyright 2004 Jones and Bartlett Publishers

337 Copyright 2004 Jones and Bartlett PublishersCrossover Designs Any change of treatment for a patient in a clinical trial involving a switch of study treatments. In planned crossovers a protocol is developed in advance, and the patient may serve as his or her own control. Unplanned crossovers exist for various reasons, such as patient’s request to change treatment. Copyright 2004 Jones and Bartlett Publishers

338 Ethical Aspects of Human ExperimentationBenefits must outweigh risks. Ethical issues: Informed consent Withholding treatment Sequential designs are used as a solution. Monitoring for side effects Can be circumvented by using animals. Deciding when to withdraw a patient Protecting the interests of patients Copyright 2004 Jones and Bartlett Publishers

339 Reporting the Results of Clinical TrialsThe CONSORT Statement is a protocol that guides the reporting of randomized trials by providing a 22-item checklist and a flowchart. Copyright 2004 Jones and Bartlett Publishers

340 Summary of Clinical TrialsStrengths: Provide the greatest control over: the amount of exposure the timing and frequency of exposure the period of observation Ability to randomize reduces the likelihood that groups will differ significantly. Copyright 2004 Jones and Bartlett Publishers

341 Summary of Clinical Trials (cont’d)Limitations: Artificial setting Limited scope of potential impact Adherence to protocol is difficult to enforce. Ethical dilemmas Copyright 2004 Jones and Bartlett Publishers

342 Copyright 2004 Jones and Bartlett PublishersCommunity Trials Community intervention trials determine the potential benefit of new policies and programs. Intervention: Any program or other planned effort designed to produce changes in a target population. Community refers to a defined unit, e.g., a county, state, or school district. Copyright 2004 Jones and Bartlett Publishers

343 Community Trials (cont’d)Start by determining eligible communities and their willingness to participate. Collect baseline measures of the problem to be addressed in the intervention and control communities. Use a variety of measures, e.g., disease rates, knowledge, attitudes, and practices. Copyright 2004 Jones and Bartlett Publishers

344 Community Trials (cont’d)Communities are randomized and followed over time. Outcomes of interest are measured. Copyright 2004 Jones and Bartlett Publishers

345 Examples of Community TrialsNorth Karelia Project Minnesota Heart Health Program Stanford Five-City Project Pawtucket Heart Health Program Community Intervention Trial for Smoking Cessation (COMMIT) Project Respect Copyright 2004 Jones and Bartlett Publishers

346 Summary of Community Trials: AdvantagesRepresent the only way to estimate directly the impact of change in behavior or modifiable exposure on the incidence of disease. Copyright 2004 Jones and Bartlett Publishers

347 Summary of Community Trials: DisadvantagesInferior to clinical trials with respect to ability to control entrance into study, delivery of the intervention, and monitoring of outcomes. Fewer study units are capable of being randomized, which affects comparability. Affected by population dynamics, secular trends, and nonintervention influences. Copyright 2004 Jones and Bartlett Publishers

348 Evaluation of Community InterventionsPosttest only--observations are made only after the program has been delivered. Pretest/Posttest--baseline and follow-up observations are made. Pretest/Posttest/Control--observations are made in both intervention and control groups before and after the program. Copyright 2004 Jones and Bartlett Publishers

349 Evaluation of Community Interventions (cont’d)Solomon Four-Group assignment: Used to overcome the Hawthorne Effect. Uses four equivalent groups, two intervention and two control: Two are observed before and after intervention. Two are observed only after intervention. Copyright 2004 Jones and Bartlett Publishers

350 Four Stages of EvaluationFormative: Will all plans and procedures work as conceived? Process: Is the program serving the target group as planned? Impact: Has the program produced any changes among the target group? Outcome: Did the program accomplish its ultimate goal? Copyright 2004 Jones and Bartlett Publishers

351 Chapter 9 Measures of Effect

352 Risk Difference (Attributable Risk)Risk difference--the difference between the incidence rate of disease in the exposed group (Ie) and the incidence rate of disease in the nonexposed group (Ine). Risk difference = Ie - Ine Copyright 2004 Jones and Bartlett Publishers 2

353 Calculation of Risk DifferenceFor women younger than age 75, the incidence (Ie) of hip fractures per 100,000 person-days was highest in the winter (0.41), and the incidence (Ine) was lowest in the summer (0.29). The risk difference between the two seasons (Ie - Ine) was , or 0.12 per 100,000 person-days. Copyright 2004 Jones and Bartlett Publishers 3

354 Statistical Measures of EffectSignificance tests The P value Confidence interval Copyright 2004 Jones and Bartlett Publishers 4

355 Copyright 2004 Jones and Bartlett PublishersNull Hypothesis Underlying all statistical tests is a null hypothesis, which states that there is no difference among the groups being compared. Copyright 2004 Jones and Bartlett Publishers 5

356 Copyright 2004 Jones and Bartlett PublishersSignificance Tests In order to decide whether or not to reject or fail to reject the null hypothesis, a test statistic is computed and compared with a critical value obtained from a set of statistical tables. Copyright 2004 Jones and Bartlett Publishers 6

357 Copyright 2004 Jones and Bartlett PublishersSignificance Level The significance level is the chance of rejecting the null hypothesis when, in fact, it is true. Copyright 2004 Jones and Bartlett Publishers 7

358 Copyright 2004 Jones and Bartlett PublishersThe P Value Indicates the probability that the findings observed could have occurred by chance alone. However, a nonsignificant difference is not necessarily attributable to chance alone. Copyright 2004 Jones and Bartlett Publishers 8

359 Copyright 2004 Jones and Bartlett PublishersThe P Value (cont’d) Possible meaning of nonsignificant differences: -- For studies with a small sample size the sampling error may be large, which can lead to a nonsignificant test even if the observed difference is caused by a real effect. Copyright 2004 Jones and Bartlett Publishers

360 Confidence Interval (CI)A computed interval of values that, with a given probability, contains the true value of the population parameter. The degree of confidence is usually stated as a percentage; commonly the 95% CI is used. Influenced by variability of the data and sample size. Copyright 2004 Jones and Bartlett Publishers 9

361 Clinical vs. Statistical SignificanceWhile small differences in disease frequency or low magnitudes of relative risk (RR) may be significant, they may have no clinical significance. Conversely, with small sample sizes, large differences or measures of effect may be clinically important. Copyright 2004 Jones and Bartlett Publishers 10

362 Copyright 2004 Jones and Bartlett PublishersStatistical Power The ability of a study to demonstrate an association if one exists. Determined by: Frequency of the condition under study. Magnitude of the effect. Study design. Sample size. Copyright 2004 Jones and Bartlett Publishers 11

363 Evaluating Epidemiologic AssociationsFive key questions to be asked: Could the association have been observed by chance? Determined through the use of statistical tests. Could the association be due to bias? Bias refers to systematic errors, i.e., how samples were selected or how data was analyzed. Copyright 2004 Jones and Bartlett Publishers 12

364 Evaluating Epidemiologic Associations (cont’d)Could other confounding variables have accounted for the observed relationship? To whom does this association apply? Representativeness of sample Participation rates Does the association represent a cause-and-effect relationship? Considers criteria of causality. Copyright 2004 Jones and Bartlett Publishers 13

365 Chapter 10 Data Interpretation Issues

366 Validity of Study DesignsTwo components of validity: Internal validity External validity Copyright 2004 Jones and Bartlett Publishers 2

367 Copyright 2004 Jones and Bartlett PublishersInternal Validity A study is said to have internal validity when there have been proper selection of study groups and a lack of error in measurement. Concerned with the appropriate measurement of exposure, outcome, and association between exposure and disease. Copyright 2004 Jones and Bartlett Publishers 3

368 Copyright 2004 Jones and Bartlett PublishersExternal Validity External validity implies the ability to generalize beyond a set of observations to some universal statement. Copyright 2004 Jones and Bartlett Publishers 4

369 Sources of Error in Epidemiologic ResearchRandom errors Systematic errors (bias) Copyright 2004 Jones and Bartlett Publishers 5

370 Copyright 2004 Jones and Bartlett PublishersRandom Errors Reflect fluctuations around a true value of a parameter because of sampling variability. Copyright 2004 Jones and Bartlett Publishers 6

371 Factors That Contribute to Random ErrorPoor precision Sampling error Variability in measurement Copyright 2004 Jones and Bartlett Publishers 7

372 Copyright 2004 Jones and Bartlett PublishersPoor Precision Occurs when the factor being measured is not measured sharply. Analogous to aiming a rifle at a target that is not in focus. Precision can be increased by increasing sample size or the number of measurements. Copyright 2004 Jones and Bartlett Publishers 8

373 Copyright 2004 Jones and Bartlett PublishersSampling Error Occurs when the sample selected is not representative of the target population. Increasing the sample size can reduce the likelihood of sampling error. Copyright 2004 Jones and Bartlett Publishers 9

374 Variability in MeasurementThe lack of agreement in results from time to time reflects random error inherent in the type of measurement procedure employed. Copyright 2004 Jones and Bartlett Publishers 10

375 Bias (Systematic Errors)“Deviation of results or inferences from the truth, or processes leading to such deviation. Any trend in the collection, analysis, interpretation, publication, or review of data that can lead to conclusions that are systematically different from the truth.” Copyright 2004 Jones and Bartlett Publishers 11

376 Factors That Contribute to Systematic ErrorsSelection bias Information bias Confounding Copyright 2004 Jones and Bartlett Publishers 12

377 Copyright 2004 Jones and Bartlett PublishersSelection Bias Arises when the relation between exposure and disease is different for those who participate and those who theoretically would be eligible for study but do not participate. Example: Respondents to the Iowa Women’s Health Study were younger, weighed less, and were more likely to live in rural, less affluent counties than nonrespondents. Copyright 2004 Jones and Bartlett Publishers 13

378 Copyright 2004 Jones and Bartlett PublishersInformation Bias Can be introduced as a result of measurement error in assessment of both exposure and disease. Types of information bias: Recall bias: better recall among cases than among controls. Example: Family recall bias. Copyright 2004 Jones and Bartlett Publishers 14

379 Information Bias (cont’d)Interviewer/abstractor bias--occurs when interviewers probe more thoroughly for an exposure in a case than in a control. Prevarication (lying) bias--occurs when participants have ulterior motives for answering a question and thus may underestimate or exaggerate an exposure. Copyright 2004 Jones and Bartlett Publishers 15

380 Copyright 2004 Jones and Bartlett PublishersConfounding The distortion of the estimate of the effect of an exposure of interest because it is mixed with the effect of an extraneous factor. Occurs when the crude and adjusted measures of effect are not equal (difference of at least 10%). Can be controlled for in the data analysis. Copyright 2004 Jones and Bartlett Publishers 16

381 Criteria of ConfoundersTo be a confounder, an extraneous factor must satisfy the following criteria: Be a risk factor for the disease. Be associated with the exposure. Not be an intermediate step in the causal path between exposure and disease. Copyright 2004 Jones and Bartlett Publishers 17

382 Simpson’s Paradox as an Example of ConfoundingDemonstrates that associations can be reversed when confounding factors are controlled. Illustrated by examining the data (% of black and gray hats) first according to two individual tables and then by combining all the hats on a single table. Copyright 2004 Jones and Bartlett Publishers

383 Copyright 2004 Jones and Bartlett PublishersSimpson’s Paradox Table Hat color # # that fit % that fit Black Gray Black Gray Copyright 2004 Jones and Bartlett Publishers 19

384 Examples of ConfoundingAir pollution and bronchitis are positively associated. Both are influenced by crowding, a confounding variable. The association between high altitude and lower heart disease mortality also may be linked to the ethnic composition of the people in these regions. Copyright 2004 Jones and Bartlett Publishers 18

385 Techniques to Reduce Selection BiasDevelop an explicit (objective) case definition. Enroll all cases in a defined time and region. Strive for high participation rates. Take precautions to ensure representativeness. Copyright 2004 Jones and Bartlett Publishers 20

386 Reducing Selection Bias Among CasesEnsure that all medical facilities are thoroughly canvassed. Develop an effective system for case ascertainment. Consider whether all cases require medical attention; consider possible strategies to identify where else the cases might be ascertained. Copyright 2004 Jones and Bartlett Publishers

387 Reducing Selection Bias Among ControlsCompare the prevalence of the exposure with other sources to evaluate credibility. Attempt to draw controls from a variety of sources. Copyright 2004 Jones and Bartlett Publishers 21

388 Techniques to Reduce Information BiasUse memory aids; validate exposures. Blind interviewers as to subjects’ study status. Provide standardized training sessions and protocols. Use standardized data collection forms. Blind participants as to study goals and classification status. Copyright 2004 Jones and Bartlett Publishers 22

389 Methods to Control ConfoundingPrevention strategies--attempt to control confounding through the study design itself. Three types of prevention strategies: Randomization Restriction Matching Copyright 2004 Jones and Bartlett Publishers 23

390 Copyright 2004 Jones and Bartlett PublishersRandomization Attempts to ensure equal distributions of the confounding variable in each exposure category. Advantages: Convenient, inexpensive; permits straightforward data analysis. Disadvantages: Need control over the exposure and the ability to assign subjects to study groups. Need large sample sizes. Copyright 2004 Jones and Bartlett Publishers 24

391 Copyright 2004 Jones and Bartlett PublishersRestriction May prohibit variation of the confounder in the study groups. For example, restricting participants to a narrow age category can eliminate age as a confounder. Provides complete control of known confounders. Unlike randomization, cannot control for unknown confounders. Copyright 2004 Jones and Bartlett Publishers 25

392 Copyright 2004 Jones and Bartlett PublishersMatching Matches subjects in the study groups according to the value of the suspected or known confounding variable to ensure equal distributions. Frequency matching--the number of cases with particular match characteristics is tabulated. Individual matching--the pairing of one or more controls to each case based on similarity in sex, race, or other variables. Copyright 2004 Jones and Bartlett Publishers 26

393 Copyright 2004 Jones and Bartlett PublishersMatching (cont’d) Advantages: Fewer subjects are required than in unmatched studies of the same hypothesis. May enhance the validity of a follow-up study. Disadvantages: Costly because extensive searching and recordkeeping are required to find matches. Copyright 2004 Jones and Bartlett Publishers 27

394 Two Analysis Strategies to Control ConfoundingStratification--analyses performed to evaluate the effect of an exposure within strata (levels) of the confounder. Multivariate techniques--use computers to construct mathematical models that describe simultaneously the influence of exposure and other factors that may be confounding the effect. Copyright 2004 Jones and Bartlett Publishers 28

395 Advantages of StratificationPerforming analyses within strata is a direct and logical strategy. Minimum assumptions must be satisfied for the analysis to be appropriate. The computational procedure is straightforward. Copyright 2004 Jones and Bartlett Publishers 29

396 Disadvantages of StratificationSmall numbers of observations in some strata. A variety of ways to form strata with continuous variables. Difficulty in interpretation when several confounding factors must be evaluated. Categorization produces loss of information. Copyright 2004 Jones and Bartlett Publishers 30

397 Multivariate TechniquesAdvantages: Continuous variables do not need to be converted to categorical variables. Allow for simultaneous control of several exposure variables in a single analysis. Disadvantages: Potential for misuse. Copyright 2004 Jones and Bartlett Publishers 31

398 Copyright 2004 Jones and Bartlett PublishersPublication Bias Occurs because of the influence of study results on the chance of publication. Studies with positive results are more likely to be published than studies with negative results. Copyright 2004 Jones and Bartlett Publishers

399 Publication Bias (cont’d)May result in a preponderance of false-positive results in the literature. Bias is compounded when published studies are subjected to meta-analysis. Copyright 2004 Jones and Bartlett Publishers

400 Chapter 11 Screening for Disease in the Community

401 Copyright 2004 Jones and Bartlett PublishersScreening for Disease Screening--the presumptive identification of unrecognized disease or defects by the application of tests, examinations, or other procedures that can be applied rapidly. Positive screening results are followed by diagnostic tests to confirm actual disease. Copyright 2004 Jones and Bartlett Publishers

402 Multiphasic ScreeningDefined as the use of two or more screening tests together among large groups of people. Information obtained on risk factor status, history of illness, and health measurements. Commonly used by employers and health maintenance organizations. Copyright 2004 Jones and Bartlett Publishers

403 Mass Screening and Selective ScreeningMass screening--screening on a large scale of total population groups regardless of risk status. Selective screening--screens subsets of the population at high risk for disease. More economical, and likely to yield more true cases. Example: Screening high-risk persons for Tay-Sachs disease. Copyright 2004 Jones and Bartlett Publishers

404 Mass Health ExaminationsPopulation or epidemiologic surveys--purpose is to gain knowledge regarding the distribution and determinants of diseases in selected populations. No benefit to the participant is implied. Copyright 2004 Jones and Bartlett Publishers

405 Mass Health Examinations (cont’d)Epidemiologic surveillance--aims at the protection of community health through case detection and intervention. Case finding (opportunistic screening)--the utilization of screening tests for detection of conditions unrelated to the patient’s chief complaint. Copyright 2004 Jones and Bartlett Publishers

406 Appropriate Situations for Screening Tests and ProgramsSocial Scientific Ethical Copyright 2004 Jones and Bartlett Publishers

407 Copyright 2004 Jones and Bartlett PublishersSocial The health problem should be important for the individual and the community. Diagnostic follow-up and intervention should be available to all who require them. There should be a favorable cost-benefit ratio. Public acceptance must be high. Copyright 2004 Jones and Bartlett Publishers

408 Copyright 2004 Jones and Bartlett PublishersScientific Natural history of the condition should be adequately understood. This knowledge permits identification of early stages of disease and appropriate biologic markers of progression. Prevalence of the disease or condition is high. Copyright 2004 Jones and Bartlett Publishers

409 Copyright 2004 Jones and Bartlett PublishersEthical The program can alter the natural history of the condition in a significant proportion of those screened. Suitable, acceptable tests for screening and diagnosis of the condition as well as acceptable, effective methods of prevention are available. Copyright 2004 Jones and Bartlett Publishers

410 Characteristics of a Good Screening TestSimple--easy to learn and perform. Rapid--quick to administer; results available rapidly. Inexpensive--good cost-benefit ratio. Safe--no harm to participants. Acceptable--to target group. Copyright 2004 Jones and Bartlett Publishers

411 Evaluation of Screening TestsReliability types Repeated measurements Internal consistency Interjudge Validity types Content Criterion-referenced Predictive Concurrent Construct Copyright 2004 Jones and Bartlett Publishers

412 Reliability (Precision)The ability of a measuring instrument to give consistent results on repeated trials. Repeated measurement reliability--the degree of consistency among repeated measurements of the same individual on more than one occasion. Copyright 2004 Jones and Bartlett Publishers

413 Copyright 2004 Jones and Bartlett PublishersReliability (cont’d) Internal consistency reliability--evaluates the degree of agreement or homogeneity within a questionnaire measure of an attitude, personal characteristic, or psychologic attribute. Interjudge reliability--reliability assessments derived from agreement among trained experts. Copyright 2004 Jones and Bartlett Publishers

414 Copyright 2004 Jones and Bartlett PublishersValidity (Accuracy) The ability of a measuring instrument to give a true measure. Can be evaluated only if an accepted and independent method for confirming the test measurement exists. Copyright 2004 Jones and Bartlett Publishers

415 Copyright 2004 Jones and Bartlett PublishersValidity (cont’d) Content validity--the degree to which a measure covers the range of meanings included within the concept. Criterion-referenced validity--found by correlating a measure with an external criterion of the entity being assessed. Copyright 2004 Jones and Bartlett Publishers

416 Copyright 2004 Jones and Bartlett PublishersValidity (cont’d) Two types of criterion-referenced validity: Predictive validity--denotes the ability of a measure to predict some attribute or characteristic in the future. Concurrent validity--obtained by correlating a measure with an alternative measure of the same phenomenon taken at the same point in time. Copyright 2004 Jones and Bartlett Publishers

417 Copyright 2004 Jones and Bartlett PublishersValidity (cont’d) Construct Validity--degree to which the measurement agrees with the theoretical concept being investigated. Copyright 2004 Jones and Bartlett Publishers

418 Interrelationships Between Reliability and ValidityIt is possible for a measure to be highly reliable but invalid. It is not possible for a measure to be valid but unreliable. Copyright 2004 Jones and Bartlett Publishers

419 Representation of Reliability and ValidityCopyright 2004 Jones and Bartlett Publishers

420 Sources of Unreliability and InvalidityMeasurement bias--constant errors that are introduced by a faulty measuring device and tend to reduce the reliability of measurements. Example: A miscalibrated blood pressure manometer. Copyright 2004 Jones and Bartlett Publishers

421 Sources of Unreliability and Invalidity (cont’d)Halo effect--bias that affects the validity of questionnaire measurements. Example: All items of a checklist evaluation of an employee may be filled out in the same general direction based on the supervisor’s opinion of the individual. Social desirability effects Respondent answers questions in a manner that agrees with desirable social norms. Copyright 2004 Jones and Bartlett Publishers

422 Copyright 2004 Jones and Bartlett PublishersFourfold Table Gold Standard Present Absent Total Test Result Positive a b a + b Negative c d c + d a + c b + d Copyright 2004 Jones and Bartlett Publishers

423 Measures of the Validity of Screening TestsSensitivity--the ability of the test to identify correctly all screened individuals who actually have the disease (a/a+c). Specificity--the ability of the test to identify only nondiseased individuals who actually do not have the disease (d/b+d). Copyright 2004 Jones and Bartlett Publishers

424 Measures of the Validity of Screening Tests (cont’d)Predictive value (+)--the proportion of individuals screened positive by the test who actually have the disease (a/a+b). Predictive value (-)--the proportion of individuals screened negative by the test who do not have the disease (d/c+d). Copyright 2004 Jones and Bartlett Publishers

425 Other Measures from the 2 by 2 TableAccuracy of a screening test--determined by the formula: (a+d)/(a+b+c+d). Prevalence--determined by the formula: (a+c)/(a+b+c+d) Copyright 2004 Jones and Bartlett Publishers

426 Copyright 2004 Jones and Bartlett PublishersSample Calculation Copyright 2004 Jones and Bartlett Publishers

427 Copyright 2004 Jones and Bartlett PublishersEffects of Disease Prevalence on the Predictive Value of a Screening Test When the prevalence of a disease falls, the predictive value (+) falls, and the predictive value (-) rises. Copyright 2004 Jones and Bartlett Publishers

428 Relationship Between Sensitivity and SpecificityTo improve sensitivity, the cut point used to classify individuals as diseased should be moved farther in the range of the nondiseased (normals). To improve specificity, the cut point should be moved farther in the range typically associated with the disease. Copyright 2004 Jones and Bartlett Publishers

429 Relationship (cont’d)Copyright 2004 Jones and Bartlett Publishers

430 Procedures to Improve Sensitivity and SpecificityRetrain screeners--reduces the amount of misclassification in tests that require human assessment. Recalibrate screening instrument--reduces the amount of imprecision. Utilize a different test. Utilize more than one test. Copyright 2004 Jones and Bartlett Publishers

431 Evaluation of Screening ProgramsRandomized control trials Subjects receive either the new screening test or usual care. Ecologic time trend studies Compare geographic regions with screening programs to those without. Case-control studies Cases--fatal cases of the disease. Controls--nonfatal cases. Exposure--screening program. Copyright 2004 Jones and Bartlett Publishers

432 Sources of Screening Evaluation BiasLead time bias The perception that the screen-detected case has longer survival because the disease was identified early. Length bias Particularly relevant to cancer screening. Tumors identified by screening are slower growing and have a better prognosis. Selection bias Motivated participants have a different probability of disease than do those who refuse to participate. Copyright 2004 Jones and Bartlett Publishers

433 Natural History of DiseaseCopyright 2004 Jones and Bartlett Publishers

434 Issues in the Classification of Morbidity and MortalityThe nomenclature and classification of disease are central to the reliable measurement of the outcome variable in epidemiologic research. Nomenclature--a highly specific set of terms for describing and recording clinical or pathologic diagnoses to classify ill persons into groups. Copyright 2004 Jones and Bartlett Publishers

435 Issues in the Classification of Morbidity and Mortality (cont’d)Classification--the statistical compilation of groups of cases of disease by arranging disease entities into categories that share similar features. Two types of criteria used for the classification of ill persons: Causal Manifestational Copyright 2004 Jones and Bartlett Publishers

436 Chapter 12 Epidemiology of Infectious Diseases

437 Epidemiologic TriangleA model used to explain the etiology of infectious diseases. Recognizes three major factors in the pathogenesis of disease: agent, host, and environment. Copyright 2004 Jones and Bartlett Publishers 2

438 Diagram of Epidemiologic TriangleCopyright 2004 Jones and Bartlett Publishers

439 Microbial Agents of Infectious DiseaseBacteria Viruses and rickettsia Mycoses (fungal diseases) Protozoa Helminths Arthropods Copyright 2004 Jones and Bartlett Publishers 3

440 Copyright 2004 Jones and Bartlett PublishersBacteria Once were the leading killers, but now are controlled by antibiotics. Remain significant causes of human illness. Tuberculosis and salmonellosis are common diseases caused by bacteria. Copyright 2004 Jones and Bartlett Publishers

441 Viruses and RickettsiaViral hepatitis A, herpes, and influenza are caused by viruses. Rickettsial agents produce Q fever and Rocky Mountain spotted fever. Copyright 2004 Jones and Bartlett Publishers

442 Mycoses (Fungal Diseases)Valley fever (coccidioidomycosis), ringworm and athlete’s foot. Opportunistic mycoses infect immunocompromised patients. Candidiasis, cryptococcosis, and aspergillosis. Copyright 2004 Jones and Bartlett Publishers 4

443 Copyright 2004 Jones and Bartlett PublishersProtozoa Cause malaria, amebiasis, babesiosis, cryptospordiosis, and giardiasis. Copyright 2004 Jones and Bartlett Publishers

444 Copyright 2004 Jones and Bartlett PublishersHelminths Found in tropical areas. Include intestinal parasites such as roundworms, pinworms, and tapeworms. Are responsible for trichinellosis and schistosomiasis. Copyright 2004 Jones and Bartlett Publishers

445 Copyright 2004 Jones and Bartlett PublishersArthropods Act as insect vectors. Examples: mosquitos, ticks, flies, mites. Transmit diseases such as malaria and encephalitis. Copyright 2004 Jones and Bartlett Publishers 5

446 Characteristics of Infectious Disease AgentsInfectivity The capacity of an agent to produce infection or disease. Measured by the secondary attack rate. Pathogenicity The capacity of the agent to cause disease in the infected host. Measured by the proportion of individuals with clinically apparent disease. Copyright 2004 Jones and Bartlett Publishers 6

447 Characteristics of Infectious Disease Agents (cont’d)Virulence Refers to the severity of the disease. Measured by the proportion of severe or fatal cases. If fatal, use case fatality rate. Toxigenicity The capacity of the agent to produce a toxin or poison. Copyright 2004 Jones and Bartlett Publishers 7

448 Characteristics of Infectious Disease Agents (cont’d)Resistance The ability of the agent to survive adverse environmental conditions. Antigenicity The ability of the agent to induce antibody production in the host. Related to immunogenicity. Copyright 2004 Jones and Bartlett Publishers 8

449 Host: Definition (Refer to Glossary)A person (or animal) who permits lodgment of an infectious disease agent under natural conditions. Copyright 2004 Jones and Bartlett Publishers

450 Copyright 2004 Jones and Bartlett PublishersHost Once an agent infects the host, the degree and severity of the infection will depend on the host’s ability to fight off the infectious agent. Two types of defense mechanisms are present in the host: nonspecific and disease-specific. Copyright 2004 Jones and Bartlett Publishers 9

451 Nonspecific Defense MechanismsExamples include skin, mucosal surfaces, tears, saliva, gastric juices, and the immune system. Nonspecific defense mechanisms such as immunity may decrease as we age. Copyright 2004 Jones and Bartlett Publishers 10

452 Disease-Specific Defense MechanismsImmunity (resistance) against a particular agent. Types of immunity: Active: administration of a microorganism to invoke an immunologic response that mimics the natural infection. Passive: short-term immunity provided by a preformed antibody. Copyright 2004 Jones and Bartlett Publishers 11

453 Copyright 2004 Jones and Bartlett PublishersActive Immunity Natural, active--results from an infection by the agent. Artificial, active--results from an injection with a vaccine that stimulates antibody production in the host. Copyright 2004 Jones and Bartlett Publishers 12

454 Copyright 2004 Jones and Bartlett PublishersPassive Immunity Natural, passive--preformed antibodies are passed to the fetus during pregnancy and provide short-term immunity in the newborn. Artificial, passive--preformed antibodies are given to exposed individuals to prevent disease. Copyright 2004 Jones and Bartlett Publishers

455 Copyright 2004 Jones and Bartlett PublishersEnvironment The domain external to the host in which the agent may exist, survive, or originate. The environment consists of physical, climatologic, biologic, social, and economic components that affect the survival of the agents and serve to bring the agent and host into contact. Copyright 2004 Jones and Bartlett Publishers 13

456 Reservoirs of Infectious DiseasesThe environment can act as a reservoir that fosters the survival of infectious agents. Examples: contaminated water supplies or food; soils; vertebrate animals. Copyright 2004 Jones and Bartlett Publishers 14

457 Copyright 2004 Jones and Bartlett PublishersAnimal Reservoirs Animals can be reservoirs of infectious agents. Zoonoses--infectious diseases that are potentially transmittable to humans by vertebrate animals. Examples: rabies and the plague. Copyright 2004 Jones and Bartlett Publishers

458 Direct Transmission from ReservoirSpread of infection through person-to-person contact. Portal of exit--site where infectious agents leave the body, e.g., respiratory system, skin lesions. Copyright 2004 Jones and Bartlett Publishers 15

459 Direct Transmission (cont’d)Portal of entry--locus of access to the human body, e.g., mouth and digestive system. Agent must exit in large enough quantities to survive in the environment and overcome the defenses at the portal of entry into the host. Copyright 2004 Jones and Bartlett Publishers

460 Copyright 2004 Jones and Bartlett PublishersInapparent Infection No symptoms of infection present. Important because disease can be transmitted to unsuspecting hosts. In asymptomatic individuals, clinicians can look for serologic evidence of infection. Example: Increase in antibodies and enzymes in patients with hepatitis A virus. Copyright 2004 Jones and Bartlett Publishers 16

461 Copyright 2004 Jones and Bartlett PublishersIncubation Period The time interval between exposure to an infectious agent and the appearance of the first signs and symptoms of disease. Provides a clue to the time and circumstance of exposure to the agent. Useful for determining the etiologic agent. Copyright 2004 Jones and Bartlett Publishers 17

462 Copyright 2004 Jones and Bartlett PublishersHerd Immunity Immunity of a population, group, or community against an infectious disease when a large proportion of individuals are immune either through vaccinations or prior infection. Copyright 2004 Jones and Bartlett Publishers 18

463 Copyright 2004 Jones and Bartlett PublishersGeneration Time Time interval between lodgment of an infectious agent in a host and the maximal communicability of the host. Can precede the development of active symptoms. Useful for describing the spread of infectious agents that have large proportions of subclinical cases. Copyright 2004 Jones and Bartlett Publishers 19

464 Colonization and InfestationColonization--agents multiply on the surface of the body without invoking tissue or immune response. Infestation--the presence of a living infectious agent on the body’s exterior surface, upon which a local reaction may be invoked. Copyright 2004 Jones and Bartlett Publishers 20

465 Iceberg Concept of InfectionActive clinical disease accounts for only a small proportion of host’s infections and exposures to disease agents. (Refer to next slide.) Copyright 2004 Jones and Bartlett Publishers 21

466 Iceberg Concept (cont’d)Copyright 2004 Jones and Bartlett Publishers

467 Indirect TransmissionThe spread of infection through an intermediary source: Vehicles--e.g., contaminated water, infected blood, food. Fomites--inanimate objects laden with disease-causing agents. Vectors--living insects or animals involved with transmission of the disease agent. Copyright 2004 Jones and Bartlett Publishers 22

468 Measures of Disease OutbreaksAttack rate Secondary attack rate Case fatality rate Copyright 2004 Jones and Bartlett Publishers 23

469 Copyright 2004 Jones and Bartlett PublishersAttack Rate Incidence rate that is used when the nature of the disease or condition is such that a population is observed for a short period of time. Formula: ___Ill __ X 100 during a time period Ill + Well Copyright 2004 Jones and Bartlett Publishers 24

470 Copyright 2004 Jones and Bartlett PublishersSecondary Attack Rate An index of the spread of disease in a family, household, dwelling unit, dormitory or similar circumscribed group. A measure of contagiousness. Useful in evaluating control measures. Copyright 2004 Jones and Bartlett Publishers 25

471 Secondary Attack Rate: DefinitionThe number of cases of infection that occur among contacts within the incubation period following exposure to a primary case in relation to the total number of exposed contacts. Copyright 2004 Jones and Bartlett Publishers

472 Secondary Attack Rate (%) (Multiply fraction by 100.)Number of new cases in group - initial case(s) Number of susceptible persons in the group - initial case(s) Initial case(s) = Index case(s) + coprimaries Index case(s) = Case that first comes to the attention of public health authorities. Coprimaries = Cases related to index case so closely in time that they are considered to belong to the same generation of cases. Copyright 2004 Jones and Bartlett Publishers 26

473 Case Fatality Rate (CFR)The number of deaths caused by a disease among those who have the disease. Examples of diseases with a high CFR are rabies and AIDS. Copyright 2004 Jones and Bartlett Publishers 27

474 Copyright 2004 Jones and Bartlett PublishersFormula For CFR Number of deaths due to disease “X “ x Number of cases of disease “X “ Sample calculation: Assume that an outbreak of plague occurs in an Asian country. Health authorities record 98 case of the disease, all of whom are untreated. Among these, 60 deaths are reported. CFR = (60/98) x 100 = 61.2% Copyright 2004 Jones and Bartlett Publishers 28

475 Investigation of Infectious Disease OutbreaksDefine the problem. Appraise existing data. Case identification Clinical observations Tabulation and spot maps Identification of responsible agent Copyright 2004 Jones and Bartlett Publishers 29

476 Investigation (cont’d)Formulate a hypothesis. Test the hypothesis. Draw conclusions and formulate practical applications. Copyright 2004 Jones and Bartlett Publishers

477 Epidemiologically Significant Infectious DiseasesFood-borne illness Water- and food-borne diseases Sexually transmitted diseases Vaccine-preventable diseases Diseases spread by person-to-person contact Zoonotic diseases Arthropod-borne diseases Fungal diseases Copyright 2004 Jones and Bartlett Publishers 30

478 Copyright 2004 Jones and Bartlett PublishersFood-borne Illness One of the most common infectious disease problems in the community. Examples include: Staphylococcus aureus--present in contaminated food. Produces a toxin. Trichinosis--associated with inadequately cooked pork products. Copyright 2004 Jones and Bartlett Publishers 31

479 Water- and Food-borne DiseasesExamples include: Amebiasis--intestinal disease. Cholera--acute enteric disease. Giardiasis Legionellosis Schistosomiasis--infection caused by adult worms in the bloodstream. The cycle involves alternate snail and human hosts. Copyright 2004 Jones and Bartlett Publishers 32

480 Sexually Transmitted Diseases: AIDS, 1981-2000Characteristics of persons with AIDS: Greater increase in cases among females than males; still more males than females. Greatest impact among men who have sex with men and among racial/ethnic minorities. Number of persons living with AIDS has increased as deaths have declined. Copyright 2004 Jones and Bartlett Publishers 33

481 Vaccine-Preventable DiseasesVaccines are routinely given to children for the prevention of the following nine diseases: Diphtheria, Haemophilus influenzae type b infections, hepatitis B, measles, mumps, pertussis, paralytic poliomyelitis, rubella, and tetanus. Copyright 2004 Jones and Bartlett Publishers 34

482 Diseases Spread by Person-to-Person ContactOne example is tuberculosis. Resurgence of TB due to: Increase in persons infected with HIV. Increase in homeless population. Importation of cases from endemic areas. Copyright 2004 Jones and Bartlett Publishers 35

483 Copyright 2004 Jones and Bartlett PublishersU.S. TB Cases, Source: Reprinted from Centers for Disease Control and Prevention. Tuberculosis morbidity—United States, 1992. MMWR, vol 42, p 696, September 17, 1993. Copyright 2004 Jones and Bartlett Publishers

484 Copyright 2004 Jones and Bartlett PublishersZoonotic Diseases Zoonosis--a disease that under natural conditions can be spread from vertebrate animals to humans. Example: Q fever. Zoonotic diseases may be either: Enzootic--similar to endemic in human diseases. Epizootic--similar to epidemic in human diseases. Copyright 2004 Jones and Bartlett Publishers 36

485 Copyright 2004 Jones and Bartlett PublishersMycoses Coccidioidomycosis (San Joaquin Valley fever )--caused by the fungus Coccidioides immitis. Usually attacks the lungs. Cases of infection usually have had contact with contaminated soil. Other examples: blastomycosis, ringworm, athlete’s foot, candidiasis, cryptococcosis, and aspergillosis. Copyright 2004 Jones and Bartlett Publishers

486 Arthropod-borne DiseasesInclude arboviral diseases. Blood-feeding arthropod vectors transmit disease agents to vertebrate hosts. Examples of vectors: sand flies, ticks, mosquitoes. Examples of diseases: encephalitis, Lyme disease Copyright 2004 Jones and Bartlett Publishers

487 Copyright 2004 Jones and Bartlett PublishersEmerging Infections Suddenly increase in incidence or geographic scope. Many infections appear when an existing pathogen gains access to new host populations. Examples: U.S. hantaviral pulmonary syndrome, Lyme disease, AIDS, hepatitis C, hemorrhagic fever. Environmental changes may contribute to their emergence. Copyright 2004 Jones and Bartlett Publishers

488 Chapter 13 Epidemiologic Aspects of Work and the Environment

489 Human Exposures to Environmental HazardsChemical agents Electromagnetic radiation Ionizing radiation Heavy metals Air pollution Copyright 2004 Jones and Bartlett Publishers

490 Health Effects Attributed to Environmental ExposuresCancer Congenital malformations Low birth weight Copyright 2004 Jones and Bartlett Publishers

491 Hazardous Agents in the Work EnvironmentIonizing radiation Infectious agents Toxic substances Drugs Carcinogenic agents Copyright 2004 Jones and Bartlett Publishers

492 Health Effects Associated with Work EnvironmentHealth risks for pregnant workers and the unborn fetus Various lung diseases Dermatologic problems Bladder cancer among dye workers Leukemia among workers exposed to benzene Copyright 2004 Jones and Bartlett Publishers 2

493 Study Designs Used in Environmental EpidemiologyDescriptive studies provide information for setting priorities, identifying hazards, and formulating hypotheses for new occupational risks. Etiologic studies can be used to show exposure-effect relationships. Copyright 2004 Jones and Bartlett Publishers 3

494 Retrospective Cohort StudiesVarious end points are used to study the effects of occupational exposures. Morbidity: self-reports of symptoms and results of clinical examinations. Mortality: comparison of mortality rates of exposed workers with nonexposed workers in the same industry. Copyright 2004 Jones and Bartlett Publishers 4

495 Collection of Exposure DataEmployment records often are used and may include: Personal identifiers to permit record linkage. Demographic characteristics. Work history. Information about potential confounding variables, e.g., medical history, smoking habits. Copyright 2004 Jones and Bartlett Publishers 5

496 The Healthy Worker EffectObservation that employed populations tend to have a lower mortality experience than the general population. The healthy worker effect may reduce the measure of effect for an exposure that increases morbidity or mortality. Copyright 2004 Jones and Bartlett Publishers 6

497 Ecologic Study DesignsOne use is the study of the health effects of air pollution. Researchers measure the association between average exposure to air pollution within census tracts and the average mortality in those census tracts. Unable to controI for individual factors, e.g., smoking habits. Copyright 2004 Jones and Bartlett Publishers 7

498 Copyright 2004 Jones and Bartlett PublishersCase-Control Studies Compared with cross-sectional study designs, case-control studies can provide more complete exposure data. However, precise quantitation of exposure and unobserved confounding may be difficult to achieve. Copyright 2004 Jones and Bartlett Publishers 8

499 Toxicologic Concepts Related to Environmental EpidemiologyDose-response Threshold Latency Synergism Copyright 2004 Jones and Bartlett Publishers 9

500 Copyright 2004 Jones and Bartlett PublishersDose-Response Curve Graph used to assess the effect of exposure to a chemical or toxic substance upon an organism. Copyright 2004 Jones and Bartlett Publishers 10

501 Copyright 2004 Jones and Bartlett PublishersThreshold Refers to the lowest dose at which a particular response may occur. Copyright 2004 Jones and Bartlett Publishers 11

502 Copyright 2004 Jones and Bartlett PublishersLatency The time period between initial exposure and a measurable response. Latency can range from seconds (acute toxic agents) to years (mesothelioma). The long latency of health events in environmental research makes the detection of hazards difficult. Copyright 2004 Jones and Bartlett Publishers 12

503 Copyright 2004 Jones and Bartlett PublishersSynergism Refers to a situation in which the combined effect of several exposures is greater than the sum of the individual effects. Example: Study conducted among asbestos insulation workers clearly demonstrated a synergistic relationship between asbestos and smoking in causing lung cancer. Copyright 2004 Jones and Bartlett Publishers 13

504 Copyright 2004 Jones and Bartlett PublishersTypes of Agents Chemical agents Metallic compounds Electric and magnetic fields Ionizing radiation Allergens and molds Physical and mechanical energy Copyright 2004 Jones and Bartlett Publishers 14

505 Copyright 2004 Jones and Bartlett PublishersChemical Agents Potential effects on human health through acute toxicity, direct skin irritation, contact dermatitis, or long-term effects such as cancer. Exposure to chemicals in occupational settings averages 1 to 100 times that in the ambient environment. Examples include pesticides and vinyl chloride. Copyright 2004 Jones and Bartlett Publishers 15

506 Chemical Agents (cont’d)Pesticides--Examples are DDT, polychlorobiphenyls, and atrazine; linked to cancer, teratogenic effects, and cognitive deficits. Vinyl chloride--used in the plastics industry; associated with angiosarcoma of the liver, cancers of the lung, and central nervous system tumors. Copyright 2004 Jones and Bartlett Publishers 16

507 Chemical Agents (cont’d)Asbestos Strictly speaking, a mineral fiber. Was used commonly for ship building, construction, insulation, and automobiles. Associated with asbestosis, mesothelioma, and lung cancer. Copyright 2004 Jones and Bartlett Publishers

508 Copyright 2004 Jones and Bartlett PublishersMetallic Compounds Mercury Used for the treatment of syphilis, as an agricultural fungicide, and in dental amalgams. Responsible for Minamata disease, which occurred in the mid-1950s in Minamata Bay, Japan. A neurological condition linked to the consumption of fish contaminated with mercury. Copyright 2004 Jones and Bartlett Publishers 17

509 Metallic Compounds (cont’d)Lead Once widely used in paint and gasoline. Associated with serious central nervous system effects even at low levels. Lead poisoning is one of the most common environmental pediatric health problems in the U.S. Has adverse effects on intelligence, behavior, and development. Copyright 2004 Jones and Bartlett Publishers 18

510 Electric and Magnetic FieldsSources include power lines, microwave ovens, stoves, clocks, cellular phones. Los Angeles and Swedish studies found an association between residential proximity to power lines and childhood cancer risk. U.S. and Norwegian studies found an increased risk for male breast cancer among male electrical workers. Copyright 2004 Jones and Bartlett Publishers 19

511 Copyright 2004 Jones and Bartlett PublishersIonizing Radiation Consists of either particle energy or light energy in the form of photons. Sources of ionizing radiation can be natural or synthetic. Copyright 2004 Jones and Bartlett Publishers 20

512 Ionizing Radiation (cont’d)Natural sources--examples are radon and cosmic rays. Environmental radon is the greatest source of human exposure to ionizing radiation and may be the cause of nearly 20% of U.S. lung cancers. Synthetic sources--examples are medical x-rays and nuclear generators. Copyright 2004 Jones and Bartlett Publishers

513 Copyright 2004 Jones and Bartlett PublishersAllergens and Molds Allergens--substances that provoke an allergic reaction in susceptible individuals. Allergic reactions range from dermatitis, asthma, and itchy eyes to anaphylactic shock. Copyright 2004 Jones and Bartlett Publishers 21

514 Physical and Mechanical EnergyInclude agents associated with accidental injury. Also include such factors as noise, vibration, and extremes of temperature. Copyright 2004 Jones and Bartlett Publishers 22

515 Monitoring and Surveillance of Occupational HazardsHazard surveillance--characterization of known chemical, physical, and biologic agents in the workplace. Sentinel health event--a case of unnecessary disease, unnecessary disability, or untimely death whose occurrence is a warning signal that the quality of preventive or medical care may need to be improved. Copyright 2004 Jones and Bartlett Publishers 23

516 Environmental Hazards Found in the Work SettingBiologic hazards--Hospital employees, sewage workers, and agricultural workers may be exposed to hazardous biologic agents. For example, HIV may infect hospital workers through accidental needle sticks. Mineral and organic dusts--Examples include coal dust (mining and black lung disease) and rubber dust (COPD). Copyright 2004 Jones and Bartlett Publishers 24

517 Environmental Hazards Found in the Work Setting (cont’d)Vapors--Include organic solvents such as benzene, which may cause cancer and damage internal organs (particularly the liver). Fumes and vapors are likely to become increasing hazards due to the growing use of chemical substances. Copyright 2004 Jones and Bartlett Publishers 25

518 Psychosocial Aspects of Employment and HealthResearch topics include work overload and coronary heart disease; job stresses and absenteeism; and health effects of physical activity at work. For example, one study found an association between work stress and periodontal disease. Copyright 2004 Jones and Bartlett Publishers 26

519 Noteworthy Community Environmental Health HazardsHazardous waste sites Air pollution Nuclear facilities Drinking water Copyright 2004 Jones and Bartlett Publishers 27

520 Copyright 2004 Jones and Bartlett PublishersHazardous Waste Sites Notorious sites in the U.S. include: Love Canal, NY; Valley of the Drums, KY; Times Beach, MO; Stringfellow acid pits, CA. Of great concern is the contamination of water supplies by toxic wastes. Some possible adverse effects of hazardous waste exposure include birth defects, neurologic disease, and cancer. Copyright 2004 Jones and Bartlett Publishers 28

521 Copyright 2004 Jones and Bartlett PublishersAir Pollution Constituents of air pollution include sulfur oxides, particulates, ozone, and lead and other heavy metals. Lethal air pollution episodes have occurred worldwide. Studies conducted in New York City, St. Louis, and Tennessee have shown a correlation between increases in daily mortality and increased air pollution. Copyright 2004 Jones and Bartlett Publishers 29

522 Environmental Tobacco Smoke (ETS)Nonsmokers who work in a smoking environment have reduced pulmonary function compared to nonsmokers in a smoke-free work environment. ETS causes 3,000 lung cancer deaths annually among non-smokers. ETS is associated with children’s bronchitis, pneumonia, and asthma. Copyright 2004 Jones and Bartlett Publishers 30

523 Copyright 2004 Jones and Bartlett PublishersNuclear Facilities Include weapons production plants, test sites, and nuclear power plants. Studies of living in close proximity to nuclear installations have shown conflicting results regarding cancer rates. Following the Chernobyl nuclear power plant accident, thyroid cancer rates have increased near the reactor. Copyright 2004 Jones and Bartlett Publishers 31

524 Copyright 2004 Jones and Bartlett PublishersDrinking Water Chemical plants and nuclear facilities may contaminate ground water. Chlorination of water supply has helped to decrease the incidence of gastroenteric diseases. Lead and asbestos particles may be present in water and have potential for toxicity. Copyright 2004 Jones and Bartlett Publishers 32

525 Chapter 14 Molecular and Genetic Epidemiology

526 Peeking into the “Black Box”Many risk factors can be quantified through questionnaires, records, and easily measured attributes (such as blood pressure and anthropometrics). The biological mechanism(s) through which these factors influence disease is not always apparent (i.e., a “black box”). Copyright 2004 Jones and Bartlett Publishers

527 Value of Mechanistic InsightBiologic plausibility is a criterion for causality. Linking lifestyle risk factors with measures of biologic effect strengthens interpretations of causality. This linkage, in turn, provides stronger support for interventions. Copyright 2004 Jones and Bartlett Publishers

528 Why Distinguish Between Molecular and Genetic Epidemiology?The basic tenets and principles of molecular and genetic epidemiology are the same. However, there are specific features regarding design, analysis and interpretation inherent in the latter. Copyright 2004 Jones and Bartlett Publishers 3

529 Definition of Genetic EpidemiologyA discipline that seeks to unravel the role of genetic factors -- and their interactions with environmental factors – in the etiology of diseases, using family and population study approaches. Copyright 2004 Jones and Bartlett Publishers 4

530 Key Aspects of This DefinitionInherited susceptibility does not mean inherited disease--environment matters! When families are studied, the observations (study subjects) are no longer independent. This dependence requires special considerations for the analysis of data. Copyright 2004 Jones and Bartlett Publishers 5

531 Genetic Epidemiology is a Method to Answer the Questions:Does a disease cluster in families? If so, is that clustering likely a result of shared non-genetic risk factors? If the clustering is not accounted for by shared lifestyle or common environment, is the pattern of disease consistent with inherited effects? If so, where is the putative gene? Copyright 2004 Jones and Bartlett Publishers 6

532 What Diseases or Risk Factors Cluster in Families?Heart disease Various cancers Alcoholism Others Copyright 2004 Jones and Bartlett Publishers

533 Epidemiologic Assessment of ClusteringCase-control study Comparison of the frequency of a positive family history Expectation under genetic influence Copyright 2004 Jones and Bartlett Publishers

534 Clustering of “Non-Genetic” Exposures in FamiliesEmployment (e.g., several family members with medical degrees) Radon from soil Religious preferences Lead in paint Others? Copyright 2004 Jones and Bartlett Publishers 7

535 Major Point of This SectionYou cannot tell easily whether clustering of a risk factor or disease within a family is due to genetics, culture, or shared environment (including social or political factors). Copyright 2004 Jones and Bartlett Publishers 8

536 Other Correlates of Family HistoryLarge family size Age of relatives (for an age-related disease) Gender distribution (consider testicular cancer, prostate disease, ovarian cysts) Copyright 2004 Jones and Bartlett Publishers

537 Copyright 2004 Jones and Bartlett PublishersAnalysis Approach Model Y (case/control status) = established risk factors. Add family history variable to denote “genetic” influence (i.e., share genes with an individual who has the outcome of interest). Copyright 2004 Jones and Bartlett Publishers

538 Copyright 2004 Jones and Bartlett PublishersAnalysis Issues Try to compare (and control if necessary) differences between cases and controls with regard to size of family. Not easy to adjust for age of family members or their risk factors. What types of data can you ask your cases and controls to provide about their relatives? Copyright 2004 Jones and Bartlett Publishers

539 Motivation for Case-Control Family StudiesTo rule out influence of shared environment, family size differences, and age on differences in the frequency of family history between cases and controls. Need to enumerate the relatives of cases and controls, and determine the disease status and risk factor profile for each relative. Copyright 2004 Jones and Bartlett Publishers

540 Conduct of Family StudiesAscertain “probands” (index cases) Define family (siblings? children? parents? grandparents?) Invite family members to participate Collect data (and, typically, biological samples) Copyright 2004 Jones and Bartlett Publishers

541 How to Select Control FamiliesMust decide how to identify controls. From spouse’s side of proband’s family? Or select a random sample from the population? Will controls be motivated to participate? Must take HIPAA rules into account. Copyright 2004 Jones and Bartlett Publishers

542 Copyright 2004 Jones and Bartlett PublishersAnalysis Issues Exclude the index cases and controls. Model disease (or behavior) of interest based on age, sex, known risk factors. Evaluate evidence for genetic effect through significance of variable(s) that indicate “relationship to index case.” Copyright 2004 Jones and Bartlett Publishers

543 Analysis Issues (cont’d)Simplest “genetic” variable (1 if relative of case, 0 if relative of control). Can also construct indicator variables to designate type of relative. If not significant after including other risk factors, then no evidence for genetic influence. Copyright 2004 Jones and Bartlett Publishers

544 Evidence of genetic influence, so far….Cases are more likely to have a family history of disease than controls. The excess risk to relatives is not accounted for by age, sex, and other risk factors. What does that tell us about the underlying genetic influence? (nothing) Copyright 2004 Jones and Bartlett Publishers

545 Other Approaches to Identify Genetic InfluencesTwin studies Segregation analysis Linkage analysis Copyright 2004 Jones and Bartlett Publishers

546 Copyright 2004 Jones and Bartlett PublishersTwin Studies A “natural experiment” of sorts. Monozygotic (MZ) twins are genetically identical. Dizygotic (DZ) twins share, on average, the same proportion of genes as siblings. Greater concordance (for dichotomous traits) or correlation (for continuous traits) for MZ than DZ twins is evidence of a genetic influence. Copyright 2004 Jones and Bartlett Publishers 9

547 Copyright 2004 Jones and Bartlett PublishersSegregation Analysis Historically, linkage analysis required knowledge of the mode of transmission of the putative gene [dominant versus recessive, allele frequency, lifetime or age-specific risk (penetrance)]. Segregation analysis has been used to estimate these parameters. Copyright 2004 Jones and Bartlett Publishers

548 Copyright 2004 Jones and Bartlett PublishersLinkage Analysis One way to distinguish cultural inheritance from genetic inheritance is to track a region of our DNA that is transmitted from parents to offspring in the same manner as the disease/outcome of interest. This procedure works well for diseases that follow simple rules of inheritance (e.g., autosomal dominant or recessive). Copyright 2004 Jones and Bartlett Publishers 10

549 Genetic Epidemiology of Complex Diseases“Complex diseases” are ones for which the genetic influence may be modest and environmental factors contribute to disease risk. Segregation analysis is not typically done for “complex diseases.” Modern approaches ignore models of inheritance (non-parametric methods). Copyright 2004 Jones and Bartlett Publishers

550 Use of Epidemiology to Understand Genetic VariationThe methods of genetic epidemiology have been applied historically to identify genes. Typically, epidemiologists are not interested in mapping genes, but rather in figuring out how genes interact with environment to influence disease risk and outcome. Copyright 2004 Jones and Bartlett Publishers

551 Molecular EpidemiologyRelated individuals are not necessarily required for studies of the association of genetic variation with risk of disease. Both cohort and case-control designs can be used. Because genetic code (germline DNA) is unchanged since conception, one readily can employ retrospective designs. Copyright 2004 Jones and Bartlett Publishers

552 Common Strategies for Genetic Marker SelectionGenome-wide approach with anonymous DNA markers (10,000 SNPs on a chip). SNPs or simple tandem repeat markers in “candidate” genes based on a priori knowledge about presumed function. SNP’s in candidate genes with known functional effect on level or activity of protein product. Copyright 2004 Jones and Bartlett Publishers

553 Primer on Single Nucleotide Polymorphisms (SNPs)Because of our redundant genetic code, some SNP’s will not alter the encoded amino acid (e.g., GGA, GGG, GGT and GGC all encode proline). SNP’s that change an amino acid may not necessarily lead to change in function of transcribed protein. Copyright 2004 Jones and Bartlett Publishers

554 Copyright 2004 Jones and Bartlett PublishersMore on SNPs SNP’s that don’t change an amino acid may still lead to alternate splicing of the transcript (and therefore be functionally important). SNP’s in promoter region may influence level of protein product - not activity (and therefore be biologically significant). Copyright 2004 Jones and Bartlett Publishers

555 Caveats About SNP StudiesIf you’re interested in gene x environment interactions--best to focus on SNPs with known functional effect. Human biology is complex: are alterations in one component of a pathway compensated for by another? Most SNPs are likely to be modest risk factors – requiring large sample sizes. Copyright 2004 Jones and Bartlett Publishers

556 Realistic ExpectationsAlmost every gene is modified after translation into protein (e.g., glycosylation, acetylation, methylation). Thus, the correlation between DNA sequence and protein is far from perfect. May be necessary to examine multiple SNPs within a gene and several genes within a pathway. 8 Copyright 2004 Jones and Bartlett Publishers

557 Molecular Epidemiology – Beyond GeneticsBiomarkers of exposure and disease extend beyond DNA. Viral or bacterial load. Morphometric analysis of tissues/cells. Hormone or lipid levels in blood or urine. Other examples? Copyright 2004 Jones and Bartlett Publishers

558 Copyright 2004 Jones and Bartlett PublishersConclusion Molecular and genetic epidemiology represent specialty areas of expertise. These specialty areas utilize and apply advances in molecular biology and molecular genetics of disease to: unravel disease etiology. enable novel approaches for early detection. inform more effective interventions by targeting those at greatest risk. Copyright 2004 Jones and Bartlett Publishers

559 CHAPTER 15 Psychologic, Behavioral, and Social Epidemiology

560 Learning Objectives, AbridgedState the role of psychologic, behavioral, and social factors in health and disease. Define status discrepancy, person-environment fit, and stressful life events. Discuss moderators of the stress-illness relationship. State outcomes of exposure to stress. Copyright 2004 Jones and Bartlett Publishers

561 Social Epidemiology: DefinitionsConcerned with the influence of a person’s position in the social structure upon the development of disease (Syme, 1974). “ the branch of epidemiology that studies the social distribution and social determinants of states of health.” (Berkman, Kawachi, 2000) Copyright 2004 Jones and Bartlett Publishers

562 Behavioral EpidemiologyStudies the role of behavioral factors in health. Examples of behavioral factors are tobacco use, physical activity, and risky sexual behavior. Copyright 2004 Jones and Bartlett Publishers

563 Copyright 2004 Jones and Bartlett PublishersBehavioral Medicine Related to behavioral epidemiology. Emphasizes the application of behavioral factors to specific clinical interventions, e.g., biobehavioral approaches to management of hypertension. Copyright 2004 Jones and Bartlett Publishers

564 Psychosocial EpidemiologyBroadly conceptualized term that includes psychological, behavioral, and social factors. Relevant to mental health states, e.g., grief and depression. Relevant to physical health states, e.g., chronic diseases. Copyright 2004 Jones and Bartlett Publishers

565 Guide to Psychosocial EpidemiologyStress Social Incongruity Person- environment fit Life events Personality factors Type A behavior Culture Social support Lifestyle and Life and job dissatisfaction Mental health Depressive symptoms Independent Variables Moderating Variables Dependent Variables Copyright 2004 Jones and Bartlett Publishers

566 Copyright 2004 Jones and Bartlett PublishersResearch Designs Studies used in this field of investigation: Case-control Cohort Cross-sectional Needed are more: Longitudinal, prospective studies Studies of women and minority groups Valid and operationalized measures Copyright 2004 Jones and Bartlett Publishers

567 Example of Longitudinal, Prospective StudyThe Early Stages of Psychopathology Study followed 3,021 adolescent and young adult residents of Munich, Germany. Begun in , subjects were followed up on average after a 42-month interval. Incidence of mental disorders examined. Copyright 2004 Jones and Bartlett Publishers

568 Social Context of HealthThe social environment contributes to the regulation of psychosocial influences upon health. Example: In less developed areas, overcrowding, poor living conditions, and lack of preventive health care promote spread of infectious diseases. Copyright 2004 Jones and Bartlett Publishers

569 Global Burden of Disease StudyAssesses the worldwide consequences of disease. The disability-adjusted life year (DALY) combines information on mortality with information on morbidity for specific causes. Lower respiratory infections: leading global DALY. Copyright 2004 Jones and Bartlett Publishers

570 Independent VariablesGeneral concepts of stress Social incongruity theory Person-environment fit Stressful life events Stress process model Copyright 2004 Jones and Bartlett Publishers

571 General Concepts of Stress: CanonCanon studied changes in gastrointestinal function accompanying stressful events. Copyright 2004 Jones and Bartlett Publishers

572 General Concepts: SelyeSelye proposed that stress is a change in the environment of the organism. General adaptation syndrome specified three stages of response to stress: alarm reaction stage of resistance stage of exhaustion General adaptation syndrome associated with corticoid secretion. Copyright 2004 Jones and Bartlett Publishers

573 General Concepts: CriderCrider proposed that adverse environmental events produce stress. Examples: noxious stimuli removal of reinforcement conflict situation The executive monkey experiments demonstrated physiological effects (e.g., gastric ulcers) associated with stress. Copyright 2004 Jones and Bartlett Publishers

574 Social Incongruity TheoryThe guiding hypothesis is that either social mobility or status incongruity may be associated with morbidity. Themes of research are correlates of changes in residence; intragenerational mobility; husband-wife discrepancy in status. Copyright 2004 Jones and Bartlett Publishers

575 Social Incongruity Theory (cont’d)Cobb, et al. (1969) examined discrepancy between husband and wife in social and educational status as associated with arthritis. Syme, et al. (1966) studied the association between cultural mobillity and coronary heart disease. Copyright 2004 Jones and Bartlett Publishers

576 Person-Environment Fit Model“conceives of adjustment as the goodness of fit between the characteristics of the person and the properties of [his or her] environment.” (French, et al., 1974) Lack of adjustment occurs when there are discrepancies between demands from the environment and supplies (resources) to meet those demands. Copyright 2004 Jones and Bartlett Publishers

577 Copyright 2004 Jones and Bartlett PublishersStressful Life Events Theory postulates that there is a relationship between the happenings in one’s life and the development of illness. Copyright 2004 Jones and Bartlett Publishers

578 Social Readjustment Rating ScaleHolmes and Rahe (1967) developed 43-item Social Readjustment Rating Scale. Each item represented a life event. The more severe the life change event and the higher the frequency of the event, the greater the chance that severe disease will occur. Copyright 2004 Jones and Bartlett Publishers

579 Ten Leading Life Change Eventsdeath of a spouse divorce marital separation jail term death of a close family member personal injury or illness marriage being fired from a job marital reconciliation retirement Copyright 2004 Jones and Bartlett Publishers

580 Pearlin’s Stress Process ModelUsed as a guide for stress research. Stress: a process occurring over time. Events chain from one another with interconnectedness among various factors: social and economic status life events and chronic strains moderating resources, e.g., coping skills stress outcomes, e.g., mental disorders Copyright 2004 Jones and Bartlett Publishers

581 Moderating Factors in the Stress-Illness RelationshipType A behavior pattern Social support Personal behavior, lifestyle, and health Copyright 2004 Jones and Bartlett Publishers

582 Type A (Coronary-Prone) Behavior PatternFound to be associated with CHD. Characteristics include aggressiveness, ambition, drive, and competitiveness. Interview measure and self-administered measure used. Copyright 2004 Jones and Bartlett Publishers

583 Copyright 2004 Jones and Bartlett PublishersSocial Support Refers to perceived emotional support that one receives from social relationships. Operates as mediator--buffers against stress. May enhance immune status. Lack of social support may contribute to onset and severity of psychological stress. Copyright 2004 Jones and Bartlett Publishers

584 Copyright 2004 Jones and Bartlett PublishersSocial Network Ties Quantitative concept that refers to the number (and patterns) of ties that one has with other people and organizations. May serve to lessen the adverse psychologic consequences of stress and reduce levels of depression. Copyright 2004 Jones and Bartlett Publishers

585 Social Network Ties: ExampleMarital status is related to the types of social network ties maintained. Married older adults have more contact with family members than with friends and receive more emotional support than unmarried older adults. Copyright 2004 Jones and Bartlett Publishers

586 Personal Behavior, Lifestyle, and HealthHealthy People 2000 is a document that established a framework in the U.S. for national health promotion and disease prevention objectives. Health promotion priority activities include physical activity and fitness, nutrition, and reduction of tobacco use. Copyright 2004 Jones and Bartlett Publishers

587 The Alameda County Study (Breslow)Seven healthful habits: moderate food intake eating regularly eating breakfast not smoking cigarettes moderate or no use of alcohol moderate exercise 7 to 8 hours of sleep daily Copyright 2004 Jones and Bartlett Publishers

588 Health-Related Aspects of Personal Behaviorrisk taking sexual behavior dietary practices and exercise levels smoking alcohol consumption choice of occupation Copyright 2004 Jones and Bartlett Publishers

589 Copyright 2004 Jones and Bartlett PublishersSmoking and Health Overall 70% excess morbidity among smokers compared to nonsmokers. Mortality from smoking increases with quantity of cigarettes smoked. Association between smoking and cardiovascular diseases, cancer, pulmonary diseases, peptic ulcer disease. Copyright 2004 Jones and Bartlett Publishers

590 Copyright 2004 Jones and Bartlett PublishersAlcohol Consumption Excessive consumption is a risk factor for cirrhosis, peptic ulcers, gastritis. Increases likelihood of motor vehicle accidents. Deterioration of family environment and job loss. Fetal alcohol syndrome. Copyright 2004 Jones and Bartlett Publishers

591 Copyright 2004 Jones and Bartlett PublishersDietary Practices Association between consumption of refined carbohydrate foods and obesity and diabetes. Lack of dietary fiber related to diseases of the bowel. Consumption of saturated fats and cholesterol associated with arteriosclerosis and heart disease. Copyright 2004 Jones and Bartlett Publishers

592 Copyright 2004 Jones and Bartlett PublishersSedentary Lifestyle Risk factor for CHD and other conditions. Morris, et al. (1973) found vigorous exercise, not light exercise, reduced incidence of CHD. Paffenbarger, et al. (1978) corroborated findings for vigorous exercise. Copyright 2004 Jones and Bartlett Publishers

593 Sociocultural Influences on HealthCulture is defined as the set of values to which a group of people subscribes, as the way of life of a group of people, or as the totality of what is learned and shared through interaction of the members of a society. Copyright 2004 Jones and Bartlett Publishers

594 CHD in Japanese Men: Marmot, et al. (1975)Compared CHD rates among men of Japanese ancestry living in Japan, Honolulu, and San Francisco. Rates lowest in Japan, highest in San Francisco, intermediate in Honolulu. Possibly due to variations between the two countries in terms of diet, occupation, and the social and cultural milieu. Copyright 2004 Jones and Bartlett Publishers

595 Utilization of Health ServicesPreference for health care services varies according to cultural background. Persons from traditional cultures may prefer folk medicine and family care. Persons from more developed societies may prefer technologically advanced medical services. Copyright 2004 Jones and Bartlett Publishers

596 Copyright 2004 Jones and Bartlett PublishersOutcome Variables These include physical health, mental health, and affective states. Some topics covered are: Life and job dissatisfaction. Mental health and stressors. Premorbid psychologic factors and cancer. Copyright 2004 Jones and Bartlett Publishers

597 Life and Job DissatisfactionSales and House (1971) demonstrated a strong negative correlation between job satisfaction and coronary disease death rates. Copyright 2004 Jones and Bartlett Publishers

598 Dissatisfaction (cont’d)Tedious work, feeling ill at ease at work, lack of recognition, difficulties with coworkers, demotion, and prolonged emotional strain associated with work overload have been shown to be related to coronary disease. Copyright 2004 Jones and Bartlett Publishers

599 Mental Health and StressorsEpidemiologic research has examined psychologic disorders and affective states as outcomes of stress-illness paradigm. Psychologic disorders: posttraumatic stress disorder and major depression. Affective states: depressive symptoms. Copyright 2004 Jones and Bartlett Publishers

600 Depression: Frerichs, et al. (1982)Prevalence of depression in a representative sample of adults in Los Angeles County was 19%. Rates of depression among women higher than men (23.5% vs. 12.9%). Depressed persons reported more physical illness than nondepressed. Copyright 2004 Jones and Bartlett Publishers

601 Cancer: Psychologic FactorsFox (1978)--two major personality types at increased risk of cancer: Yielding, compliant, eager to please. Extroverted, nonneurotic individuals who tend toward heaviness. Fox’s 1995 review showed contradictory findings regarding psychologic variables and cancer. Copyright 2004 Jones and Bartlett Publishers

602 Effects of Major Diseases on PersonalitySevere illness may bring about personality changes in the individual, spouse, children, and coworkers. Wives of heart attack victims experience depression, fear, anxiety, and guilt. Heart attack victims may experience similar feelings. Copyright 2004 Jones and Bartlett Publishers

603 Personality and Smoking: Surgeon General’s Report (1979)Personality factors related to smoking behavior may include extroversion, neuroticism, antisocial tendencies, and belief that one is externally controlled. Smokers may show greater risk-taking, impulsiveness, and interest in sex. Copyright 2004 Jones and Bartlett Publishers

604 Habitual Mental Outlook and Health StatusHabitual mental outlook includes mental health, adult adjustment, cheerfulness, and sense of humor. Valliant (1979) demonstrated association between good mental health and physical health. Results of other studies inconsistent. Copyright 2004 Jones and Bartlett Publishers