45 Questions
What is serum 25(OH)D a biomarker of?
Vitamin D exposure
Why is it important to consider the exposure-disease pathway?
To understand the causal events or states leading to disease
What happens as you move down the exposure-disease pathway?
What you measure is closer to the causal agent
What type of exposure is easy to define in terms of dose?
Binary exposures
Is exposure to secondary smoke a binary exposure?
Sometimes
What shifts as you move along the exposure-disease pathway?
The perspective of the study
What is a challenge when trying to define exposure?
It can be culturally specific
Why is it necessary to choose a surrogate measure of exposure?
Because true exposure is often not measurable
When choosing a surrogate measure, what should be balanced?
Sensitivity and specificity
What is an example of exposure occurring through multiple sources?
Caffeine intake through coffee and other sources
What is the first step in measuring exposure?
Acknowledge that true exposure is often not measurable
What is the purpose of isolating the biological agent of interest?
To make the measurement of exposure more specific
Why is it important to specify the active agent when measuring exposure?
To make the measurement of exposure more specific and sensitive
What is an example of a specific biological agent of interest?
Mercury in vaccines
What is a common source of human exposure to mercury?
Eating fish and shellfish
What type of chemicals are formed during the digestion of processed meat?
Nitrates and nitrites
What is the biological agent of interest in the context of mercury exposure?
Methylmercury
What is a key consideration when selecting an exposure measurement?
How the exposure relates causally to the outcome of interest
What type of cancer is associated with the consumption of red meat?
Colon cancer
What is a surrogate measure of exposure in the context of smoking?
The number of cigarettes smoked
What is the exposure-disease pathway in the context of mercury exposure?
Mercury is released into the environment, causing health problems in utero and early in life
What is the critical exposure window, and how does it relate to exposure measurement error?
The critical exposure window is the time period during which the exposure has the greatest causal effect on the outcomes. Including exposures outside of this window results in exposure measurement error.
Why is it essential to consider the timing of exposure in epidemiological studies?
Considering the timing of exposure is essential because not all exposures matter, only those that occur during the critical or etiological window.
What is an example of how the timing of exposure affects the outcome in prenatal development?
The effect of exposures during different trimesters of pregnancy on the outcome, such as birth defects or developmental abnormalities.
How can the exposure timing affect the outcome in the context of cannabis use and schizophrenia-like deficits?
Exposure to cannabis during the peripubertal period is a risk factor for the emergence of schizophrenia-like deficits.
What is the importance of considering the timing of exposure in relation to menopause in cardiovascular disease research?
Considering the timing of exposure in relation to menopause is important because postmenopausal women have a higher risk for cardiovascular disease, and not all women start menopause at the same age.
Why is it essential to define the exposure accurately in epidemiological studies?
Defining the exposure accurately is essential to avoid measurement error and ensure that the exposure is being measured during the critical or etiological window.
What is the implication of including exposures outside of the etiological window on exposure measurement?
Including exposures outside of the etiological window results in exposure measurement error.
Why is it necessary to consider the timing of exposure in case-control studies?
Considering the timing of exposure is necessary in case-control studies to ensure that the exposure is being measured during the critical or etiological window, and to avoid measurement error.
What is the importance of considering the time since last exposure in determining disease risk, especially for causes that occur late in the sequential cause chain?
It is important because those who were recently exposed will be at greatest risk, as seen in the example where current smokers have a threefold risk of myocardial infarction.
What is regency analysis, and when is it used?
Regency analysis considers only recent exposure and is used for exposures that are causal in the later part of the sequential cause chain.
How can the timing of exposure be related to disease risk using statistical approaches?
Statistical approaches can be used to relate the timing of exposure to disease risk by examining cumulative exposure dose for different non-overlapping time periods, multiple overlapping periods in separate models, or using weighted cumulative exposure with different weights for each time window.
What should be considered when measuring exposure to ensure accurate results?
When measuring exposure, it is essential to consider the research question, biological agent of interest, where in the exposure-disease pathway to measure exposure, and the ideal and most feasible method of measurement.
Why is it essential to specify the timing of exposure in measuring exposure?
Specifying the timing of exposure is crucial because it can affect the accuracy of the measurement and the subsequent association with disease risk.
What should be considered when selecting an exposure measurement method?
When selecting an exposure measurement method, it is essential to consider the duration and frequency of exposure, as well as the timing of exposure.
Why is it necessary to adjust for other exposure windows when examining the association between exposure and disease risk?
It is necessary to adjust for other exposure windows because components of dose and time are correlated, and exploratory modeling tends to overestimate the effect size.
What are the three key steps in measuring exposure?
The three key steps in measuring exposure are identifying what to measure, identifying how and when to measure, and identifying what, how, and when to measure.
Why is it important to exclude exposures that occurred in the induction or latent period when computing cumulative dose in a case-control study?
To avoid reverse causality and ensure that the exposure is truly related to the disease outcome.
What is the purpose of latency analysis or exposure lagging in relating timing of exposure to disease risk?
To exclude exposures that occurred in the induction or latent period and focus on the etiological window.
What type of exposure measurements are considered reliable in case-control studies?
Fixed exposures over time, such as genetic information.
Why is it important to establish a reference date in case-control studies when assessing behavioral exposures?
To ensure that exposures are only included before any symptoms occur, avoiding reverse causality.
What is the purpose of exposure window analysis in relating timing of exposure to disease risk?
To only count exposures that occurred in the etiological window, excluding exposures before and after.
Why is time since first exposure or age at first exposure important in some causes?
Because these causes are early on the sequential cause chain, and timing of exposure is critical.
What is a challenge when trying to relate timing of exposure to disease risk?
The timing of the etiological window, induction period, and latent period are often not known.
Why is it important to consider the timing of exposure in case-control studies?
To avoid reverse causality and ensure that the exposure is truly related to the disease outcome.
Study Notes
Exposure in Epidemiology
- Exposure can be difficult to define and may fluctuate over time, even within the same person.
- True exposure is often not measurable, and a surrogate is needed, balancing sensitivity, specificity, accuracy, patient burden, and cost.
Sources of Exposure
- Exposure can occur through many sources, such as environmental factors, lifestyle habits, and biological agents.
- Example: Exposure to aluminum welding fumes can cause pulmonary fibrosis.
Biological Agent of Interest
- Isolating the biological agent of interest helps measure exposure accurately.
- Specify the active agent to make the measurement of exposure more precise.
- Example: If caffeine is the exposure of interest, exclude decaffeinated coffee and include all sources of caffeine, such as sports gels and medication.
Examples of Exposure
- Vaccination and autism due to exposure to mercury from thimerosal in vaccines.
- Eating meat and the risk of colon cancer due to naturally occurring chemicals, added nitrates, and nitrites.
- Smoking and prostate cancer, considering different types of smoking and toxic components.
Considerations for Selecting Exposure Measurement
- How does exposure relate causally to the outcome of interest?
- What is the best way to represent the amount or dose of exposure?
- Example: Serum 25(OH)D as a biomarker of exposure to vitamin D.
The Exposure-Disease Pathway
- Exposure to disease is a pathway of multiple steps or causal events.
- Exposures can be measured at multiple steps or states.
- Disease can be measured at multiple steps or states.
- As you move down the exposure-disease pathway, what one measures is closer to the causal agent, making it more likely to show a non-biased association between exposure and disease.
Exposure Measurement in Epidemiological Studies
- In case-control studies, behavioral exposures should only be included before symptoms occur, and a reference date should be established for both cases and controls.
- Example: 2 years for colon cancer.
Timing of Exposure
- Timing of exposure is crucial in determining disease risk, and different methods can be used to relate timing of exposure to disease risk.
- Methods include:
- Latency analysis or exposure lagging: exclude exposures that occurred in the induction or latent period.
- Exposure window analysis: only count exposures that occurred in the etiological window, excluding those before and after.
- Example: a cumulative dose of asbestos for the time window 10 to 25 years before diagnosis/reference date had the greatest power to detect an association with lung cancer.
Etiological Window
- The etiological window is the critical exposure window during which the exposure has the greatest causal effect on outcomes.
- Including exposures outside of the etiological window results in exposure measurement error.
- Examples of etiological windows include:
- Prenatal exposure (different effects in 1st, 2nd, and 3rd trimesters)
- Exposures during different phases of childhood
- Peripubertal period (e.g., cannabis exposure and schizophrenia-like deficits)
- Time in relation to menopause (e.g., postmenopausal women and cardiovascular disease)
Additional Methods
- Time since first exposure or age at first exposure: important for causes that are early on the sequential cause chain.
- Example: age at immigration and risk of melanoma.
- Regency analysis: considers only recent exposure and works for exposures that are causal in the later part of the sequential cause chain.
- Example: smoking in the past year is the best exposure window for the association with myocardial infarction.
Statistical Approaches
- Examining cumulative exposure dose for different non-overlapping time periods in the same model.
- Examining multiple overlapping periods in separate models and comparing models for goodness of fit.
- Using weighted cumulative exposure, with each time window carrying different weights.
- Caution: exploratory modeling tends to overestimate the effect size, and components of dose and time are correlated, so need to adjust for other exposure windows.
Measuring Exposure
- Step 1:
- Identify research question
- Identify biological agent of interest
- Determine where in the exposure-disease pathway to measure exposure
- Step 2:
- Identify ideal and feasible method of measurement
- Ensure measurement method is sensitive and specific
- Determine timing of exposure to include
- Step 3:
- Determine duration of exposure
- Determine frequency of exposure
This quiz explores the concept of exposure in epidemiology, discussing its definition, fluctuations, and measurement. It also touches on the importance of choosing a surrogate when true exposure is not measurable.
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