l14 epi causation

Give 4x approaches for studying disease etiology.

Animal studies

 

•In vitro systems (e.g., cell culture)

 

•Drawing conclusions about whether a substance causes disease in humans requires observations in human populations

 

•Due to ethical concerns, we are often dependent on nonrandomized observational studies

List 2x approaches to disease etiology in humans.

 

1. We determine whether there is an association or correlation between an exposure or characteristic and the risk of a disease. To do so, we use:

•Studies of group characteristics: ecologic studies 

•Studies of individual characteristics: cohort, case-control, and other types of observational studies

 

2. If an association is demonstrated, we determine whether the observed association is likely to be a causal one.

 

List 4x types of associations.

Real vs. spurious associations

 

•If the observed association is real, the next question is whether it is causal or non-causal

 

•Associations that are observed due to confounding are non-causal

 

•Distinguishing causal/non-causal relationships is key to the success of future interventions

Describe the 2x types of casual relationships?

A causal pathway can be either direct or indirect

 

Direct: factor directly causes a disease without any intermediate step

 

Indirect: factor causes a disease but only through an intermediate step or steps

List the 4 types of causes of casual relationships.

Necessary and sufficient

2.Necessary but not sufficient

3.Sufficient but not necessary

4.Neither sufficient nor necessary

Describe necessary and sufficient in terms of factors.

• Without the factor, the disease never develops (necessary)

 

•In the presence of the factor, the disease always develops (sufficient)

Necessary but NOT sufficient?

Each factor is necessary but not sufficient, in itself, to cause the disease (i.e., multiple factors are required)

Sufficient but not necessary??

The factor alone can produce the disease, but so can other factors that are acting alone

Neither sufficient or necessary??

Factor by itself cannot cause disease and other factors acting alone can cause disease

Describe evidence of casual relationships? With example?

1. The organism is always found with the disease.

   2.The organism is not found with any other disease

   3.The organism when isolated from one who has the disease and cultured through several generations produces the disease (in experimental animals).

Koch’s Postulates

List 9 ways to judge if a relationship is casual?

1. Temporal relationship

2. Strength of the association

3. Dose-response relationship

4. Replication of the findings

5. Biologic plausibility

6. Consideration of alternate explanations

7. Cessation of exposure

8. Consistency with other knowledge

9. Specificity of the association

Give example of deriving casual inferences?

Until the 1980s: major causes of peptic ulcer disease were thought to be stress and lifestyle factors, including smoking

Example for deriving inferences continued?

1. Temporal relationship

•Helicobacter pylori is linked to chronic gastritis. Approximately 11% of chronic gastritis patients will go on to have duodenal ulcers over 10 years.

 

2. Strength of the association

•Helicobacter pylori is found in at least 90% of patients with duodenal ulcers. In a northern Australian aboriginal tribe that is isolated from other people, duodenal ulcers norHelicobacter pylori have been found.

 

3. Dose-response relationship

•The density of Helicobacter pylori per square millimeter of the gastric mucosa is higher in patients with duodenal ulcers than those without duodenal ulcers.

4. Replication of the findings

•Many of the observations regarding Helicobacter pylori have been replicated.

 

5. Biologic plausibility

•Helicobacter pylori induces mediators of inflammation.

•Helicobacter pylori-infected mucosa is weakened, making it more susceptible to the damaging effects of acid.

 

6. Consideration of alternate explanations

•Data suggest that smoking can increase the risk of duodenal ulcer in Helicobacter pylori–infected patients but is not a risk factor in patients in whom H. pylori has been eradicated.

 7. Cessation of exposure

•Long-term ulcer recurrence rates were zero after Helicobacter pylori was eradicated.

8. Consistency with other knowledge

•The prevalence of ulcer disease is believed to have peaked in the latter part of the 19th century, and the prevalence of Helicobacter pylori may have been much higher at that time because of poor living conditions. This reasoning is also based on current observations that the prevalence of Helicobacter pylori is much higher in developing countries.

 

9. Specificity of the association

•Prevalence of Helicobacter pylori in patients with duodenal ulcers is 90%–100%. However, it is found in some patients with gastric ulcers and even in asymptomatic individuals