Cause An antecedent event, condition, or characteristic that
was necessary for the occurrence of the disease at the moment it
occurred, given that other conditions are fixed A cause of a
disease occurrence is an event, condition, or characteristic that
preceded the disease onset and that, had the event, condition, or
characteristic been different in a specified way, the disease
either would not have occurred at all or would not have occurred
until some later time 2
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Cause can also be defined as something that brings about an
effect or a result. Cause may lead to an effect (disease) but, it
is not simple since several diseases are multifactorial. Cause
Slide 4
Smoking causes lung cancer, chronic obstructive pulmonary
disease, peptic ulcers, bladder cancer, coronary artery disease.
Concepts of Cause
Slide 5
Coronary Artery disease has multiple causes: cigarette smoking,
high levels of LDL, stress, hormonal effects, hypertension,
hypercholesterolemia, life style, lack of physical activity,
heredity etc. Concepts of Cause contd..
Slide 6
Because of diseases being multifactorial, the influence of
peoples behaviours or characteristics of their environments and
life style are also important causes of diseases than the
pathogenic mechanisms. Concepts of Cause contd..
Slide 7
Cardiovascular and cancer deaths can largely be traced to
behavioural and environmental factors. The spread of AIDS is due
primarily to sexual behaviours and drug use. Example
Slide 8
Interpretations of causation 1. Mechanistic interpretation of
causation (Lab researcher)To be termed a cause an agent must be
both necessary and sufficient e.g. Kochs postulate One must be
mindful that although Kochs postulate was developed for infectious
diseases, they are not met for majority of these diseases e.g.
polio virus, HIV/AIDS
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Interpretations of causation Mechanistic interpretations do not
take into account inter-individual differences in susceptibility or
interactions among causative agents.
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Interpretations of causation 2. Probabilistic interpretation
Under this interpretation, a cause is something which leads to an
increased probability that disease will occur. This interpretation
also allows for the concept of interaction between causes. e.g.
While it is believed that HIV causes AIDS, there is evidence that
the probability of developing AIDS is lower in people who are
infection by certain strains of the HIV virus.
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Interpretations of causation 3. Operational interpretation
(public health based concept) A factor is a cause of if its
elimination, or reduction in the level of exposure, leads to a
decrease in occurrence of disease.
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Types of Causal Relationships A causal pathway can be either
direct or indirect. In direct causation, a factor directly causes a
disease without any intermediate step. In indirect causation, a
factor causes a disease, but only through an intermediate step or
steps. In human biology, intermediate steps are virtually always
present in any causal process.
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Types of Causal Relationships contd.. If a relationship is
causal, four types of causal relationships are possible: (1)
necessary and sufficient; (2) necessary, but not sufficient; (3)
sufficient, but not necessary; and (4) neither sufficient nor
necessary.
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Figure 1. Direct versus indirect causes of disease. Downloaded
from: StudentConsult (on 7 January 2014 09:14 AM) 2005
Elsevier
Slide 15
Figure 2. Types of causal relationships: I. A factor is both
necessary and sufficient. Downloaded from: StudentConsult (on 7
January 2014 09:14 AM) 2005 Elsevier
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Figure 3. Types of causal relationships: II. Each factor is
necessary, but not sufficient. Downloaded from: StudentConsult (on
7 January 2014 09:14 AM) 2005 Elsevier
Slide 17
Figure 4. Types of causal relationships: III. Each factor is
sufficient, but not necessary. Downloaded from: StudentConsult (on
7 January 2014 09:14 AM) 2005 Elsevier
Slide 18
Figure 5. Types of causal relationships: IV. Each factor is
neither sufficient nor necessary. Downloaded from: StudentConsult
(on 7 January 2014 09:14 AM) 2005 Elsevier
Slide 19
Criteria for causality The following list is derived from an
article by Sir Austin Bradford Hill (1965). The criteria were
developed as a means to summarize scientific data on a postulated
cause-effect relationship Today, with insights into disease
manifestations as well as our limited knowledge of certain emerging
diseases, not all criteria remain widely accepted, yet some do
remain important.
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Criteria for causality Consistency of findings Strength of a
relationship: Temporal sequence Dose response relationship
Specificity: Biological plausibility Experimental evidence
Reasoning by analogy Coherence of evidence
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1. Consistency of findings This refers to the repeated
observations in other studies in different populations, different
places, different times and under different circumstances. 2.
Strength of a relationship: Magnitude of OR or RR Was OR or RR
statistically significant However, weak relationships can still be
of importance to public health if both exposure and disease are
common.
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3. Temporal sequence: This refers to the temporal sequence of
exposure and outcome is this sequence in the right direction Did
the exposure cause the disease? Did the disease cause the exposure?
Best evidence is from RCT and prospective study
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4. Dose response relationship (biological gradient): Those who
are exposed more heavily, have a higher risk of disease than those
exposed to lower doses. However associations that do not show an
apparent trend of effect with an increase in dose, beware of
unknown confounder Consider therefore: 1. Is a dose response
relationship due to an unknown confounder 2. There may be threshold
effects
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5. Specificity: One cause one outcome, i.e. the cause should
lead to an effect not multiple effects Exposure: A disease should
be specifically caused by a single exposure( not true in public
health practice) Disease: An exposure should specifically cause one
disease ( not true in public health practice) Specificity belongs
more to mechanistic interpretation of cause rather than modern
epidemiological interpretation.
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6. Biological plausibility: Does this association make sense?
What are the known facts about the disease? 7. Experimental
evidence: This refers to the quality of the chosen study type. You
should ask yourself: Is the study type the strongest that could
have been used under the circumstances (feasible and ethical)?
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8. Reasoning by analogy: This refers to the kind of reasoning
which states- if one drug can cause birth defects then maybe
another drug can also produce similar outcomes. 9. Coherence of
evidence: This implies that a cause and effect interpretation of
result does not conflict with what is generally known about the
natural history and biology of disease.
Slide 27
CriterionProblems with the criterion StrengthStrength depends
on the prevalence of other causes and, thus, is not a biologic
characteristic; could be confounded ConsistencyExceptions are
understood best with hindsight SpecificityA cause can have many
effects TemporalityIt may be difficult to establish the temporal
sequence between cause and effect Biologic gradientCould be
confounded; threshold phenomena would not show a progressive
relation PlausibilityToo subjective CoherenceHow does it differ
from consistency and plausibility? Experimental evidenceNot always
available AnalogyAnalogies abound Table. Causal criteria of Hill
27
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Assessment of the Evidence suggesting Helicobacter Pylori as a
causative agent of duodenal ulcers Temporal relationship.
Helicobacter pylori is clearly linked to chronic gastritis. About
11% of chronic gastritis patients will go on to have duodenal
ulcers over a 10-year period. In one study of 454 patients who
underwent endoscopy 10 years earlier, 34 of 321 patients who had
been positive for Helicobacter pylori (11%) had duodenal ulcer
compared with 1 of 133 Helicobacter pylori-negative patients
(0.8%).
Slide 29
Assessment of evidence contd.. Strength of the relationship.
Helicobacter pylori is found in at least 90% of patients with
duodenal ulcer. In at least one population reported to lack
duodenal ulcers, a northern Australian aboriginal tribe that is
isolated from other people, it has never been found. Dose-response
relationship. Density of Helicobacter pylori per square millimeter
of gastric mucosa is higher in patients with duodenal ulcer than in
patients without duodenal ulcer. Also see item 2 above.
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Assessment of evidence contd.. Replication of the findings.
Many of the observations regarding Helicobacter pylori have been
replicated repeatedly. Biologic plausibility. Although originally
it was difficult to envision a bacterium that infects the stomach
antrum causing ulcers in the duodenum, it is now recognized that
Helicobacter pylori has binding sites on antral cells and can
follow these cells into the duodenum. Helicobacter pylori also
induces mediators of inflammation. Helicobacter pylori-infected
mucosa is weakened and is susceptible to the damaging effects of
acid.
Slide 31
Assessment of evidence contd.. 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 Helicobacter pylori has been
eradicated. Cessation of exposure. Eradication of Helicobacter
pylori heals duodenal ulcers at the same rate as histamine receptor
antagonists. Long-term ulcer recurrence rates were zero after
Helicobacter pylori was eradicated using triple-antimicrobial
therapy, compared with a 60% to 80% relapse rate often found in
patients with duodenal ulcers treated with histamine receptor
antagonists.
Slide 32
Assessment of evidence contd.. Specificity of the association.
Prevalence of Helicobacter pylori in patients with duodenal ulcers
in 90% to 100%. However, it is found in some patients with gastric
ulcer and even in asymptomatic individuals. Consistency with other
knowledge. Prevalence of Helicobacter pylori infection is the same
in men as in women. The incidence of duodenal ulcer, which in
earlier years was believed to be higher in men than in women, has
been equal in recent years.
Slide 33
Assessment of evidence contd.. 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 observations today that the prevalence of
Helicobacter pylori is much higher in developing countries.