Hypothesis Generation
Goals
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Discuss the importance of hypothesis
generation
Describe approaches to generating
hypotheses
Present Internet resources useful for
literature reviews
What is Hypothesis Generation and
Why is it Important?
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A hypothesis is an educated “guess”
about the source of the outbreak
Generating hypotheses enables the
investigators to test these hypotheses
in an analytic study
The success of the investigation
depends upon the quality of the
hypotheses
Overview of Hypothesis
Generation Strategy
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Ways to approach generating
hypotheses about the cause of the
outbreak
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Examine the line listing data
Review the existing body of knowledge
Administer open-ended hypothesisgenerating questionnaire to several cases
Overview of Hypothesis
Generation Strategy
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Develop specific hypotheses
Test the hypotheses in an analytic study
using a structured questionnaire
concerning the specific hypotheses
Overview of Hypothesis
Generation Strategy
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Review the existing body of knowledge
to learn about previous outbreaks
caused by the same organism or
disease
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Read medical, epidemiology, microbiology,
and veterinary (if relevant) literature
Talk to experts in the field
Overview of Hypothesis
Generation Strategy
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Literature reviews help identify
organisms, risk factors, and sources of
exposures that have been observed in
the past
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Example: diarrheal disease
Overview of Hypothesis
Generation Strategy
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Some outbreaks are caused by
unrecognized agents or through
unrecognized modes of transmission
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Examples: hantavirus and West Nile virus
Overview of Hypothesis
Generation Strategy
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Familiarity with the microbiology,
natural history, and ecologic niche of
the organism may also be helpful
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Example: Blastomyces dermatitidis and
hantavirus pulmonary syndrome
Overview of Hypothesis
Generation Strategy
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Utilization of existing hypothesisgenerating resources may save time
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CDC has a standard questionnaire
template for conducting initial interviews
and generating hypotheses in foodborne
disease outbreak investigations:
http://www.cdc.gov/foodborneoutbreaks/
standard_questionnaire.htm
Overview of Hypothesis
Generation Strategy
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Estimate the maximum incubation
period from the illness onset date
Use interviews to elicit information
about exposure during the incubation
period
Using the Internet
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Sources of electronic full-text
information
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Centers for Disease Control and Prevention
(CDC): http://www.cdc.gov
Morbidity and Mortality Weekly Report
(MMWR): http://www.cdc.gov/mmwr
Using the Internet
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General searches on the Internet can
also be helpful
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Example: http://www.google.com
Not all information on the Internet is
accurate: be mindful of the potential
credibility of different Internet-based
sources
Using the Internet
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PubMed allows individuals to search
journal abstracts from biomedical
literature for free
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http://www.ncbi.nlm.nih.gov/PubMed
Some states or academic institutions also
have agreements to provide access to
journal abstracts or full-texts
Using the Internet
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While abstracts provide valuable
information, it may be necessary to
read some articles in their entirety
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Articles may be available for free online
Articles may be copied from journals in a
library
“Loansome Doc” allows users to order fulltext copies of articles for a fee
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http://www.nlm.nih.gov/loansomedoc/loansom
e_home.html
How to Perform a PubMed
Search
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Use the Boolean operators “AND,” “OR,”
and “NOT”
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Boolean operators should be capitalized
Boolean operators are processed from left
to right
Parentheses can be used to group terms
together
How to Perform a PubMed
Search
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Example:
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A search for “Salmonella AND eggs OR
chicken” will retrieve all articles about
Salmonella and eggs as well as all articles
about chicken (in general)
A search for “Salmonella AND (eggs OR
chicken)” will retrieve all articles about
Salmonella and eggs as well as all articles
about Salmonella and chicken
How to Perform a PubMed
Search
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Ways to broaden or limit a search
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Example:
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“Salmonella” returns approximately 50,000
articles
“Salmonella AND outbreak AND food” returns
approximately 500 articles
“Salmonella AND outbreak AND eggs” returns
approximately 100 articles
How to Perform a PubMed
Search
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Another useful tool is the “Cubby”
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Requires a user-defined log-in and
password, but is free
Allows the user to run a search
Click Cubby link to store the search
Click the “What’s new for selected” button
to retrieve any new articles since the last
search
How to Perform a PubMed
Search
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The “History” button is also helpful
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Is located on the “Features” bar
Is only available after performing a search
Allows one to view a list and number of
searches in the order in which they were
run
How to Perform a PubMed
Search
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Tips for printing citations or abstracts
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After performing a search, select
“Summary” from the “Display” drop-down
bar and "Text” from the “Send to” dropdown bar
Click on “Send to” for a printable version of
the citations
Select the “Abstract” option from the
“Display” drop-down bar to print the
abstract
Case Study
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1997 outbreak of E coli O157:H7
infections in Michigan and Virginia
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Hypothesis-generating interviews
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Demographic profile
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Lettuce and alfalfa sprouts
70% women
Median age was 31
Hypothesis testing
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Case-control study method
Conclusion
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Hypothesis generation should be guided
by:
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Descriptive epidemiology from the
outbreak
Information learned from past outbreaks
However, keep an open mind and
always consider alternative explanations
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Example: Legionnaires’ Disease
Conclusion
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Hypothesis generation is a critical step
in any outbreak investigation
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A literature review may be necessary
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The Iinternet is a useful resource
Preliminary data collection with
standardized questionnaires may implicate
hypotheses that warrant additional data
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Open-ended interviews can be a useful tool to
obtain this information
References
1. CDC. Outbreak of acute illness-Southwestern United
States, 1993. MMWR Morb Mortal Wkly Rep.
1993;44(22):421-424.
2. CDC. Public health dispatch: West Nile Virus infection
in organ donor and transplant recipients --- Georgia
and Florida, 2002. MMWR Morb Mortal Wkly Rep.
2002;51(35):790.
3. Davies SF, Sarosi GA. Epidemiological and clinical
features of pulmonary Blastomycosis. Semin Respir
Infect. 1997;12 (3):206-218.
References
4. Breuer T, Benkel DH, Shapiro RL, et al. A multistate
outbreak of Escherichia coli O157:H7 infections linked
to alfalfa sprouts grown from contaminated
seeds. Emerg Infect Dis. 2001;7(6):977-982.
Available from
http://wwwcdc.gov/ncidod/eid/vol7no6/breuer.htm.
5. Garbe PL, Davis BJ, Weisfeld JS, et al. Nosocomial
Legionnaires' disease. Epidemiologic demonstration of
cooling towers as a source. JAMA. 1985;254:521-524.