Hypothesis Generation

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Hypothesis Generation
2
Goals

• Discuss the importance of hypothesis generation
• Describe approaches to generating hypotheses
• Present Internet resources useful for literature
  reviews

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What is Hypothesis Generation and Why is it
Important?

• 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

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Overview of Hypothesis Generation Strategy

• Ways to approach generating hypotheses about the
  cause of the outbreak
• Examine the line listing data
• Review the existing body of knowledge
• Administer open-ended hypothesis-generating
  questionnaire to several cases

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Overview of Hypothesis Generation Strategy

• Develop specific hypotheses
• Test the hypotheses in an analytic study using a
  structured questionnaire concerning the specific
  hypotheses

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Overview of Hypothesis Generation Strategy

• Review the existing body of knowledge to learn
  about previous outbreaks caused by the same
  organism or disease
• Read medical, epidemiology, microbiology, and
  veterinary (if relevant) literature
• Talk to experts in the field

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Overview of Hypothesis Generation Strategy

• Literature reviews help identify organisms, risk
  factors, and sources of exposures that have been
  observed in the past
• Example diarrheal disease

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Overview of Hypothesis Generation Strategy

• Some outbreaks are caused by unrecognized agents
  or through unrecognized modes of transmission
• Examples hantavirus and West Nile virus

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Overview of Hypothesis Generation Strategy

• Familiarity with the microbiology, natural
  history, and ecologic niche of the organism may
  also be helpful
• Example Blastomyces dermatitidis and hantavirus
  pulmonary syndrome

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Overview of Hypothesis Generation Strategy

• Utilization of existing hypothesis-generating
  resources may save time
• CDC has a standard questionnaire template for
  conducting initial interviews and generating
  hypotheses in foodborne disease outbreak
  investigations
• http//www.cdc.gov/foodborneoutbreaks/standard_qu
  estionnaire.htm

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Overview of Hypothesis Generation Strategy

• Estimate the maximum incubation period from the
  illness onset date
• Use interviews to elicit information about
  exposure during the incubation period

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Using the Internet

• Sources of electronic full-text information
• Centers for Disease Control and Prevention (CDC)
  http//www.cdc.gov
• Morbidity and Mortality Weekly Report (MMWR)
  http//www.cdc.gov/mmwr

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Using the Internet

• General searches on the Internet can also be
  helpful
• Example http//www.google.com
• Not all information on the Internet is accurate
  be mindful of the potential credibility of
  different Internet-based sources

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Using the Internet

• PubMed allows individuals to search journal
  abstracts from biomedical literature for free
• http//www.ncbi.nlm.nih.gov/PubMed
• Some states or academic institutions also have
  agreements to provide access to journal abstracts
  or full-texts

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Using the Internet

• While abstracts provide valuable information, it
  may be necessary to read some articles in their
  entirety
• Articles may be available for free online
• Articles may be copied from journals in a library
• Loansome Doc allows users to order full-text
  copies of articles for a fee
• http//www.nlm.nih.gov/loansomedoc/loansome_home.h
  tml

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How to Perform a PubMed Search

• Use the Boolean operators AND, OR, and NOT
• Boolean operators should be capitalized
• Boolean operators are processed from left to
  right
• Parentheses can be used to group terms together

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How to Perform a PubMed Search

• Example
• 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

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How to Perform a PubMed Search

• Ways to broaden or limit a search
• Example
• Salmonella returns approximately 50,000
  articles
• Salmonella AND outbreak AND food returns
  approximately 500 articles
• Salmonella AND outbreak AND eggs returns
  approximately 100 articles

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How to Perform a PubMed Search

• Another useful tool is the Cubby
• 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 Whats new for selected button to
  retrieve any new articles since the last search

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How to Perform a PubMed Search

• The History button is also helpful
• 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

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How to Perform a PubMed Search

• Tips for printing citations or abstracts
• After performing a search, select Summary from
  the Display drop-down bar and "Text from the
  Send to drop-down 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

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Case Study

• 1997 outbreak of E coli O157H7 infections in
  Michigan and Virginia
• Hypothesis-generating interviews
• Lettuce and alfalfa sprouts
• Demographic profile
• 70 women
• Median age was 31
• Hypothesis testing
• Case-control study method

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Conclusion

• Hypothesis generation should be guided by
• Descriptive epidemiology from the outbreak
• Information learned from past outbreaks
• However, keep an open mind and always consider
  alternative explanations
• Example Legionnaires Disease

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Conclusion

• Hypothesis generation is a critical step in any
  outbreak investigation
• A literature review may be necessary
• The Iinternet is a useful resource
• Preliminary data collection with standardized
  questionnaires may implicate hypotheses that
  warrant additional data
• Open-ended interviews can be a useful tool to
  obtain this information

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References

• 1. CDC. Outbreak of acute illness-Southwestern
  United States, 1993. MMWR Morb Mortal Wkly Rep.
  199344(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. 200251(35)790.
• 3. Davies SF, Sarosi GA. Epidemiological and
  clinical features of pulmonary Blastomycosis.
  Semin Respir Infect. 199712 (3)206-218.

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References

• 4. Breuer T, Benkel DH, Shapiro RL, et al. A
  multistate outbreak of Escherichia coli O157H7
  infections linked to alfalfa sprouts grown from
  contaminated seeds.  Emerg Infect Dis.
  20017(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. 1985254521-524.
•