Hypothesis Generation

1. Hypothesis Generation

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

3. 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

4. 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

5. Overview of Hypothesis Generation Strategy • Develop specific hypotheses • Test the hypotheses in an analytic study using a structured questionnaire concerning the specific hypotheses

6. 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

7. 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

8. Overview of Hypothesis Generation Strategy • Some outbreaks are caused by unrecognized agents or through unrecognized modes of transmission • Examples: hantavirus and West Nile virus

9. 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

10. 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_questionnaire.htm

11. 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

12. 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

13. 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

14. 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

15. 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.html

16. 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

17. 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

18. 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

19. 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 “What’s new for selected” button to retrieve any new articles since the last search

20. 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

21. 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

22. Case Study • 1997 outbreak of E coli O157:H7 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

23. 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

24. 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

25. 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.

26. 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.