Background:
Vaccination for the 2009 pandemic did not occur until late in the outbreak, which limited its benefits. Influenza A (H7N9) is causing increasing morbidity and mortality in China, and researchers have modified the A (H5N1) virus to transmit via aerosol, which again heightens concerns about pandemic influenza preparedness.
Objective:
To determine how quickly vaccination should be completed to reduce infections, deaths, and health care costs in a pandemic with characteristics similar to influenza A (H7N9) and A (H5N1).
Design:
Dynamic transmission model to estimate health and economic consequences of a severe influenza pandemic in a large metropolitan city.
Data Sources:
Literature and expert opinion.
Target Population:
Residents of a U.S. metropolitan city with characteristics similar to New York City.
Time Horizon:
Lifetime.
Perspective:
Societal.
Intervention:
Vaccination of 30% of the population at 4 or 6 months.
Outcome Measures:
Infections and deaths averted and cost-effectiveness.
Results of Base-Case Analysis:
In 12 months, 48 254 persons would die. Vaccinating at 9 months would avert 2365 of these deaths. Vaccinating at 6 months would save 5775 additional lives and $51 million at a city level. Accelerating delivery to 4 months would save an additional 5633 lives and $50 million.
Results of Sensitivity Analysis:
If vaccination were delayed for 9 months, reducing contacts by 8% through nonpharmaceutical interventions would yield a similar reduction in infections and deaths as vaccination at 4 months.
Limitation:
The model is not designed to evaluate programs targeting specific populations, such as children or persons with comorbid conditions.
Conclusion:
Vaccination in an influenza A (H7N9) pandemic would need to be completed much faster than in 2009 to substantially reduce morbidity, mortality, and health care costs. Maximizing non-pharmaceutical interventions can substantially mitigate the pandemic until a matched vaccine becomes available.
Primary Funding Source:
Agency for Healthcare Research and Quality, National Institutes of Health, and Department of Veterans Affairs.
References
- 1.
Herfst S ,Schrauwen EJ ,Linster M ,Chutinimitkul S ,de Wit E ,Munster VJ ,et al . Airborne transmission of influenza A/H5N1 virus between ferrets. Science. 2012;336:1534-41. [PMID:22723413 ] CrossrefMedlineGoogle Scholar - 2.
Imai M ,Watanabe T ,Hatta M ,Das SC ,Ozawa M ,Shinya K ,et al . Experimental adaptation of an influenza H5 HA confers respiratory droplet transmission to a reassortant H5 HA/H1N1 virus in ferrets. Nature. 2012;486:420-8. [PMID:22722205 ] CrossrefMedlineGoogle Scholar - 3.
Ke Y ,Wang Y ,Zhang W ,Huang L ,Chen Z . Deaths associated with avian influenza A(H7N9) virus in China [Letter]. Ann Intern Med. 2013;159:159-60. [PMID:23856693 ] LinkGoogle Scholar - 4.
Chen H ,Yuan H ,Gao R ,Zhang J ,Wang D ,Xiong Y ,et al . Clinical and epidemiological characteristics of a fatal case of avian influenza A H10N8 virus infection: a descriptive study. Lancet. 2014;383:714-21. [PMID:24507376 ] CrossrefMedlineGoogle Scholar - 5.
Rambhia KJ ,Watson M ,Sell TK ,Waldhorn R ,Toner E . Mass vaccination for the 2009 H1N1 pandemic: approaches, challenges, and recommendations. Biosecur Bioterror. 2010;8:321-30. [PMID:21043791 ] CrossrefMedlineGoogle Scholar - 6. World Health Organization. Cumulative number of confirmed human cases for avian influenza A (H5N1) reported to WHO, 2003-2012. Accessed at www.searo.who.int/entity/emerging_diseases/EN_GIP_20120810CumulativeNumberH5N1cases.pdf on 9 December 2013. Google Scholar
- 7.
Dawood FS ,Iuliano AD ,Reed C ,Meltzer MI ,Shay DK ,Cheng PY ,et al . Estimated global mortality associated with the first 12 months of 2009 pandemic influenza A H1N1 virus circulation: a modelling study. Lancet Infect Dis. 2012;12:687-95. [PMID:22738893 ] CrossrefMedlineGoogle Scholar - 8.
Choo AY ,Broderick KE ,Kim JJ ,Sardesai NY . DNA-based influenza vaccines: evaluating their potential to provide universal protection. IDrugs. 2010;13:707-12. [PMID:20878593 ] MedlineGoogle Scholar - 9. Centers for Disease Control and Prevention. Seasonal influenza (flu)—selecting the viruses in the influenza (flu) vaccine. Accessed at www.cdc.gov/flu/professionals/vaccination/virusqa.htm on 5 April 2012. Google Scholar
- 10.
Weinstein MC ,Siegel JE ,Gold MR ,Kamlet MS ,Russell LB . Recommendations of the Panel on Cost-effectiveness in Health and Medicine. JAMA. 1996;276:1253-8. [PMID:8849754 ] CrossrefMedlineGoogle Scholar - 11.
Cooper HM ,Hedges LV . The Handbook of Research Synthesis. New York: Russell Sage Foundation; 1994. Google Scholar - 12. U.S. Census Bureau. State & County QuickFacts: New York (City), New York. Accessed at http://quickfacts.census.gov/qfd/states/36/3651000.html on 5 April 2012. Google Scholar
- 13.
Taubenberger JK . The virulence of the 1918 pandemic influenza virus: unraveling the enigma. Arch Virol Suppl. 2005;:101-15. [PMID:16355870 ] MedlineGoogle Scholar - 14.
Ferguson NM ,Cummings DA ,Fraser C ,Cajka JC ,Cooley PC ,Burke DS . Strategies for mitigating an influenza pandemic. Nature. 2006;442:448-52. [PMID:16642006 ] CrossrefMedlineGoogle Scholar - 15.
Longini IM Jr ,Nizam A ,Xu S ,Ungchusak K ,Hanshaoworakul W ,Cummings DA ,et al . Containing pandemic influenza at the source. Science. 2005;309:1083-7. [PMID:16079251 ] CrossrefMedlineGoogle Scholar - 16.
Fox JP ,Cooney MK ,Hall CE ,Foy HM . Influenzavirus infections in Seattle families, 1975-1979. II. Pattern of infection in invaded households and relation of age and prior antibody to occurrence of infection and related illness. Am J Epidemiol. 1982;116:228-42. [PMID:7114034 ] CrossrefMedlineGoogle Scholar - 17.
Dawood FS ,Jain S ,Finelli L ,Shaw MW ,Lindstrom S ,Garten RJ ,et al ;Novel Swine-Origin Influenza A (H1N1) Virus Investigation Team . Emergence of a novel swine-origin influenza A (H1N1) virus in humans. N Engl J Med. 2009;360:2605-15. [PMID:19423869 ] CrossrefMedlineGoogle Scholar - 18. Centers for Disease Control and Prevention. Seasonal influenza: flu basics. Accessed at www.cdc.gov/flu/about/disease.htm on 11 December 2013. Google Scholar
- 19.
Hayden FG ,Fritz R ,Lobo MC ,Alvord W ,Strober W ,Straus SE . Local and systemic cytokine responses during experimental human influenza A virus infection. Relation to symptom formation and host defense. J Clin Invest. 1998;101:643-9. [PMID:9449698 ] CrossrefMedlineGoogle Scholar - 20.
Leekha S ,Zitterkopf NL ,Espy MJ ,Smith TF ,Thompson RL ,Sampathkumar P . Duration of influenza A virus shedding in hospitalized patients and implications for infection control. Infect Control Hosp Epidemiol. 2007;28:1071-6. [PMID:17932829 ] CrossrefMedlineGoogle Scholar - 21. Centers for Disease Control and Prevention. FluSurge 2.0. Accessed at www.cdc.gov/flu/pandemic-resources/tools/flusurge.htm on 12 December 2013. Google Scholar
- 22.
Smith CB ,Cox NJ ,Subbarao K ,Taber LH ,Glezen WP . Molecular epidemiology of influenza A(H3N2) virus reinfections. J Infect Dis. 2002;185:980-5. [PMID:11920323 ] CrossrefMedlineGoogle Scholar - 23.
Monto AS ,Davenport FM ,Napier JA ,Francis T Jr . Modification of an outbreak of influenza in Tecumseh, Michigan by vaccination of schoolchildren. J Infect Dis. 1970;122:16-25. [PMID:5433709 ] CrossrefMedlineGoogle Scholar - 24. Schnirring L. Debate on H5N1 death rate and missed cases continues. Minneapolis, Minnesota: Center for Infectious Disease Research and Policy; 2012. Accessed at www.cidrap.umn.edu/cidrap/content/influenza/avianflu/news/feb2412seroprev.html on 10 December 2012. Google Scholar
- 25.
Wang TT ,Parides MK ,Palese P . Seroevidence for H5N1 influenza infections in humans: meta-analysis. Science. 2012;335:1463. [PMID:22362880 ] CrossrefMedlineGoogle Scholar - 26.
Taubenberger JK ,Morens DM . 1918 Influenza: the mother of all pandemics. Emerg Infect Dis. 2006;12:15-22. [PMID:16494711 ] CrossrefMedlineGoogle Scholar - 27.
Bootsma MC ,Ferguson NM . The effect of public health measures on the 1918 influenza pandemic in U.S. cities. Proc Natl Acad Sci U S A. 2007;104:7588-93. [PMID:17416677 ] CrossrefMedlineGoogle Scholar - 28.
Fielding JE ,Grant KA ,Tran T ,Kelly HA . Moderate influenza vaccine effectiveness in Victoria, Australia, 2011. Euro Surveill. 2012;17:. [PMID:22449867 ] CrossrefMedlineGoogle Scholar - 29.
Thorpe LE ,Mostashari F ,Karpati AM ,Schwartz SP ,Manning SE ,Marx MA ,et al . Mass smallpox vaccination and cardiac deaths, New York City, 1947. Emerg Infect Dis. 2004;10:917-20. [PMID:15200831 ] CrossrefMedlineGoogle Scholar - 30. European Medicines Agency. Assessment report: Pandemrix. London: European Medicines Agency; 21 July 2011. Accessed at www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Assessment_Report_-_Variation/human/000832/WC500118056.pdf on 10 December 2013. Google Scholar
- 31. GlaxoSmithKline Canada. Arepanrix H1N1 [Product information leaflet]. Accessed at www.hc-sc.gc.ca/dhp-mps/alt_formats/pdf/prodpharma/legislation/interimorders-arretesurgence/prodinfo-vaccin-eng.pdf on 10 December 2013. Google Scholar
- 32.
Neustadt RE ,Fineberg HV . The Swine Flu Affair: Decision-Making on a Slippery Disease. : National Academies Pr; 2008. Google Scholar - 33.
Partinen M ,Saarenpää-Heikkilä O ,Ilveskoski I ,Hublin C ,Linna M ,Olsén P ,et al . Increased incidence and clinical picture of childhood narcolepsy following the 2009 H1N1 pandemic vaccination campaign in Finland. PLoS One. 2012;7:e33723. [PMID:22470463 ] CrossrefMedlineGoogle Scholar - 34.
Nohynek H ,Jokinen J ,Partinen M ,Vaarala O ,Kirjavainen T ,Sundman J ,et al . AS03 adjuvanted AH1N1 vaccine associated with an abrupt increase in the incidence of childhood narcolepsy in Finland. PLoS One. 2012;7:e33536. [PMID:22470453 ] CrossrefMedlineGoogle Scholar - 35. World Health Organization. WHO Global Influenza Preparedness Plan: The Role of WHO and Recommendations for National Measures Before and During Pandemics. Geneva: World Health Organization: 2005. Accessed at www.omh.ny.gov/omhweb/disaster_resources/pandemic_influenza/doctors_nurses/who_pandemic_guidlines.html on 9 December 2013. Google Scholar
- 36.
Aiello AE ,Murray GF ,Perez V ,Coulborn RM ,Davis BM ,Uddin M ,et al . Mask use, hand hygiene, and seasonal influenza-like illness among young adults: a randomized intervention trial. J Infect Dis. 2010;201:491-8. [PMID:20088690 ] CrossrefMedlineGoogle Scholar - 37.
Cowling BJ ,Chan KH ,Fang VJ ,Cheng CK ,Fung RO ,Wai W ,et al . Facemasks and hand hygiene to prevent influenza transmission in households: a cluster randomized trial. Ann Intern Med. 2009;151:437-46. [PMID:19652172 ] LinkGoogle Scholar - 38.
Glass LM ,Glass RJ . Social contact networks for the spread of pandemic influenza in children and teenagers. BMC Public Health. 2008;8:61. [PMID:18275603 ] CrossrefMedlineGoogle Scholar - 39.
Davey VJ ,Glass RJ ,Min HJ ,Beyeler WE ,Glass LM . Effective, robust design of community mitigation for pandemic influenza: a systematic examination of proposed US guidance. PLoS One. 2008;3:e2606. [PMID:18596963 ] CrossrefMedlineGoogle Scholar - 40. U.S. Department of Commerce Bureau of Economic Analysis. National Data: National Income and Product Accounts Tables. Accessed at www.bea.gov/iTable/iTable.cfm?ReqID=9&steP=1#reqid=9&step=3&isuri=1&903=13 on 4 February 2014. Google Scholar
- 41.
Talbird SE ,Brogan AJ ,Winiarski AP ,Sander B . Cost-effectiveness of treating influenzalike illness with oseltamivir in the United States. Am J Health Syst Pharm. 2009;66:469-80. [PMID:19233995 ] CrossrefMedlineGoogle Scholar - 42.
Dasta JF ,McLaughlin TP ,Mody SH ,Piech CT . Daily cost of an intensive care unit day: the contribution of mechanical ventilation. Crit Care Med. 2005;33:1266-71. [PMID:15942342 ] CrossrefMedlineGoogle Scholar - 43. U.S. Census Bureau. Statistical Abstract of the United States: 2012. Accessed at www.census.gov/compendia/statab/2012/tables/12s0137.pdf on 12 December 2013. Google Scholar
- 44.
Rabin R ,de Charro F . EQ-5D: a measure of health status from the EuroQol Group. Ann Med. 2001;33:337-43. [PMID:11491192 ] CrossrefMedlineGoogle Scholar - 45.
Green C ,Brazier J ,Deverill M . Valuing health-related quality of life. A review of health state valuation techniques. Pharmacoeconomics. 2000;17:151-65. [PMID:10947338 ] CrossrefMedlineGoogle Scholar - 46. Centers for Medicare & Medicaid Services. National Health Expenditure Data. Accessed at www.cms.gov/Research-Statistics-Data-and-Systems/Statistics-Trends-and-Reports/NationalHealthExpendData/index.html on 12 December 2013. Google Scholar
- 47.
Fryback DG ,Dasbach EJ ,Klein R ,Klein BE ,Dorn N ,Peterson K ,et al . The Beaver Dam Health Outcomes Study: initial catalog of health-state quality factors. Med Decis Making. 1993;13:89-102. [PMID:8483408 ] CrossrefMedlineGoogle Scholar - 48. World Health Organization. Pandemic influenza vaccine manufacturing process and timeline. Pandemic (H1N1) 2009 briefing note 7. Geneva: World Health Organization; 6 August 2009. Accessed at www.who.int/csr/disease/swineflu/notes/h1n1_vaccine_20090806/en/index.html on 13 April 2012. Google Scholar
- 49.
Glezen WP . Cell-culture-derived influenza vaccine production. Lancet. 2011;377:698-700. [PMID:21329970 ] CrossrefMedlineGoogle Scholar - 50. Centers for Disease Control and Prevention. 2009 H1N1 vaccine doses allocated, ordered, and shipped by project area. Accessed at www.cdc.gov/h1n1flu/vaccination/vaccinesupply.htm on 10 December 2013. Google Scholar
- 51. Centers for Disease Control and Prevention. Seasonal influenza (flu): cell-based flu vaccines. Accessed at www.cdc.gov/flu/protect/vaccine/cell-based.htm on 10 December 2013. Google Scholar
- 52.
Jegerlehner A ,Zabel F ,Langer A ,Dietmeier K ,Jennings GT ,Saudan P ,et al . Bacterially produced recombinant influenza vaccines based on virus-like particles. PLoS One. 2013;8:e78947. [PMID:24260136 ] CrossrefMedlineGoogle Scholar - 53.
Dormitzer PR ,Suphaphiphat P ,Gibson DG ,Wentworth DE ,Stockwell TB ,Algire MA ,et al . Synthetic generation of influenza vaccine viruses for rapid response to pandemics. Sci Transl Med. 2013;5:185ra68. [PMID:23677594 ] CrossrefMedlineGoogle Scholar - 54.
Earn DJ ,He D ,Loeb MB ,Fonseca K ,Lee BE ,Dushoff J . Effects of school closure on incidence of pandemic influenza in Alberta, Canada. Ann Intern Med. 2012;156:173-81. [PMID:22312137 ] LinkGoogle Scholar - 55.
Arino J ,Brauer F ,van den Driessche P ,Watmough J ,Wu J . Simple models for containment of a pandemic. J R Soc Interface. 2006;3:453-7. [PMID:16849273 ] CrossrefMedlineGoogle Scholar - 56. World Health Organization. Global alert and response (GAR): pandemic (H1N1) 2009. Accessed at www.who.int/csr/disease/swineflu/en/index.html on 12 December 2013. Google Scholar
- 57. New York City Department of Health and Mental Hygiene. Health alert #22: novel H1N1 influenza update: June 12, 2009. Accessed at www.nyc.gov/html/doh/downloads/pdf/cd/2009/09md22.pdf on 12 December 2013. Google Scholar
- 58.
Centers for Disease Control and Prevention (CDC) . Outbreak of swine-origin influenza A (H1N1) virus infection—Mexico, March-April 2009. MMWR Morb Mortal Wkly Rep. 2009;58:467-70. [PMID:19444150 ] MedlineGoogle Scholar - 59.
Centers for Disease Control and Prevention (CDC) . Update: infections with a swine-origin influenza A (H1N1) virus—United States and other countries, April 28, 2009. MMWR Morb Mortal Wkly Rep. 2009;58:431-3. [PMID:19407737 ] MedlineGoogle Scholar - 60.
Atkinson MP ,Wein LM . Quantifying the routes of transmission for pandemic influenza. Bull Math Biol. 2008;70:820-67. [PMID:18278533 ] CrossrefMedlineGoogle Scholar - 61.
Centers for Disease Control and Prevention (CDC) . 2009 pandemic influenza A (H1N1) virus infections—Chicago, Illinois, April-July 2009. MMWR Morb Mortal Wkly Rep. 2009;58:913-8. [PMID:19713879 ] MedlineGoogle Scholar - 62. Centers for Disease Control and Prevention. CDC estimates of 2009 H1N1 influenza cases, hospitalizations and deaths in the United States, April-December 12, 2009. Accessed at www.cdc.gov/h1n1flu/estimates/April_December_12.htm on 12 December 2013. Google Scholar
- 63. U.S. Department of Health and Human Services. Health and Human Services pandemic influenza plan. Accessed at www.cdc.gov/flu/pdf/professionals/hhspandemicinfluenzaplan.pdf on 12 December 2013. Google Scholar
- 64.
Li FC ,Choi BC ,Sly T ,Pak AW . Finding the real case-fatality rate of H5N1 avian influenza. J Epidemiol Community Health. 2008;62:555-9. [PMID:18477756 ] CrossrefMedlineGoogle Scholar - 65.
Taubenberger JK ,Morens DM . Pandemic influenza—including a risk assessment of H5N1. Rev Sci Tech. 2009;28:187-202. [PMID:19618626 ] CrossrefMedlineGoogle Scholar - 66.
Griffin MR ,Monto AS ,Belongia EA ,Treanor JJ ,Chen Q ,Chen J ,et al ;U.S. Flu-VE Network . Effectiveness of non-adjuvanted pandemic influenza A vaccines for preventing pandemic influenza acute respiratory illness visits in 4 U.S. communities. PLoS One. 2011;6:e23085. [PMID:21857999 ] CrossrefMedlineGoogle Scholar - 67. Centers for Disease Control and Prevention. Seasonal influenza (flu): key facts about seasonal flu vaccine. Accessed at www.cdc.gov/flu/protect/keyfacts.htm on 10 December 2013. Google Scholar
- 68.
Chió A ,Cocito D ,Leone M ,Giordana MT ,Mora G ,Mutani R ;Piemonte and Valle d'Aosta Register for Guillain-Barré Syndrome . Guillain-Barré syndrome: a prospective, population-based incidence and outcome survey. Neurology. 2003;60:1146-50. [PMID:12682322 ] CrossrefMedlineGoogle Scholar - 69.
Mendell JR ,Kissel JT ,Cornblath DR . Diagnosis and management of peripheral nerve disorders. New York: Oxford University Pr; 2001. Google Scholar - 70.
Turner DA ,Wailoo AJ ,Cooper NJ ,Sutton AJ ,Abrams KR ,Nicholson KG . The cost-effectiveness of influenza vaccination of healthy adults 50-64 years of age. Vaccine. 2006;24:1035-43. [PMID:16183177 ] CrossrefMedlineGoogle Scholar - 71. Centers for Disease Control and Prevention. Vaccines for Children (VFC): CDC vaccine price list. Accessed at www.cdc.gov/vaccines/programs/vfc/awardees/vaccine-management/price-list/index.html on 10 December 2013. Google Scholar
- 72. Bureau of Labor Statistics. Occupation employment and wages, May 2011. Accessed at www.bls.gov/oes/2011/may/oes291111.htm on 10 December 2013. Google Scholar
- 73. Bureau of Labor Statistics. Table B-3. Average hourly and weekly earnings of all employees on private nonfarm payrolls by industry sector, seasonally adjusted. Accessed at www.bls.gov/news.release/empsit.t19.htm on 12 December 2012. Google Scholar
- 74. MetLife. The 2012 MetLife market survey of nursing home, assisted living, adult day services, and home care costs. Accessed at www.metlife.com/mmi/research/2012-market-survey-long-term-care-costs.html#keyfindings on 12 December 2013. Google Scholar
Author, Article and Disclosure Information
From Stanford University Medical Center and Center for Health Policy/Center for Primary Care and Outcomes Research, Stanford, California; University of Michigan, Ann Arbor, Michigan; Harvard University, Cambridge, Massachusetts; and Veterans Affairs Palo Alto Health Care System, Palo Alto, California.
Disclaimer: The content is solely the responsibility of the authors and does not necessarily represent the official views of the Agency for Healthcare Research and Quality.
Acknowledgment: The authors thank Charlotte Chae for her assistance with the graphics.
Grant Support: In part by Agency for Healthcare Research and Quality (grant 5 K08 HS 019816; Dr. Khazeni), National Institutes of Health (grant 5 R01 DA015612-12; Dr. Owens), and Veterans Affairs Palo Alto Health Care System (Dr. Owens).
Disclosures: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M13-2071.
Reproducible Research Statement: Study protocol, statistical code, and data set: An annotated version of the model is available in Supplement 1.
Corresponding Author: Nayer Khazeni, MD, MS, Division of Pulmonary and Critical Care Medicine, Stanford University Medical Center, 300 Pasteur Drive, Room H3143, Stanford, CA 94305; e-mail, [email protected]
Current Author Addresses: Dr. Khazeni: Division of Pulmonary and Critical Care Medicine, Stanford University Medical Center, 300 Pasteur Drive, Room H3143, Stanford, CA 94305.
Drs. Hutton and Collins: Department of Health Management & Policy, 1415 Washington Heights, University of Michigan, Ann Arbor, MI 48109.
Dr. Garber: Office of the Provost, Harvard University, Cambridge, MA 02138.
Dr. Owens: Center for Health Policy/Center for Primary Care and Outcomes Research, 117 Encina Commons, Stanford University, Stanford, CA 94305.
Author Contributions: Conception and design: N. Khazeni, D.W. Hutton, D.K. Owens.
Analysis and interpretation of the data: N. Khazeni, D.W. Hutton, A.M. Garber, D.K. Owens.
Drafting of the article: N. Khazeni, D.W. Hutton, C.I.F. Collins.
Critical revision of the article for important intellectual content: N. Khazeni, D.W. Hutton.
Final approval of the article: N. Khazeni, D.W. Hutton, C.I.F. Collins, A.M. Garber, D.K. Owens.
Provision of study materials or patients: N. Khazeni.
Statistical expertise: N. Khazeni, D.W. Hutton, A.M. Garber, D.K. Owens.
Obtaining of funding: N. Khazeni, D.K. Owens.
Administrative, technical, or logistic support: N. Khazeni, A.M. Garber, C.I.F. Collins.
Collection and assembly of data: N. Khazeni, C.I.F. Collins.
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