流行性感冒常造成老年人嚴重疾病或死亡，也使用了相當多的醫療資源，而目前已知最有效預防流行性感冒方式為接種流行性感冒疫苗，可以降低造成嚴重疾病、合併症死亡的機率。現階段台灣的流感疫苗接種率逐漸上升，衛生政策建議老年人應該每年定期接種流感疫苗來預防流感，因此藉由了解目前台灣老年人的流感疫苗連續接種情形，長期追蹤接種變化並比較醫療資源使用之差異，期待能有更完善之衛生政策來提升老年人之健康，並能妥善利用有限之醫療資源。
本研究屬回溯性研究(retrospective cohort study)，利用全民健康保險資料庫(National Health Insurance, NHI)來分析流感疫苗的接種狀態與醫療資源使用。本研究之研究期間為2001年至2007年，追蹤65歲以上老年人六個接種季節的接種情況，並往後追蹤一年醫療資源使用，利用傾向分數 (Propensity score) 配對，將樣本分為當季接種流感疫苗和當季未接種流感疫苗兩大群組，再細分為過去未曾接種流感疫苗、曾有中斷接種以及連續接種，交叉組合接種情況，觀察2007年因急性或慢性呼吸道疾病而使用門診、住院和急診的醫療資源使用，以及不論任何原因之死亡。
利用傾向分數配對年紀、性別與疾病數之後，在2001年至2007年間共追蹤54,958人。過去連續接種者中，當季有接種流感疫苗者能降低門診使用之費用，若過去為間斷接種者，當季有接種流感疫苗者則能降低住院使用之費用。此外，當季有接種流感疫苗能降低門診使用與死亡之風險，但未能降低急診與住院之風險；而若連續六年都有接種流感疫苗，可以降低住院與死亡之風險，但是第一次接種流感疫苗僅可降低門診使用風險；在第一次接種、間斷接種與連續接種的比較中，連續接種能顯著降低死亡之風險。
老年人連續接種流感疫苗能降低流感對於健康造成之危害，政策制定者應針對資訊收集能力較低的老年人，提供足夠流感疫苗的接種資訊，並積極推動每年的流感疫苗接種，來維護民眾健康，並降低老年人的醫療資源使用情況。

Research Objectives
Influenza often results in serious illness or death in the elderly and utilizes a considerable amount of health care resources as well. At present, influenza vaccine is the most effective way of preventing influenza and can reduce the possibility of serious illness, complications, and death. At this stage, the rate of influenza vaccine administered has gradually increased; health policies recommend that the elderly should receive regular annual vaccination to prevent influenza. Therefore, by understanding the current situation of sequential vaccination in the elderly in Taiwan, observing long-term vaccination changes, and comparing the differences in medical resource utilization, a better health policy for improving the health of the elderly and better utilization of limited medical resources can be expected.
Study Design
We conducted a retrospective cohort study using the database from National Health Insurance to analyze the influenza vaccination status and medical resource utilization from 2001 to 2007. The propensity score was used for pairing. Individuals were divided into two large groups: those who received influenza vaccine and those who did not receive the vaccine during the vaccination period. Furthermore, each group was divided into individuals who were never vaccinated, who received vaccination but discontinued, and those received sequential vaccination. The vaccination situations were cross-compiled and compared, and the outpatients who utilized medical resources in clinics, hospitals, or emergency rooms in 2007 due to acute or chronic respiratory disease were observed, regardless of the cause of death.
Population Studied
We tracked the vaccination situation of individuals who were ≥65 years of age over 6 vaccination periods and the medical resource utilization a year later.
Principle Findings
The propensity score was used to pair ages, gender, and the extent of disease. From 2001 to 2007, 54,958 people have been tracked. In the past, in the sequential vaccination group, a decrease in the cost of clinical visits was observed when patients were vaccination in the vaccination period. A decrease in hospital costs has also been observed if patients have breaks between vaccinations. In addition, among patients who received vaccination in the vaccination period, the number of clinical visits and the risk of death decreased; however, decrease in the number of emergency room or hospital visits was not observed. Therefore, if vaccination is continued for 6 years, the number of hospital visits and risk of death can decrease; however, the number of clinical visits may not decrease after the first vaccination. On comparing the group vaccinated for the first time, the group with breaks between vaccinations, and the group that received sequential vaccination, it was observed that sequential vaccination can significantly decrease the risk of death.
Conclusion
In conclusion, sequential vaccination in the elderly can decrease the potential harm that influenza causes to their health and can further decrease medical resource utilization. Therefore, policy makers should focus on the elderly group with low information-gathering ability to provide sufficient inoculation information on the influenza vaccine. Moreover, by promoting annual influenza vaccination to maintain the health of the elderly, medical resources will be utilized appropriately and the quality of medical care will improve.

論文審定書 I
摘要 II
ABSTRACT IV
致謝 VI
目錄 VII
圖目錄 IX
表目錄 X
第一章 緒論 1
第一節 研究背景與動機 1
第二節 研究目的與問題 2
第二章 文獻探討 3
第一節 流行性感冒與流感疫苗 3
第二節 流感疫苗接種相關研究 8
第三節 配對模型 14
第三章 研究方法 16
第一節 研究設計與研究架構 16
第二節 研究假設 19
第三節 研究材料與對象 20
研究材料 20
研究對象 22
第四節 研究變項定義 24
第五節 統計分析 26
第四章 研究結果 27
第一節 描述性統計 27
第二節 推論性統計─當季接種 35
第三節 推論性統計─連續接種 46
第四節 假設驗證 53
第五章 研究討論 55
第六章 研究限制與建議 58
第一節 研究限制 58
第二節 研究建議與貢獻 59
文獻 60

Austin, P. C. (2012). The performance of different propensity score methods for estimating marginal hazard ratios. Stat Med. doi: 10.1002/sim.5705
Baxter, R., Ray, G. T., & Fireman, B. H. (2010). Effect of influenza vaccination on hospitalizations in persons aged 50 years and older. Vaccine, 28(45), 7267-7272. doi: 10.1016/j.vaccine.2010.08.088
Chang, Y. C., Chou, Y. J., Liu, J. Y., Yeh, T. F., & Huang, N. (2012). Additive benefits of pneumococcal and influenza vaccines among elderly persons aged 75 years or older in Taiwan--a representative population-based comparative study. J Infect, 65(3), 231-238. doi: 10.1016/j.jinf.2012.04.014
Chen, Y. H., Liou, S. H., Chou, C. C., Su, W. L., Loh, C. H., & Lin, S. H. (2004). Influenza and pneumococcal vaccination of the elderly in Taiwan. Vaccine, 22(21-22), 2806-2811. doi: 10.1016/j.vaccine.2004.01.003
Davis JW, L. E., Taira DA, & Chung RS. (2001). Influenza Vaccination, Hospitalizations, and Costs Among members of a medicare managed care plan. Med Care., 39(12), 1273-1280.
DB., R. (1997). Estimating causal effects from large data sets using propensity scores. Ann Intern Med., 127(8 Pt 2), 757-763.
Dean, A. S., Moffatt, C. R., Rosewell, A., Dwyer, D. E., Lindley, R. I., Booy, R., & MacIntyre, C. R. (2010). Incompletely matched influenza vaccine still provides protection in frail elderly. Vaccine, 28(3), 864-867. doi: 10.1016/j.vaccine.2009.03.024
Dominguez, A., Castilla, J., Godoy, P., Delgado-Rodriguez, M., Martin, V., Saez, M., . . . Controls in Pandemic Influenza Working Group, S. (2012). Effectiveness of pandemic and seasonal influenza vaccines in preventing pandemic influenza-associated hospitalization. Vaccine, 30(38), 5644-5650. doi: 10.1016/j.vaccine.2012.06.090
GC., X. (2005). Predictors of influenza immunization in persons over age 65. J Am Board Fam Pract., 18(5), 426-433.
Gilman, B. H., Bonito, A. J., & Eicheldinger, C. (2007). Impact of influenza immunization on medical expenditures among Medicare elderly, 1999-2003. Am J Prev Med, 32(2), 107-115. doi: 10.1016/j.amepre.2006.10.010
Groenwold, R. H., Hoes, A. W., & Hak, E. (2009). Impact of influenza vaccination on mortality risk among the elderly. Eur Respir J, 34(1), 56-62. doi: 10.1183/09031936.00190008
Herrera, G. A., Iwane, M. K., Cortese, M., Brown, C., Gershman, K., Shupe, A., . . . Bridges, C. B. (2007). Influenza vaccine effectiveness among 50-64-year-old persons during a season of poor antigenic match between vaccine and circulating influenza virus strains: Colorado, United States, 2003-2004. Vaccine, 25(1), 154-160. doi: 10.1016/j.vaccine.2006.05.129
Hottes, T. S., Skowronski, D. M., Hiebert, B., Janjua, N. Z., Roos, L. L., Van Caeseele, P., . . . De Serres, G. (2011). Influenza vaccine effectiveness in the elderly based on administrative databases: change in immunization habit as a marker for bias. PLoS One, 6(7), e22618. doi: 10.1371/journal.pone.0022618
Jimenez-Garcia, R., Hernandez-Barrera, V., Carrasco-Garrido, P., Lopez de Andres, A., & de Miguel, A. G. (2009). Predictors of influenza vaccination in adults with chronic bronchitis. Respir Med, 103(10), 1518-1525. doi: 10.1016/j.rmed.2009.04.006
Joffe MM, R. P. (1999). Invited commentary: propensity scores. Am J Epidemiol., 150(4), 327-333.
Jordan, R. E., Hawker, J. I., Ayres, J. G., Tunnicliffe, W., Adab, P., Olowokure, B., . . . Cheng, K. K. (2007). A case-control study of elderly patients with acute respiratory illness: effect of influenza vaccination on admission to hospital in winter 2003-2004. Vaccine, 25(46), 7909-7913. doi: 10.1016/j.vaccine.2007.09.005
Jr., D. A. R. (1998). Propensity score methods for bias reduction in the comparison of a treatment to a non-randomized control group. Stat Med., 17(19), 2265-2281.
Keitel WA, C. T., Couch RB, Huggins LL, & Hess KR. (1997). Efficacy of repeated annual immunization with inactivated influenza virus vaccines over a five year period. Vaccine., 15(10), 1114-1122.
Lee, C. C., Ho, H. C., & Chou, P. (2010). Multivariate analyses to assess the effect of surgeon volume on survival rate in oral cancer: a nationwide population-based study in Taiwan. Oral Oncol, 46(4), 271-275. doi: 10.1016/j.oraloncology.2010.01.006
Li, Y. C., & Liu, C. M. (2009). Threat-responsiveness and the decision to obtain free influenza vaccinations among the older adults in Taiwan. BMC Public Health, 9, 275. doi: 10.1186/1471-2458-9-275
Lin HH, H. K., Ko WW, Yang YC, Chang YW, Yu MC, & Chen KT. (2010). Cost-effectiveness of influenza immunization in adult cancer patients in Taiwan. Clin Microbiol Infect., 16(6), 663-670. doi: 10.1111/j.1469-0691.2009.02937.x.
Looijmans-Van den Akker, I., Verheij, T. J., Buskens, E., Nichol, K. L., Rutten, G. E., & Hak, E. (2006). Clinical effectiveness of first and repeat influenza vaccination in adult and elderly diabetic patients. Diabetes Care, 29(8), 1771-1776. doi: 10.2337/dc05-2517
Mok E, Y. S.& Chan MF. (2006). Prevalence of influenza vaccination and correlates of intention to be vaccinated among Hong Kong Chinese. Public Health Nurs., 23(6), 506-515.
Nichol KL, N. J., Mullooly J, Lask R, Fillbrandt K, & Iwane M. (2003). Influenza vaccination and reduction in hospitalizations for cardiac and stroke among the elderly. N Engl J Med., 348(14), 1322-1332.
Nichol KL, N. J., Nelson DB, Mullooly JP, & Hak E. (2007). Effectiveness of influenza vaccine in the community-dwelling elderly. N Engl J Med., 357(14), 1373-1381.
Nitsch-Osuch A, W. K. (2009). Influenza vaccine coverage in age-related risk groups in Poland, 2004-2007. Cent Eur J Public Health., 17(4), 198-202.
Ohmit, S. E., Gross, J., Victor, J. C., & Monto, A. S. (2009). Reduced reaction frequencies with repeated inactivated or live-attenuated influenza vaccination. Vaccine, 27(7), 1050-1054. doi: 10.1016/j.vaccine.2008.11.100
Palache, A. (2011). Seasonal influenza vaccine provision in 157 countries (2004-2009) and the potential influence of national public health policies. Vaccine, 29(51), 9459-9466. doi: 10.1016/j.vaccine.2011.10.030
Phillips, C. J., Woolpert, T., Sevick, C., Faix, D., Blair, P. J., & Crum-Cianflone, N. F. (2013). Comparison of the Effectiveness of Trivalent Inactivated Influenza Vaccine and Live, Attenuated Influenza Vaccine in Preventing Influenza-Like Illness Among US Military Service Members, 2006-2009. Clin Infect Dis, 56(1), 11-19. doi: 10.1093/cid/cis860
Tai, Y., Lee, T. C., Chang, H. L., & Chen, K. T. (2009). Epidemiology and outcomes of hospitalization of influenza in the cancer population in Taiwan. J Cancer Res Clin Oncol, 135(8), 1061-1066. doi: 10.1007/s00432-009-0545-0
Talbot, H. K., Griffin, M. R., Chen, Q., Zhu, Y., Williams, J. V., & Edwards, K. M. (2011). Effectiveness of seasonal vaccine in preventing confirmed influenza-associated hospitalizations in community dwelling older adults. J Infect Dis, 203(4), 500-508. doi: 10.1093/infdis/jiq076
Tsai YW, H. W., Wen YW, & Chen PF. (2007). The relationship between influenza vaccination and outpatient visits for upper respiratory infection by the elderly in Taiwan. Value Health., 10(2), 117-127.
Voordouw AC, S. M., Dieleman JP, Stijnen T, Smith DJ, van der Lei J, & Stricker BH. (2004). Annual revaccination against influenza and mortality risk in community-dwelling elderly persons. JAMA., 292(17), 2089-2095.
Voordouw BC, v. d. L. P., Simonian S, van der Lei J, Sturkenboom MC, & Stricker BH. (2003). Influenza vaccination in community-dwelling elderly impact on mortality and influenza-associated morbidity. Arch Intern Med., 163(9), 1089-1094.
Wang, C. S., Wang, S. T., Lai, C. T., Lin, L. J., & Chou, P. (2007). Impact of influenza vaccination on major cause-specific mortality. Vaccine, 25(7), 1196-1203. doi: 10.1016/j.vaccine.2006.10.015
Wang CS, W. S., Lai CT, Lin LJ, Lee CT, Chou P. (2004). Reducing major cause-specific hospitalization rates and shortening hospital stays after influenza vaccination. Clin Infect Dis., 39(11), 1604-1610.
WHO (2012). Influenza. Retrieved from http://www.who.int/topics/influenza/en/
Centers for Disease Control and Prevention. Seasonal influenza(2012). Retrieved from http://www.cdc.gov/flu/other_flu.htm
行政院衛生署疾病管制局. (2011). 認識流感疫苗 教學手冊。取自http://flu.cdc.gov.tw/ct.asp?xItem=16312&ctNode=3878&mp=150
行政院衛生署疾病管制局. (2012)。流感防治網。取自http://flu.cdc.gov.tw/mp.asp?mp=150
吳肖琪. (2005). 台灣地區幼兒、老人及飼養禽畜業者接種流感疫苗效益評估.