流行性感冒是常見的傳染病，併發症常造成死亡，對於老年人口眾多的台灣，潛藏危機令人憂慮。流行性感冒引起的疾病負擔，不容易完全加以探知，在亞熱帶的台灣，也尚未經由流行病學方法確實的研究。衛生署在疑慮及雜音之下，辦理高危險群老人流行性感冒疫苗注射計畫。本研究是由民國88年10月高雄縣11,046位曾因糖尿病、心肺疾病住院的高危險群老人，注射後追蹤至民國89年12月底，研究接受流感疫苗注射與否對死亡率的影響。結果發現，接種組與未接種組在總死因死亡率的相差危險性-9.06％,95％信賴區間(-10.27％,-7.85％),相對危險0.45, 95％信賴區間（0.41, 0.51），預防分量55%。在糖尿病、心臟病、肺炎、慢性阻塞性肺病、腦中風、癌症等個別死因死亡率，也有顯著的差異。以先前住院的主或次診斷來區分，糖尿病患接種流感疫苗與否，對死亡率的相差危險性、相對危險, 預防分量，都有顯著意義的差別；先前住院診斷為心臟病、肺炎或慢性阻塞性肺病者，接種與否，死亡率也有顯著的差別。多變項對數複回歸分析發現，年齡、性別、與接種疫苗﹐是影響總死因死亡率的顯著因素。以糖尿病、心肺疾病等個別住院診斷來區分，接種疫苗與否，在對數複回歸分析，都有顯著意義的差別，而以腦中風和肺炎病患接種疫苗的保護效果最好。根據各月份死亡人數，以Kaplan-Meier曲線畫成存活分布圖，log-rank test檢驗發現接種與未接種組有顯著意義差異。
本研究證實，曾住院的高危險群，接種流感疫苗後，可顯著減少死亡率。這個結果對其他尚未推行流感注射計畫的國家，可望提供流行病學證據；醫護人員亦可據此結果，向民眾推廣，以求提高流感疫苗的注射率。

Free influenza vaccine program aimed at high risk cohort was implemented in Kaohsiung County, Taiwan, Oct 99, followed for 15 months. The purpose of the study was to compare the risk difference and risk ratio in mortality between influenza vaccinated and non-vaccinated high risk discharge patients. We collected data by retrospective cohort study. Subjects who had been admitted due to diabetic or cardiopulmonary diseases in previous 5 years was defined as high risk cohort, 5732 among them received influenza vaccination, and 5314 had not. We follow the high risk cohort from 1999 Oct to 2000 Dec by using mortality archives from national mortality statistics. Kaplan-Meier curves were used to demonstrate survival distribution and log-rank test showed significant difference. Risk difference of mortality from all possible causes between groups was —9.06% and risk ratio 0.45. The risk ratios and preventive fractions of cause-specific mortality due to malignant neoplasms, diabetics, cardiovascular diseases, cerebrovascular diseases, pneumonia, COPD, between the vaccinated and unvaccinated groups were significant. According to the major discharge diagnosis in previous discharge, diabetic subjects showed greatest difference in mortality between vaccinated and unvaccinated groups. Logistic regression analysis revealed that age, and vaccination were significant factors for all-cause mortality. High risk elders who had been admitted due to diabetic or cardiopulmonary diseases benefit substantially from influenza vaccination in reducing mortality.

第一章 序論
第一節問題背景 2
第二節研究動機 5
第三節研究目的 6
第四節論文架構 7
第五節研究假設 8
第二章 材料與方法
第一節流感疫苗接種計畫 9
第二節研究對象 10
第三節資料收集 11
第四節研究流程 12
第五節資料統計與分析 13
第六節住院及死因診斷分類定義 14
第三章 研究結果
第一節基本資料 16
第二節接種組與未接種組各月存活情形 19
第三節死亡者的基本資料 21
第四節各項死因別死亡率的差異 23
第五節對數複回歸分析 28
第六節依據先前住院主診斷接種疫苗與否死於同樣疾病的差異 30
第七節住院主或次診斷對死亡影響的對數複回歸分析 33
第四章 討論
第一節總論 34
第二節疫苗接種政策 37
第三節針對高危險群（出院病患）的接種策略 40
第四節疫苗接種率 42
第五節通知系統 44
第六節流感疫苗與個別疾病的關係 46
第七節研究限制 55
第八節結論與建議 58

參考文獻 60
附錄 66

參考文獻1.Armstrong K.Berlin M.Schwartz JS.Propert K. Ubel PA.Educational content and the effectiveness of influenza vaccination reminders. Journal of General Internal Medicine. 14(11):695-8, 1999.2.Barker WH, Mullooly JP. Underestimation of the role of pneumonia and influenza in causing excess mortality. Am J Public Health.71: 643,1981.3.Barker WH, Mulloly WH. Pneumonia and influenza deaths during epidemics: implications for prevention. Archives of Internal Medicine. 142(1):85-9,1982.4.Berry BB,Ehlert DA,Battiola RJ,Sedmak G.Influenza vaccination is safe and immunogenic when administered to hospitalized patients. Vaccine. 19(25-26):3493-8,2001.5.Carrat F. Valleron A-J. Influenza mortality among the elderly in France, 1980-90: How many deaths may have been avoided through vaccination? Journal of Epidemiology & Community Health. 49(4):419-25,1995.6.Centers for Disease Control. Prevention and Control of Influenza .Recommendations of the Immunization Practices Advisory Committee (ACIP).MMWR 35:317-326,331,1986.7 Centers for Disease Control.Assessing adult vaccination status at age 50 years. MMWR Morb Mortal Wkly Rep.44:561-3,1995.8.Centers for Disease Control . Update: influenza activity —United states and worldwide, 1999-2000 season, and composition of the 2000-1 influenza vaccine. MMWR — Morbidity & Mortality Weekly Report. 49(17): 375-81, 2000.9.Center for Disease Control. Prevention and control of influenza: recommendations of the Advisory Committee on Immunization Practices(ACIP). MMWR.49(No.RR-3),2000.10. Dexter PR, Perkins S, Overhage JM, Maharry K, Kohler RB, McDonald CJ. A computerized reminder system to increase the use of preventive care for hospitalized patients. New England Journal of Medicine. 345(13):965-70,2001.11.Diepersloot RJ, Bouter KP, Hoekstra JB,Influenza infection and diabetes mellitus. Case for annual vaccination. Diabetes Care. 13(8):876-82,1990.12.Donnan PT. Leese GP. Morris AD. The Diabetes Audit and Research in Tayside, Scotland/Medicine Monitoring Unit Collaboration. Hospitalizations for people with type 1 and type 2 diabetes compared with the nondiabetic population of Tayside, Scotland: a retrospective cohort study of resource use. Diabetes Care. 23(12):1774-9, 2000.13.Fedson DS, Kessler HA. A hospital-based influenza immunization program, 1977-78. Am J Public Health 73:442-445,1983.14.Fedson DS, Wajda A, Nicol JP, Roos LL. Disparity between influenza vaccination rates and risks for influenza-associated hospital discharge and death in Manitoba in 1982-1983. Ann Intern Med 116:550-555,1992.15.Fedson DS. Hirota Y. Shin HK. Cambillard PE. Kiely J. Ambrosch F. Hannoun C. Leese J. Sprenger MJ. Hampson AW. Bro-Jorgensen K. Ahlbom AM. Nokleby H. Valle M. Olafsson O. Salmeron F. Cloetta J. Rebelo de Andrade H. Snacken R. Donatelli I. Jennings LC. Strikas RA. Influenza vaccination in 22 developed countries: an update to 1995. Vaccine. 15(14):1506-11,1997.16.Fedson DS,Houck P,Bratzler D.Hospital-based Influenza and Pneumococcal Vaccination: Sutton’s Law applied to prevention.Infection control and hospital epidemiology 21:692-699,2000.17.Foster DA, Talsma A, Furumoto-Dawson A, Ohmit SE, Margulies JR, Arden NH, et al. Influenza vaccine effectiveness in preventing hospitalization for pneumonia in the elderly. Am J Epidemiol. 136:296-307,1992.18.Ganz PA, Shanley JD, Cherry JD, Responses of patients with neoplastic diseases to influenza virus vaccine Cancer 42: 2244-2247,197819.Glezen WP. Serious morbidity and mortality associated with influenza epidemics. Epidemiol Rev 4:25-44,1982.20.Glezen WP, Decker M, Perrotta DM. Survey of underlying conditions of persons hospitalized with acute respiratory disease during influenza epidemics in Houston, 1978-1981. Am Rev Respir Dis. 136:550-5,1987.21.Gordon T, Thom T. The recent decrease in CHD mortality. Prev Med. 4:115-125,1975.22.Grau AJ. Buggle F. Heindl S. Steichen-Wiehn C. Banerjee T. Maiwald M. Rohlfs M. Suhr H. Fiehn W. Becher H. Recent infection as a risk factor for cerebrovascular ischemia. . Stroke. 26(3):373-9, 1995.23.Gross PA, Hermogenes AW, Sacks HS, Lau J, Levandowski RA. The efficacy of influenza vaccine in elderly persons. A meta-analysis and review of the literature. Ann Intern Med 123:518-27,1995.24.Hak E. van Essen GA. Stalman WA. de Melker RA. Improving influenza vaccination coverage among high-risk patients: a role for computer-supported prevention strategy? Family Practice. 15(2):138-43,1998.25.Hirota Y, Fedson DS and Kaji M. Japan lagging in influenza jabs. Nature. 380,18,1996.26.Hirota, Y. and Kaji, M. Scepticism about influenza vaccine efficacy in Japan(letter). Lancet 344, 408-9,1994.27.Kempe A. Hall CB. MacDonald NE. Foye HR. Woodin KA. Cohen HJ. Lewis ED. Gullace M. Gala CL. Dulberg CS. Influenza in children with cancer. Journal of Pediatrics. 115(1):33-9,1989.28.Lin RS, Lee WC. Trends in mortality from diabetes mellitus in Taiwan, 1960-1988. Diabetologia 35:973-9,1992.29.Lin T, Chou P, Lai MS, Tsai ST, Tai TY .Direct costs-of-illness of patients with diabetes mellitus in Taiwan. Diabetes research and clinical practices 54 Suppl.1,S43-46,2001.30.Liu C. Influenza. In: Hoeprich PD eds. Infectious diseases. 3rd ed. Philadelphia: Harper & Row publishers,323-8,1983.31.Loeb M, McGeer A, McArthur N, Walter S, Simo RAE, Risk factors for pneumonia and other lower respiratory tract infections in elderly residents of long-term care facilities. Archives of Internal Medicine. 159(17):2058-64,1999.32.Meier CR. Jick SS. Derby LE. Vasilakis C. Jick H. Acute respiratory-tract infections and risk of first-time acute myocardial infarction. Lancet. 351(9114):1467-71,1998. 33.Nichol KL, Baken L,Nelson A. Relation between Influenza Vaccination and Outpatient Visits, Hospitalization, and Mortality in Elderly Persons with Chronic Lung Disease. Ann Intern Med.130:397-403,1999.34.Nguyen-Van-Tam JS. Nicholson KG. Influenza immunization; vaccine offer, request and uptake in high-risk patients during the 1991/2 season. Epidemiology & Infection. 111(2):347-55,1993. 35.Nordin J, Mullooly J, Poblete S, Strikas R, Petrucci R, Wei F, Rush B, Safirstein B, Wheeler D, Nichol KL. Influenza vaccine effectiveness in preventing hospitalizations and deaths in persons 65 years or older in Minnesota, New York, and Oregon: data from 3 health plans. Journal of Infectious Diseases. 184(6):665-70, 2001.36.Poland GA, Rottinghaus ST, Jacobson RM. Influenza vaccines: a review and rational for use in developed and underdeveloped countries. Vaccine 19：2216-2220,2001.37.Pozzilli P, Leslie RDG: Infections and diabetes, Diabetic Med. 11:935-41, 1994.38.Public health service. Healthy people 2000: national health promotion and disease prevention objectives─full report, with commentary. Washington, DC: US Department of Health and Human Services,1991: DHHS publication no.(PHS)91-50212:521.39.Reichert TA, Sugaya N, Fedson DS, Glezen WP. Simonsen L, Tashiro M.The Japanese experience with vaccinating schoolchildren against influenza. New England Journal of Medicine. 344(12):889-96,2001. 40.Shortridge KF: Influenza —a continuing detective story. Lancet 354 Suppl:SIV29, 1999.41.Simonsen L, Clarke MJ, Williamson DG et al.The impact of influenza epidemics on mortality: introducing a severity index. Am J Public Health 87; 1944-50,1997.42.Simonsen L.The global impact of influenza on morbidity and mortality. Vaccine 17; s3-s10, 1999.43.Singleton JA, Greby SM, Walker FJ, Strikas R. Influenza, pneumococcal, and Tetanus toxoid vaccination of adults─United states, 1993-1997. MMWR (49) No.SS-9.39-62,2000.44.Siscovick DS, Raghunathan TE, Lin D, Weirmann S, Arbogast P, Lemaitre RN, Psaty BN, Alexander R,Cobb LA. Influenza vaccination and the risk of primary cardiac arrest. American Journal of Epidemiology. 152(7):674-7,2000.45.Smith DM. Zhou XH. Weinberger M. Smith F. McDonald RC. Mailed reminders for area-wide influenza immunization: a randomized controlled trial. Journal of the American Geriatrics Society. 47(1):1-5,1999.46.Tillett HE, Smith JW, Gooch CD. Excess deaths attributable to influenza in England and Wales: age at death and certified cause. International Journal of Epidemiology. 12(3):344-52,1983.47.Vinicof. Doctors should add a flu shot to care regimen for diabetics. North Carolina medical journal 59(6):340,1998.48.Wang CS, Wang ST, Chou P. Efficacy of influenza vaccination for the elderly.Vaccine（in print）49.Wannamethee SG. Shaper AG. Ebrahim S. Respiratory function and risk of stroke. Stroke. 26(11):2004-10,1995.50.Woodhouse PR, Khaw KT, Plummer M, Foley A, Meade TW. Seasonal variations of plasma fibrinogen and factor VII activity in the elderly: winter infections and death from cardiovascular disease. Lancet.343: 435-439,1994.51.Yamaya M.Yanai M. Ohrui T. Arai H. Sasaki H.Interventions to prevent pneumonia among older adults. Journal of the American Geriatrics Society. 49(1): 85-90,2001.52.內政部 台閩地區人口統計53.行政院衛生署，衛生統計,台北， 1985-1998。 54.行政院衛生署，流感疫苗接種效益評估，未發表。55.行政院衛生署，衛生統計動向,台北，2000年。56.李淑娟主編 葉金川策劃 發現台灣公衛行腳 .陳拱北預防醫學基金會 台北p137-165，2001年57.邱淑君 林智輝 劉定萍 陳豪勇，1999-2000年台灣地區及世界流感病毒分離概況，疫情報導 16卷11期 p515-526,2000. 58.呂宗學 石台平 賴華山 李麗雪 李孟智 周明智 台灣地區死因統計準確度評估Ｉ：可能錯誤來源與評估方法 中華衛誌 14(2):179-190,1995.59.呂宗學，為什麼高血壓不是第一大死因？－談原死因選擇規則的相關問題，台灣衛誌 20（1）：5-14,2001.60.衛生署，【高危險群老人流行性感冒疫苗接種計畫】，2000年