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完整後設資料紀錄
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.advisor | 林淑文 | |
dc.contributor.author | Yu-Min Chang | en |
dc.contributor.author | 張鈺敏 | zh_TW |
dc.date.accessioned | 2021-05-16T16:18:15Z | - |
dc.date.available | 2018-09-24 | |
dc.date.available | 2021-05-16T16:18:15Z | - |
dc.date.copyright | 2013-09-24 | |
dc.date.issued | 2013 | |
dc.date.submitted | 2013-08-15 | |
dc.identifier.citation | 1. Walsh TJ, Anaissie EJ, Denning DW, et al. Treatment of aspergillosis: clinical practice guidelines of the Infectious Diseases Society of America. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America 2008;46:327-60.
2. Hussaini T, Ruping MJ, Farowski F, Vehreschild JJ, Cornely OA. Therapeutic drug monitoring of voriconazole and posaconazole. Pharmacotherapy 2011;31:214-25. 3. Park WB, Kim NH, Kim KH, et al. The effect of therapeutic drug monitoring on safety and efficacy of voriconazole in invasive fungal infections: a randomized controlled trial. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America 2012;55:1080-7. 4. Menzin J, Meyers JL, Friedman M, et al. Mortality, length of hospitalization, and costs associated with invasive fungal infections in high-risk patients. American Journal of Health-System Pharmacy 2009;66:1711-7. 5. Hsiue HC, Wu TH, Chang TC, et al. Culture-positive invasive aspergillosis in a medical center in Taiwan, 2000-2009. European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology 2012;31:1319-26. 6. De Pauw B, Walsh TJ, Donnelly JP, et al. Revised definitions of invasive fungal disease from the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) Consensus Group. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America 2008;46:1813-21. 7. Segal BH, Herbrecht R, Stevens DA, et al. Defining responses to therapy and study outcomes in clinical trials of invasive fungal diseases: Mycoses Study Group and European Organization for Research and Treatment of Cancer consensus criteria. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America 2008;47:674-83. 8. Limper AH, Knox KS, Sarosi GA, et al. An official American Thoracic Society statement: Treatment of fungal infections in adult pulmonary and critical care patients. American journal of respiratory and critical care medicine 2011;183:96-128. 9. Pagano L, Akova M, Dimopoulos G, Herbrecht R, Drgona L, Blijlevens N. Risk assessment and prognostic factors for mould-related diseases in immunocompromised patients. The Journal of antimicrobial chemotherapy 2011;66 Suppl 1:i5-14. 10. Nivoix Y, Velten M, Letscher-Bru V, et al. Factors associated with overall and attributable mortality in invasive aspergillosis. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America 2008;47:1176-84. 11. Lass-Florl C. Triazole antifungal agents in invasive fungal infections: a comparative review. Drugs 2011;71:2405-19. 12. Johnson LB, Kauffman CA. Voriconazole: a new triazole antifungal agent. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America 2003;36:630-7. 13. Clancy CJ, Nguyen MH. In vitro efficacy and fungicidal activity of voriconazole against Aspergillus and Fusarium species. European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology 1998;17:573-5. 14. Voriconazole in DRUGDEX (R) System [Intranet database]. Greenwood Village, Colo: Thomson Reuters (Healthcare) Inc. Updated periodically. ( cited: 5/15, 2013). 15. 西藥、醫療器材、含藥化妝品許可證查詢. 行政院衛生署藥物食品管理局. (Accessed 06/30, 2013, at http://www.fda.gov.tw/MLMS/(S(t4mazt55lazjzhmlg3fzmfuz))/H0001.aspx). 16. Prod Info VFEND(R) IV injection ot, suspension, 2008. . US Food and Drug Administration. 17. Cecil JA, Wenzel RP. Voriconazole: a broad-spectrum triazole for the treatment of invasive fungal infections. Expert review of hematology 2009;2:237-54. 18. Imataki O, Ohnishi H, Kitanaka A, Kubota Y, Ishida T, Tanaka T. Visual disturbance comorbid with hallucination caused by voriconazole in the Japanese population. International journal of hematology 2008;88:3-6. 19. Theuretzbacher U, Ihle F, Derendorf H. Pharmacokinetic/pharmacodynamic profile of voriconazole. Clinical pharmacokinetics 2006;45:649-63. 20. Kuo If. Role of Therapeutic Drug Monitoring of Voriconazole in the Treatment of Invasive Fungal Infections. Can J Hosp Pharm 2009;62:469-82. 21. Trifilio SM, Yarnold PR, Scheetz MH, Pi J, Pennick G, Mehta J. Serial plasma voriconazole concentrations after allogeneic hematopoietic stem cell transplantation. Antimicrob Agents Chemother 2009;53:1793-6. 22. Troke PF, Hockey HP, Hope WW. Observational study of the clinical efficacy of voriconazole and its relationship to plasma concentrations in patients. Antimicrob Agents Chemother 2011;55:4782-8. 23. Dolton MJ, Ray JE, Chen SC, Ng K, Pont LG, McLachlan AJ. Multicenter study of voriconazole pharmacokinetics and therapeutic drug monitoring. Antimicrob Agents Chemother 2012;56:4793-9. 24. Pascual A, Calandra T, Bolay S, Buclin T, Bille J, Marchetti O. Voriconazole therapeutic drug monitoring in patients with invasive mycoses improves efficacy and safety outcomes. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America 2008;46:201-11. 25. Ueda K, Nannya Y, Kumano K, et al. Monitoring trough concentration of voriconazole is important to ensure successful antifungal therapy and to avoid hepatic damage in patients with hematological disorders. International journal of hematology 2009;89:592-9. 26. Kim SH, Yim DS, Choi SM, et al. Voriconazole-related severe adverse events: clinical application of therapeutic drug monitoring in Korean patients. International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases 2011;15:e753-8. 27. Miyakis S, van Hal SJ, Ray J, Marriott D. Voriconazole concentrations and outcome of invasive fungal infections. Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases 2010;16:927-33. 28. Suzuki Y, Tokimatsu I, Sato Y, et al. Association of sustained high plasma trough concentration of voriconazole with the incidence of hepatotoxicity. Clinica chimica acta; international journal of clinical chemistry 2013;424C:119-22. 29. Bates DW, Su L, Yu DT, et al. Mortality and costs of acute renal failure associated with amphotericin B therapy. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America 2001;32:686-93. 30. 臺大醫院藥劑部院內網. http://140.112.125.99/phar/intranet/druginfo/. 31. Chen SC, Slavin MA, Sorrell TC. Echinocandin antifungal drugs in fungal infections: a comparison. Drugs 2011;71:11-41. 32. Slobbe L, Polinder S, Doorduijn JK, et al. Outcome and medical costs of patients with invasive aspergillosis and acute myelogenous leukemia-myelodysplastic syndrome treated with intensive chemotherapy: an observational study. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America 2008;47:1507-12. 33. Kim A, Nicolau DP, Kuti JL. Hospital costs and outcomes among intravenous antifungal therapies for patients with invasive aspergillosis in the United States. Mycoses 2011;54:e301-12. 34. Ananda-Rajah MR, Cheng A, Morrissey CO, et al. Attributable hospital cost and antifungal treatment of invasive fungal diseases in high-risk hematology patients: an economic modeling approach. Antimicrob Agents Chemother 2011;55:1953-60. 35. Cagatay AA, Cosan F, Karadeniz A, et al. The clinical and pharmacoeconomic analysis of invasive aspergillosis in adult patients with haematological diseases. Mycoses 2008;51:328-35. 36. Ament AJ, Hubben MW, Verweij PE, et al. Economic evaluation of targeted treatments of invasive aspergillosis in adult haematopoietic stem cell transplant recipients in the Netherlands: a modelling approach. The Journal of antimicrobial chemotherapy 2007;60:385-93. 37. Garbino J, Schnetzler G, Roberts C. Invasive aspergillosis: is treatment with 'inexpensive' amphotericin B cost saving if 'expensive' voriconazole is only used on demand? Swiss medical weekly 2006;136:624-30. 38. Greene RE, Mauskopf J, Roberts CS, Zyczynski T, Schlamm HT. Comparative cost-effectiveness of voriconazole and amphotericin B in treatment of invasive pulmonary aspergillosis. American journal of health-system pharmacy : AJHP : official journal of the American Society of Health-System Pharmacists 2007;64:2561-8. 39. Jansen JP, Kern WV, Cornely OA, et al. Economic evaluation of voriconazole versus conventional amphotericin B in the treatment of invasive aspergillosis in Germany. Value in health : the journal of the International Society for Pharmacoeconomics and Outcomes Research 2006;9:12-23. 40. Jansen JP, Meis JF, Blijlevens NM, van't Wout JW. Economic evaluation of voriconazole in the treatment of invasive aspergillosis in the Netherlands. Current medical research and opinion 2005;21:1535-46. 41. Lewis JS, Boucher HW, Lubowski TJ, Ambegaonkar AJ, Day DL, Patterson TF. Cost advantage of voriconazole over amphotericin B deoxycholate for primary treatment of invasive aspergillosis. Pharmacotherapy 2005;25:839-46. 42. Rotstein C, Laverdiere M, Marciniak A, Ali F. An economic evaluation of voriconazole versus amphotericin B for the treatment of invasive aspergillosis in Canada. The Canadian journal of infectious diseases & medical microbiology = Journal canadien des maladies infectieuses et de la microbiologie medicale / AMMI Canada 2004;15:277-84. 43. Wenzel R, Del Favero A, Kibbler C, et al. Economic evaluation of voriconazole compared with conventional amphotericin B for the primary treatment of aspergillosis in immunocompromised patients. The Journal of antimicrobial chemotherapy 2005;55:352-61. 44. Wingard JR, Herbrecht R, Mauskopf J, Schlamm HT, Marciniak A, Roberts CS. Resource use and cost of treatment with voriconazole or conventional amphotericin B for invasive aspergillosis. Transplant infectious disease : an official journal of the Transplantation Society 2007;9:182-8. 45. Rousseau A, Laroche ML, Venisse N, et al. Cost-effectiveness analysis of individualized mycophenolate mofetil dosing in kidney transplant patients in the APOMYGRE trial. Transplantation 2010;89:1255-62. 46. Salih MR, Bahari MB, Shafie AA, et al. Cost-effectiveness analysis for the use of serum antiepileptic drug level monitoring in children diagnosed with structural-metabolic epilepsy. Epilepsy research 2013;104:151-7. 47. Cies JJ, Varlotta L. Clinical pharmacist impact on care, length of stay, and cost in pediatric cystic fibrosis (CF) patients. Pediatric pulmonology 2012. 48. Touw DJ, Neef C, Thomson AH, Vinks AA. Cost-effectiveness of therapeutic drug monitoring: a systematic review. Therapeutic drug monitoring 2005;27:10-7. 49. Ostad Haji E MK. Potential Cost-effectiveness of Therapeutic Drug Monitoring for Depressed Patients Treated With Citalopram. Ther Drug Monit 2013;35:396-401. 50. Darko W, Medicis JJ, Smith A, Guharoy R, DE. L. Mississippi Mud No More: Cost-Effectiveness of Pharmacokinetic Dosage Adjustment of Vancomycin to Prevent Nephrotoxicity. Pharmacotherapy 2003;23:643-50. 51. Naranjo CA, Busto U, Sellers EM, et al. A method for estimating the probability of adverse drug reactions. Clinical pharmacology and therapeutics 1981;30:239-45. 52. 黃玉婷. 侵入性黴菌感染使用voriconazole之療劑監測研究. 2011:1-122. 53. Luong ML, Husain S, Rotstein C. Pharmacoeconomic assessment of therapy for invasive aspergillosis. Mycoses 2013. 54. 醫療服務給付項目及支付標準查詢. 衛生福利部中央健康保險署. (Accessed 07/23, 2013, at http://www.nhi.gov.tw/query/query2.aspx?menu=20&menu_id=710&webdata_id=3633&WD_ID=900). 55. 陳珮君. 住院患者重複發生藥物不良反應之危險因子與醫療耗用探討. 長庚大學醫務管理研究所 2011. | |
dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/5908 | - |
dc.description.abstract | 背景:
Voriconazole為新一代三唑類抗黴菌藥品,臨床上為治療侵入性麴菌感染的首選用藥。由於非線性的藥品動態學特性以及其他影響因子,造成個體間或個體內的血中濃度差異性大。研究皆顯示voriconazole血中濃度與臨床療效、藥品不良反應相關,且可改善臨床黴菌治療效果。在其他疾病的藥品療劑監測成本效果分析中,發現療劑監測可改善臨床治療效果等,但也可能造成臨床醫療花費負擔增加。目前尚無voriconazole 療劑監測的成本效果分析,本研究於國立臺灣大學醫學院附設醫院回溯性收案使用voriconazole的病人並執行voriconazole療劑監測的成本效果分析。 研究目的: 以醫院觀點分析執行voriconazole療劑監測前後,對於黴菌感染的治療反應影響、藥品不良反應、醫療花費的影響並且執行成本效果分析,提供醫療決策者將來是否納入voriconazole療劑監測作為醫院常規檢測項目以及實行方式之參考依據。 研究方法: 本研究回溯性收案於2010年1月1日至2010年12月31日在國立臺灣大學醫學院附設醫院新使用voriconazole治療侵入性黴菌感染並接受一次以上voriconazole療劑監測的病人作為療劑監測組 (Therapeutic drug monitoring ,TDM group)。以2008年1月1日至2008年12月31日新使用voriconazole但未接受療劑監測者為對照組 (Historical control , HC group)。自病人第一天用藥開始,觀察90天內病人voriconazole及其他抗黴菌藥品處方型態、藥物不良反應及處理方式、醫療直接成本。並請感染科醫師評估適應症與治療反應。以研究觀察期結束時的病人黴菌治療反應作為主要研究終點,以voriconazole治療天數、因發生不良反應導致病人停藥作為次要研究終點,並執行兩組之間的成本效果分析與敏感度分析。統計方法以卡方檢定、T檢定、Wilcoxon signed rank test、log rank test進行組間比較。 研究結果: 本研究HC組共有69位病人,TDM組為71位病人。兩組病人的年齡、性別、潛在疾病類似,皆以血液疾病為主,TDM組病人為neutropenia的比例與HC組相似 (45.1%與40.6%),研究期間發生neutropenia則TDM組比HC組多22%。兩組病人接受骨髓移植的比例相近但TDM組接受周邊血液幹細胞移植比例較高 (4.4% 與17%)。在慢性肝臟疾病方面,TDM組有B型肝炎者比例也多於HC組。病人大多為因為確定或極有可能的肺部黴菌感染而開始用藥。 在持續使用voriconazole上,TDM組的持續使用率較HC組高出9.1 %且具有統計意義(p=0.04),voriconazole使用天數也顯著多於HC組。在黴菌感染治療反應方面,治療成功比例在TDM組與HC組分別為 45%與58%,治療無進展或疾病惡化為29.6%與33.3 %,但都不具有統計顯著意義。在死亡率則以TDM組較高 (22.5%與7.3%)。在藥物不良反應方面,TDM與HC兩組分別發生60筆與12筆與voriconazole使用相關性較高的不良反應,其中有8.3% (5/60)和50% (6/12)的不良反應導致病人停藥,具有統計顯著意義。若是因為不良反應而停止用藥的病人,則兩組分別為7% (5/71)與13% (9/69),但不具有統計上意義。 醫療成本部分,TDM組總醫療花費中位數為734,014元,HC組為428,062元,抗黴菌藥品中位數分別為262,548與120,744元,兩組醫療成本差別主要發生在觀察的第一個月。 執行TDM後,若欲增加病人首選之抗黴菌藥物治療長度一天,依額外總醫療成本、抗黴菌藥品成本計算的ICER值分別為8,741元和4,052元。當要減少1% 病人因為藥物不良反應而導致停藥時,依額外總醫療成本與抗黴菌藥品成本計算的ICER值分別為50,992元和23,634元。敏感度分析顯示voriconazole成本可能影響ICER值的改變。 結論: Voriconazole 療劑監測可減少病人因發生藥物不良反應而導致停藥,並持續首選藥物的治療且增長病患接受藥物治療的長度,但需要額外的醫療成本支出。 | zh_TW |
dc.description.abstract | Background:
Voriconazole, a second generation triazole, is the drug of choice in the treatment of invasive aspergillosis (IA). Therapeutic drug monitoring (TDM) of voriconazole has been recognized as an effective way to improve clinical outcomes but may increase economic burden in the healthcare system. Currently, the impact of TDM on the pharmacoeconomic aspect has not been studied. Objective: The objective of this study is to evaluate the cost-effectiveness of voriconazole TDM from the hospital perspective in a 2500-bed medical center in Taiwan. Methods: New voriconazole users who underwent TDM in 2010 were enrolled in the TDM group. The historical control (HC) group consisted of new users in 2008 when pharmacists-managed TDM service was not established. Treatment of IA and clinical outcomes were collected from medical records. Treatment response of invasive fungal infections on 90th day or at the end of follow-up period was the primary endpoint. Adverse drug reactions which resulted in discontinuation of voriconazole and treatment duration of voriconazole were secondary endpoints. Direct medical costs included information from insurance reimbursement profiles, patient cash payment documents, and TDM costs. χ2 test and Fisher’s exact test were used for categorical variable analysis. T-test or Wilcoxon rank, wilcoxon signed rank test, log rank test were used for continuous variable analysis. Results The mean age, gender and underlying diseases were similar between 71 patients in the TDM group and 69 patients in the HC group. However, more patients in the TDM group had neutropenia and received peripheral blood stem cell transplantation. Most people used voriconazole for possible fungal infection in lungs. Treatment success rate was 45% vs. 58% in the TDM group and HC group, respectively. The percentage of stable disease or progression were 29.6% and 33.3% in 2 groups without statistical significance. More people died with fungal infection in the TDM group (22.5 %) compared to HC group (7.3%) with statistical significance. On the aspect of the continuation rate of voriconazole, TDM group was 9.1% higher than HC group with statistical significance (p=0.04). Treatment duration of voriconazole was also 35 days longer in TDM group compared with HC group. There were 60 and 12 drug adverse reactions in TDM and HC group and caused 8.3% (5/60) and 50% (6/12) discontinuation of voriconazole, respectively (p<0.001). The median of total medical cost and antifungal expenses were higher in TDM group compared with HC group, with NTD 734,014 v.s.428,062 in total cost and 262,548 v.s.120,744 in antifungal expense. The major difference of total medical costs between 2 groups occurred in the first observation month. The daily antifungal costs, however, were similar between two groups. The incremental cost effectiveness ratios (ICERs) were NTD 8,741 (total medical cost) and NTD 4,052 (antifungal expense) per voriconazole treatment day gained. ICERs were NTD 50,992 (total medical cost) and NTD 23,634 (antifungal expense) per 1 % patients who were prevented from discontinuation of voriconazole treatment due to adverse drug reaction. Sensitivity test analysis showed that ICER was sensitive to variation of voriconazole expenses. Conclusion: Voriconazole TDM did not affect the treatment outcomes in this study. It may reduce the discontinuation rate of voriconazole due to adverse drug reaction with the tendency of increased medical cost. | en |
dc.description.provenance | Made available in DSpace on 2021-05-16T16:18:15Z (GMT). No. of bitstreams: 1 ntu-102-R00451006-1.pdf: 1733771 bytes, checksum: 6b4f3751c2ba658fb2a091770f00683e (MD5) Previous issue date: 2013 | en |
dc.description.tableofcontents | 致謝 i
中文摘要 i Abstract iv 圖表目錄 ix 表目錄 ix 圖目錄 x 縮寫表 xi 第一章 緒論 1 第二章 文獻探討 2 2.1 侵入性黴菌感染與治療 2 2.1.1 侵入性黴菌感染簡介 2 2.1.2 侵入性黴菌感染預後影響因子 3 2.1.3 Voriconazole簡介 4 2.1.4 Voriconazole療劑監測(Therapeutic Drug Monitoring, TDM) 8 2.1.5 其他抗絲狀黴菌藥物簡介 11 2.2 侵入性黴菌感染與治療的經濟評估 12 2.2.1 侵入性黴菌感染的經濟評估 12 2.2.2 Voriconazole使用的經濟評估 13 2.3 各種藥物療劑監測的經濟評估 13 第三章 研究目的 15 第四章 研究方法 16 4.1 研究架構 16 4.2 研究地點與對象 16 4.2.1 TDM組與Historical control組 16 4.2.2 納入與排除條件 17 4.3 療劑監測執行方法 17 4.4 研究觀察起始與研究觀察期結束定義 17 4.4.1 侵入性黴菌感染臨床適應症與療效評估 18 4.5 臨床研究終點 (clinical endpoint)定義 22 4.6 藥品不良反應評估 23 4.6.1 不良反應相關性 (probability) 23 4.7 相關資料收集 24 4.8 經濟成本計算 24 4.8.1 資料來源 24 4.8.2 成本種類與計算 24 4.9 成本效果分析 25 4.10 敏感度分析 (Sensitivity test analysis) 26 4.11 統計分析方法 26 第五章 研究結果 27 5.1 收案病人流程 27 5.1.1 病人基本資料 (Baseline characteristics) 29 5.2 臨床結果 (Clinical endpoint) 32 5.3 醫療花費 38 5.4 成本效果分析 (Cost-effectiveness analysis) 42 5.5 Sensitivity test analysis 44 第六章 討論 47 6.1 相關討論 47 6.1.1 病人納入過程與族群特性 47 6.1.2 臨床效果 48 6.1.3 醫療成本 50 6.1.4 成本效果分析 51 6.2 研究限制 52 6.3 未來展望 54 第七章 結論 55 參考文獻 56 | |
dc.language.iso | zh-TW | |
dc.title | Voriconazole 療劑監測於侵入性黴菌感染之成本效果分析 | zh_TW |
dc.title | Cost-Effectiveness Analysis of Voriconazole Therapeutic Drug Monitoring in the Treatment of Invasive Fungal Infections | en |
dc.type | Thesis | |
dc.date.schoolyear | 101-2 | |
dc.description.degree | 碩士 | |
dc.contributor.coadvisor | 蕭斐元 | |
dc.contributor.oralexamcommittee | 陳宜君,李啟誠,沈麗娟 | |
dc.subject.keyword | 成本效果分析,voriconazole,療劑監測,侵入性黴菌感染, | zh_TW |
dc.subject.keyword | Cost-effectiveness,voriconazole,therapeutic drug monitoring (TDM),invasive aspergillosis, | en |
dc.relation.page | 60 | |
dc.rights.note | 同意授權(全球公開) | |
dc.date.accepted | 2013-08-15 | |
dc.contributor.author-college | 醫學院 | zh_TW |
dc.contributor.author-dept | 臨床藥學研究所 | zh_TW |
顯示於系所單位: | 臨床藥學研究所 |
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