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系統識別號 U0026-0812200911133084
論文名稱(中文) 機械性質與加工條件對硬脆材料劃切加工之影響
論文名稱(英文) The effect of mechanical properties and cutting parameters on the scribing of brittle materials
校院名稱 成功大學
系所名稱(中) 機械工程學系碩博士班
系所名稱(英) Department of Mechanical Engineering
學年度 92
學期 2
出版年 93
研究生(中文) 陳啟宗
學號 n1691174
學位類別 碩士
語文別 中文
口試日期 2004-07-20
論文頁數 71頁
口試委員 指導教授-王俊志
口試委員-李驊登
口試委員-李偉賢
關鍵字(中) 裂片
劃切力
劃切
延脆轉換
硬脆材料
關鍵字(英) scribing force
brittle-ductile transition
Scribing
breaking
Brittle materials
學科別分類
中文摘要   本文提出一套以劃切及裂片製程得到材料機械性質的方法,並分析製程應用於硬脆材料之加工特性。文中以不同劃切深度及刀刃後傾角進行實驗,觀察劃切痕跡之表面狀態。由劃切力量探討不同材料(包含:矽晶、光學玻璃、Cu2600及Al6061)的比切削能,再由裂片力量求出材料之機械性質如:楊氏係數、彎曲強度及破壞韌性。
  另由實驗結果顯示切削深度由淺到深變化,加工材料將經歷延性、延脆轉換與脆性破壞三種移除機制。比切削能隨著切削深度由淺到深呈現下降之趨勢。最後分析結果得知對矽晶而言,切深大於1mm為脆性破壞,切深小於0.4mm為延性破壞;對STV-Glass而言切深大於2mm為脆性破壞,切深小於0.6mm為延性破壞。


英文摘要   This paper proposes a method which obtains mechanical properties of materials by scribing and breaking processes. This paper also analyzes the machining characteristics of brittle materials by these processes, and observed the scribing surface morphology by experimenting on different cutting traces and rake angles. The specific cutting energy of different materials such as silicon, optical glass, Cu2600 and Al6061 is discussed. Moreover, mechanical properties such as Young’s modulus, bending force and fracture toughness are calculated from breaking force.
  The result of experiments shows that the cutting conditions will experience ductile, brittle–ductile transition and then brittle destruction when the cutting depth changes from shallow to deep. The deeper the cutting depth is, the less the specific cutting energy is. Finally, the process will be brittle or ductile process when the depth for silicon is more than 1mm or less than 0.4mm and it will be brittle or ductile process when the depth for STV-Glass is more than 2mm or less than 0.6mm.


論文目次 總目錄 
中文摘要 I
英文摘要 II
誌 謝 III
總目錄 VI
表目錄 VIII
圖目錄 IX
符號說明 XIII
第一章 序論 1
1.1 研究動機 1
1.2 文獻回顧 1
1.2.1切削力模式 2
1.2.2矽晶圓劃切 2
1.2.3光學玻璃之劃切 4
1.3 研究範疇及論文架構 5
第二章 硬脆材料劃切及裂片模式之相關理論 6
2.1 切削力之介紹  6
2.2晶圓劃切之介紹 9
2.3 光學玻璃裂片之介紹 9
2.4彎曲強度之介紹與求法 10
2.5 楊氏模數之介紹與求法 11
2.6 破壞韌性之介紹 14
2.7 臨界切削深度  16
第三章 硬脆材料切削實驗 17
3.1 儀器設備介紹  17
3.2 實驗參數規劃  21
3.3 實驗方法與流程 23
3.3.1矽晶圓與STV Glass劃切實驗方法 23
3.3.2三點測試裂片方法 24
3.4 實驗數據 25
3.4.1劃切力量與深度關係 25
3.4.2比切削能與垂直方向切削係數之介紹 28
3.4.3矽晶與STV-Glass在不同後傾角其切削能與切削係數之比
較與討論 28
3.4.4固定刀具後傾角角度,比較矽晶、STV-Glass、Al6061及Cu2600之比切削能與垂直方向切削力常數關係 33
3.4.5矽晶圓劃切顯微結構觀察 35
3.4.6 STV Glass劃切顯微結構觀察 38
3.4.7顯微結構觀察與討論 40
第四章 利用劃切及裂片製程求得硬脆材料之機械性質 41
4.1 前言 41
4.2 利用裂片製程求得矽晶之機械性質 42
4.2.1 矽晶圓的方向性 42
4.2.2 利用硬度測試求取矽晶圓的破壞韌性 44
4.2.3 利用三點測試求矽晶圓的楊氏系數 48
4.2.4利用三點測試裂片求矽晶圓的彎曲強度及破壞韌性 48
4.3利用裂片製程求得STV Glass之機械性質 51
4.3.1 玻璃的簡介51
4.3.2 利用硬度測試求取STV Glass的破壞韌性 51
4.3.3 利用三點測試求取STV Glass的楊氏係數 55
4.3.4 利用三點測試裂片求STV Glass的彎曲強度並求取破壞韌性 55
4.3.5 金屬Cu2600與Al6061材料成分與硬度值 55
4.4 加工後試片的觀察 57
4.4.1 延性加工區 58
4.4.2 延性轉脆性破壞區 60
4.4.3 脆性破壞區 61
4.5 脆韌轉換點之介紹 62
4.6硬度、破壞韌性、楊氏係數等性質對加工特性的影響 64
第五章 結論與建議 66
5.1 結論 66
5.2 建議與改良方法 68
參考文獻 69
自 述  71
參考文獻 1.W. J. Eneres, R.E. DeVor, and S. G. Kapoor, “A Dual -Mechanism Approach to the
Prediction of Machining Forces,” ASME Journal of Engineering for Industry,
Vol. 117, pp. 526-541, 1995.
2.I. Yellowley, “Observations on the Mean Values of Forces, Torque and Specific
Power in the Peripheral Milling Process,” International Journal of Machine
Tool Design and Research, Vol. 25(4), pp. 337-346, 1985.
3.A. J. P. Sabberwal, “Chip Section and Cutting Force During the Milling
Operation, ” Annals of the CIRP, Vol. 10, pp. 197-203, 1961.
4.E. Budak, Y. Altintas, E. J. A. Armarego, “Prediction of Milling Force
Coefficients from Orthogonal Cutting Data,” Transactions of ASME, 118, pp.
216-224, 1996.
5.Th. Schaller, L. Bohn, J. Mayer, K. Schubert, “Microstructure groove with a
width of less than 50mm cut with ground hard metal micro end mills,” Precision
Engineering, 23, pp.229-235, 1999.
6.H. Jared Bradley, A. Dow Thomas, “Investigation of the direction of chip
motion in diamond turning,” Precision Engineering, 25, pp.155-164, 2001.
7.Jeong-Du Kim, Dong-Sik Kim, “Surface characteristics of magnetic-disk cutting
using a sing-crystal diamond tool in an ultraprecision lathe,” Journal of
Materials Processing Technology, 59, pp.303-308, 1996.
8.Nobuyuki Moronuki, Yuan Liang, Yuji Furukawa, “Experiments on the effect of
material properties on microcutting processes” Butterworth-Heinemann, 16,
pp.124-131, 1994.
9.D. A. Lucca, P. Chou, R. J. Hocken, “Effect of Tool Edge Geometry on the
Nanometric Cutting of Ge,” Annals of the CIRP, 47, pp.475-478, 1998.
10.R. A. Allaire and J. C.Lapp, “Scoring of AMLCD Glass,” Corning Incorporated,
Technical Information Paper, 2001.
11.F.Z. Fang, L. J. Chen, “Ultra-Precision Cutting for ZKN7 Glass,” Annals of
the CIRP, 49, pp.17-20, 2000.
12.Corning Incorporated, “Fracture Analysis, a Basic Tool to Solve Breakage
Issues,” Technical Information Paper, 2001.
13.Ming Zhou, B.K. A. Ngoi, Z. W.Zhong and C.S. Chin, “Brittle-Ductile
Transition In Diamond Cutting of Silicon Single Crystals,” Materials and
Manufacturing Processes, 16(4), pp.447-460, 2001.
14.W. J. Eneres, R.E. DeVor and S. G. Kapoor, “A Dual-Mechanism Approach to the
Prediction of Machining Forces,” ASME Journal of Engineering for Industry,
Vol.117, pp. 526-541, 1995.
15.John Mauro, “Hardness and Toughness,” CES 305: Laboratory
Experiment # 7, NYS College of Ceramics, 1999.
16. V. Weiss, “Application of Fracture Mechanical to Design,” Sagamore Army
Materials Research Conference Proceedings, pp.1-22, 1975.
17.http://www.ozoneglass.co.uk/guidance/mechanical
18.http://www.corning.com/lightingmaterials/images/
19.http://www.memsnet.org/material/
20.T. G. Bifano, T.A. Dow, and R. D. Scattergood, “Ductile-Regime Grinding, Anew
Technology for Machining Brittle Materials,” ASME Journal of Engineering for
Industry, Vol.113, pp.184-189, 1991.

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系統識別號 U0026-0812200911354871
論文名稱(中文) 醫院競爭與處方行為之關係-以門診糖尿病口服降血糖藥品治療為例
論文名稱(英文) The Relationship between Hospital Competition and Prescribing Behaviors-A Case study of Oral Hypoglycemic Agents in Ambulatory Care
校院名稱 成功大學
系所名稱(中) 臨床藥學研究所
系所名稱(英) Institute of Clinical Pharmacy
學年度 93
學期 2
出版年 94
研究生(中文) 歐凰姿
學號 s6692103
學位類別 碩士
語文別 中文
口試日期 2005-07-05
論文頁數 246頁
口試委員 指導教授-葉鳳英
口試委員-謝啟瑞
指導教授-高雅慧
指導教授-劉亞明
關鍵字(中) 醫院競爭
評鑑層級醫院
處方行為
口服降血糖藥品
糖尿病
關鍵字(英) the prescribing behavior
diabetes
oral hypoglycemic agents
the accreditation system
hospital competition
學科別分類
中文摘要 研究背景
  實證顯示在台灣全民健保採論量計酬(fee-for service; FFS)為主的支付制度,在病患有自由選擇就醫的權利下,係以「病患為主導的競爭(patient-driven competition)」環境,促使醫院間從事「非價格(品質)競爭(non-price competition)」,亦即醫院間競相提供高科技醫療服務,以吸引病患,實證上喻為「醫武競賽(medical arms race; MAR)」。醫院間非價格競爭的結果,往往造成醫院成本的上升,但對於醫療品質之影響實證上仍無一致的結論,並且仍缺乏以「處方行為」此競爭行為之代理變數。而目前相關研究係以美國為主,但相較其多元化的保險體制,我國為單一保險人、以論量計酬的支付制度為主及醫師與醫院之從屬關係較為單純,因此在台灣保險體制下預期可更清楚來觀察醫院競爭與行為之關係,且台灣醫院市場結構重要特色之一是有評鑑層級醫院分佈,因此更進一步在各醫院市場內各層級醫院交互競爭行為上,實為目前台灣需待評估之研究題材。目前台灣醫療產業支出,係偏重於門診部分,就特定疾病而言,糖尿病照護較其他疾病為高,且大部分糖尿病患係透過門診照護,因此門診糖尿病患的照護,一定程度上可反映台灣醫院醫療服務行為。

研究目的
  1. 分析醫院市場競爭程度與各家醫院口服降血糖藥品(oral hypoglycemic agents; OHAs; 以下簡稱OHAs)處方行為的關係;
  2. 分析不同市場結構下,各層級醫院競爭程度與各層級醫院OHAs處方行為的關係。

研究方法
  主要資料為民國86~91年「全民健康保險學術資料庫」及「健保給付藥品Anatomical Therapeutic Chemical代碼對照檔」。主要變項,醫院市場定義係以行政地域為界;且將各市場依市場內「各層級醫院組成」再歸納三種「市場結構」別,以觀察各層級醫院間競爭行為;市場競爭程度以門診人次計算賀氏指數(Herfindahl-Hirschman Index)來衡量;競爭行為,以「高價OHAs」處方行為,代表高價醫療服務;以「新進OHAs」及「低處方品質OHAs」處方行為,分別代表「高、低」處方品質。主要統計分析,採「工具變項」處理衡量市場競爭程度時所可能產生的偏誤,再利用複線性迴歸模型控制相關影響因素。

研究結果
  本研究樣本六年度共包含2,110家醫院觀察值、18,045個糖尿病患(以身分字號歸戶)觀察值與158,655人次。醫院競爭與處方行為關係,在控制相關影響因素下,醫院市場競爭與醫院「低處方品質OHAs」行為呈現顯著正相關。各層級醫院交互競爭行為方面,就區域醫院,控制相關影響因素後,第一種市場結構(存在三種層級醫院)下,區域醫院競爭與其「低處方品質OHAs」行為呈現顯著負相關;而在第二種市場結構(存在區域及地區醫院)下,區域醫院競爭與其「低處方品質OHAs」行為呈現顯著正相關;對地區醫院而言,在控制相關影響因素後,第一種市場結構下,地區醫院競爭與其「低處方品質OHAs」行為呈現顯著負相關;第二種市場結構下,區域醫院競爭與地區醫院「新進OHAs」行為呈現顯著負相關;第二或三種市場結構(僅存地區醫院)下,地區醫院競爭與其「高價OHAs」行為呈現顯著正相關。

結論
  整體而言,以「低處方品質OHAs」處方行為進行衡量時,台灣醫院間競爭與處方品質呈現顯著負相關;但此一結果,較難排除病患藥品認知不足、「資訊不對稱」與醫師處方習慣等因素可能帶來的影響。各層級醫院競爭行為方面,研究結果顯示相對於第二或三種市場結構,在第一種市場結構下,市場機制使區域或地區醫院傾向有較高處方品質。若「市場結構」別,可意涵為各市場「醫療資源之豐缺」,則我們推測可能相對於第二或三種市場結構,第一種市場結構(含三種層級醫院,代表醫療資源相對充足區),可藉由較高醫療資訊密集度或流通性,改善「資訊不對稱」,以較接近「完全之訊息」條件,使「市場機制」較能夠充分發揮。因此,本研究建議各市場醫療資源應達適當配置,並配合資訊透明化,如建構處方監測機制或藥事服務,提升民眾藥品認知與處方品質,在促使資訊有效流通下,以期接近完全訊息之條件,使市場機制發揮下爲台灣醫院產業帶來正面影響。
英文摘要   Background Recently, several empirical studies suggested non-price competition among hospitals in Taiwan under fee-for service (FFS) by means of advanced medical amenities, the so-called “medical arms race.” But there is an ambiguous effect of hospital competition on the quality of care, and few studies used the prescribing behavior to estimate this relationship. From the perspective on hospital competition, relatively limited data in the Unites States which may be due to complicated insurance and payment system. Studies regarding the interaction of hospital competition from different accreditation types in Taiwan are still absent. In addition, the utilization of outpatient services in Taiwan is relatively high compared to OECD countries, and health care for diabetes is mainly delivered in an outpatient setting. Thus, diabetes is a good representative health condition to examine the quality of care delivered in hospitals.

  Objective 1) Estimating the relationship between hospital competition and prescribing oral hypoglycemic agents (OHAs); 2) Estimating the relationship between hospital competition at different accreditation level and prescribing OHAs under various market structures.

  Methods Health care claim data from the National Health Insurance (NHI) program during the period 1997-2002, and the ATC 7-digit coding system of NHI Pharmaceutical Subsidy was used as the interface for analyzing the pharmaceutical claim data. Hospital market was defined by geographic boundary, and hospital competition was measured by the Herfindahl-Hirschman index based on the market share of outpatient visits. Prescribing behaviors, including prescribing high cost OHAs implies providing cost-enhancing services, and new OHAs and poor quality OHAs imply the high and low level of the prescribing quality respectively. The caseload of diabetes was estimated by indicated complexity of pharmacology. Instrumental variables are employed to identify the endogeneity and measurement error.

  Results There are 2,110 observations of the hospitals, and 18,045 observations of the outpatients and 158,655 outpatient visits documented with diabetes in six years. For overall hospitals, there is a positive relationship between hospital competition and prescribing poor quality OHAs. For regional hospitals, under the market with three levels of hospitals, there is a negative relationship between regional hospital competition and prescribing poor quality OHAs. But under the market with two levels of hospitals, there is a positive relationship between regional hospital competition and prescribing poor quality OHAs. For district hospitals, under the market with three levels of hospitals, there is a negative relationship between district hospital competition and prescribing poor quality OHAs. Under the market with two levels of hospitals, there is a negative relationship between regional hospital competition and district hospital prescribing new OHAs. Under the market with two levels of hospitals or only district hospitals, there is a positive relationship between district hospital competition and prescribing high cost OHAs.
  
  Conclusion We found the negative impact of hospital competition on the prescribing quality, but couldn’t to rule out the potential effects of the physician prescribing habits and asymmetric information. In addition, our findings suggest market mechanisms may improve the prescribing quality of regional and district hospitals under the market with three levels of hospitals. It appears to be that the market with three levels of hospitals may be the area with abundant medical resources, likely being able to provide more pharmaceutical services and information to patients to alleviate the asymmetric information problem. Therefore, appropriate allocation of medical resources to enhance patients’ drug knowledge may be one way to improve the effect of market mechanism on the prescribing quality.
論文目次 目錄
中文摘要 i
Abstract iii
誌謝 v
第一部分 醫院競爭與醫院處方行為之關係 -以門診糖尿病患口服降血糖藥品治療為例 1
第一章 緒論 1
第一節 研究緣起 1
第二節 研究目標 5
第二章 文獻回顧 6
第一節 醫院的競爭行為 6
第一項 醫院市場結構 6
第一點 醫院市場的定義 6
第二點 醫院市場競爭性之影響因素與其衡量方式 10
第三點 政府管制措施與對市場結構之影響 11
第二項 醫院的非價格性競爭行為 20
第一點 醫院競爭行為之型態與相關影響因素 20
第二點 醫院市場競爭程度與醫院非價格競爭行為之實證研究 24
第三點 台灣醫院的競爭行為 32
第二節 糖尿病與糖尿病之臨床處置 37
第一項 糖尿病之簡介 37
第一點 糖尿病定義與病徵、分類與病因、診斷與併發症 37
第二點 糖尿病之流行病學 39
第三點 糖尿病之醫療耗用 42
第二項 糖尿病之臨床處置 44
第一點 糖尿病之臨床治療 44
第二點 糖尿病共同照護網 49
第三節 糖尿病用藥處方型態之實證分析與處方品質指標之設置 54
第一項 糖尿病用藥處方型態之實證分析 54
第二項 糖尿病用藥處方型態之影響因素 57
第三項 糖尿病用藥處方品質指標之設置 64
第一點 處方品質指標之設置 64
第二點 糖尿病用藥處方品質指標 66
第三章 研究方法 68
第一節 研究資料來源與處理 68
第一項 研究資料來源 68
第二項 各檔案間串聯及對應關係 70
第二節 研究變項及其操作型定義 73
第一項 基本變項定義 73
第二項 自變項與其操作型定義 76
第三項 應變項與其操作型定義 78
第四項 工具變項與其操作型定義 79
第三節 研究假說與架構 87
第一項 研究假說一 87
第一點 研究假說一 87
第二點 研究架構一 88
第三點 研究假說一之摘要 88
第二項 研究假說二 89
第一點 研究假說二 89
第二點 研究架構二 90
第三點 研究假說二之摘要 90
第四節 研究工具 92
第一項 統計分析 92
第二項 統計圖表的呈現 92
第五節 統計分析 93
第一項 工具變項(instrumental variables; IV) 93
第一點 工具變項(instrumental variables; IV)定義 94
第二點 工具變項(instrumental variables, IV)複迴歸模型 95
第二項 描述性統計(descriptive analysis) 97
第三項 推論性統計(inferential statistics) 98
第一點 複線性迴歸(multiple linear regression)模型 98
第四章 研究結果 100
第一節 工具變項之選取與預測之醫院市場與醫院層級之集中程度 100
第二節 樣本之統計量敘述 102
第一項 各層級醫院分佈情形 102
第二項 不同市場結構下,醫院觀察值與各層級醫院觀察值分佈情形 102
第三項 各醫院市場結構變化情形 102
第四項 降血糖藥品分佈情形 104
第三節 研究變項之統計量敘述 106
第一項 醫院市場與各醫院層級之集中程度 106
第二項 醫院OHAs處方行為 106
第三項 相關控制變項 108
第四節 描述型分析 109
第一項 醫院市場之集中程度與各醫院OHAs處方行為之關係 109
第五節 複迴歸分析 110
第一項 醫院市場集中程度與各醫院OHAs處方行為之關係 110
第二項 不同市場結構下,各層級醫院之集中程度與各層級醫院藥品處方行為之關係 112
第一點 第一種市場結構下 112
第二點 第二種市場結構下 116
第三點 第三種市場結構下 119
第六節 重要結果之摘要 121
第一項 醫院市場集中程度與各醫院處方行為之關係 121
第一點 高價OHAs處方行為 121
第二點 新進OHAs處方行為 121
第三點 低處方品質OHAs處方行為 121
第二項 不同市場結構下,各層級醫院集中程度與各個層級醫院處方行為之關係 123
第一點 高價OHAs處方行為 123
第二點 新進OHAs處方行為 124
第三點 低處方品質OHAs處方行為 125
第五章 研究討論與結論 127
第一節 重要結果之討論 127
第二節 研究限制 138
第三節 研究結論 139
第六章 研究建議 140
第一節 研究建議 140
第二節 未來研究方向 142
第二部分 臨床藥事服務-門診糖尿病藥物順從性之評估 143
第一章 臨床藥事服務背景 143
第二章 文獻回顧 144
第一節 藥師於糖尿病患照護之角色 144
第一項 藥事服務於糖尿病照護之重要性 144
第二項 藥師參與糖尿病患照護之簡介 146
第一點 國外社區藥師參與糖尿病照護 146
第二點 國內藥師於糖尿病照護現況 147
第二節 服藥順從性之評估 149
第一項 服藥順從性之定義與其影響因素 149
第二項 服藥順從性之評估方法 150
第三章 臨床藥事服務目的 151
第四章 臨床藥事服務方法與材料 152
第一節 藥事服務單位 152
第二節 衛教對象 152
第三節 藥事服務方法 152
第四節 臨床藥事服務材料 153
第一項 降血糖藥品順從性問卷 153
第二項 降血糖藥品衛教單張 154
第五章 臨床服務之結果 156
第一節 衛教個案基本統計量 156
第二項 危險因子之評估 157
第三項 降血糖藥物認知之評估 158
第四項 衛教項目 160
第六章 結論與建議 161
第一節 結論 161
第二節 建議 163
參考文獻 165
附錄 177
附錄1降血糖藥品之ATC編碼與DDD 177
附錄2「高價口服降血糖藥品(OHAs)之品項」表(各年度) 179
附錄3樣本篩選結果 180
附錄4a各醫院市場結構變化之情形-醫院市場內醫院家數(依年度與醫院市場別) 182
附錄4b各醫院市場結構變化之情形-醫院市場之集中程度(依年度與醫院市場別) 183
附錄5a醫院市場與市場內各醫院層級之集中程度(依年度別) 184
附錄5b醫院市場與市場內各醫院層級之集中程度(依年度別) 185
附錄6a平均每家醫院,高價OHAs佔有比例(依年度別與六年度) 186
附錄6b平均每家醫院,高價OHAs佔有比例(依年度別) 187
附錄7a各層級醫院平均每家醫院,高價OHAs佔有比例(依年度別) 188
附錄7b各層級醫院平均每家醫院,高價OHAs佔有比例(六年度) 188
附錄7c各層級醫院平均每家醫院,高價OHAs佔有比例(依年度別) 189
附錄8a平均每家醫院,新進OHAs佔有比例(依年度別與六年度) 190
附錄8b平均每家醫院,新進OHAs佔有比例(依年度別) 191
附錄9a各層級醫院平均每家醫院,新進OHAs佔有比例(依年度別) 192
附錄9b各層級醫院平均每家醫院,新進OHAs佔有比例(六年度) 192
附錄9c各層級醫院平均每家醫院,新進OHAs佔有比例(依年度別) 193
附錄10a平均每家醫院,低處方品質OHAs佔有比例(依年度別與六年度) 194
附錄10b平均每家醫院,低處方品質OHAs佔有比例(依年度別) 195
附錄11a各層級醫院之平均每家醫院,低處方品質OHAs佔有比例(依年度別) 196
附錄11b各層級醫院之平均每家醫院,低處方品質OHAs佔有比例(六年度) 196
附錄11c各層級醫院平均每家醫院,低處方品質OHAs佔有比例(依年度別) 197
附錄12a相關的控制變項於各家醫院分佈情形(六年度) 198
附錄12b相關的控制變項於各層級醫院分佈情形(六年度) 199
附錄13a高、中及低集中程度的醫院市場內,平均每家醫院高價OHAs佔有比例(依年度別) 200
附錄13b高、中及低集中程度的醫院市場內,平均每家醫院高價OHAs佔有比例(88、90、91年度) 201
附錄14a高、中及低集中程度的醫院市場內,平均每家醫院新進OHAs佔有比例(依年度別) 202
附錄14b高、中及低集中程度的醫院市場內,平均每家醫院新進OHAs佔有比例(89、90、91年度) 203
附錄15a高、中及低集中程度的醫院市場內,平均每家醫院低處方品質OHAs佔有比例(依年度別) 204
附錄15b高、中及低集中程度的醫院市場與平均每家醫院低處方品質OHAs佔有比例(86、88、90年度) 205
附錄16a醫院市場集中程度與各醫院高價OHAs處方行為之複迴歸分析結果 206
附錄16b醫院市場集中程度與各醫院新進OHAs處方行為之複迴歸分析結果 207
附錄16c醫院市場集中程度與各醫院低處方品質OHAs處方行為之複迴歸分析結果 208
附錄17a第一種市場結構下,各層級醫院集中程度與醫學中心高價OHAs處方行為之複迴歸分析結果 209
附錄17b第一種市場結構下,各層級醫院集中程度與醫學中心新進OHAs處方行為之複迴歸分析結果 210
附錄17c第一種市場結構下,各層級醫院集中程度與醫學中心低處方品質OHAs處方行為之複迴歸分析結果 211
附錄18a第一種市場結構下,各醫院層級集中程度與區域醫院高價OHAs處方行為之複迴歸分析結果 212
附錄18b第一種市場結構下,各層級醫院集中程度與區域醫院新進OHAs處方行為之複迴歸分析結果 213
附錄18c第一種市場結構下,各層級醫院集中程度與區域醫院低處方品質OHAs處方行為之複迴歸分析結果 214
附錄19a第一種市場結構下,各層級醫院集中程度與地區醫院高價OHAs處方行為之複迴歸分析 215
附錄19b第一種市場結構下,各層級醫院集中程度與地區醫院新進OHAs處方行為之複迴歸分析 216
附錄19c第一種市場結構下,各層級醫院集中程度與地區醫院低處方品質OHAs處方行為之複迴歸分析 217
附錄20a第二種市場結構下,各層級醫院集中程度與區域醫院高價OHAs處方行為之複迴歸分析結果 218
附錄20b第二種市場結構下,各層級醫院集中程度與區域醫院新進OHAs處方行為之複迴歸分析結果 219
附錄20c第二種市場結構下,各層級醫院集中程度與區域醫院低處方品質OHAs處方行為之複迴歸分析結果 220
附錄21a第二種市場結構下,各層級醫院集中程度與地區醫院高價OHAs處方行為之複迴歸分析結果 221
附錄22a第二種市場結構下,各層級醫院集中程度與地區醫院新進OHAs處方行為之複迴歸分析結果 222
附錄21c第二種市場結構下,各層級醫院集中程度與地區醫院低處方品質OHAs處方行為之複迴歸分析結果 223
附錄22a第三種市場結構下,地區層級醫院集中程度與地區醫院高價OHAs處方行為之複迴歸分析結果 224
附錄22c第三種市場結構下,地區層級醫院集中程度與地區醫院新進OHAs處方行為之複迴歸分析結果 225
附錄22c第三種市場結構下,地區層級醫院醫院市場集中程度與地區醫院低處方品質OHAs處方行為之複迴歸分析結果 226
附錄23全民健康保險糖尿病醫療給付改善方案試辦計畫支付標準 227
附錄24臨床藥事服務-藥物順從性評估之問卷 229
附錄25臨床藥事服務-降血糖藥品衛教單張 231
自述 246
表目錄
表1 醫院市場的定義分類及其相關方法 9
表2臺灣醫院的權屬別結構 16
表3臺灣醫院市場競爭程度之變化(西元1994年及西元2000年) 18
表4美國醫院競爭行為之型態及其相關影響因素 23
表5醫療品質之衡量層面與衡量指標 25
表6非價格(品質)競爭行為之實證研究-以美國醫院為例 30
表7醫院資金來源的分佈(西元1998年) 34
表8糖尿病之分類與其病因 38
表9糖尿病盛行率前十名國家 40
表10依開發國家狀況推估糖尿病盛行率及成長率 40
表11中國及亞洲族群之糖尿病盛行率 41
表12全國糖尿病患門診及住院就醫層級之分佈 43
表13胰島素種類及其性質 46
表14口服降血糖藥物(OHAs)之作用機轉及可能之副作用 48
表15糖尿病共同照護網實施之成效評估 53
表16影響降血糖藥品處方型態之因素 63
表17結構面、過程面、結果面的處方品質指標之定義與其實例 65
表18藥品、疾病、病患為方向的處方品質指標及其應用實例 65
表19糖尿病之過程面處方品質指標 67
表20a基本變項定義及其操作型定義 80
表20b自變項定義及其操作型定義 83
表20c應變項定義及其操作型定義 85
表20d工具變項定義及其操作型定義 86
表21醫院市場之集中程度與各家醫院OHAs處方行為之關係 88
表22a三種市場結構內,各醫院層級之集中程度與各層級醫院高價OHAs處方行為之關係 90
表22b三種市場結構內,各醫院層級之集中程度與各層級之醫院新進OHAs處方行為之關係 91
表22c三種市場結構內,各醫院層級之集中程度與各層級醫院低處方品質OHAs處方行為之關係 91
表23預測之醫院市場與醫院層級之集中程度 101
表24不同市場結構下,醫院觀察值與各層級醫院觀察值分佈情形(六年度) 103
表25降血糖藥品總處方次數與金額,於總樣本與各醫院層級樣本分佈情形(六年度) 105
表26注射型胰島素與OHAs佔有比例,於平均每家醫院與各醫院層級平均每家醫院之分佈情形 105
表27醫院市場之集中程度與各醫院OHAs處方行為之關係的描述型與複迴歸分析結果之摘要 122
表28a不同市場結構下,各層級醫院之集中程度與各層級醫院高價OHAs處方行為之關係複迴歸分析結果之摘要 123
表28b不同市場結構下,各層級醫院之集中程度與各層級醫院新進OHAs處方行為之關係複迴歸分析結果之摘要 124
表28c不同市場結構下,各層級醫院集中程度與各層級醫院低處方品質OHAs處方行為之關係複迴歸分析結果之摘要 126
表29a臨床服務之病患基本資料 156
表29b臨床服務之病患危險因子之評估 157
表29c臨床服務之病患降血糖藥物認知之評估 158
圖目錄
圖1第二型糖尿病患藥物治療之簡則 45
圖2各檔案間串檔變項及對應關係 71
圖3研究變項選取流程 72
圖4將各醫院市場,歸類為三種「市場結構」 75
圖5醫院市場之競爭程度與各醫院OHAs處方行為之關係 88
圖6臨床服務之衛教項目 160





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系統識別號 U0026-0812200911381363
論文名稱(中文) 藥師介入憂鬱症治療成效評估
論文名稱(英文) Pharmacist Interventions in Depression Care
校院名稱 成功大學
系所名稱(中) 臨床藥學研究所
系所名稱(英) Institute of Clinical Pharmacy
學年度 93
學期 2
出版年 94
研究生(中文) 楊雅雯
學號 s6692403
學位類別 碩士
語文別 中文
口試日期 2005-06-24
論文頁數 205頁
口試委員 指導教授-楊延光
指導教授-李怡慧
指導教授- 高雅慧
指導教授- 林嘉音
口試委員-沈武典
關鍵字(中) 精神科醫師
處方抗憂鬱劑
藥師
憂鬱症
關鍵字(英) pharmacist
prescribing antidepressants
psychiatrists
depression
學科別分類
中文摘要 中文摘要
  憂鬱症是一個耗費個人和社會成本很高的疾患。臨床上治療方式有藥物、心理治療及電氣痙攣治療或光治療等。其中抗憂鬱劑至少須服藥2-4週以上才有療效,其一個治療的療程至少需6個月時間,以減少再次復發的危險性,然而此類病患的遵醫囑性及回診率都不高。分析此類病患服藥順從性不佳的原因,多半是因為對此類疾病認識不深、因初期使用覺得有療效就停藥及對藥物使用的治療時間長短、副作用等認知不足所致;也是造成憂鬱症反覆發作的主因。目前國外針對於藥師介入憂鬱症治療的研究,多藉由提供藥物資訊及解決用藥相關問題及評估用藥合理性等方式,來促使病患服藥順從性增加,治療成效提升;國內藥師參與憂鬱症治療的研究相當缺乏,所以想經由此研究了解藥師介入成效。

  本研究分成兩部分。第一部分為前瞻性,隨機分配性研究,探討藉由臨床藥師的介入,提升病患對於疾病與藥物使用的認知,提高憂鬱症治療的效果。其方法於成大醫院精神科初診及複診收集診斷為重度及輕度憂鬱症者為研究對象,共收納初診病患30人,複診病患60人,各分為介入與無介入者為各一半。一組採藥師介入憂鬱症照顧,一組無藥師介入;追蹤三個月,於追蹤過程中由同一位藥師解說憂鬱症相關知識,並給予用藥指導。藥師於診間介入三個月後,觀察到初診與複診病患的藥物知識程度變化,藥師介入組與非介入組間比較達到統計上差異。初診患者於藥師介入後,治療相信度、滿意度、服藥順從性有提升趨勢。

  第二部分為評估醫師處方抗憂鬱劑考量因素,由於目前所有抗憂鬱劑療效相當,選用原則多依據藥物副作用、耐受性、病患臨床表徵等方面來考量,但臨床上病人常伴有其他因素如焦慮、非典型表徵等,亦會影響藥物選擇。目前研究多著重處方趨勢,少有探索選擇藥物原因,而國內亦少有此方面研究,所以想經由此研究了解醫師臨床思維。其結果顯示,主要考量因素有:病患合併有特殊症狀出現、希望避免藥物的副作用、病患合併有其他疾病,及參考過去就醫經驗等。其中焦慮與失眠為最常被考量的合併有特殊症狀;最被醫師關切希望避免的藥物副作用是胃腸不適。
英文摘要 Abstract
 Major depression is associated with significant costs as well as functional and social disability. Clinical guidelines indicate that patients should take antidepressants for at least 6 months to prevent relapse and recurrence, but early discontinuation and other forms of nonadherence to antidepressant treatment are concerned. However, depressive patients are frequently discontinued because of adverse effects, poor understanding of the regimen, and delayed therapeutic effects. The pharmacist’s role in the management of depression is evolving in USA. Pharmacists may help improve the pharmacological management of depression by patient education, medication selection and appropriate dosing, enhancing medication compliance, monitoring treatment effectiveness, and identifying and managing adverse effects. But the data about pharmacists’ intervention in depressive care in Taiwan are deficient.

 This study was divided into two parts. In the first part, a prospective, randomized study was to examine the effects of pharmacist’s montoring on depressive patients by offering knowledge about antidepressant. Ninty patients with major depression or dysthymia were enrolled and randomized to intervention group or control group. Attitude about antidepressants is increased in all patients of pharmacist intervention group after 3 months. Pharmacists also improve patient satisfaction, and adherence with antidepressant medication therapy, especially for those not on antidepressants at enrollment, although outcome differences were not stastistically significant.

 In the second part of this study, we examined the factors psychiatrists would consider when prescribing antidepressants. The most common factors influencing antidepressant selection were the avoidance of specific side effects, the presence of comorbid psychiatric disorders, the presence of specific clinical symptoms and prior treatment history. Anxiety and insomnia were most frequently reported to influence medication selection. Gastrointestinal upset was the side effects that physicians had the greatest concern upon medication selection.
論文目次 目錄
中文摘要 I
Abstract III
誌謝 V
目錄 VI
表目錄 X
圖目錄 XII
第一章 研究背景 1
第二章 文獻回顧 3
第一節 、憂鬱性疾患 3
1.1 流行病學 3
1.2 憂鬱症分類 4
1.3 病理機轉 6
1.4 診斷與臨床表徵 9
1.5 治療方式、目標 13
1.6 復發機率 16
第二節 、抗憂鬱劑的治療 17
2.1 分類、作用機轉、使用劑量 17
2.2 選擇抗憂鬱劑的原則 24
2.4 療效的比較 31
2.5 副作用比較 36
2.6 使用情形與趨勢 41
2.7 藥物治療失敗的處理 42
第三節 、憂鬱症患者之服藥順從性 43
3.1 憂鬱患者服藥順從性情形 43
3.2 服藥順從性之影響 45
3.3 影響順服性之原因 46
3.4 藥師參與憂鬱症治療之研究 48
第四節 、處方抗憂鬱劑考量的研究 52
4.1 病患特質對處方的影響 52
4.2 合併疾病對處方的影響 53
I 、併有其他精神疾病 53
II 、併有其他內科疾病 53
4.3 合併特殊症狀(失眠、焦慮、食慾減退、自殺傾向等) 56
4.4 藥品特質(療效、副作用、藥價、交互作用) 56
4.5 醫師對藥品特質的認知 57
4.6 醫藥相關人員或藥廠的推薦或促銷 62
4.7 非藥物層面的考量 62
第三章 研究目的 63
第四章 研究方法 64
第一節 、藥師提供藥事服務對於憂鬱症治療成效之影響 64
1.1 研究設計 64
1.2 研究時間 64
1.3 研究對象 64
1.4 研究材料與工具 66
1.5 問卷信效度 67
1.6 研究步驟 68
1.7 研究資料分析方法 71
第二節 、精神科醫師處方抗憂鬱劑治療時所考量的因素 73
2.1 研究設計 73
2.2 研究時間 73
2.3 研究對象 73
2.4 研究材料與工具 73
2.5 研究步驟 73
2.6 研究資料分析方法 74
第五章 研究結果 75
第一節 、藥師提供藥事服務對於憂鬱症治療成效之影響 75
1.1 初診病人 75
I. 病患基本資料分佈情形與比較 75
II. 治療療效差異 78
III. 藥物知識認知差異 80
IV. 抗憂鬱劑治療相信度差異 84
V. 使用抗憂鬱劑滿意程度的差異 84
VI. 抗憂鬱劑的服藥順從性差異 85
VII. 抗憂鬱劑知識與服用滿意度及相信度相關性 86
1 .2複診病人 87
I. 病患基本資料分佈情形與比較 87
II. 治療療效差異 90
III. 藥物知識認知差異 92
IV. 抗憂鬱劑的服藥順從性差異 96
V. 抗憂鬱劑治療相信度差異 96
VI. 使用抗憂鬱劑滿意程度的差異 97
第二節 、精神科醫師處方抗憂鬱劑治療時所考量的因素 98
2.1 處方藥品使用分佈情形 98
2.2 處方抗憂鬱劑所考量的因素 100
2.3 藥物選擇與處方考量因素的分佈情形 105
第六章 討論 111
第一節 、藥師提供藥事服務對於憂鬱症治療成效之影響 111
1.1 藥師介入對於回診率的影響 111
1.2 藥師介入對於療效的影響 112
1.3 藥師介入對於知識教導成效 115
1.4 藥師介入對於服藥順服性的成效 121
1.5 藥師介入對於治療相信度、滿意度的影響 123
第二節 、精神科醫師處方抗憂鬱劑治療時所考量的因素 125
2.1處方考量因素與其他研究比較 125
2.2醫師對於藥品特質認知的比較 135
第三節 、研究限制 139
3.1 藥師提供藥事服務對於憂鬱症治療成效之影響 139
3.2 精神科醫師處方抗憂鬱劑治療時所考量的因素 139
第七章 結論與建議 140
第一節 結論 140
第二節 建議 141
1.1 藥師提供藥事服務對於憂鬱症治療成效之影響 141
1.2 精神科醫師處方抗憂鬱劑治療時所考量的因素 143
參考文獻 144
附錄一 153
附錄二 164
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系統識別號 U0026-0812200911383201
論文名稱(中文) 抗精神病藥物於精神分裂症患者之使用評估
論文名稱(英文) Utilization of Antipsychotic Agents in Patients with Schizophrenia
校院名稱 成功大學
系所名稱(中) 臨床藥學研究所
系所名稱(英) Institute of Clinical Pharmacy
學年度 93
學期 2
出版年 94
研究生(中文) 洪永潤
學號 s6692102
學位類別 碩士
語文別 中文
口試日期 2005-07-19
論文頁數 185頁
口試委員 指導教授-高雅慧
指導教授-李怡慧
指導教授-楊延光
指導教授-蔡慧珊
關鍵字(中) 抗精神病藥物
處方型態
病患衛教
精神分裂症
關鍵字(英) prescribing pattern
antipsychotic
schizophrenia
patient education
學科別分類
中文摘要 中文摘要
  精神分裂症最主要治療的方式為藥物治療。因目前為止,藥物處方開立,並無統一性準則參考,且隨著新抗精神病藥物的研發上市,增加醫師處方的選擇性,加以其它多種因素的影響,改變醫師處方型態。所以本研究想瞭解精神科專科醫師對精神分裂症症患者之抗精神病藥物之處方型態。

  精神分裂症患者需長期使用抗精神病藥物來預防復發。但研究統計社區精神分裂症病患未按醫囑服用藥者約有50%,甚至更多。本研究想瞭解影響病患服藥順服性的因素,以便進一步改善病患服藥順服性。

  本研究分成三部分,第一部分為抗精神病藥物的使用評估,分析成大醫院門診精神分裂症病患使用抗精神病藥物之處方型態,包括:抗精神病藥物的處方比例、使用劑量、抗精神病藥物多重用藥及合併其它精神藥物的使用情況。第二部分就成大資訊室提供病患就醫資料庫,分析門診精神分裂症患者之就醫型態及可能之藥物順服性。並比較長期追踪患者及新個案就醫型態之異同。第三部分以問卷訪談方式,評估長期於門診追踪之精神分裂患者之藥物的態度、知識及順服性。

  2003年成大醫院精神分裂症病患治療處方模式,在786名病患中,有78%為單一抗精神病藥物的治療,以第一代抗精神病藥物(39.8%)為主,第二代抗精神病藥物的處方是增加的。在藥物劑量方面,大部分抗精神病藥物的處方劑量偏低於國外準則建議治療劑量範圍,有少部分的藥品甚至低於建議的治療劑量。在抗精神病藥物的多重用藥方面,抗精神病藥物合併使用比例,2003年22.1%合併使用抗精神病藥物較2001年的併用比例增加。併用時間超過2個月的人數約有14.5%,每位病患平均併用天數約6個月。二個第一代抗精神病藥物併用由2001年87%降低至2003年52%,取而代之的併用型態為第一代合併第二代抗精神病藥物。在併用其它精神藥物方面,高逹83.6%曾併用其它精神藥品,平均每位病患併用2.1種精神藥品。抗巴金森氏症藥物處方比例及使用劑量在單一長效針劑組及多重用藥的分組中為最高。曾經被處方benzodiazepine類藥品(包括失眠藥品及抗焦慮藥品)、情緒穩定劑及抗憂鬱藥品的人數比例分別為81%(52.8%+28.2%)、12.7%及11.7%。多重抗精神病藥物治療組於併用安眠藥品、抗焦慮藥品及抗巴金森氏症藥物的使用劑量高於單一抗精神病藥物治療組。

  病患服藥順性方面,2002至2003年精神分裂症病患成大醫院資料庫觀察發現,2002年在成大醫院精神科門診且2003年持續門診追踪的舊病患較2002年未曾在成大醫院精神科門診就診但2003年在門診追踪的新病患之回診天數(大於282天以上)及服用藥物持續性大於80%的人數比例高(33% vs 11%, p<0.05)。問卷訪視結果發現,病患對使用抗精神病藥物是持負面態度及明顯不足的使用藥物知識。

  評估精神分裂症治療發現有高比例會合併使用抗精神病藥物及其它精神藥物,所造成的藥物交互作用的安全性考量是值得重視。另外,本研究抗精神病藥物的使用劑量相較於國外使用劑量建議準則有偏現象,是否會影響療效?需要進一步研究。教育患者正確用藥態及知識,可幫助我們提供精神分裂症病患更有效、更安全的醫療照顧。
英文摘要 Abstract
 Background: Pharmacotherapy is an important management for patients with schizophrenia. Up to date, the prescribing pattern was affected by many factors which includes drug of choice, inconsistency of treatment guideline, patient’s condition, and physicians’ behavior etcetera. Schizophrenia is a kind of chronic illness that needs long-term antipsychotic treatment to control patients’ condition without getting worse and to prevent the risk of relapse. Statistical data have revealed that more than 50% outpatients behaved poor medication compliance and increased the risk of relapse. Hence, we aim to study the cause of poor medication compliance of patients with schizophrenia, and to seek therapeutic alliance strategies of improvement.

 Method: The prescribing patterns were investigated retrospectively by using the outpatient database of Psychiatry Department in the National Cheng-Kung University Hospital (NCKUH) from January 2003 to December 2003. For assessing patient compliance, we analysed whether there are differences between the long term outpatients and new outpatients regarding the duration of follow-up. Besides, we conducted the questionnaires and interview to evaluate medication compliance, attitude and knowledge in the long-term follow-up patients with schizophrenia.

 Results: Data of 786 patients with schizophrenia were used in this study. 78 percent of the patients received only one kind of antipsychotic, within which 313 patients (39.8%) were prescribed with the first generation antipsychotics (FGAs). The data also presented that the doses of most of antipsychotics were prescribed in the lower recommended range.

 Combination use of antipsychotics is increasing gradually. According to the study, in 2003, the use of combination antipsychotics was 22.1% and the mean of duration of combination use was 4.5months. The use of antipsychotic polypharmacy for more than 2 months were 14.5%, and the mean combination duration were about 6 months. In 2001, the rate of combination use of two FGAs was 87%, and was reduced to 52% in 2003. However, the combination of FGAs plus second generation antipsychotic (SGAs) was increased.

 In multiple psychotropic pharmacotherapy, 83.6% patients were prescribed with other psychotropic agents, and the mean of items in psychotropic agents was 2.1. The frequency of prescribing antiparkinson drug is highest in the depot antipsychotic group and polypharmacy group. Patients were prescribed 81% benzodiazepine, 12.7% mood stabilizer, and 11.7% antidepressants repectively. More doses of hypnotic, anxiolytic drug, and antiparkinson drug were prescribed in antipsychotic polypharmacy group than antipsychotic alone group.

 In the aspect of drug compliance, the statistical data have shown that the long-term follow-up outpatients have higher rate (>80%)than others. From the analysis of questionnaire data, in all, not only the patients in the oral group but also the injectable group presented negative attitude of medication and inadequate knowledge toward the usage of medication. .

 Conclusion: Nowadays, the trend of polypharmacy in combining antipsychotic and psychotropic agents was demonstrated high percentage in schizophrenia therapy. Consequently, more attentions should be dreqwn toward safety concerns due to potential drug-drug interaction. Furthermore, the education of accurate medication attitude and knowledge could help the patients receive more effective and safer medical care.
論文目次 目錄
中文摘要…………………………………………………………………I
英文摘要……………………………………………………………….III
誌謝……………………………………………………………………..V
目錄…………………………………………………………………….VI
表目錄………………………………………………………………….XI
圖目錄 ………………………………………………………………XIV
附錄…………………………………………………………………...XV
第一章 研究背景………………………………………………………..1
第二章 文獻回顧………………………………………………………..3
第一節 精神分裂症 3
1.1精神分裂症 3
1.2精神分裂的流行病學 3
1.3精神分裂症的病因 4
1.4精神分裂臨床表徵 6
第二節 精神分裂症治療 8
2.1藥物治療 8
2.1.1第一代抗精神病藥物 9
2.1.1.1藥理作用 12
2.1.1.2藥動學特性 12
2.1.1.3副作用 13
2.1.2第二代抗精神病藥物 15
2.1.2.1藥理作用 15
2.1.2.2藥物動力學特性 18
2.1.2.3 藥物的交互作用 21
2.1.2.4副作用 25
2.1.3長效針劑 27
2.1.3.1藥物動力學特性 27
2.2非藥物性治療 28
第三節 抗精神病藥物於精神分裂症病患之處方型態 30
3.1精神分裂症病患之抗精神病藥物使用情形 30
3.2單一抗精神病藥物治療 33
3.3精神分裂症病患之多重用藥 39
3.3.1抗精神病藥物多重用藥 40
3.3.1.1抗精神病藥物多重用藥使用 41
3.3.1.2抗精病藥物多重用藥的併用型態 41
3.3.2併用其它精神藥物治療 44
3.4治療劑量 46
3.5台灣的研究 50
3.6台灣抗精神病藥物的使用規範 50
第四節 精神分裂症病患之順服性 52
4.1藥物治療對精神分裂症患者之重要性 52
4.2影響精神分裂症病患順服性因素 52
4.3藥物順服性的測量方式 54
第三章 研究目的………………………………………………………55
第四章 研究方法………………………………………………………56
第一部分 抗精神病藥物之使用評估 56
第一節 研究設計 56
1.1研究類型 56
1.2研究藥品 56
1.3研究對象 60
1.4研究時間及研究方法 60
1.5研究工具 61
第二節 變項之定義 62
第三節 資料分析方法 64
第二部分 以資料庫分析精神分裂病患之順服性 65
第一節 研究設計 65
1.1研究類型 65
1.2研究對象 65
1.3研究時間及研究方法 65
第二節 變項之定義 66
第三節 資料分析方法 66
第三部分 以問卷記錄分析精神分裂病患之順服性 67
第一節 研究設計 67
1.1研究類型 67
1.2研究對象 67
1.3研究材料 67
第二節 資料分析方法 71
第五章 研究結果………………………………………………………73
第一部分 抗精神病藥物之使用評估 73
第一節 使用抗精神病藥物病患之基本資料 73


第二節 抗精神病藥物的處方及使用型態 75
2.1藥品之總處方天數分佈情形 75
2.2依抗精神病藥品分類之處方次數 76
2.3各抗精神病藥物之處方次數 77
2.4各抗精神病藥物之處方劑量 80
2.5使用單一種類抗精神病藥物之病患特性 81
2.6性別與處方型態 82
2.7抗精神病藥物合併使用情形 82
2.8相關精神藥物合併使用情形 88
第二部分 以資料庫分析精神分裂病患之順服性 94
第三部分 以問卷記錄方式分析精神分裂病患之順服性 97
1.1研究對象的基本資料 97
1.2病患對抗精神病藥物之藥物態度 100
1.3病患對抗精神病藥物之藥物知識 105
1.4病患對抗精神病藥物之治療行為 110
第六章 討論…………………………………………………………..115
第一節 抗精神病藥物之使用評估 115
1.1抗精神病藥物使用比例 115
1.2抗精神病藥物使用劑量 116
1.3抗精神病藥物的合併使用 119
1.4其它精神藥物的合併使用 123
第二節 以資料庫分析之精神分裂病患之順服性 126
第三節 以問卷訪談記錄分析之精神分裂病患之順服性 127


第七章 研究限制……………………………………………………..130
第八章 結論與建議…………………………………………………..131
第一節 結論 131
第二節 建議 133
參考文獻………………………………………………………………134
附錄表…………………………………………………………………145


表目錄
表1-1 精神分裂症五大臨床表徵 7
表2-1 第一代口服抗精神病藥物 11
表2-2 腦中多巴胺路徑及功能 12
表2-3 體外所測得第二代抗精神病藥物受體結合親和力(nmol/L) 18
表2-4 第二代口服抗精神病藥物 20
表2-5 第二代抗精神病藥物和CYP酵素誘導劑或抑制劑併用之血中濃度變化 24
表2-6 長效肌肉注射抗精神病藥物的藥物動力學特性 28
表3-1 第一代及第二代抗精神病藥物使用比例 33
表3-2 成大醫院90-93年使用抗精神病用藥於各科之分佈狀況 35
表3-3 成大醫院90-93年抗精神病用藥耗用量於各科之分佈狀況 36
表3-4 成大醫院90-93年使用抗精神病藥物的病患診斷排名 37
表3-5 多重用藥之可能原因與可能危險因素 39
表3-6 各個國家多重用藥的比例 41
表3-7 抗精神病藥物使用劑量 49
表4-1 抗精神病藥品分類 57
表4-2 精神藥品分類(1) 58
表4-2 精神藥品分類(2) 59
表5-1 精神科門診病患使用抗神病藥物之適應症排名 74
表5-2 92年使用抗精神病藥物之病患資料 74
表5-3 92年抗精神病藥物處方天數分佈 75
表5-4 依藥品分類佔總藥品處方次數之比例 76

表5-5 92年精神分裂病患使用抗精神病藥物處方比例及耗用量 78
表5-6 92年抗精神病藥物於精神分裂新、舊病患處方比例 79
表5-7 各抗精神病藥品之平均醫師處方劑量 80
表5-8 第一代、第二代及長效針劑抗精神病藥物使用之病患特質 81
表5-9 性別與處方型態 82
表5-10 90年和92年精神分裂症病患抗精神病藥品多重用藥使用情況 84
表5-11 90年和92年精神分裂症病患之抗精神病藥品的併用型態比例 84
表5-12 90年和92年精神分裂症病患最常見的藥物組合型態 85
表5-13 長期追踪之精神分裂病患單一使用長效針劑或併用其它口服抗精神病藥物之病患特質比較 87
表5-14 使用第一代、第二代及長效針劑抗精神病藥品之病患併用相關精神藥品之處方比例 90
表5-15 使用第一代、第二代及長效針劑抗精神病藥品之病患併用相關精神藥品之使用劑量 91
表5-16 單一及多重使用抗精神病藥物 併用其它精神藥物之病患特性比較 92
表5-17 併用各個精神藥物處方比例 93
表5-18 新、舊病患連續性分佈 95
表5-19 醫師處方抗精神病藥物之分布 97
表5-20-1 研究對象基本資料 98
表5-20-2 研究對象基本資料 99
表5-21-1 病患對抗精神病藥物的態度與影響因素之相關性分析 101
表5-21-2 病患對抗精神病藥物的態度與影響因素之相關性分析 102
表5-22 研究對象對於抗精神病藥物態度量表 103
表5-23 研究對象對於各向度抗精神病藥物態度量表 104
表5-24 預測研究對象對藥物依醫囑態度之逐步迴歸分析 104
表5-25 研究對象的疾病歸因 107
表5-26 自覺療法的有效性 107
表5-27 病患對抗精神病藥物之處方及藥效認知與影響因素相關性分析 108
表5-28 研究對象對於處方及藥效的認知 109
表5-29 預測研究對象對處方及藥效認知之逐步迴歸分析 109
表5-30 研究對象服藥行為 111
表5-31 研究對象規則/未規則服用藥物原因 112
表5-32-1 研究對象藥物副作用嚴重程度 113
表5-32-2 研究對象藥物副作用嚴重程度 114
表5-33 研究對象對副作用處置方式 114
表6-1 抗精神病藥物使用劑量 118
表6-2 本研究與瑞典及紐西蘭抗精神病藥物使用劑量比較 119
表6-3 抗精神病藥物併用型態分佈研究比較 122
表6-4 抗精神病藥物和精神藥物的藥物交互作用 125


圖表錄

圖2-1 腦內血清胺調節多巴胺釋放機轉 17
圖3-1 90-93年成大醫院精神科門診 之精神分裂症病患使用抗精神病藥物的處方比例 38
圖4-1 多重用藥定義 63
圖5-1 92年不同病人別精神分裂症病患之 各抗精神病藥物分類處方比例 77
圖5-2 90年和92年精神分裂症病患抗精神病藥品併用型態比例 85
圖5-3 持續處方抗精神病藥物的比例和時間 94
圖5-4 總處方天數與連續性的分布 96



附錄
附錄一 『精神分裂症的藥物治療之相關量表』同意書 145
附錄二 受訪者同意書及受訪問卷 146
附錄三 簡短精神症狀評量表 154
附錄四 精神分裂症藥物衛教手冊 156
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系統識別號 U0026-0812200912023849
論文名稱(中文) 不同加工條件下劃切現象之分析
論文名稱(英文) The Analysis of Scribing Phenomenon under Different Cutting Parameters
校院名稱 成功大學
系所名稱(中) 機械工程學系碩博士班
系所名稱(英) Department of Mechanical Engineering
學年度 94
學期 2
出版年 95
研究生(中文) 彭馨寬
學號 n1693460
學位類別 碩士
語文別 中文
口試日期 2006-07-06
論文頁數 66頁
口試委員 指導教授-王俊志
口試委員-李榮顯
口試委員-李偉賢
關鍵字(中) 比切削能
摩擦係數
後傾角
劃切
關鍵字(英) friction coefficient
specific energy
rake angle
scribing
學科別分類
中文摘要 本文探討劃切製程之刀具幾何、後傾角、材料與切削速度對劃切力、比切削能和表面形貌的影響。
首先分析後傾角對刀具切入幾何的影響,在同樣切深下不同後傾角影響刀具接觸材料的面積造成垂直比切削係數隨後傾角改變。並且由實驗觀察到在稜線擠壓劃切,後傾角越小,比切削能越大;刀面推刮劃切時,後傾角越小時,比切削能則越小。
分離切削力中的摩擦力後,比切削能對後傾角的變化趨勢仍然與未分離前相同。經由無摩擦影響的比切削能可觀察到在劃切延性材料時低切深有較高比切削能的尺寸效應,在劃切硬脆材料時因切削機制轉換造成比切削能有降低的趨勢。由實驗的摩擦係數與刀具接觸材料的面積可得到接觸面積越小,摩擦係數越低,並依此來判斷最佳的加工後傾角。並觀察到隨著切削速度提昇,比切削能有降低的趨勢且溝槽幾何較為完整。


英文摘要 This thesis will discuss the influences of scribing force, specific energy, and surface geometry on the tool geometry, rake angle, material, and cutting velocity of scribing process.
The influences of cutting geometry on the rake angle are analyzed to observe the variation of the area contacted between tool flank and machined surface for different rake angles in the same cutting depth, and radial cutting coefficient changed with the rake angle. The results of experiments show that scribing leading by edge, the smaller the rake angle is, the greater the specific energy is. While scribing leading by face, the smaller the rake angle is, the smaller the specific energy is.
After separating friction from cutting force, the variation trend of the rake angle and the specific energy which does not consider friction is the same with the case that friction is considered. By observing the specific energy which does not consider friction, size effect makes higher specific energy in lower cutting depth in scribing ductile material. While scribing brittle material, the transformation of cutting mechanism makes the specific energy become lower. From relationship between friction coefficient and the material area contacted with tool, the smaller the area is, the lower the friction coefficient is. This phenomenon can be used to decide the optimal rake angle of cut. It also can be observed that the promotion of the cutting velocity makes specific energy is reduced and groove geometry is more complete.


論文目次 中文摘要..............................I
Abstract.............................II
誌謝................................III
總目錄...............................IV
表目錄..............................VII
圖目錄.............................VIII
符號說明............................XIV
第一章 緒論..........................1
1.1 前言..............................1
1.2研究動機與目的.....................2
1.3 文獻回顧..........................2
1.3.1延性材料劃切力...................2
1.3.2脆性材料劃切力...................4
1.4研究範疇及論文架構.................5
第二章 劃切加工切削力模式.............7
2.1切削力與比切削能之介紹.............7
2.1.1 正交切削........................7
2.1.2 後傾角改變的影響................9
2.1.3斜交切削........................10
2.1.4 比切削能.......................11
2.1.5 臨界切深.......................11
2.2 切削幾何與加工條件..............13
2.2.1 各方向之面積投影量變化.........13
2.2.2 後傾角與切削接觸面積之關係.....15
2.3 摩擦力之分離.....................18
第三章 劃切實驗......................22
3.1 實驗目的.........................22
3.2 實驗設備.........................23
3.3 三軸力量感測平台校正.............26
3.4 實驗參數.........................30
3.5 刀具切削幾何與後傾角實驗方法.....32
3.6變切速實驗........................32
第四章 實驗結果與討論................34
4.1 實驗結...........................34
4.1.1 實驗參數與對實驗結果之影響.....34
4.1.2摩擦力分離下比切削能與摩擦係數..44
4.1.3 切削速度對比切削能之影響.......56
4.2 討論.............................59
第五章 結論與建議....................61
5.1 結論.............................61
5.2 建議.............................62
參考文獻.............................64
自述.................................66
參考文獻 1. E. Budak, Y. Altintas and E. J. A. Armarego, “Prediction of Milling Force Coefficients from Orthogonal Cutting Data,” Transaction of ASME, 118, pp. 216-224, 1996.
2. T. Schaller, L. Bohn, J. Mayer and K. Schubert, ” Microstructure groove with a width of less than 50μm cut with ground hard metal micro end mills,” Precision Engineering, 23, pp. 229-235, 1999.
3. N. Moronuki, Y. Liang and Y. Furukawa, ”Experiments on the effect of material properties on microcutting processes,” Butterworth-Heinemann, 16, pp. 124-131, 1994.
4. C. Friedrich and M, Vasile, “ Development of the micro milling process for high aspect ratio microstructures,“ Journal of Mechanical Engineering Material Science, 5(1), pp.33-38, 1996.
5. Z. Lu and T. Yoneyama, “Micro cutting in the micro lathe turning system,” International Journal of Machine Tools & Manufacture, 39, pp.1171-1193, 1999.
6. N. Ikawa, R. Fonaldson, R. Komanduri, W. Konig, P. Mckeown and T. Moriwaki,“ Ultraprecision metal cutting—The past, the present, and the future,“ Annals of the CIRP, 40(2), pp. 587–595, 1991
7. http://www.compoundsemiconductor.net/articles/magazine
/10/3/4/1
8. M. Zhou, B. K. A. Ngoi, Z. W. Zhong and C. S. Chin, “Brittle-Ductile Transition in Diamond Cutting of Silicon Single Crystals,“ materials and manufacturing processes, 16(4), pp. 447-460, 2001.
9. D. A. Lucca, P. Chou and R. J. Hocken, “Effect of Tool Edge Geometry on the Nanometric Cutting of Ge,” Annals of the CIRP, 47, pp. 475-478, 1998.
10. R. A. Allaire and J. C. Lapp, “Scoring of AMLCD Glass,“ Corning Incorporated, Technical Information Paper, 2001.
11. 陳貴榮, 陳孟群, 陳志明等, “影響切割裂片品質的因素探討, ”機械工業雜誌, 258, pp. 236-247, 2004.
12. W. J. Eneres, R. E. DeVor and S. G. Kapoor, ”A Dual-Mechanism Approach to the Prediction of Machining Forces,“ ASME Journal of Engineering for Industry, 117, pp.1-22, 1975.
13. R. Komanduri, N. Chandrasekaran and L. M. Raff, “Effect of Tool Geometry in Nanometric Cutting: A Molecular Dynamics Simulation Approach,“ wear, 219, pp. 84-97, 1998.
14. V. Weiss, “Application of Fracture Mechanical to Design,” Sagamore Army Materials Research Conference Proceedings, pp.1-22, 1975.
15. T. G. Bifano, T.A. Dow and R. D. Scattergood, “Ductile-Regime Grinding, Anew Technology for Machining Brittle Materials,” ASME Journal of Engineering for Industry, Vol.113, pp.184-189, 1991.
16. F. Z. Fang and L .J. Chen, “Ultra-Precision Cutting for ZKN7 Glass,” Annals of the CIRP, 49, pp.17-20, 2000.
17. 陳啟宗, “機械性質與加工條件對硬脆材料劃切加工之影響,” 國立成功大學機械工程研究所, pp.57-65, 2004.
18. J. J. Wang and Y. Y. Liao, “Estimating Critical Depth of Cut and Tool Factor for a Mechanical Scribing Process,” Journal of the Chinese Society of Mechanical Engineers, 27, pp. 153-157, 2006.

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系統識別號 U0026-0812200913484669
論文名稱(中文) 制度發展---以我國全民健康保險制度發展為例
論文名稱(英文) The institutional Development---Regard Development in Taiwan National Health Insurance as the Example
校院名稱 成功大學
系所名稱(中) 政治經濟學研究所
系所名稱(英) Graduate Institute of Political Economy
學年度 95
學期 2
出版年 96
研究生(中文) 張俐雯
學號 U1694101
學位類別 碩士
語文別 中文
口試日期 2007-06-14
論文頁數 170頁
口試委員 指導教授-王慶輝
口試委員-劉亞明
口試委員-黃世杰
關鍵字(中) 健保支付制度
新制度主義
醫藥分業政策
全民健康保險制度
關鍵字(英) National Health Insurance (NHI)
New Institutionalism
National Health Insurance (NHI) payment system
Separation of Prescribing & Dispensing (SPD) pol
學科別分類
中文摘要 政府於民國84年 所開辦的全民健康保險,使全體國民皆有平等機會參與並滿足全民對健康的需求。大致而言,全民健康保險政策不僅影響著國民的生活,更為營業額超過三千億之國營事業,使全民健康保險之議題長期以來一直被社會各界所關注與討論。我國全民健康保險制度之實施,將當時約40%大部分為14歲以下的兒童及青少年和65歲以上老人之沒有納保人口涵蓋在健康保險體系的保護傘之內。依此可見,全民健康保險政策所涵蓋的人口數,與其所動用的社會資源可堪稱為影響政府甚鉅的一項政策作為。於全民健康保險開辦初期已約有六成五民眾滿意全民健保,截至民國93年底全民健保的民眾滿意程度更高達八成,可謂成效卓越。但無可否認地,在健保高度滿意表面下,並不足以代表全民健保制度即可高枕無憂,反之,全民健保制度仍存在相當可供改革之處。綜觀全民健保開始實施之初,實際上醫界、政府等各界認為全民健保是在政府急於開辦壓力之下倉促上路,導致許多政策與制度之實施,缺乏長期宣導,相關措施與社會的共識度無法一致,全民健康保屢傳財務失衡的危機,而全民健保是否能永續經營,有賴於健保財務能保持穩定,因以如何挽救全民健保之財務成為政府醫療施政的重要課題。另一方面,高度醫療費用支出中,藥費支出比例始終居高不下亦為影響醫療費用支出不斷攀升之一大主因。
是以,本研究以新制度主義理論架構加以分析醫藥分業與支付制度之發展,民國86年醫藥分業政策實施,關於支付制度的改革則有宏觀層次上,總額支付制度的採行與微觀層次上,由「論量計酬支付制」逐步在國內實施「論病例計酬支付制」之努力。
英文摘要 The National Health Insurance initiated by government in 1995 enables all nationals to have an equal chance to join and to meet the demand of health. As a whole, the policy on NHI not only influences the standard of living deeply, but has been paid attention and discussed in public on the issue that focuses on state-run business with turnover more than 300 billions for a period of time. The enforcement of NHI system is to add those below 14 and above 65 without the protection of health care to the umbrella of health insurance system. According to this, the policy of NHI ranging from the population to social resources is one policy that have a great impact on government.About 65% are satisfied with NHI in the beginning of initiation, with up to 80% satisfied in late 2004. But it can’t be denied that being highly satisfied with NHI isn’t good enough to represent great effectiveness. On the contrary, the system of NHI still has some space to reform elsewhere.Practically, any sector such as medical field or government all thought that the enforcement of NHI which government initiated is on a rush way under pressure. Hence, many policies and system’s enforcement about related measure failed to have consensus with society without consecutive advertisement in public and resulted in financial crisis. So it depends on the stability of finance to see if the NHI can run everlastingly. And how to save NHI to achieve the balance of finance for government is becoming the first topic on medical implement. On the other hand, the ratio of medicine expenditure among high medical expense is the first major cause that resulted in the rise on expenditure of medical expense.
This research with the new institutionalism analyze the development of National Health Insurance,Separation of Prescribing & Dispensing and National Health Insurance payment system. In 1997 the SPD policy implement, concerning pay institutional reform to then include macroscopic , Global Budget System adoption and tiny view , is carried out effort fee-for-service payment system to DRG payment system.
論文目次 中文摘要 I
ABSTRACT II
致謝 III
目次 IV
表目錄 VI
圖目錄 VII
第一章 緒論 1
第一節 研究背景 1
第二節 研究動機與目的 3
第三節 研究問題 8
第四節 文獻回顧 10
第五節 研究方法、章節安排 21
第二章 理論架構 23
第一節 新制度主義理論架構 23
第二節 研究架構 31
第三章 我國全民健康保險制度之發展 32
第一節 全民健保實施前-社會保險制度之發展 32
第二節 全民健保實施前的現實問題與環境 41
第三節 全民健康保險制度的成立 53
第四章 我國全民健康保險制度之變遷 72
第一節 全民健康保險之制度變遷 72
第二節 健康保險支付制度之制度變遷 91
第三節 醫藥分業之制度變遷 113
第五章 新制度主義與全民健康保險制度 125
第一節 新制度主義與全民健康保險制度的形成 125
第二節 新制度主義與全民健康保險支付制度變遷 131
第三節 新制度主義與醫藥分業制度變遷 135
第四節 小結 139
第六章 結論與建議 142
第一節 研究發現 142
第二節 政策建議 146
附錄一 我國社會主要保險之發展 159
附錄二 全民健康保險大事記 160
附錄三 衛生署醫藥分業政策大事紀 170
參考文獻 壹、中文部份
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二、期刊、雜誌:
工商雜誌編輯部特別企畫,<全民健保工商界有話說>,《工商雜誌》,(1994 年,7月),頁22-53。
林本炫:<全民健保法審議過程的觀察>,《國家政策雙週刊》,第92期(1994年),頁10-11。
林志鴻、呂建德:<社會團體對於全民健保政策參與管道與能力之探討---以總額支付制度運作為例>,《政大法學評論》,第76期(2003年12月),頁159-210。
林欽法:<總額支付制度之因應>,《台灣醫界》,第9卷第6期(2005年11月),頁798-802。
林國民:<國家與醫療專業權力:台灣醫療保險體系費用支付制度社會學分析>,《台灣社會學研究》,第1期(1997年12月),頁77-136。
林秀美、黃維民、莊士杰:<台灣全民健保制度下論病例計酬對醫師診療行為之影響>,2002年管理創新與新願景研討會。
李玉春:<全民健保支付制度—實施現況與改革方向建議>,《政策月刊》,第35期,(1998年),頁14-16。
李卓倫、吳凱勳:<公勞保診療費用支付制度沿革與醫療費用支出關係>,《公共衛生》,第17卷第2期,(2000年7月),頁121-135。
呂育誠:<公共組織變革的另類思維:歷史制度主義觀點的啟示>,《公共行政學報》,第6期(2002年),頁1-28。
吳肖琪:〈全民健保推動之源始〉,《研考雙月刊》,第24卷第1期(2000年 2 月),頁56-62。
吳運東:<健保支付制度下醫療品質之檢討與改革之芻議>,《台灣醫界》,第43卷第2期(2000年2月),頁10-11。
邱永仁: <從美國DRGs制度談台灣DRGs制度之實施>,《台灣醫界》,第42卷第2期(1999年 2月),頁50-52。
<2002年健保問題總檢討>,《台灣醫界》,第46卷第2期(2003年2月),頁39-41。
<健保轉診制度之研析>,《醫事廣場》,第48卷第8期(2005年8月),頁43-47。
周麗芳、陳曾基:<由經濟政策觀點檢視全民健保總額支付制度>,《台灣醫界》,第44卷第1期(2001年1月),頁45-50。
胡婉玲:<論歷史制度主義的制度變遷理論>,《新世紀智庫論壇》,第16期(2001年12月),頁86-95。
紀櫻珍、林裕能、王美玉、吳振龍。<臺北市立醫院自主管理之初步評估>,《北市醫學雜誌》,第2 卷第1 期(2005 年1 月),頁61-70。
莊文忠:<制度的研究:新制度論觀點的比較與後現代制度論的發展>,《理論與政策》,第16卷第4期(2003),頁15-44。
陳敦源:<新制度論的範圍與方法:一個理性選擇觀點的方法論解釋>,《行政暨政策學報》,第3期(2001),頁129-184。
張育嘉、黎伊帆、汪芳國、鄭守夏:<全民健保總額預算制度之初步影響評估:以牙醫與西醫基層為例>,《台灣公共衛生雜誌》,第25卷第2期,(2006年4月),頁152-162。
黃琡雅:<李主任委員玉春政策專訪---台灣健保支付制度之改革>,《醫院中華民國醫院協會雜誌》,第36卷第5期(2003年10月),頁1-3。
黃明和:<全民健保改革謅議>,《國策期刊》,第17期,(2001年5月),頁5-7。
傅立業:<台灣社會保險制度的社會控制本質>,《台灣社會研究季刊》,第15期(1993年11月),頁39-64。
<臺灣與美國全民健保政策發展的政治經濟分析>,載鄭麗嬌主編《中西社會福利政策與制度》,台北:中央研究院歐美研究所,(1995 年),頁31-72。
楊漢湶:<全民健康保險總額支付制度之實施背景及推展>,《台灣醫界》,第40卷第7期(1997年7月),頁10-12。
楊文惠、黃松共、楊宜璋:<醫藥分業後民眾選擇藥局調劑之決策因素研究-以台北市為例>,《公共衛生》,第27捲第4期(2001年1月),頁227-244。
葉德豐、楊銘欽、王俊文、張睿詒:<基層醫師對實施總額預算初期成效之評價---以健保中區分局轄區為例>,《台灣公共衛生雜誌》,第24卷第6期(2005年12月),頁539-547。
葉德豐、王俊文:<西醫基層總額支付制度實施前後費用趨勢之研究---以中部四縣市為例>,《醫務管理期刊》,第3卷第4期(2002年12月),頁11-29。
鄭文輝: <從財源規劃探討全民健保財務問題>,《研考雙週刊》,第18 卷,第1期(1994年2月),頁39-59。
劉淑惠:<行政權與立法權的合理互動關係>,《國家政策雙週刊》,第85期(1994年),頁28-31。
劉見祥:<從立法委員選舉看我國全民健保法修正>,《社會建設》,第93期(1996年),頁41-48。
賴美淑:<全民健保財務收支現況與未來展望>,《社區發展季刊》,第88期(1999年12月),頁68-76。
韓揆:<診斷組合在臺推行問題(上)---DRGs之支付精神,支付邏輯及侷限>,《醫務管理期刊》,第6卷第1期(2005年3月),頁1-19。
韓揆:診斷組合在臺推行問題(下)---<論病例計酬及實施準備>,《醫務管理期刊》,第6卷第1期(2005年3月),頁20-36。
韓幸紋:<由德英荷三國之經驗剖析我國健保總額之採行>,《保險實務與制 度》,第2卷第1期(2003年3月),頁83-98。
謝啟瑞、林建甫、游慧光:<台灣醫療保健支出成長原因的探討>,《人文及社會科學集刊》,第10卷第1期(1998年),頁1-32。
謝俊義:<新制度主義的發展與展望>,《中國行政》,第8期(2000),頁1-26。
三、論文:
林洸民:《新制度主義的迷思:我國全民健康保險制度之分析》,東海大學政治學
系碩士論文,2002年。
林鳳玉:《加重部分負擔對區域級以上醫院西醫門急診利用之影響─以健保局東區分局被保險人為例》,國立東華大學企業管理學系,2004年6月。
洪明皇:《全民健保新制部分負擔對不同社會群體影響之探討》,國立政治大學財政學系碩士論文,2001年。
胡紀光:《全民健康保險藥品給付制度方案選擇之研究》,國立交通大學高階主管管理學程碩士班碩士論文,2003年。
許銘恭:《基層醫療實施論人計酬支付制度之可行性探討》,台北醫學大學醫務管理學系碩士論文,2003年7月。
許航瑞:《我國全民健保醫療支出問題的政經分析:一個新制度主義的觀點》,國立成功大學政治經濟學研究所碩士論文,2001年12月。
許銘恭:《基層醫療實施論人計酬支付制度之可行性探討》,臺北醫學大學醫務管理學系碩士論文,2003年。
許國川:《我國全民健保總額支付制度之研究 ─實施現況與檢討》,逢甲大學經營管理碩士在職專班碩士論文,2005年。
常壽康:《全民健保牙醫總額支付制度之評估與未來應用》,淡江大學保險學系保險經營碩士班碩士論文,2002年。
張沅嬪:《醫院實施總額支付制之探討》,東海大學企業管理學系碩士論文,2001年。
陳敏和:《國家在全民健康保險政策形成與轉型過程中所扮演角色之探討》,國立暨南國際大學社會政策與社會工作系碩士論文,1998年。
曾幼筑:《牙醫師推動總額支付制度集體行動之研究》,國立陽明大學衛生福利研究所碩士論文,2001年2月。
黃品憲:《全民健保實行總額支付制度之探討─以加拿大與台灣之施行現況為例》,臺中健康暨管理學院國際企業研究所碩士論文,2004年。
黃品嘉:《全民健保支付制度演進與醫院生產效率》,國立中央大學產業經濟研究所碩士論文,2006年6月。
黃品憲:《全民健保實行總額支付制度之探討─以加拿大與台灣之施行現況為例》,台中健康暨管理學院國際企業研究所碩士論文,2004年。
葉蓉茹:《全民健保問題的重構與政策變遷》,東海大學公共行政研究所碩士論文,1998年。
鄒篤麟:《我國黨政關係之研究:以國民黨為例》,國立政治大學政治研究所博士論文,1993年。
鄭瓊秋:《公共選擇與投票行為理論之研究》,國立政治大學財政研究所碩士論文,1992年。
蔡富櫻:《我國全民健康保險支出政策變遷之探討:以醫院卓越計畫為例》,國立東華大學公共行政研究所碩士論文,2006年。
鄒佩玲:《全民健康保險醫療費用支付制度與醫療專業代理問題之研究》,國立政治大學公共行政研究所碩士論文,2004年7月。
歐崇亞:《新制度主義與公共組織分析》,私立東海大學公共行政研究所碩士論文,1997年6月。
劉宜君:《我國全民健康保險政策之執行評估-國家機關、政策網絡與財務管控能力之分析》,國立台北大學公共行政暨政策學研究所博士論文,2000年。
劉慧心:《牙醫師對推動總額支付制度集體行動之研究》,國立陽明大學衛生福利研究所碩士論文,1999年。
劉玉婷:《健保醫療資源區域分配之公平性》,高雄第一科技大學風險管理與保險系碩士論文,2001年6月。
劉淑惠:《黨國體制下全民健康保險政策的政治分析(1994~2000)》,國立臺灣大學政治學研究所碩士論文,2002年。
四、官方文獻:
黃文鴻:<全民健保藥品給付範圍及藥價基準之研究>,(台北:行政院經建會委託研究計畫,1990年)。
全民健康保險制度規劃技術報告,(台北:經建會都市及住宅發展處,全民健康保險研究計畫專案小組,1990年)。
行政院經濟建設委員會:<全民健康保險制度規劃報告>,(台北:行政院經濟建設委員會,1990a)。
行政院經濟建設委員會:<全民健康保險制度規劃技術報告>,(台北:行政院經濟建設委員會,1990b)。
行政院衛生署:<國民醫療保健支出>,(台北市行政院衛生署,1999a)。
行政院衛生署:<公共衛生年報>,(台北市行政院衛生署,1999b)。
行政院衛生署委託研究計畫:陳孝平:<全民健康保險財務責任制度>,(台北市行政院衛生署,1992年)。
行政院研究發展考核委員會:<我國社會保險制度現況分析及整合問題>,(台
北:行政機關出版品,1993年)。
行政院衛生署八十六年度委託研究計畫:<全民健康保險診療報酬預估支付制度之研究(第四年度)>,(藍忠孚,1997)。
行政院衛生署:<牙醫門診總額支付制度試辦計畫>,(台北市行政院衛生署,1998年)。
行政院衛生署:<衛生統計重要指標>,(台北市行政院衛生署,2000年)。
行政院衛生署:《二代健保規劃叢書-全民健保改革綜論》,(台北市行政院衛生署,2004年)。
行政院衛生署:《二代健保規劃叢書-全民健保醫療資源配置與合理使用》,(台
北市行政院衛生署,2004年)。
行政院衛生署:《二代健保規劃叢書-全民健保組織體制改革規劃-公共行政暨政策的觀點 》,(台北市行政院衛生署,2004年)。
行政院衛生署:<全民健康保險實施二年評估報告>,(台北市行政院衛生署,2004年)。
四、報紙:
《中央日報》,民國82年10月至民國84年1月。
《中時晚報》,民國82年10月至民國84年1月。
《聯合晚報》,民國82年10月至民國84年1月。
《聯合晚報》,民國89年5月9日,第七版。
《民生報》,民國90年10月3日。
五、網站:
林雨靜:<何謂「合理門診量」>(2001年12月)。網址:
http://www.npf.org.tw/PUBLICATION/SS/090/SS-B-090-002.htm(瀏 覽日期:2007年4月28日)。
中央健康保險局:〈全民健康保險統計動向2003年〉(2005年4月)。網址:
http://www.nhi.gov.tw/webdata/webdata.asp?menu=1&menu_id=4&webdata_id=815(瀏覽日期:2006年11月23日)。
中央健康保險局:〈健康局簡介〉(2006年1月)。網址:
http://www.nhi.gov.tw/webdata/webdata.asp?menu=1&menu_id=3&webdata_id=1159(瀏覽日期:2006年11月23日)。
中央健康保險局:〈民眾服務-最新健保數據〉(2006年8月)。網址:
http://www.nhi.gov.tw/webdata/webdata.asp?menu=1&menu_id=4&webdata_id=805(瀏覽日期:2006年11月28日)。
洪素卿:<一代健保費率 明年將漲至5.28%>,《自由電子報》,(2006年5月4日)。網址:http://www.libertytimes.com.tw/2006/new/may/4/today-life7.htm(瀏覽日期:2006年12月5日)。
劉在銓:<全民健保的成就與困境>(2005年1月)。網址:
http://tsd.social.ntu.edu.tw/NHIachievementandlimit.pdf(瀏覽日期:2006年11月24日)。
臺灣年鑑:<全民健保大事紀>,(2006年)。網址:
http://www.gov.tw/EBOOKS/TWANNUAL/show_book.php?path=8_009_ 004(瀏覽日期:2006年12月22日)。
全民健康保險「藥價差」問題Q&A,(2006年5月3日)。網址: http://72.14.253.104/search?q=cache:h1Cftt8s6BYJ:www.nhi.gov.tw/information/second/files/95%E5%B9%B4%E8%97%A5%E5%83%B9%E5%B7%AE%E8%AD%B0%E9%A1%8CQA-950503.doc+%E8%97%A5%E5%83%B9%E9%BB%91%E6%B4%9E&hl=zh-TW&ct=clnk&cd=4&gl=tw&lr=lang_zh-TW(瀏覽日期:2007年4月22日)。
衛生署公告:<西醫診所用藥品質及安全提升兩年方案>,網址:http://www.chma.org.tw/phpBB2/viewtopic.php?p=4832&sid=743cc1abe785ebc037a0a68a8d2957d8(瀏覽日期:2007年4月27日)。
貳、英文部分
B. Guy Peters, Institutional Theory in political Science—The New Institutionalism (New York: Pinter Press, 1999).
Cheng, P.W.H and Su, J.R. “The Incidence of Expenditures and Revenues in Taiwan’s National Health Insurance, ”(Taipei International Conference on Health Economic, Taipei, March , 1999).
Collier Ruth B., and David Collier, Shaping the Political Arena. Princeton.(NJ: Princeton University Press, 1991).
Downs, Anthony. At Economic Theory of Democracy. (New York, Happer and Row, 1957)
Douglass C. North, Institutions, Institutional Change and Economic Performance, (Cambridge: Cambridge University Press, 1990).
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Hoffmeyer, U.K. and McCarthy, T.R. Financing Health Care. (Dordrecht, Netherlands: Kluwer Academic Publishers, 1996).
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Hu, T.W. and Hung Y.Y., “Health Care Reform in Taiwan and U.S. : What We Can Learn from Each Other, ”(Keynote Address, Taipei International Conference on Health Economic, Taipei, March, 1999 ).
Hu, T.W. and Heish, C.R. “An Economic Analysis of Health Care Reform in Taiwan,”(第四屆梁國樹教授紀念學術研討會,台大經濟系,臺北,1999年) 。
Hall, P. A. and C.R. Taylor “Political Science and The Three New Institutionalism,” Political Studies, No.45, 1996, pp.936-957.
Immergut, Ellen M.,“The Theoretical Core of the New Institutionalism.” Politics and Society, Vol. 26, 1998, pp.5-34.
Junko Kato, “Review Article: Institutions and Rationality in Politics—Three Varieties of Neo-Institutionalists,” British Journal of Political Science, Vol. 26,1996,pp.553-582.
Kranser, Stephen D. “Approaches to The State: Alternative Conceptions and Historical Dynamics,” Comparative Politics, No.16, 1984, pp.223-246.
Koeble, Thomas A.,“The New Institutionalism in Political Science and Sociology.” Comparative Politics, Vol.27, 1995, pp. 231-245.
Kathleen Thelen, “Historical Institutionalism in Comparative Politics,” Annual Review of Political Science, Vol. 2, June 1999, pp. 369-404.
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Moe, Terry, “Power and Political Institution, ” paper presented at the Conference on Crafting and Operating Institution, Yalu University, New Haven.
Paul J. DiMaggio, and Walter W. Powell, The New Institutionalism In Organizational Analysis. (Chicago: the University of Chicago Press, 1991).
Pierson, Paul, “The Path to European Integration: A Historical Institutionalist Analysis.” Comparative Political Studies, Vol. 29, 1996, pp.123-163.
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------------------------------------------------------------------------ 第 7 筆 ---------------------------------------------------------------------
系統識別號 U0026-0812200913494362
論文名稱(中文) 心房顫動病患使用抗血栓劑之處方型態分析
論文名稱(英文) Prescribing pattern of antithrombotic therapy in patients with atrial fibrillation
校院名稱 成功大學
系所名稱(中) 臨床藥學研究所
系所名稱(英) Institute of Clinical Pharmacy
學年度 95
學期 2
出版年 96
研究生(中文) 鄭名惠
學號 s6694102
學位類別 碩士
語文別 中文
口試日期 2007-06-20
論文頁數 184頁
口試委員 口試委員-林志勝
指導教授-高雅慧
指導教授-林立人
口試委員-羅傳堯
指導教授-戴淑華
關鍵字(中) 中風
抗凝血劑
抗血栓劑
健保資料庫
處方型態
心房顫動
關鍵字(英) prescribing pattern
stroke
atrial fibrillation
antithrombotic therapy
學科別分類
中文摘要 研究背景
雖然國際準則建議心房顫動病患中具高度中風危險性的患者應使用warfarin作為預防,但各國調查warfarin的使用率仍然偏低。本研究的目的為:研究臺灣地區心房顫動病患使用抗血栓劑與ACC/AHA/ ESC心房顫動準則(2001)建議之一致性,並找出影響心房顫動患者處方抗血栓劑的因子。

研究方法
本研究納入全民健康保險資料庫2003年7月1日至2004年6月30日期間,門、住診曾經出現兩次「427.31」診斷碼的心房顫動病患,分析其抗血栓劑的使用情形,並利用單變項分析及邏輯複回歸分析找出影響與準則的一致性以及抗血栓劑處方的因子。

研究結果
研究最終納入39541人,其中90%的患者為高度中風危險性以上;抗血栓劑的使用與ACC/AHA/ESC(2001)準則的一致性僅24.7%,即使扣除有出血危險因子的患者,與準則一致性仍只有26%。影響warfarin處方的因素,除了出血危險因子以外,高血壓、冠狀動脈疾病以及年齡增加都會降低warfarin的處方機會不同。不同醫師專科別中與準則配合度以心臟外科最佳,其次為神經內科、心臟內科、其他專科、家醫科以及一般內科;醫院層級越高,與準則配合程度越好。

結論
臺灣地區心房顫動的患者並未接受適當的抗血栓劑預防中風。病患罹病特性、醫師專科以及醫院層級皆會影響抗血栓劑的處方。
英文摘要 Introduction
Although the value of warfarin in preventing thromboembolic events in atrial fibrillation (AF) patients has been well established, the prescribing rate of warfarin was still under expected. The objectives of this study were to evaluate the adherence rate with antithrombotic guideline (ACC/AHA/ ESC 2001) in Taiwan and to identify factors affecting the antithrombotic therapy.
Methods
We included AF patients who were documented with ICD9-CM coded of “42731” twice in non-sampled NHI claim database from 1 July 2003 through 30 June 2004. Utilization of antithrombotic therapy among these patients was analyzed. Univariate and multiple logistic regressions were performed to identify factors associated with antithrombotic therapy and guideline adherence.
Results
Among 39541 AF patients, up to 90% were identified with high risk of thromboembolic events. Only 24.7% of them had received the appropriate antithrombotic therapy. As we had excluded patients with bleeding risk factors, the adherence rate was still 26%. Other than bleeding risk factors, hypertension, coronary heart disease and increased age presented an inverse association with warfarin use. Among physician’s specialty, cardiac surgeons were most likely to adhere to the Guideline, followed by neurologist, cardiologist, other specialist, family physician and other internist. Patients were more likely to receive appropriate antithrombotic therapy when the hospital level was higher.
Conclusion
Most AF patients in Taiwan did not receive appropriated antithrombotic therapy. Patient’s comobidity, physician’s specialty and hospital level all had influenced on the prescription of antithrombotic therapy.
論文目次 第一部份 心房顫動患者抗血栓劑之處方型態分析 1
第一章 研究背景 1
第二章 文獻回顧 2
第一節 心房顫動疾病簡介 2
一. 流行病學 2
二. 心房顫動分類 3
三. 心房顫動的致病機轉與致病因子 5
四. 臨床表現 7
五. 治療原則 8
第二節 心房顫動與血栓性栓塞 11
一. 抗血栓劑在心房顫動患者的應用 11
二. 抗血栓劑在心房顫動患者的臨床試驗說明 14
三. 栓塞危險性的評估與國際準則建議 23
四. Warfarin出血危險性 24
五. 心房顫動患者抗血栓劑國際準則建議 29
六. 抗血栓劑於臨床應用現況 30
第三章 研究方法 33
第一節 研究型態 33
第二節 研究材料 33
第三節 研究工具 34
一. 健保給付藥品Anatomical Therapeutic Chemical (ATC) classification代碼對照檔2004 34
二. 國際疾病傷害及死因分類標準ICD 9CM 34
三. Excel套裝軟體及SAS for Windows 9.1套裝軟體 34
第四節 研究對象 34
一. 納入條件 34
二. 排除條件 34
第五節 研究變項及操作定義說明 35
一. 研究名詞定義 35
二. 研究變項定義 37
第六節 研究流程 40
一. 檔案前置處理 40
二. 資料處理流程 41
第四章 統計分析 43
第一節 統計模式設定 43
第二節 資料分析方法 43
一. 描述性統計 43
二. 推論性統計 43
第五章 研究結果 45
第一節 病患族群分佈 45
第二節 處方型態 46
第三節 抗血栓劑處方預測因子 47
第四節 醫院層級、醫師專科與準則一致性的關係 48
第六章 研究討論 49
第一節 研究族群人口特性 49
第二節 與準則一致性 51
第三節 抗血栓劑的處方影響因子 53
一. 最高危險性相關栓塞危險因子 53
二. 高危險性相關危險因子 54
三. 最低危險性及低危險性族群 57
四. 出血危險因子與抗血栓劑處方的關係 58
第四節 臨床醫師遵循準則的障礙 59
第五節 Warfarin平均監測頻率 62
第六節 研究限制 63
第七章 未來研究方向 64
第八章 結論與建議 66
第二部分 臨床藥事服務 67
第一章 服務背景 67
第二章 服務方法 68
第一節 服務對象 68
第二節 服務材料 68
第三節 服務流程 69
第三章 服務結果 70
第四章 心得與建議 71
第一節 衛教經驗分享 71
第二節 未來改進方向 73
一. 衛教內容 73
二. Warfarin用藥手冊 73
三. 持續追蹤 73
四. 藥事服務參考手冊 74
五. 抗凝血劑監測服務 76
附錄1. 住院病患warfarin使用評估表 127
附錄2. Warfarin認知程度調查表 129
附錄3. Warfarin藥事服務參考手冊 130

表目錄
表1. 心房顫動的病因或致病因子 77
表2. 節律控制的藥物選擇 78
表3. 節律控制與速率控制臨床試驗比較 79
表4. Aspirin在各疾病的最低有效劑量 80
表5. 抗血栓劑在心房顫動患者的應用:臨床試驗整理 81
表6. 抗血栓劑臨床試驗:主要研究事件及重大出血事件發生率 82
表7. 抗血栓劑研究結果總整理 85
表8. 抗血栓劑於心房顫動患者的應用,綜整性分析結果整理 86
表9. 心房顫動患者急性中風之後探討抗血栓劑效果的臨床試驗 87
表10. 中風危險性評估方法 88
表11. Warfarin在不同中風危險性的效果(利用CHADS2評估方法) 89
表12. 不同中風危險性,抗血栓劑的NNT(利用ACCP評估方法) 89
表13. 依據腸胃道出血與栓塞危險性,抗血栓劑的使用建議 91
表14. 專家對於warfarin引起的ICH處置的建議 92
表15. ACCP於心房顫動患者抗血栓劑使用建議 93
表16. ACC/AHA/ESC (2001)對心房顫動患者抗血栓劑使用建議 94
表17. ACC/AHA/ESC (2006)對心房顫動患者抗血栓劑使用建議 95
表18. Warfarin於臨床實務應用調查 96
表19. 研究族群之人口特性 98
表20. 研究族群責任醫療院所及醫師專科分佈 100
表21. 中風危險分級與抗血栓劑使用分佈 101
表22. 中風危險分級與抗血栓劑使用分佈(排除有出血危險因子的患者) 102
表23. 與準則一致的比例 103
表24. Warfarin在120天內平均監測頻率 104
表25. Warfarin處方預測因子 105
表26. 與用warfarin比較,使用其他抗血栓劑的機會與危險因子的關係 106
表27. 抗血栓劑處方行為與栓塞及出血危險因子數目之關係 107
表28. 醫師專科與醫院層級與準則一致性之關係 108
表29. 本研究研究族群人口特性與其他研究之比較 109
表30. 本研究族群改以其他國際準則分類 110
表31. 本研究與過去文獻warfarin處方預測因子比較 111
表32. 老年患者較不容易使用抗凝血劑的原因 113
表33. 各年齡層符合準則的比例 113
表34. 抗凝血劑使用禁忌症評估 114
表35. 比較開立抗血栓劑的醫師與健保資料庫所記載的共病症之差異 115
表36. Warfarin使用患者之基本資料 116
表37. Warfarin認知程度調查結果 117
表38. Warfarin認知程度分數分佈 117

圖目錄
圖1. INR值與顱內出血、缺血性中風之相關性 118
圖2. Meta-analysis:Warfarin與安慰劑比較 119
圖3. Meta-analysis:Aspirin與安慰劑比較 119
圖4. Meta-analysis:Warfarin與Aspirin比較 120
圖5. 急性心肌梗塞後抗血栓劑處理原則 121
圖6. 年齡分層與栓塞危險共病症數目的關係 122
圖7. 年齡分層與出血危險因子數目的關係 122
圖8. 中風危險分級與抗血栓劑的使用分佈 123
圖9. 中風危險分級與抗血栓劑的使用分佈(排除有出血危險因子的患者) 123
圖10. ACC/AHA/ESC 2001年準則與2006年準則中風危險性分類對照 124
圖11. Warfarin衛教流程表 125
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系統識別號 U0026-0812200914155726
論文名稱(中文) Fluoroquinolones於台灣地區結核病患者使用之處方型態分析
論文名稱(英文) The Prescribing Patterns of Fluoroquinolones in Patients with Tuberculosis in Taiwan
校院名稱 成功大學
系所名稱(中) 臨床藥學研究所
系所名稱(英) Institute of Clinical Pharmacy
學年度 96
學期 2
出版年 97
研究生(中文) 江怡蓉
學號 s6695403
學位類別 碩士
語文別 中文
口試日期 2008-06-26
論文頁數 127頁
口試委員 口試委員-張漢煜
指導教授-林嘉音
口試委員-柯文謙
指導教授-高雅慧
關鍵字(中) 處方型態分析
結核病
關鍵字(英) fluoroquinolone
tuberculosis
prescribing patterns
學科別分類
中文摘要 研究背景
Fluoroquinolones (FQ)因具有使用方便及廣效殺菌等效果,容易被選擇做為經驗性抗生素,用於結核病發病初期不具特異性之感染症狀治療。然而FQ除了一般細菌外,也能有效的治療結核菌,故對於實際上是結核菌感染的患者使用FQ做為治療,即等同於單線藥品治療結核菌。然而這樣的處方行為,會造成結核病診斷延遲,抗藥性及預後不佳的狀況。此外,國內屬結核病流行區,FQ被處方於結核病患者的機率越高,很可能會造成抗藥性及診斷延遲比率增加,進而造成傳染率增加,因此有必要對於國內的處方情形進行研究。

研究方法
利用2000-2004全民健保資料庫門、住診檔,擷取出2003/01/01至12/31定義新確診結核病患(ICD9-code 010-018),分析FQ於結核病指標日期(首次被登記結核病診斷碼日期)前365天做為經驗性治療及指標日期後365天內之使用情形,研究處方適當性以及找出處方預測因子,以及經驗性fluoroquinolones的使用與診斷、治療及預後之間的關係,以提供臨床人員及抗生素管控決策之參考。

研究結果
本研究發現14,466位新確診結核病患者中,15.25%於首次被登記結核病診斷碼(指標日期)前曾使用過FQ的紀錄(FQ組),66.15%使用FQ以外之抗生素(Abx組)。年齡、女性、共病症、就診區域、醫師專科、醫院層級等皆為FQ處方之預測因子。而指標日期前處方抗生素之總就診次數中登記痰塗片及分枝桿菌培養醫令比率偏低(12.74%)。而FQ的使用除了造成診斷(30天)及治療延遲(24天)外,與死亡發生也有相關性(多變項分析OR=4.506),在指標日期後15.69%患者具有被處方FQ之記錄,而肝硬化、糖尿病、老年人、肺外結核、醫師專科及醫院層級等為處方之預測因子。

結論
本研究發現國內結核病患者在診斷前被處方抗生素(包括FQ)的次數及機率偏高,且FQ於診斷前的使用會導致診斷延遲,且與預後不佳有高度相關性。而於診斷之後,仍有一定比率患者被處方FQ,特別是對患有肝硬化或是年紀大的病患,然而詳細處方原因仍待進一步釐清。
英文摘要 Background
Due to its broad-spectrum antibaterial activity and convenient administration, FQ is likely to be widespread used as empirical therapy when TB patients present non-specific infectious symptoms. In addition to the anti-bacterial activity, FQ also has effective anti-TB activity. Several studies have demonstrated such empirical use of FQ can result in TB diagnosis delay, resistance and poor prognosis. Because of the TB prevalence and increasing resistance rate in Taiwan, there is a necessity to investigate the appropriateness FQ prescribing patterns in TB patients.

Method
We used the 2000-2004 National Health Insurance claims data base, to extract 2003 difinite new diagnosis TB patients (ICD-9 code 010-108). The objective is to investigate the antibiotics prescribing patterns (FQ and others), predictors in 365 days before and after their TB diagnosis date (index date) and the association between fluoroquinolones and prognosis.

Result
We have found 14,466 consistent with the definitions of definite TB diagnosis patients in 2003. 15.25% (FQ group) was prescribed with FQ before TB index date, and 66.15% was prescribes with other antibiotics (Abx group). Age, sex, comorbidity, and the geographic area, the level and the physician specialist were the predictors for FQ prescription. FQ was also associated with poor prognosis, and can result in 30 days delay diagnosis and 24 days treatment delay compared with Abx group. The sputum smear test was also infrequent (12.74% of total visits). 15.69% patient were prescribed with FQ after index date.The predictors of FQ prescribing after index date included liver cirrhosis,elder,extrapulmonpary TB,and DM.

Conclusion
Antibiotics were frequently prescribed in TB patients before TB diagnosis.FQ use can lead to delay of TB diagnosis and associate with poor prognosis. FQ prescribing after TB diagnosis was also common, especially in elder or patients with liver cirrhosis.
論文目次 目錄
第一章 研究背景 1

第二章 文獻回顧 3
第一節 結核疾病簡介 3
2.1.1 國內外疫情概況 3
2.1.2 政府現行防疫措施及瓶頸 3

第二節 Fluoroquinolones簡介 10
2.2.1 藥物特性 10
2.2.2 Fluoroquinolones用於結核病治療所扮演的角色 16

第三節 Fluoroquinolones經驗性治療對結核病診斷及預後之影響 24
2.3.1 可能延遲結核病治療以及造成死亡率提高 24
2.3.2 可能使acid fast bacillus(AFB)呈陰性的機會增加 25
2.3.3 可能使結核菌對fluoroquinolones敏感性降低 26
2.3.4 結核病患在診斷前使用fluoroquinolones的情形-國外保險資料庫研究 26

第四節 Fluoroquinolones之抗藥性問題及現階段專家學者意見 27
2.4.1 全球廣泛性抗藥性結核菌株(XDR-TB)的發生 27
2.4.2 結核菌對於fluoroquinolones產生抗藥性的情形 28
2.4.3 專家學者意見 30

第三章 研究目的及方法 31
第一節 研究目的 31

第二節 研究型態 31

第三節 研究材料 31
3.3.1 全民健保資料庫 31
3.3.2 國際疾病傷害及死因分類標準ICD-9-CM 1992年版 32
3.3.3 健保給付藥品Anatomical Therapeutic Chemical (ATC) classification代碼對照檔(高雅慧、郭垂文、洪榮輝、郭士禎所編訂) 32

第四節 研究對象 32

第五節 操作變項定義 33
3.5.1 研究對象定義 33
3.5.2 指標日期前fluoroquinolones之處方型態分析部分 34
3.5.3 指標日期後365天內之fluoroquinolones處方型態分析部分 37
3.5.4 處方預測因子分析 37
3.5.5 對於診斷及治療預後的影響分析 39

第六節 資料處理 41
3.6.1 資料處理流程 41
3.6.2 指標日期前fluoroquinolones之處方型態分析 42
3.6.3 診斷後fluoroquinolones之處方型態分析 43
3.6.4 Fluoroquinolones之處方行為預測因子分析: 43
3.6.5 Fluoroquinolones對於結核病診斷及治療預後影響 44

第四章 統計分析 46
第一節 資料分析方法 46
4.1.1 敘述型統計 46
4.1.2 推論型統計 46

第二節 統計模式設定 47

第三節 統計工具 47

第五章 研究結果 48
第一節 病患基本特性分佈 48

第二節 指標日期前fluoroquinolones之處方型態分析 50
5.2.1 定義新確診結核病患者其抗生素組別與基本特質分佈 50
5.2.2 患者使用fluoroquinolones或其他抗生素之比率與次數 52
5.2.3 指標日期前痰塗片及分枝桿菌培養之監測情形 54
5.2.4 Fluoroquinolones及其他類抗生素處方情形 56

第三節 指標日期後患者使用fluoroquinolones之情形 59
5.3.1 特定fluoroquinolones處方情形 59

第四節 Fluoroquinolones處方之預測因子 60
5.4.1 於指標日期前fluoroquinolones之使用 60
5.4.2 於指標日期後特定fluoroquinolones之使用 60

第五節 Fluoroquinolones使用對於結核病診斷及治療預後之影響 66
5.5.1 診斷及治療延遲方面 66
5.5.2 住院天數方面 68
5.5.3 結核病用藥治療天數方面 68
5.5.4 指標日期之後住院比率方面 68
5.5.5 死亡率方面 68

第六章 研究討論 72
第一節 研究族群人口特性 72

第二節 指標日期前之經驗性抗生素使用狀況 75
6.2.1 使用抗生素之比率 75
6.2.2 痰塗片及分枝桿菌培養之監測情形 76
6.2.3 指標日期前fluoroquinolones之處方情形與預測因子 77

第三節 指標日期後fluoroquinolones之處方情形及處方預測因子 80

第四節 經驗性抗生素使用對於結核病診斷及治療延遲之影響 82
6.4.1 Fluoroquinolones之影響 82
6.4.2 其他類抗生素之影響 83
6.4.3 其他可能造成診斷延遲的因素 83

第五節 經驗性抗生素對於結核病患者預後之影響 85
6.5.1 患者住院天數影響與指標日期後住院之比率 85
6.5.2 死亡率之影響 85

第七章 研究限制 87

第八章 未來研究方向 89

第九章 結論與建議 90

臨床藥事服務 92

參考文獻 118

作者簡介 127


表目錄
表5-1 新確診結核病患之基本特徵 51
表5-2 於指標日期前患者被處方抗生素之門診次數 53
表5-3 於指標日期前,對於具呼吸道感染相關診斷之就診記錄(不論是否處方抗生素),登記痰塗片及分枝桿菌培養監測情形 55
表5-4 於指標日期前,對於具呼吸道感染相關診斷且具抗生素處方之就診登記痰塗片及分枝桿菌培養監測情形 55
表5-5 Fluoroquinolones於”指標日期前”處方之預測因子 (FQ組vs.Abx組) 61
表5-6 Fluoroquinolones於”指標日期前”處方之預測因子 (FQ組vs.控制組) 63
表5-7 結核病於”指標日期後”fluoroquinolones處方之預測因子 (FQ組 vs. Non-FQ組) 64
表5-8比較FQ vs. Abx組門診診斷患者診斷延遲天數 66
表5-9 針對指標日期前曾接受過痰塗片或分枝桿菌培養之門診診斷患者,分析醫令檢測時間、診斷及藥物治療時間之延遲天數比較 67
表5-10 死亡之危險因子-14,466位患者(1,434人於開始用藥/指標日期後180天內死亡) 70
表5-11 死亡之危險因子-無共病症8,743人(550人於開始用藥/指標日期後180天內死亡) 71

附錄1 Fluoroquinolone全民健康保險給付規定 99
附錄2 WHO(2003)、International standard care of TB(2006)及國內2006出版肺結核病診治指引建議之診斷流程-經驗性抗生素使用時機 (改編) 100
附錄3 抗生素適應症之ICD9-CM (1992) 101
附錄4 Fluoroquinolones使用於結核病治療效果之相關大型研究結果整理 108
附錄5 臨床藥事服務 112


圖目錄
圖5-1 研究結果-定義新確診結核病患者篩選過程 49
圖5-2 FQ組於指標日期前各類fluoroquinolones處方筆數分佈 57
圖5-3 於指標日期前Fluoroquinolones處方適應症、醫院層級以及醫師專科分佈 57
圖5-4 於指標日期前非fluoroquinolones之抗生素品項處方筆數分佈 58
圖5-5 於指標日期前Abx組患者使用抗生素之處方適應症、醫院層級以及醫師專科分佈 58
圖5-6 於指標日期後特定fluoroquinolones處方之醫院層級及科別分佈 59
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系統識別號 U0026-0812200915294517
論文名稱(中文) 心衰竭病患使用Spironolactone與減少心房顫動發生之探討
論文名稱(英文) Relationship between Atrial Fibrillation and Use of Spironolactone in Heart Failure Patients
校院名稱 成功大學
系所名稱(中) 臨床藥學研究所
系所名稱(英) Institute of Clinical Pharmacy
學年度 97
學期 2
出版年 98
研究生(中文) 曹可欣
學號 s6696101
學位類別 碩士
語文別 中文
口試日期 2009-07-17
論文頁數 100頁
口試委員 指導教授-林立人
口試委員-莊善安
口試委員-李貽恆
指導教授-高雅慧
關鍵字(中) 健保資料庫
處方型態
心房顫動
心衰竭
關鍵字(英) prescribing pattern
spironolactone
heart failure
atrial fibrillation
學科別分類
中文摘要 研究背景
心衰竭病患發生心房顫動的危險性比無心衰竭病患高出4-6倍。一旦發生心房顫動,將增加2-7倍的中風發生率,在心衰竭病患更增加2-3倍的死亡率。有研究指出,心衰竭病患使用spironolactone併用傳統療法,可以減少心律不整之發生。本研究之目的除了探討在實際臨床使用中,使用spironolactone與心房顫動發生之相關性,亦將提供國內心臟衰竭治療之藥品處方型態,探討在臺灣心衰竭準則建議治療是否落實於實際臨床使用。

研究方法
利用2000年-2004年未抽樣之全民健康保險資料申報檔,針對2001年1月1日至2003年12月31日期間,取樣門診或住院診斷碼出現心衰竭診斷且年齡大於65歲(含)的病患。首先,分析納入日期90天內之藥品處方型態,之後進行一個嵌入在心衰竭世代研究的心房顫動病例-對照研究,兩組之間以年齡(± 5歲)、性別和納入時間為配對條件,每一個病例最多將配對到8個對照患者,使用條件式邏輯回歸,心血管用藥與疾病史為校正因子,分析心衰竭患者使用spironolactone與心房顫動發生之相關性。

研究結果
心衰竭世代研究共納入275,061位病患。心衰竭準則建議用藥中,利尿劑之總處方率最高(57%),其餘依次為ACEIs/ARBs (49%)、β-blockers (32%)、digitalis glycosides (25%),spironolactone的處方率僅佔9%。心衰竭世代研究中,發生心房顫動之9,969位病例與70,679名對照患者完成配對,加以分析spirnolactone曝露程度之影響。指標日期前180天內,spironolactone曝露程度過低者將等同未曾處方者,歸類為非曝露者;而曝露組再區分為現正曝露組以及近期曝露組。以多變項邏輯回歸分析,結果顯示指標日期前180天內,與spironolactone非曝露組相較,近期曝露組對心房顫動之發生並沒有影響,而現正曝露則可明顯減少心房顫動發生之風險( p < 0.01)。進一步分析發現spironolactone之累積劑量達到心衰竭建議治療劑量的一半(30個定義每日劑量,相當於180天內每日平均劑量12.5 mg) 以及180天內處方天數達90天以上者,皆可有效減少心房顫動發生之風險。

結論
依據ACC/AHA 心衰竭治療準則(2005),臺灣之心衰竭病患並未接受適當的心衰竭治療。雖然處方率與同時期之國外研究相近,未來需要更多研究分析國內心衰竭準則建議用藥之處方率與疾病預後之相關性,以評估臺灣心衰竭治療之成效。
心衰竭病患使用spironolactone與其心房顫動之發生,和spironolactone的曝露量有關。使用spironolactone連續達90天以上或累積劑量達30個定義每日劑量(相當於180天內每日平均劑量12.5 mg) 以上,可減少心衰竭病患發生心房顫動之風險。因此,建議心衰竭病患在沒有禁忌症的前提之下,皆應該使用spironolactone進一步減少心房顫動之發生。
英文摘要 Background
Heart failure (HF) increases the risk of atrial fibrillation (AF) 4-6 fold. Compared with patients without AF, the risk of stroke of AF patients will increase 2-7 folds. The mortality of HF patients would even higher while they developed AF. Although clinical consensus suggested that using spironolactone with conventional therapy may decrease AF in HF patients, the clinical data are still limited. The aims of this study were to evaluate the relationship between AF and use of spironolactone in HF patients, and to provide prescribing pattern of HF treatment in Taiwan to examine the guideline adherence in clinical practice.

Methods
We conducted a case-control study nested in the study of HF patients who were documented with HF diagnosis in ambulatory or inpatient records and were older than 65 years during 1 January 2001 and 31 December 2003 using non- sampled National Health Insurance Research Database (NHIRD). Prescription rates were examined within 90 days after enrollment.
Then we excluded patients according to exclusion criteria and assigned patients with low extent of exposure to spironolactone non-exposure group;exposure group was further divided to current and recent exposure group. A case was defined as a HF patient who developed AF during follow-up. Each case of AF was matched with up to 8 control patients by age(± 5)、gender and the time of enrollment. Conditional logistic regression was performed to identify the relationship between AF and use of spironolactone.

Results
In the HF study, we enrolled 275,061 HF patients (52 % women) with mean age 76 years. Diuretics were prescribed most frequently (57 %), following ACEIs/ARBs (49 %) 、β-blockers (32 %) and digitalis glycosides (25 %). Spironolactone was the least prescribed drug (9 %).
During follow-up, total 80,648 patients were matched (case:9,969,control:70,679). Compared with non-exposure group, recent exposure group had no effect on the risk of AF while current exposure group was showed to significantly reduce the risk of AF ( p < 0.01). For the 180-day period before the index date, spironolactone user with cumulated dose between 30 - 120 DDD or with medication possession rate (MPR) ≥ 0.5 would both significantly reduce the risk of AF.

Conclusions
In Taiwan, evidence-based treatments which reduce morbidity and mortality were underused in HF patients.
The relationship between spironolactone use and AF was based on the spironolactone’s extent of exposure. Using spironolactone for at least 90 days or 30 DDD (equal to mean daily dose 12.5 mg in 180 days) may reduce the risk of AF in HF patients. It’s recommended that all HF patients who are without contraindication should use spironolactone to further reduce the risk of AF.
論文目次 第一篇 心衰竭病患使用Spironolactone 與減少心房顫動發生之探討................. 1
第一章 研究背景...................................................................................................... 1
第二章 文獻回顧...................................................................................................... 2
第一節 心衰竭與心房顫動之疾病簡介.......................................................... 2
2.1.1 心衰竭............................................................................................ 2
2.1.1.1 流行病學....................................................................... 2
2.1.1.2 心衰竭疾病特性及分級............................................... 4
2.1.1.3 心衰竭之準則建議治療............................................... 6
2.1.1.4 心衰竭治療之藥物流行病學....................................... 13
2.1.2 心房顫動........................................................................................ 18
2.1.2.1 心房顫動分類............................................................... 18
2.1.2.2 流行病學....................................................................... 19
2.1.2.3 致病機轉....................................................................... 20
第二節 心衰竭與心房顫動之相關性.............................................................. 22
2.2.1 流行病學........................................................................................ 22
2.2.2 心衰竭病患發生心房顫動對預後之影響.................................... 23
2.2.3 心衰竭病患發生心房顫動之致病機轉........................................ 24
2.2.3.1 心房纖維化................................................................... 24
2.2.3.2 Aldosterone 在心房纖維化的角色.............................. 26
第三節 使用Spironolactone 與減少心房顫動發生之探討............................ 29
第三章 研究目的...................................................................................................... 32
第四章 研究方法...................................................................................................... 33
第一節 研究設計................................................................................................ 33
4.1.1 研究類型........................................................................................ 33
4.1.2 研究材料與工具............................................................................ 33
4.1.3 研究對象........................................................................................ 34
4.1.3.1 納入條件....................................................................... 34
4.1.3.2 排除條件....................................................................... 34
第二節 研究變項及操作定義說明.................................................................... 35
4.2.1 研究名詞定義................................................................................ 35
4.2.2 研究變項定義................................................................................ 37
第三節 研究流程.............................................................................................. 40
4.3.1 檔案檢查與串聯.......................................................................... 40
4.3.2 資料處理流程.............................................................................. 41
VIII
第四節 統計分析.............................................................................................. 42
4.4.1 統計模式設定.............................................................................. 42
4.4.2 資料分析方法.............................................................................. 42
第五章 研究結果...................................................................................................... 44
第一節 處方型態分析.................................................................................... 44
5.1.1 病患基本特性分布...................................................................... 44
5.1.2 心衰竭治療之藥品處方型態...................................................... 44
第二節 使用Spironolactone 與心房顫動發生之相關性分析........................ 51
5.2.1 共病症對心房顫動發生之影響.................................................. 52
5.2.2 心血管用藥對心房顫動發生之影響.......................................... 56
5.2.3 Spironolactone 對心房顫動發生之影響..................................... 60
第六章 研究討論...................................................................................................... 64
第一節 心衰竭治療之處方型態分析.............................................................. 64
6.1.1 研究族群人口特性...................................................................... 64
6.1.2 與Jhund 等人之研究的比較....................................................... 67
第二節 使用Spironolactone 與減少心房顫動發生之相關性........................ 70
6.2.1 共病症對心房顫動發生之影響.................................................. 70
6.2.2 心血管用藥對心房顫動發生之影響.......................................... 71
6.2.3 Spironolactone 對心房顫動發生之影響..................................... 72
第三節 研究限制.............................................................................................. 75
第七章 結論與建議.................................................................................................. 76
第二篇 臨床藥事服務 – Amiodarone(臟得樂)之用藥衛教.................................... 77
第一章 服務緣起........................................................................................................ 77
第二章 服務方法........................................................................................................ 78
第一節 服務對象.............................................................................................. 78
第二節 服務材料.............................................................................................. 78
第三節 服務流程.............................................................................................. 79
第三章 服務結果........................................................................................................ 84
第一節 病患特性.............................................................................................. 84
第二節 交互作用檢視結果.............................................................................. 84
第三節 Amiodarone 藥品使用認知評估......................................................... 84
第四節 衛教結果.............................................................................................. 85
第四章 心得與建議.................................................................................................... 89
第一節 衛教需求............................................................................................. 89
第二節 良好溝通............................................................................................. 90
第三節 經驗分享—副作用之解說................................................................. 90
第四節 結語..................................................................................................... 93
參考文獻...................................................................................................................... 95
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------------------------------------------------------------------------ 第 10 筆 ---------------------------------------------------------------------
系統識別號 U0026-1208201018104000
論文名稱(中文) 臺灣全身性類固醇處方型態分析
論文名稱(英文) Prescribing Pattern of Systemic Corticosteroids in Taiwan
校院名稱 成功大學
系所名稱(中) 臨床藥學研究所
系所名稱(英) Institute of Clinical Pharmacy
學年度 98
學期 2
出版年 99
研究生(中文) 劉玟琦
學號 s6697401
學位類別 碩士
語文別 中文
口試日期 2010-07-15
論文頁數 89頁
口試委員 指導教授-高雅慧
口試委員-劉明煇
口試委員-許美英
關鍵字(中) 處方型態分析
糖皮質類固醇
類固醇
健保資料庫
關鍵字(英) Prescribing pattern
Corticosteroids
Glucocorticoids
Steroids
學科別分類
中文摘要 研究背景
全身性類固醇在全球被廣泛使用在內分泌疾病、發炎、過敏及免疫系統異常等疾病上,不過長期使用會導致許多的副作用。英美國家已有需多類固醇的處方型態研究和類固醇使用與副作用間的關聯性。然而,關於類固醇使用之情形在臺灣尚未有流病學資料,而坊間也常傳聞類固醇不適當使用的事例。因此本研究致力於探討臺灣使用類固醇的處方現況,以利後續相關議題的討論和深入研究。
研究方法
利用2000~2004年全民健康保險資料庫,健保給付藥品ATC代碼對照檔藥品代碼開頭為「H02」者為全身性類固醇的使用,再與門診和住院醫令明細檔串檔,定義為全身性類固醇的使用者。
本研究有兩種不同研究族群:
1) 處方型態分析:對象為2004年1月1日至2004年12月31日期間,接受過一次全身性類固醇處方者。
2) 長期使用者:對象為2001年1月1日至2003年12月31日期間,連續使用全身性類固醇超過3個月(92天)處方者。
研究結果
在處方型態分析中,有4,416,874人曾使用過一次以上的類固醇,盛行率為每千人195人。將近72%的使用者,只接受過1至2次處方箋。Prednisolone 是最常被處方的藥品,耗用量是4.8 DDD/inhabitant/day。住院病患中90至95歲的老年人有最高耗用量(11 DDD),在門診病人中則是75至85歲有最高的耗用量(12.5 DDD)。住院病人最常見的疾病是腫瘤,而門診診患者則是呼吸系統疾病。

在長期使用者中,有123,159人長期使用類固醇,2003年盛行率是每千人2.9人。而在小於20歲、20至64歲和大於64歲者之盛行率分別是每千人0.5、2.4、12.6人。最常使用的劑量是每天5至7.5毫克。而最常見的疾病是呼吸系統疾病(32%),其次是風濕性疾病(23%)。然有高達24%的長期使用者無相對應長期使用類固醇合適的診斷。
結論
藉由全民健康保險資料庫,本研究發現臺灣類固醇使用人數遠高於其他國家,在門診大部分都是短期的使用者,常用於治療上呼吸道感染。使用全身性類固醇治療一般的上呼吸道感染之適當性,仍需仔細評估。
長期使用者的盛行率與其他國家相似,約每千人有3人長期使用。然而,盛行率和每天劑量(不同年齡層的比例)隨著年紀增加而上升,因此,在臨床上需更注意老年人在如此高劑量的暴露下是否發生副作用。
關鍵字
處方型態分析、糖皮質類固醇、類固醇、健保資料庫。
英文摘要 Background
Systemic corticosteroids (CSs) are used to treat patients with endocrine, inflammatory, allergic, or immunological disorders, which may cause in many adverse effects in chronic use. There are lots of studies about the prescription patterns of CSs and the association between CSs use and adverse effects in western countries. However, information describing the population-based use of corticosteroids in Taiwan remains unavailable. Therefore, this study was aimed to investigate utilization of systemic CSs in Taiwan.
Methods
We included systemic CSs users who were documented prescriptions of H02 in ATC code from the non-sampled National Health Insurance Research Database (NHIRD).
There were two groups to classified for the analysis:
1) who had received one or more prescriptions of systemic CSs during 1 January 2004 and 31 December 2004 .
2) who had continued treatment more than 3 months (92 days) during 1 January 2001 and 31 December 2003
Results
In the cross-sectional study, we enrolled 4,416,874 CSs users, and the prevalence was 195 per 1000 persons. Nearly 72% of CSs users received only 1 or 2 prescriptions in 2004. Prednisolone was the most frequently prescribed CSs, and the consumption was 4.8 DDD/inhabitant/day. The highest consumption of CSs was found with people between 90 and 95 years of age (11 DDD) in impatient service and 75 and 85 years of age (12.5 DDD) in ambulatory patients. The most frequently recorded diagnosis associated with CSs use was neoplasm, and respiratory disease in impatient service and ambulatory care, respectively.
In the part of long-term users, we enrolled 123,159 CSs long-term users, and the annual prevalence was 2.9 per 1000 people in 2003. The prevalence of long-term users <20, 20 to 64, and >64 years of age was 0.5, 2.4 and 12.6, respectively. The most frequently prescribed dose was between 5 and 7.5 mg/day. The most common diagnosis associated CSs use was respiratory disease (32%), followed by rheumatic disease (23%). Nearly 24% of long-term users had no documented diagnosis indicating the appropriateness of CSs use.

Conclusions
A large number of patients enrolled in NHIRD had received one or more CSs in 2004 which was more prevalent than other countries. Most of them were short-term users, and the most frequently diagnosis associated CSs use was upper respiratory tract infection. The utilization pattern awakes future investigate.
The prevalence of long-term users was similar with other country. While age was increasing, the prevalence raised as well as the percentage of daily dose. The risk and benefit of systemic CSs in the elderly should be concerned.
Keywords
Prescribing pattern, Corticosteroids, Glucocorticoids, Steroids
論文目次 中文摘要 I
Abstract III
誌謝 V
目錄表目錄 VI
表目錄 IX
圖目錄 X
第一篇 臺灣全身性類固醇處方型態分析 1
第一章 研究背景 1
第二章 文獻回顧 2
第一節 內生性和人工合成皮質類固醇簡介 2
2.1.1腎上腺皮質激素11 2
2.1.1.1糖皮質激素 2
2.1.1.2礦物皮質激素11 3
2.1.2腎上腺皮質激素藥物11 4
2.1.2.1糖皮質類固醇藥物 4
2.1.2.2礦物皮質類固醇藥物 5
第二節 糖皮質類固醇導致的副作用 7
2.2.1皮膚和軟組織的副作用 7
2.2.2庫欣氏症候群和體重增加 8
2.2.3眼部的副作用 8
2.2.4心血管的副作用 9
2.2.5腸胃道的副作用 10
2.2.6腎臟和循環系統的副作用 10
2.2.7生殖系統的副作用 11
2.2.8骨骼肌肉的副作用 11
2.2.9中樞神經的副作用 13
2.2.10新陳代謝或內分泌的副作用 13
2.2.11血液學的副作用 13
2.2.12 總結 14
第三節 類固醇處方型態分析 15
2.3.1 各國處方型態 15
2.3.2 總結 17
第三章 研究目的 19
第四章 研究方法 20
第一節 研究設計 20
4.1.1 研究類型 20
4.1.2 研究材料及工具 20
4.1.3 納入條件 21
4.1.4 排除標準 22
第二節 研究變項及操作定義 23
4.2.1 研究藥品 23
4.2.2 研究名詞定義 24
第三節 資料處理流程 28
4.3.1檔案串檔 28
4.3.2研究流程 29
第四節 統計分析 30
4.4.1 統計工具 30
4.4.2 統計模式設定 30
4.4.3 資料分析方法 30
第五章 研究結果 31
第一節 處方型態分析 31
5.1.1 類固醇藥品 31
5.1.2 研究族群人口特性 32
第二節 長期使用者 41
第六章 研究討論 48
第一節 處方型態分析 48
6.1.1 研究族群人口特性 48
第二節 長期使用者 52
第三節 研究限制 56
第七章 結論與建議 57
第二篇 臨床藥事服務口服類固醇之用藥衛教和類固醇引起的骨質疏鬆症之衛教 58
第一章 服務緣起 58
第二章 服務方法 60
第一節 服務對象 60
第二節 服務材料 60
第三節 服務流程 61
第三章 服務結果 62
第一節 病患特性 62
第二節 類固醇藥品和骨質疏鬆藥品衛教 64
第四章 心得 66
參考文獻 67
附錄一 75
附錄二 78
作者簡介 89

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系統識別號 U0026-1502201209270400
論文名稱(中文) 發光二極體的光取出與散熱改善之研究
論文名稱(英文) Investigation and Fabrication of Light Emitting Diodes with Improved Light Extraction and Heat Dissipation
校院名稱 成功大學
系所名稱(中) 微電子工程研究所碩博士班
系所名稱(英) Institute of Microelectronics
學年度 100
學期 1
出版年 101
研究生(中文) 陳冠群
學號 Q1894115
學位類別 博士
語文別 英文
口試日期 2012-01-19
論文頁數 58頁
口試委員 指導教授-蘇炎坤
召集委員-吳孟奇
口試委員-莊賦祥
口試委員-黃建榮
口試委員-許進恭
口試委員-張忠誠
口試委員-許渭州
口試委員-張守進
口試委員-莊文魁
關鍵字(中) 發光二極體
光取出
散熱
雷射劃線
電極
關鍵字(英) Light Emitting Diodes
light extraction
heat dissipation
laser scribing
electrodes
學科別分類
中文摘要 本論文針對發光二極體(LEDs) 的光取出與散熱問題進行研究。本論文提出兩種不同的方法來增加發光二極體的光取出強度。另一方面本論文提出利用電鍍的技術來改善高功率發光二極體的散熱問題。
本論文為了改善發光二極體的光取出的問題,提出兩種可以有效增加光取出的方法,並分成兩部份來探討,第一部份,我們發現現今被用來切割發光二極體晶粒的雷射劃線(laser scribing)技術,不僅不會造成發光二極體的側面光取出強度,甚至於可以經由優化雷射劃線的參數進一步增加發光二極體的側面光取出強度。本論文的研究結果顯示,優化後的雷射劃線參數可以增加發光二極體大約12%的光取出強度,本論文證明增加側光取出強度的重要關鍵是因為雷射畫線參數的優化,而使得藍寶石基板的側壁變的更加地粗糙,粗糙的側壁降低了光在藍寶石基板/空氣的界面發生全反射(total internal reflection)的機率。第二部分,本論文為了改善發光二極體的電極吸光效應,因此本論文改變了傳統發光二極體的電極結構。本論文將一般常用來作為發光二極體的金(gold)電極改為銀(silver)。由於銀的反射率(90%)遠大於金的反射率(55%),因此有助於改善發光二極體的電極吸光效應。由本論文的實驗結果顯示,比較銀電極與金電極所製作而成的發光二極體,可以明顯比較出使用銀作為電極的發光二極體的光取出強度相較於使用金電極的發光二極體增加約15%。另一方面,隨著黃金價格十年來不斷高漲,本論文估算結果顯示將發光二極體的金電極改用銀電極可以大幅降低生產成本。
在高功率發光二極體的研究範疇中,我們提出以電鍍銅的技術來取代封裝結構中用來固定晶片的膠,因為膠的熱傳導係數通常遠小於銅。在傳統的發光二極體結構中, 固晶膠是用來將發光二極體晶片固定在散熱座( heat sink)或是支架(lead frame)上的材料,然而卻因為它的熱傳導係數低而造成高功率發光二極體的散熱能力受到限制,因而使得發光二極體的性能在高電流條件操作下受到嚴重的損壞。本論文為了改善由固晶膠所造成的散熱問題因此改以電鍍銅層來取代封裝結構中的固晶膠體,實驗結果顯示不僅可以有效地改善高功率發光二極體的散熱問題,並且大幅地增加元件的光輸出功率。
英文摘要 In this thesis, we focus our research on light extraction and heat dissipation of light emitting diodes (LEDs). We proposed two different methods for light extraction, while also using electroplating technology to improve heat dissipation of high power LEDs.
The light extraction research was divided into two parts. In the first part, we discovered that laser scribing not only failed to lower LED side light extraction, but actually increased it through the optimization of laser scribing parameters. The results showed that laser scribing increased light extraction of LEDs by about 12%. One of the critical elements is that the LED side wall increased in roughness, thus lowering the chance of total internal reflection at the sapphire/air interface. In the second part of our research, we changed the conventional electrode composition of LEDs in general common-saver from gold-based to silver-based electrodes to improve the absorption of light by electrodes. Results from the experiment showed that, when compared to gold-based electrodes, silver-based electrodes not only significantly increased light extraction of LEDs by approximately 15%, but can also significantly reduced the manufacturing cost of LEDs.
When studying high power LED heat dissipation, we recommend that electroplated copper be used to replace resin in package structure to overcome the characteristic of resin as a low thermal conductivity material. In conventional high power LED package structure, resin is used to affix LEDs to the heat sink (lead frame). But since resin’s low thermal conductivity limit the heat dissipation ability of high power LEDs and can cause major damage to LED performances during high current conduction operation, using electroplating copper in place of resin in package structure can effectively improve the heat dissipation problem, and thus increase the output power of LEDs.
論文目次 Abstract (in Chinese) i
Abstract (in English) ii
Acknowledgement iii
Contents iv
Table Captions v
Figure Captions vi
Chapter 1 Introduction 1
1-1 A Brief History of Light-Emitting Diodes (LED) 1
1-2 Organization of this Dissertation 4
Chapter 2 Current Status and Challenges of Light Emitting Diodes 6
2-1 Manufacture of Light Emitting Diodes 6
2-2 Conventional LED Technical Challenges 7
Chapter 3 Enhanced Light Extraction from GaN-based LEDs 11
3-1 Laser Scribing of Sapphire Substrate to Increase Side Light Extraction of GaN-Based Light Emitting Diodes 12
3-1-1 Motivation 12
3-1-2 Device Fabrication 14
3-1-3 Results and Discussion 15
3-1-4 Summary 18
3-2 Enhancement in Light Extraction of GaN-based Light Emitting Diodes with High Reflectivity Electrodes 19
3-2-1 Motivation 19
3-2-2 Device Fabrication 20
3-2-3 Results and Discussion 21
3-2-4 Summary 23
Chapter 4 Thermal Management and Novel Package Design of High Power Light-Emitting Diodes 38
4-1 Motivation 38
4-2 Experiment 39
4-3 Results and Discussion 40
4-4 Summary 41
Chapter 5 Conclusion and Prospect 47
5-1 Conclusion 47
5-2 Prospect 48
Reference 49
Publication list 56
Vita 58
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系統識別號 U0026-1508201310394400
論文名稱(中文) Fluoroquinolone 於臺灣小兒病患使用之處方型態分析
論文名稱(英文) The Prescribing Pattern of Fluoroquinolone in Pediatric Patients in Taiwan
校院名稱 成功大學
系所名稱(中) 臨床藥學與藥物科技研究所
系所名稱(英) Institute of Clinical Pharmacy and Pharmaceutical sciences
學年度 101
學期 2
出版年 102
研究生(中文) 徐憶芬
學號 s66001036
學位類別 碩士
語文別 中文
口試日期 2013-07-23
論文頁數 115頁
口試委員 指導教授-高雅慧
口試委員-劉清泉
口試委員-柯文謙
口試委員-高淑敏
口試委員-鄭靜蘭
關鍵字(中) Fluoroquinolone
小兒
抗生素
處方型態
骨骼肌肉不良反應
關鍵字(英) Fluoroquinolone
antibiotics for pediatrics
prescribing patterns
musculoskeletal disorders
學科別分類
中文摘要 研究背景
Fluoroquinolone殺菌範圍廣泛,於臨床上具有重要治療角色。然而,自1962年第一位因使用fluoroquinolone而發生骨骼肌肉不良反應的案例發表後,至1977年間,許多動物試驗也顯示用於發育未成熟的動物,易發生骨關節病變,尤其以下肢承重關節最為常見。因此,開始有專家認為fluoroquinolone不應使用於小兒族群。2006年美國小兒科醫學會提出,建議限制fluoroquinolone用於18歲以下小兒病患。在國內fluoroquinolone抗生素,仍經常被處方使用於上呼吸道感染的小兒族群,國內處方盛行率又略高於美國。因此,本研究目的希望藉由觀察1998~2010年,長達13年的健保資料庫之就醫資料,分析fluoroquinolone於臺灣小兒族群與處方型態與處方合理性等,並初步探討使用fluoroquinolone並且同時被診斷為骨骼肌肉相關疾病的發生率。

研究方法
本研究利用1997年至2010年全民健康保險資料庫,於2010年抽樣之百萬人抽樣歸人檔,篩選18歲以下,其用藥紀錄含有依ATC(Anatomical Therapeutic Chemical) code為全身性fluoroquinolone之國內已上市藥品。排除1997 年以前,曾被處方全身性fluoroquinolone 抗生素之病患,並排除2010
年11 月30 日前,尚未完成治療療程之處方。分析研究族群之基本資料、處方盛行率、診斷合理性、藥品使用趨勢等。並自處方日至停藥後30 天內,評估處方fluoroquinolone,與於觀察時間內同時被診斷骨骼肌肉相關疾病的發生率、共病症以及首次處方fluoroquinolone 前180 天內,已被診斷骨骼肌肉相關疾病的比率等情況。

研究結果
1998~2010年,門診處方共124,121筆,就醫人數共50,138人;住院處方共790筆,就醫人數共695人。處方盛行率於2000年最高為5.34%,之後便逐年下降。門診處方以上呼吸道感染為主要診斷,並以ofloxacin為主要處方藥品。住院處方則以泌尿生殖系感染與肺炎為主要診斷,以ciproflocxacin為主要處方藥品。處方fluoroquinolone並於觀察時間內,同時被診斷骨骼肌肉相關疾病之比率為0.6~0.95%。其中,以處方levofloxacin為最多。

結論
Fluoroquinolone於臺灣小兒病患處方有逐年下降的趨勢。但門診處方用於上呼吸道感染比率(50.62%)偏高,可能屬於不合理現象。因此,建議藉由醫療政策介入,加強醫療人員與小兒病患父母,對抗生素與上呼吸道感染疾病的認知,以期降低不合理處方。而處方fluoroquinolone並同時有骨骼肌肉相關疾病之診斷比率低於國外,然其因果關係仍須進一步探究。
英文摘要 Background
Fluoroquinolone are broad-spectrum antibiotics that play an important role in treatment of serious bacterial infections. However, in 1962, the first case of musculoskeletal adverse events occurred after taking fluoroquinolone. Until 1977, many animal studies revealed that juvenile animals developed bone and joint disease, particularly in bearing joints of lower limbs. Therefore, pediatric specialists recommended that fluoroquinolone antibiotics would not be given to children. In 2006, a recommendation was proposed by the American Academy of Pediatrics that fluoroquinolone should not be prescribed to children under age of eighteen. Nevertheless, fluoroquinolone antibiotics are commonly used on pediatric patients with upper respiratory tract infection in Taiwan; moreover, the prescriptions of fluoroquinolone are given more frequently in Taiwan than in US. Therefore, the purpose of this research is to analyze the prevalence and rationality of giving fluoroquinolone in pediatrics, and investigating the incidence of coexisting of giving fluoroquinolone to child and diagnosing as musculoskeletal diseases.

Methods
In this research, we used the Longitudinal Health Insurance Database 2010(LHID 2010), which consisted health data of one million populations. We excluded the individuals had been prescribed systemic use of fluoroquinolone and the study population aged under or equal to 18 years old. We analyzed the prescribing pattern and evaluated the musculoskeletal diseases diagnosed during the observation time.

Results
In the cohort of LHID 2010, from 1998 to 2010, the numbers of fluoroquinolone of prescriptions for pediatric patients we listed in following. The outpatient prescription number was 124,121 and the patient visit was 50,138 the inpatient prescription number was 790 and the patient visit was 695. The prevalence of fluoroquinolone prescription was 5.34% in 2000 and decreasing. The major diagnose given to outpatient was upper respiratory tract infection and was commonly prescribed with oflocxacin. On the other hand, ciprofloxacin was prescribed to inpatients with diagnoses of genitourinary infection and pneumonia. The coexisting rate of prescription of fluoroquinolone over the diagnoses of musculoskeletal diseases was 0.6% to 0.95%. During the observational period, levofloxacin was used most frequently; nevertheless, the causal relationship should be studied further in the future.

Conclusion
The prescription number of fluoroquinolone antibiotics in pediatrics was decreasing. However, it might not be reasonable that fluoroquinolone given to outpatient children with upper respiratory tract infection (50.62%).Therefore, to improve the awareness of antibiotics usage in the upper respiratory tract infection in clinical practitioners and parents to decrease irrational prescriptions. The coexisting rate prescription of fluoroquinolone over the diagnoses of musculoskeletal in Taiwan is lower than the rate in foreign countries. However, further study on association is suggested.
論文目次 目錄
摘要 I
Abstract III
致謝 V
目錄 VI
表目錄 IX
圖目錄 XI
第一篇、 Fluoroquinolone 於臺灣小兒病患使用之處方型態分析 1
第一章、研究背景 1
第二章、文獻回顧 2
第一節、Fluoroquinolone抗生素簡介 2
第二節、Fluoroquinolone臨床治療建議與在小兒族群之使用限制 5
第三節、Fluoroquinolone處方型態相關研究 7
壹、抗生素處方管制 7
貳、小兒抗生素處方型態分析研究 7
叁、Fluoroquinolone於小兒族群處方分析研究 8
第三節、Fluoroquinolone與骨骼肌肉不良反應 10
壹、Fluoroquinolone與骨骼肌肉藥物不良反應的相關性 10
貳、Fluoroquinolone引起骨關節、肌腱、肌肉藥物不良反應的機轉 12
叁、Fluoroquinolone於小兒族群引起骨骼肌肉不良反應之研究 15
第五節、總結 20
第三章、研究目的與重要性 21
壹、研究目的 21
貳、重要性 21
第四章、研究方法 22
第一節、研究設計 22
壹、研究類型 22
貳、研究材料及工具 22
參、研究對象 24
肆、研究分組 24
伍、資料呈現 24
陸、研究流程 26
第二節、研究變項與操作定義 29
壹、研究藥物定義 29
貳、Fluoroquinolone處方型態分析 31
參、骨骼肌肉不良反應分析 35
第三節、資料處理流程 39
第四節、統計資料分析 40
壹、統計工具 40
貳、統計資料分析 40
第五章、研究結果 41
第一節、研究族群納入與排除 41
第二節、處方數、就醫人數 43
壹、門診與住院處方數與就醫人數 43
貳、門診處方治療時間與藥品申報比率 45
第三節、研究族群基本資料 50
壹、研究族群就醫人數之性別、年齡分布比率 50
貳、就醫層級、就醫地區之就醫人次分布 54
叁、就醫科別 56
第四節、處方型態 58
壹、處方盛行率 58
貳、處方趨勢分析 58
貳、Fluoroquinolone處方數之用藥品項分析 60
叁、診斷分析 64
第五節、骨骼肌肉不良反應 71
壹、骨骼肌肉不良反應者基本特性 71
貳、骨骼肌肉不良反應結果 72
叁、共病症 80
肆、回溯不良反應者過去180天出現骨骼肌肉不良反應比率 81
伍、骨骼肌肉不良反應比率 82
陸、Fluoroquinolone相關骨骼肌肉不良反應之藥品比率 83
第六章、研究討論 85
第一節、研究族群基本資料分析 85
第二節、處方趨勢與處方盛行率分析 86
第三節、藥品使用趨勢分析 88
第四節、處方診斷分析 89
壹、感染診斷率 89
貳、住院處方感染診斷分析 89
叁、門診處方感染診斷分析 92
第五節、骨骼肌肉不良反應分析 95
第六節、研究限制 97
第七章 結論與建議 99
第八章、未來研究方向 100
第二篇、探討改善住院藥局歸藥錯誤之成效 101
第一章、 服務背景 101
第二章、目的與方法 102
第一節、服務目的 102
第二節、服務方法 102
第三節、執行流程 104
第四章、服務結果 105
第五章、討論 107
第六章、臨床藥事服務心得 109
參考文獻 110


表目錄
第一篇
Table 2.1-1 國內已上市fluoroquinolone藥品 4
Table 2.3-1 各藥品引起骨骼肌肉不良反應毒性與發生率 18
Table 2.2-2 骨骼肌肉不良反應發生時間與緩解時間 19
Table 4.1.2-1各檔案間串檔變項說明 22
Table 4.2.1-1全身性fluoroquinolone抗生素 29
Table 4.2.2-1醫療院所地理區域 37
Table4.2.2-2 感染相關診斷之ICD-9 Code 37
Table 4.2.3-1骨骼肌肉不良反應與ICD-9 Codes 38
Table 4.2.3-2共病症與ICD-9 Codes 38
Table 5.2.2-1門診處方治療時間 3846
Table 5.2.2-2門診處方申報分布比率 3847
Table 5.3.1-1 1998-2010年研究族群就醫人數性別分布 51
Table 5.3.1-2 1998~2010年研究族群就醫人數與18歲以下就醫人數年齡布 53
Table 5.3.2-1 1998~2010年就醫層級之就醫人次分布 55
Table 5.3.2-2 1998~2010年就醫地區之就醫人次分布比率 55
Table 5.3.3-1門診與住院就醫科別之就醫人次分布 57
Table 5.4.1-1門診與住院就醫人數與18歲以下病患就醫人數 59
Table 5.4.2-1 Fluoroquinolone用藥品項分布比率 62
Table 5.4.2-2 1998~2010年fluoroquinolone門診總處方數用藥品項分布率 63
Table 5.4.2-3 1998~2010年fluoroquinolone住院總處方數用藥品項分布率 63
Table 5.4.3-1 1998~2010年門診感染相關診斷分布 67
Table 5.4.3-2 1998~2010年住院感染相關診斷分布 68
Table 5.4.3-3 1998~2010年門診前10項主要診斷統計 69
Table 5.4.3-4 1998~2010年住院前10項主要診斷統計 69
Table 5.5.1-1與fluoroquinolone可能引起的骨骼肌肉不良反應相關性低之
ICD-9 code 統計 74
Table 5.5.1-2各年度發生骨骼肌肉不良反應人數與就醫人數 75
Table 5.5.1-3骨骼肌肉不良反應者之基本特性 76
Table 5.5.1-4骨骼肌肉相關不良反應之ICD-9 code前三碼比率分析 77
Table 5.5.1-5骨骼肌肉不良反應主要診斷 78
Table 5.5.3-1骨骼肌肉不良反應者回溯其不良反應起始日前730天共病率 80
Table 5.5.6-1 Fluoroquinolone與骨骼肌肉不良反應相關之藥品比率 84


第二篇
Table 2.2-1 歸藥時需重複核對品項 102
Table 2.2-1 臨時歸藥和藥品外觀標示圖 103
Table 4.1-1 研究期間通報歸藥錯誤品項與筆數 106
Table 4.1-2 「重複核對」花費時間與退藥數量、歸藥錯誤筆數統計 106


圖目錄
第一篇
Figure 4.1.6-1研究流程 27
Figure 4.1.6-2骨骼肌肉不良反應研究流程 28
Figure 4.2.1-1處方數之定義 30
Figure 5.1-1 研究族群納入與排除 42
Figure 5.2.1-1門診處方數與就醫人數 42
Figure 5.2.1-2住院處方數與就醫人數 42
Figure 5.2.2-1門診處方申報分布比率 42
Figure 5.3.1-1 1998~2010年研究族群就醫人數年齡分布比率 52
Figure 5.4.1-1各年度fluoroquinolone處方盛行率 59
Figure 5.4.2-1 Fluoroquinolone藥品處方分布比率 61
Figure 5.4.3-1 1998~2010 年門診就醫人次診斷分布 70
Figure 5.4.3-2 1998~2010 年住院就醫人次診斷分布 70
Figure 5.4.3-3 1998~2010年門診單一感染診斷統計 70
Figure 5.5.1-1骨骼肌肉不良反應研究流程與結果 73
Figure 5.5.1-2各年度發生骨骼肌肉不良反應人數與就醫人數百分比 75
第二篇
Figure 4.1-1 「重複核對」步驟於臨時歸藥盒發現之歸藥錯誤筆數……….100
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系統識別號 U0026-1607201218221300
論文名稱(中文) 台灣小兒門診抗憂鬱劑之處方型態分析
論文名稱(英文) Prescribing pattern of antidepressants for pediatric patients in ambulatory care in Taiwan
校院名稱 成功大學
系所名稱(中) 臨床藥學與藥物科技研究所
系所名稱(英) Institute of Clinical Pharmacy and Pharmaceutical sciences
學年度 100
學期 2
出版年 101
研究生(中文) 吳承誌
學號 s66981066
學位類別 碩士
語文別 中文
口試日期 2012-07-04
論文頁數 111頁
口試委員 指導教授-高雅慧
口試委員-楊延光
口試委員-李怡慧
口試委員-林嘉音
關鍵字(中) 抗憂鬱劑
處方型態
兒童青少年
台灣
全民健康保險資料庫
關鍵字(英) antidepressants
prescribing pattern
children and adolescents
Taiwan
NHIRD
學科別分類
中文摘要 研究背景
抗憂鬱劑已被證實能有效改善憂鬱症或焦慮症等精神疾患症狀。受限於倫理因素,往往較難於兒童與青少年族群進行臨床試驗,而無法取得使用於該族群之核准適應症。各國於2003年起陸續發布的警訊指出抗憂鬱劑使用於小兒族群可能提高自殺風險。上述因素皆顯示出缺乏小兒族群使用抗憂鬱劑之療效與安全性資訊,更彰顯利用資料庫進行兒童與青少年族群的回溯研究重要性。
目前台灣使用抗憂鬱劑相關研究付之闕如,惟部分研究著眼於精神疾患盛行率或以成年人為研究對象,較難外推至兒童與青少年族群使用抗憂鬱劑之情況。因此,本研究旨在討論兒童與青少年族群之抗憂鬱劑使用之處方型態,探討其使用盛行率、各類抗憂鬱劑之比例及病患之臨床特性等議題。

研究方法
本研究利用全民健康保險資料庫進行分析,檔案擷取2006年至2007年,年齡小於18歲之兒童或青少年,以3:1的比例隨機抽樣,先行檢視2006年與2007年之盛行率。納入2006/07/01至2007/12/31於門診新使用抗憂鬱劑處方的病患,分析其第一筆處方。研究對象依其使用藥物種類分成selective serotonin reuptake inhibitors (SSRI)、serotonin norepinephrine reuptake inhibitors (SNRI)、tricyclic antidepressant (TCA)及其他 (others)等四組,分析其使用種類、臨床特性,包括人口學特徵、精神相關診斷(mental disorder)、共病症(co-morbidity)、合併使用精神藥物(psychotropic co-medication)情形、精神門診就醫次數(psychiatric visits)與住院次數(psychiatric hospitalization)、開立處方醫師專科別與醫療機構等級。
研究結果
兒童與青少年於2006年及2007年使用抗憂鬱劑之盛行率分別為0.39%及0.44%。在SSRI、SNRI、TCA、其他類等四組使用頻率最高之藥品分別為fluoxetine、venlafaxine、imipramine和trazodone。大部分抗憂鬱劑使用族群為女性及13-18歲,SSRI使用於憂鬱症、焦慮症、強迫症、飲食疾患與雙極性情感疾患,TCA多使用於偏頭痛、夜尿或頻尿等疾病,SNRI則常用於憂鬱症、焦慮症及睡眠障礙。最常與抗憂鬱劑合併使用之精神藥物依序為anxiolytics、hypnotics & sedatives和stimulant。

結論
TCA與其他抗憂鬱劑(SSRI、SNRI和others)的使用情形有較大差異,包括年齡、性別等。SSRI、SNRI及其他類藥物以治療精神相關疾病為主,TCA有較高比例用於偏頭痛及尿液相關疾病。
英文摘要 Background
Antidepressants are proved to be effective on alleviating the depressive or anxious symptoms. Lack of clinical trials including children and adolescents due to ethical considerations would limit efficacy and safety data of antidepressants use, and restrict authorized indications. Promulgated warnings in pediatric population indicate that antidepressants use may elevate suicidal risk. According to those mentioned above, it is worth conducting retrospective database research to obtain some information in this population.
There were some studies on antidepressants conducted in Taiwan. Weakness such as lack of drug use information and limited subjects impeded an overview of antidepressants use in these populations in real world, and could not be extrapolated from adult population. The study aimed to focus on the prescribing pattern of antidepressants use on children and adolescents, and investigate the prevalence of antidepressants use in 2006 and 2007, the proportion of different categories of antidepressants, and clinical characteristics of target population.

Methods
First of all, we surveyed the antidepressants prevalence in 2006 and 2007 utilizing the 3:1 sampled National Health Insurance claims database (NHIRD) composed of children and adolescents younger than 18 years old. Next, we identified the first outpatient antidepressant prescription between 1 July 2006 and 31 December 2007, and we focus on analyzing the first prescription. We divided those population into four groups based on antidepressants use: SSRI, SNRI, TCA, and others. Clinical characteristics, such as demographic traits, mental disorder, co-morbidity, psychotropic co-medication, psychiatric visits, psychiatric hospitalization, physician specialty, hospital ranking, would be further investigated.

Results
The study showed that prevalence of antidepressants use in children and adolescents was 0.39% and 0.44% in 2006 and 2007, respectively. Leading drugs of SSRI, SNRI, TCA, and others were fluoxetine, venlafaxine, imipramine and trazodone, respectively. Those who were female or age between 13-18 years old were the major antidepressant users. SSRI were applied to treat depressive disorder, anxiety disorder, obsessive compulsive disorder, eating disorder, and bipolar disorder. TCA were mostly used for migraine, enuresis and urinary frequency. Lastly, SNRI were found to be prescribed for depressive disorder, anxiety disorder, and sleep disorder. The most concurrent psychotropic agents were anxiolytics, hypnotics & sedatives, and stimulants.

Conclusions
Utilization of TCA group presented a different trait compared with other groups, including age and gender. SSRI, SNRI, and others were mainly used for psychiatric diseases, while TCA was observed that migraine and urinary diseases were the major application.
論文目次 摘要 I
Abstract III
誌謝 V
目錄 VII
表目錄 X
圖目錄 XII
第一篇、台灣小兒門診抗憂鬱劑之處方型態分析 1
第一章、研究背景 1
第二章、文獻回顧 3
第一節、抗憂鬱劑之藥理機轉、特性與臨床作用 3
一、SSRI 3
二、SNRI 5
三、TCA 5
四、MAOI 6
五、Others 7
六、小結 7
第二節、抗憂鬱劑於小兒族群之臨床試驗、各國核准適應症與小兒精神疾患臨床治療指引 12
第三節、抗憂鬱劑處方型態相關研究 19
一、盛行率(prevalence)、性別與年齡分布 19
二、抗憂鬱劑種類與臨床診斷 20
第三章、研究目的與重要性 22
第四章、研究方法 23
第一節、研究設計 23
一、研究類型 23
二、研究材料與工具 23
三、研究對象與排除條件 25
四、基本資料 25
五、分組 26
六、研究流程 26
第二節、研究名詞、研究變項與操作定義 28
一、研究對象與研究藥品之定義 28
二、研究族群基本資料之定義 28
第三節、資料處理流程 34
第四節、統計資料分析 35
一、統計工具 35
二、統計模式設定 35
三、統計資料分析 35
第五章、研究結果 37
第一節、研究對象收入、排除與分組 37
第二節、兒童與青少年使用抗憂鬱劑之盛行率 37
第三節、各類抗憂鬱劑使用品項 37
第四節、病患基本特性 38
第五節、SSRI及TCA於憂鬱症治療之情形 46
第六章、研究討論 51
第一節、研究對象排除、收入與分組之分析 51
第二節、台灣小兒族群使用抗憂鬱劑盛行率分析 52
第三節、各類抗憂鬱劑使用品項之探討 55
一、SSRI 55
二、SNRI 56
第四節、病患基本特性之探討 57
一、抗憂鬱劑類別與性別年齡分布 57
二、Mental disorder & co-morbidity 58
三、精神門診就醫次數及精神疾患住院次數 62
第五節、SSRI及TCA於治療憂鬱症之探討 64
第六節、研究限制 66
第七章、結論與建議 67
第八章、未來研究方向 68
第二篇、過敏藥警訊系統建置與介面構想 69
第一章、服務背景 69
第二章、服務目的、工具與編纂流程 71
第一節、服務目的 71
第二節、服務工具與編纂流程 71
第三章、服務結果 73
第四章、服務結果探討與討論 78
第五章、如何改善過敏藥警訊系統? 85
第六章、實際應用 89
第七章、結論及未來方向 91
參考文獻 92
附錄:ATC code of categories 102

第一篇
Table 2.1-1 Pharmacological profile of SSRIs 4
Table 2.1-2 Overview of antidepressant use on psychiatric and non-psychiatric diagnoses & side effects 8
Table 2.2-1 Clinical studies of SSRI & SNRI 10
Table 2.2-2 FDA-, TFDA-, and UK-approved indication on antidepressants in pediatric population 10
Table 2.2-2 FDA-, TFDA-, and UK-approved indication on antidepressants in pediatric population (cont.) 11
Table 2.2-3 Clinical recommendation on psychiatric disorders in pediatric population 14
Table 2.3-1 Prevalence of antidepressants use in pediatric population 16
Table 2.3-2 Antidepressant subclasses and diagnoses in pediatric patients 17
Table 4.1-1各檔案間串檔變項說明 24
Table 4.2-1 Antidepressants and corresponding ATC codes 30
Table 4.2-2 Region of residence in Taiwan 31
Table 4.2-3共同使用精神相關藥品 31
Table 4.2-4 ICD-9-CM codes and corresponding diagnoses 33
Table 5.2-1 Prevalence of antidepressants use in Taiwan in 2006 and 2007 40
Table 5.4-1 Baseline characteristics of antidepressant users in pediatric population 42
Table 5.5-1 Baseline characteristics of SSRI &TCA users diagnosed with depressive disorder 48
Table 5.5-2 Average daily dosage in TCA users 50
Table 5.5-3 Dosage of TCA for depression treatment in pediatric population 50
Table 6.4-1 Comparison of antidepressants categories, gender & age distribution, and clinical diagnosis among different studies 59
第二篇
Table 2.2-1 Example of ciprofloxacin based on ATC system 72
Table 2.3-1初步排除範疇之範例列舉 74
Table 2.3-2正確性評估之項目範例列舉 74
Table 2.3-4純口服藥品<只列出前十名> 76
Table 2.3-5純針劑藥品<只列出前十名> 76
Table 2.3-6兼具針劑與口服劑型之藥品<只列出前十名> 77
Table 4.1-1藥品品項討論爭議與共識 81
Table 5.1-1 Common categories of drug allergy profiles 87
Table 6.1-1醫療品質暨病人安全委員會提案單 (節錄) 89
Table 6.1-2 Concise drug allergy categories 90
附錄:ATC code of categories 102

第一篇
Fig 4.1-1研究流程 27
Fig 5.1-1研究對象收入、排除與分組情況 39
Fig 5.3-1 Leading drugs of different pharmacological properties on antidepressants 41
Fig 6.2-1 Prevalence in different countries 54
第二篇
Fig 2.2-1 Algorithm of editing process 72
Fig 2.3-1 Algorithm of editing process & results 73
Fig 2.3-2正確性評估比例圖 77
Fig 5.1-1 Proposed design of drug allergy alerting system 86

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系統識別號 U0026-1608201117252800
論文名稱(中文) 臺灣機械性心臟瓣膜置換病患之抗血栓劑使用評估
論文名稱(英文) Utilization of Antithrombotic Agents in Patients with Mechanical Heart Valves in Taiwan
校院名稱 成功大學
系所名稱(中) 臨床藥學研究所
系所名稱(英) Institute of Clinical Pharmacy
學年度 99
學期 2
出版年 100
研究生(中文) 王郁文
學號 s6696402
學位類別 碩士
語文別 中文
口試日期 2011-07-18
論文頁數 174頁
口試委員 指導教授-高雅慧
指導教授-葉鳳英
口試委員-林立人
口試委員-羅傳堯
關鍵字(中) 機械性心臟瓣膜
心臟瓣膜置換
抗血栓劑
處方型態
關鍵字(英) mechanical heart valve
heart valve replacement
antithrombotic
prescribing patterns
學科別分類
中文摘要 研究背景
數十年來,學界一致認為置換過機械性心臟瓣膜的病人必須終身使用口服抗凝血劑。然而,在抗凝血劑的使用之下,每年仍然有1‐3%的病人發生嚴重栓塞事件,因此開始有人提倡加上抗血小板製劑來預防。經眾多臨床試驗證實,併用抗血小板製劑確實可以顯著降低血栓栓塞風險,但也伴隨著出血風險的提高。在風險與效益難以清楚斷定之下,美國三大相關學會(ACC、AHA、ACCP)及歐洲心臟學會(ESC)對於機械性心臟瓣膜置換病患,是否需併用抗凝血劑和抗血小板製劑,十多年來一直處於意見分歧的情況。本研究之目的即在於檢視臺灣病患置換機械性心臟瓣膜後,抗血栓劑的使用情況,並且探討其接受口服抗凝血劑和抗血小板藥品合併治療的影響因子。

研究方法
利用未抽樣的全民健康保險資料申報檔,找出在2001年1月1日至2004年6月30日之間置換機械性心臟瓣膜之病患。手術出院後30天內在門診曾被處方任一口服抗血栓劑(warfarin、aspirin、ticlopidine、clopidogrel或 dipyridamole)者始納入研究。追蹤所有研究對象在指標日期後30天內五種抗血栓劑的使用情況,並使用羅吉斯複迴歸找出臺灣機械性心瓣置換病患接受抗凝血劑與抗血小板製劑合併療法的影響因子。

結果
共2,830人納入抗血栓劑使用型態的分析,平均年齡為55.4歲,其中2,818人(99.6%)在追蹤期間曾使用warfarin。追蹤期間(30天)內併用warfarin與任一抗血小板製劑達15天以上者共223人(7.9%),之中有95%的病患是由同一位醫師同時處方warfarin和抗血小板製劑。進一步分析影響病人接受到合併療法的因素,置換瓣膜同時施行冠狀動脈繞道手術(OR: 8.12, 95% CI: 5.70-11.57, p<0.0001)和有心肌梗塞病史(OR: 2.02, 95% CI: 1.21-3.40, p=0.0077)會顯著增加合併療法處方率。

結論
臺灣機械性心臟瓣膜置換者服用口服抗凝血劑的比例接近百分之百,此外,確實有少部分的病患使用口服抗凝血劑與抗血小板製劑合併療法,顯著影響合併療法處方率的因素僅有「同時施行冠狀動脈繞道手術」和「心肌梗塞」。
英文摘要 Background
Lifelong oral anticoagulant treatment has been recommended for all patients with mechanical heart valves for several decades. However, even with the use of oral anticoagulants, major systemic embolism still occurs at a rate of 1-3% per year. To further reduce the risk, addition of an antiplatelet agent has been evaluated and advocated. According to the results of several clinical trials, adding antiplatelet to oral anticoagulation decreased the risk of systemic embolism, but slightly increased the risk of bleeding. Because there is no definitive benefit of adding antiplatelet, recommendations of combining anticoagulant and antiplatelet for patients with mechanical valves are inconsistent between ACC/AHA, ACCP and ESC guidelines. The aim of this study was to survey the utilization patterns of antithrombotic agents in patients after mechanical heart valve replacement in Taiwan and identify factors associated with receiving combination therapy of anticoagulant and antiplatelet.

Methods
We identified patients undergoing mechanical heart valve replacement between 1 January 2001 and 30 June 2004 from non-sampled National Health Insurance claims database. Patients were eligible if having prescriptions of any antithrombotics (warfarin, aspirin, ticlopidine, clopidogrel or dipyridamole) within 30 days after discharge. We investigated the utilization of antithrombotic agents for 30 days after valve replacement. Combination therapy was defined as receiving warfarin and any antiplatelet both for 15 days and over during follow-up. Logistic regression was performed to identify factors associated with combination therapy by using SAS version 9.2.

Results
2,830 patients were identified and met the inclusion and exclusion criteria (mean age 55.4 years). 2,818 patients (99.6%) had received warfarin during 30 days follow-up. 223 patients (7.9%) received combination of warfarin and antiplatelets at least 15 days, and 95% of them had been prescribed warfarin and antiplatelets by the same doctor. Concomitant coronary artery bypass grafting (OR: 8.12, 95% CI: 5.70-11.57, p<0.0001) and a history of myocardial infarction (OR: 2.02, 95% CI: 1.21-3.40, p=0.0077) significantly increased the probability of receiving combination therapy.

Conclusions
Nearly 100% of patients received oral anticoagulant after mechanical heart valve replacement in Taiwan. Besides, some of them received combination therapy of anticoagulant and antiplatelet. Independent predictors of combination therapy were concomitant CABG and history of myocardial infarction.
論文目次 第一篇、臺灣機械性心臟瓣膜置換病患之抗血栓劑使用評估 1
第一章、研究背景 1
第二章、文獻回顧 3
第一節、機械性心臟瓣膜之簡介 3
一、機械性心臟瓣膜之發展 3
二、機械性瓣膜與生物性瓣膜(bioprosthetic valves)之比較 6
第二節、瓣膜性心臟病與瓣膜置換手術 8
一、簡介與流行病學 8
二、風濕熱與風濕性心臟病 9
第三節、機械性心臟瓣膜引起血栓之理論機制 11
第四節、機械性心臟瓣膜置換病人之抗血栓劑療法 16
一、人工瓣膜相關的血栓栓塞風險 16
二、抗血栓劑個論 17
三、機械性心臟瓣膜置換病人之抗血栓劑治療發展 22
第五節、抗凝血劑與抗血小板製劑合併療法應用在機械性心臟瓣膜置換病人之臨床試驗 26
一、Aspirin與抗凝血劑合併療法 28
二、Dipyridamole與抗凝血劑合併療法 29
三、Ticlopidine與抗凝血劑合併療法 31
四、Clopidogrel與抗凝血劑合併療法 32
五、總結 33
第六節、國際準則建議之抗血栓劑療法 35
一、準則所建議的目標INR範圍 36
二、準則建議須併用OAC與抗血小板製劑的時機 37
三、準則所列出之血栓栓塞風險因子 38
四、準則建議併用的抗血小板製劑 39
五、總結 40
第三章、研究目的 46
第四章、研究方法 47
第一節、研究設計 47
一、研究類型 47
二、研究材料與工具 47
三、研究對象 49
四、研究名詞定義 51
五、觀察時間與觀察內容 52
六、影響研究對象是否接受合併療法的因子 52
七、分組 53
八、研究流程 54
第二節、研究變項與研究事件之操作定義 55
一、研究變項定義 55
二、研究事件定義 59
第三節、研究變項校正與每日劑量的計算 60
一、年齡校正 60
二、性別校正 60
三、藥品每日劑量計算 61
四、給藥天數校正 61
第四節、統計方法 62
一、統計工具 62
二、統計模式設定 62
三、資料分析方法 62
第五章、研究結果 64
第一節、研究對象納入、排除與分組 64
第二節、研究對象之特性分佈 67
第三節、置換瓣膜之廠牌與住院死亡率 75
一、置換瓣膜之廠牌 75
二、機械性心臟瓣膜置換手術之住院死亡率 76
第四節、追蹤期間抗血栓劑使用型態 78
一、機械性心臟瓣膜置換手術後口服抗凝血劑之使用率 78
二、追蹤期間(指標日期後30天內)抗血栓劑使用型態 78
第五節、OAC與抗血小板製劑合併療法預測因子 86
一、主要分析結果:併用OAC與任一種抗血小板製劑之預測因子 86
二、次分析結果:併用OAC與Aspirin之預測因子 91
第六章、研究討論 96
第一節、納入、排除條件與結果之探討 96
一、出院後30天內有門診處方的抗血栓劑為納入條件 96
二、排除年齡小於18歲者 97
三、排除懷孕者 98
第二節、研究族群人口特性 99
第三節、住院死亡率 100
一、與國內外研究之比較 100
二、瓣膜置換手術合併冠狀動脈繞道手術 101
第四節、抗血栓劑使用型態 105
一、抗血栓劑使用率 105
二、Warfarin之使用劑量 106
三、Dipyridamole之使用劑量 108
四、併用Aspirin或Dipyridamole之比較 109
第五節、OAC與抗血小板製劑合併療法預測因子 111
一、心肌梗塞 111
二、同時施行冠狀動脈繞道手術 113
第六節、研究限制 115
第七章、結論與建議 116
第八章、未來研究方向 117
第二篇、臨床藥事服務-Warfarin 與富含維生素K食物交互作用之文獻回顧與建議處置 118
第一章、服務背景 118
第二章、文獻回顧 119
第一節、維生素K簡介 119
第二節、Warfarin與維生素K交互作用之機轉 121
第三節、烹調造成的維生素K含量變動 123
第四節、不同食物來源的維生素K生體可用率差異 124
第五節、每日維生素K攝取量的安全變動範圍 125
第三章、建構臺灣常見富含維生素K食物的含量換算 133
第一節、參考資料與換算流程 133
第二節、臺灣常見富含維生素K食物之維生素K含量表 135
第三節、臺灣常見富含維生素K食物的含量換算表 139
第四章、Warfarin使用者日常食用富含維生素K食物之建議處置 140
第一節、相關文獻探討 140
第二節、建議處置 144
第三節、每日可容許的額外蔬果攝取量 146
第五章、結論 148
參考文獻 149
附錄一、各準則建議的抗血栓劑療法 161
附錄二、Warfarin與其他食物之交互作用 167

表目錄
表1、建議置換機械性心臟瓣膜的情況 7
表2、建議置換生物性心臟瓣膜的情況 7
表3、人工瓣膜相關的血栓栓塞風險 16
表4、抗血栓劑治療與否之血栓栓塞事件發生率 24
表5、血栓栓塞事件的多變項分析 25
表6、2007年ESC準則所訂定的目標INR 37
表7、1998年ACC/AHA準則建議之抗血栓劑療法 41
表8、2008年ACC/AHA準則建議之抗血栓劑療法 42
表9、1998年ACCP準則建議之抗血栓劑療法 43
表10、2001年ACCP準則建議之抗血栓劑療法 44
表11、2008年ACCP準則建議之抗血栓劑療法 45
表12、第一階段四項排除條件的排除人數 66
表13、分組的定義與人數 66
表14、研究對象之人口特性 70
表15、研究對象置換機械性心臟瓣膜的廠牌比例 75
表16、本研究之住院死亡率 77
表17、追蹤期間(30天)各個抗血栓劑的使用人數與每日劑量 80
表18、追蹤期間(30天)抗凝血劑與各個抗血小板製劑併用之型態 81
表19、Warfarin在兩組之間的每日劑量比較 83
表20、合併療法組的處方開立分析 84
表21、不同瓣膜置換部位之warfarin劑量 85
表22、OAC與抗血小板製劑合併療法之預測因子 87
表23、OAC與Aspirin合併療法之預測因子 92
表24、機械性心臟瓣膜置換手術之住院死亡率 103
表25、Warfarin平均劑量與INR測量值之華人(Chinese)研究 107
表26、2004年Schurgers等人之試驗流程 126
表27、口服抗凝血劑與維生素K交互作用之臨床試驗 131
表28、臺灣常見富含維生素K食物之維生素K含量表 135
表29、臺灣常見富含維生素K食物的含量換算表 139
表30、各種蔬菜每份之維生素K得分對照表 145
表31、每日可容許的額外蔬果攝取量 146
表32、凝血因子名稱與其半衰期 147

圖目錄
圖1、籠球型瓣膜 3
圖2、籠盤型瓣膜 3
圖3、傾斜圓盤型瓣膜 4
圖4、雙葉型瓣膜 5
圖5、心臟瓣膜 8
圖6、凝血路徑 14
圖7、血小板與凝血系統共同形成血栓之流程 15
圖8、Warfarin之作用機轉 18
圖9、Dipyridamole之作用機轉 20
圖10、合併療法組範例 53
圖11、研究對象納入與排除情況 65
圖12、在各年齡分層中合併療法病患佔全部族群比例 67
圖13、在各年齡分層中單一療法病患佔全部族群比例 67
圖14、追蹤期間warfarin與抗血小板製劑併用天數的比例分佈 82
圖15、納入病患的指標日期與指標出院日期之天數差距 97
圖16、實驗所用的碗 134
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178. Jarvis S, Li C, Bogle RG. Possible interaction between pomegranate juice and warfarin. Emerg Med J. Jan 2010;27(1):74-75.
179. Komperda KE. Potential interaction between pomegranate juice and warfarin. Pharmacotherapy. Aug 2009;29(8):1002-1006.
180. Blickstein D, Shaklai M, Inbal A. Warfarin antagonism by avocado. Lancet. Apr 13 1991;337(8746):914-915.

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系統識別號 U0026-1908201023332500
論文名稱(中文) 以振動輔助劃切法加工硬脆材料之研究
論文名稱(英文) An Investigation of Vibration-Assisted Scribing for Brittle Materials
校院名稱 成功大學
系所名稱(中) 機械工程學系碩博士班
系所名稱(英) Department of Mechanical Engineering
學年度 98
學期 2
出版年 99
研究生(中文) 柳世恆
學號 n1697462
學位類別 碩士
語文別 中文
口試日期 2010-07-07
論文頁數 56頁
口試委員 指導教授-王俊志
口試委員-李偉賢
口試委員-林昌進
關鍵字(中) 振動輔助劃切
延脆轉變深度
臨界切深
硬脆材料
關鍵字(英) vibration-assisted scribing
brittle-ductile transition depth
brittle material
critical depth of cut (CDC)
學科別分類
中文摘要 本文利用壓電致動器在刀具上產生橢圓振動,並以此振動劃切硬脆材料劃切形成振動輔助劃切。文中以鑽石刀劃切單晶矽,觀察振動輔助劃切與傳統劃切對矽的延脆轉變深度的大小,以及加工後在脆性破壞區及延性切削區的表面粗糙度。
硬脆材料的臨界切深與材料及刀具幾何有關,而本文使用的鑽石刀劃切矽之臨界切深為0.17μm,而在振動輔助劃切時,臨界切深會隨進給速度下降與切深方向振幅增加而增加,以進給速度10 μm/s、切深方向5μm的振動輔助劃切單晶矽,延脆轉變深度可達2μm,此值為傳統劃切的10倍。
振動輔助切削與傳統劃切在脆性破壞區時,溝槽底面的表面粗糙度Ra分別為0.3μm與0.9μm,Rmax分別為4 μm~10 μm及10 μm~14 μm。藉由振動輔助劃切可以降低矽的裂紋長度,使表面比傳統劃切平整。

關鍵字:振動輔助劃切;延脆轉變深度;臨界切深;硬脆材料
英文摘要 This thesis combines the elliptical tool vibration and brittle materials scribing process to generate vibration-assisted scribing. We use the vibration that is produced by the piezoelectric actuator to make the elliptical vibration on the tool. In this thesis, we select diamond tool to scribe silicon. This thesis also investigates the difference of brittle-ductile transition depth and surface roughness Ra, Rmax on finished silicon in both brittle and ductile regime between vibration-assisted scribing and traditional scribing.
The critical depth of cut (CDC) depends on material properties and tool geometry. The CDC is 0.17 μm as using the diamond tool we choose to scribe silicon, and CDC increase as feed rate decrease or cut depth vibration increase in vibration-assisted scribing. At feed rate 10 μm/s and cut depth vibration 5μm condition, CDC is 2 μm as 10 times than traditional scribing.
Compared with vibration-assisted scribing and traditional scribing in brittle zone, the surface roughness Ra is 0.3 μm and 0.9 μm respectively, and Rmax¬ is 4 μm~10 μm and 1 0μm~14 μm respectively by vibration-assisted scribing, the surface will be smoother than traditional scribing process in brittle zone because vibration-assisted scribing reduce the crack growth.

keywords:vibration-assisted scribing;brittle-ductile transition depth;brittle material;critical depth of cut (CDC)
論文目次 摘要 I
Abstract II
總目錄 III
表目錄 VI
圖目錄 VII
符號說明 XI
第一章 緒論 1
1.1 前言 1
1.2 研究動機 2
1.3 研究目的 2
1.4 文獻回顧 3
1.4.1 振動切削 3
1.4.2 硬脆材料加工 4
1.5 研究範疇及論文架構 6
第二章 振動輔助劃切 7
2.1 前言 7
2.2 矽晶圓劃切之介紹 8
2.3 振動輔助劃切介紹 9
2.4 臨界切深 12
2.5 橢圓切削之切屑厚度 13
第三章 硬脆材料劃切實驗 17
3.1 前言 17
3.2 實驗目的 18
3.3 實驗設備 18
3.4 實驗參數規劃 22
3.5 實驗方法與流程 26
3.5.1 單晶矽之劃切實驗方法 26
3.5.2 單晶矽之振動輔助劃切實驗方法 26
3.6 實驗流程與步驟 27
第四章 實驗結果與分析 28
4.1 前言 28
4.2 橢圓振動與力量感測器之校正 29
4.2.1 橢圓振動之校正 29
4.2.2 力量感測器之校正 30
4.2 傳統劃切與振動輔助劃切結果與比較 31
4.3.1 傳統劃切之實驗結果 31
4.3.2 振動輔助劃切之實驗結果 35
4.3.3 傳統劃切與振動輔助劃切之實驗結果比較 45
第五章 結論與建議 50
5.1 結論 50
5.2 建議 52
參考文獻 54
自述 56
參考文獻 1. Shamoto, E. and Moriwaki, T., ‘‘Study on Elliptical Vibration Cutting,’’ Annals of the CIRP, 43(1), pp. 35-38, 1994.
2. L. J. Wang and J. Zhao, ‘‘Influence on Surface Roughness in Turning with Ultrasonic Vibration Tool,’’ International Journal of Machine Tool andManifacture, Volume 27, pp. 181-190, 1987.
3. V. I. Babitsky and A. V. Mitrofanov, and V. V. Silberschmidt, ‘‘Ultrasonvically assisted turning of aviation materials: simulations and experimental study,’’ Proceedings of Ultrasonics International, Volume 42, pp. 81-86, 2004
4. J. Pujanaa and A. Riveroa, ‘‘Analysis of ultrasonic-assisted drilling of Ti6Al4V,’’ International Journal of Machine Tools and Manufacture ,Volume 49, pp. 500-508, 2009
5. Taghi Tawakoli and Bahman Azarhoushang, ‘‘Influence of ultrasonic vibrations on dry grinding of soft steel,’’ International Journal of Machine Tools and Manufacture, Volume 48, pp. 1585-1591,2008
6. V. I. Babitsky, and A. N. Kalashnikov, ‘‘Autoresonant control of ultrasonically assisted cutting,’’ Mechatronics Volume 14, pp. 91-114 ,2004
7. Taghi Tawakolia and Bahman Azarhoushang, ‘‘A study on ultrasonic elliptical vibration cutting of tungsten carbide,’’ Journal of Materials Processing Technology Volume 209, pp. 4459-4464, 2009
8. C. Zhang, R. Rentsch and E. Brinksmeier ‘‘Advances in micro ultrasonic assisted lapping of microstructures in hard–brittle materials: a brief review and outlook,’’ International Journal of Machine Tools and Manufacture Volume 50, pp. 728-736, 2010
9. Y.S. Liaoa and G.M. Yang ‘‘Vibration assisted scribing process on LCD glass substrate,’’ International Journal of Machine Tools and Manufacture Volume 50, pp. 532-537, 2010

10. D. A. Lucca, P. Chou, R. J. Hocken, ‘‘Effect of Tool Edge Geometry on the Nanometric Cutting of Ge,’’ Annals of the CIRP, 47, pp. 475-478, 1998
11. Jeong-Du Kim, Dong-Sik Kim, ‘‘Surface characteristics of magnetic-disk cutting using a single-crystal diamond tool in an ultraprecision lathe,’’ Journal of Materials Processing Technology, 59, pp.303-308, 1996
12. Siva Venkatachalama, Xiaoping Lib and Steven Y. Liang, ‘‘Predictive modeling of transition undeformed chip thickness in ductile-regime micro-machining of single crystal brittle materials’’ Journal of Materials Processing Technology, Volume 209, pp.3306-3319, 2009
13. P. Blake and R. Scattergood, ‘‘Ductile regime machining of germanium and silicon,’’ Journal of American Ceramic Society, 73 (4), pp. 949–957, 1990
14. Y.Y. Liao, ‘‘An Investigation of Material Responses in an Abrasive Machining of Brittle Materials’’ Doctorial Dissertation, Department of Mechanical Engineering of National Chang Kung University, 2009.
15. T.G. Bifano, T.A. Dow and R.O. Scattergood, ‘‘Ductile-regime grinding: a new technology for machining brittle materials’’, Journal of Engineering Industry Technology ASME, 113, pp. 184–189, 1991
16. M. Emartellotti, ‘‘An Analysis of the Milling Process,’’ Transaction of ASME, Vol. 63, pp. 677-700, 1941
17. M. Emartellotti, ‘‘An Analysis of the Milling Process,’’ Part 2: Down Milling,’’ Transaction of ASME, Vol. 67, pp. 233-251, 1945

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系統識別號 U0026-1908201416243200
論文名稱(中文) 台灣地區SLE病人類固醇之處方型態分析
論文名稱(英文) Pattern of Glucocorticoids in Taiwan SLE Patients
校院名稱 成功大學
系所名稱(中) 臨床藥學與藥物科技研究所
系所名稱(英) Institute of Clinical Pharmacy and Pharmaceutical sciences
學年度 102
學期 2
出版年 103
研究生(中文) 陳俊名
學號 s66001044
學位類別 碩士
語文別 中文
口試日期 2014-07-15
論文頁數 144頁
口試委員 指導教授-高雅慧
召集委員-劉明煇
口試委員-張慧真
口試委員-戴淑華
關鍵字(中) 類固醇
處方型態
全身性紅斑狼瘡
帶狀皰疹
關鍵字(英) Glucocorticoid
Prescribing patterns
Systemic lupus erythematosus
Herpes zoster
學科別分類
中文摘要 研究背景
全身性紅斑狼瘡(systemic lupus erythematosus,SLE)是一種侵犯到多重器官的慢性自體免疫疾病,患者必須長期使用藥物以控制病情。其中,類固醇是最常使用到的藥物。但類固醇長期服用,可能導致各種副作用的發生。然而類固醇使用的安全劑量目前尚未被明確定義,但每日劑量< 7.5毫克prednisone/天似乎有較少的副作用發生。因此,本研究希望能分析台灣地區SLE病人之治療用藥及類固醇的處方型態,並探討病患於SLE確診後,經由類固醇治療可能產生的各項共病症發生率為何。且針對類固醇使用與帶狀皰疹發生的相關性進行探討。

研究方法
本研究是一個全國性,以人群為基礎的回溯性世代研究,以台灣全民健康保險研究資料庫數據為資料來源。利用全民健康保險研究資料庫之重大傷病證明明細檔,擷取診斷代碼為「710.0」全身性紅斑狼瘡患者,且其第一筆重大傷病卡申請日期需介於2001年1月1日至2005年12月31日之間,定義為新確診之SLE患者。分析SLE確診後五年期間類固醇以及其他SLE治療用藥處方型態,並進行類固醇相關之共病症發生率分析。此外,本研究亦進行嵌入型病例對照研究。病例組與對照組兩組之間以年齡、性別為配對條件,每一個感染帶狀皰疹且住院之病例組患者最多將配對到8個對照組患者。以多變項條件式邏輯迴歸分析法,並以免疫抑制劑使用與疾病史為校正因子,分析SLE患者類固醇使用與帶狀皰疹發生之相關性。

研究結果
本研究共納入4,894位SLE患者。其中包含4,333位女性患者(88.54 %)。平均年齡為38.55±14.93年。於觀察期間,類固醇平均每日劑量為6.47毫克prednisone相等劑量/天。患者會在第一年使用較高的類固醇劑量(類固醇平均每日劑量為10.79毫克prednisone相等劑量/天),之後逐年減少。病患在確診後第一年罹患與類固醇使用相關之共病症發生率較高,之後亦呈現逐年減少的趨勢。
另一嵌入型病例對照研究法分析SLE患者其類固醇使用與帶狀皰疹發生之相關性。共納入1,927位SLE患者,含發生帶狀皰疹且住院之病例組215位及1:8比例匹配年齡及性別之無帶狀皰疹發生且住院之對照組1,712位。結果顯示,指標日期前365天內,病例組相對於對照組,類固醇的暴露劑量較高。以多變項條件式邏輯回歸分析,暴露高劑量類固醇的(類固醇平均每日劑量≥7.5毫克prednisone相等劑量/天)會增加帶狀皰疹發生之風險( p < 0.001)。

結論
在台灣地區,類固醇是SLE患者最常使用到的藥物。這群病患必須小心監測與類固醇相關副作用的發生。當使用到高劑量類固醇時,亦須特別注意帶狀皰疹的發生。
英文摘要 Glucocorticoids are the mainstay of therapy for SLE, but have been associated with the development of many adverse effects. A daily dose of prednisone < 7.5 mg seems to minimize these adverse effects. This study was aimed to investigate the prescribing patterns of glucocorticoids, the incidence of treatment-related comorbidities and the relationship between the use of glucocorticoids and herpes zoster in Taiwan SLE patient.
This nationwide, population-based, retrospective cohort study used data from the National Health Insurance Research Database of Taiwan. We identified patients who was issued a catastrophic illness certificate for SLE for the first time during 2001-2005 and had used glucocorticoids during the following 5 years. A total of 4,894 incident SLE patients were included. Mean age was 38.55±14.93 years. During the 5-year follow-up, the mean daily dose of glucocorticoid patients received was 6.47 mg prednisone equivalent, respectively. Patients received higher glucocorticoid dose and higher incidence of the comorbidities in the first year and gradually reduced annually.
In another nested case-control study, SLE patients were classified as cases if herpes zoster were occurred in hospital during the following 5 years after SLE diagnosed. SLE patients who never had herpes zoster were eligible as controls and were matched 8:1 to cases for age and sex. The results showed that 365 days before the index date, the case group exposure higher dose of glucocorticoid. In the multivariate logistic regression analysis, exposure of higher dose of glucocorticoids (daily prednisone dose ≥7.5mg) increased the risk of herpes zoster.
論文目次 第一篇、 台灣地區全身性紅斑狼瘡病人類固醇之處方型態分析……………1
第一章、 研究背景………………………………………………………………1
第二章、 文獻回顧………………………………………………………………2
第一節、 流行病學………………………………………………………………2
第二節、 病因學…………………………………………………………………3
第三節、 臨床表徵………………………………………………………………5
第四節、 診斷……………………………………………………………………6
第五節、 治療……………………………………………………………………8
第六節、 SLE治療用藥處方型態分析…………………………………………11
第七節、 類固醇的使用與副作用………………………………………………12
第三章、 研究目的與重要性……………………………………………………17
第四章、 研究方法………………………………………………………………18
第一節、 研究設計(一) 類固醇處方型態分析………………………………18
第二節、 研究設計(二) 類固醇使用與帶狀皰疹發生之相關性……………29
第三節、 資料處理流程…………………………………………………………38
第四節、 統計方法………………………………………………………………39
第五章、 研究結果………………………………………………………………41
第一節、 SLE治療用藥處方型態分析…………………………………………41
第二節、 類固醇處方型態分析…………………………………………………47
第三節、 類固醇使用與帶狀皰疹發生之相關性分析…………………………56
第六章、 研究討論………………………………………………………………72
第一節、 SLE治療用藥處方型態分析…………………………………………72
第二節、 類固醇處方型態分析…………………………………………………76
第三節、 類固醇使用與帶狀皰疹發生之相關性分析…………………………78
第四節、 研究優勢與限制………………………………………………………84
第七章、 結論與建議……………………………………………………………86
第八章、 未來研究方向…………………………………………………………87
第二篇、 建立有效方法改善藥品包裝與標示…………………………………88
第一章、 研究背景………………………………………………………………88
第二章、 研究目的及重要性……………………………………………………93
第三章、 研究方法………………………………………………………………94
第四章、 研究統計方法…………………………………………………………96
第五章、 研究名詞、研究變項與操作定義……………………………………97
第六章、 研究結果與討論………………………………………………………99
第一節、 建立藥品標示及包裝評估準則………………………………………99
第二節、 口服藥品標示及包裝評比……………………………………………99
第三節、 台灣廠及國外廠口服藥品標示及包裝評比…………………………109
第四節、 門診病患口服藥品完整包裝交付率…………………………………127
第七章、 結論與建議……………………………………………………………133
參考文獻…………………………………………………………………………134
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系統識別號 U0026-1908201515155100
論文名稱(中文) 以健保資料庫分析台灣地區發炎性腸道疾病之處方型態與疾病復發因子
論文名稱(英文) Analyzing the Drug Utilization Pattern of Inflammatory Bowel Disease (IBD) and Risk Factors for Disease Flare Up in Taiwan by Using National Health Insurance Research Database
校院名稱 成功大學
系所名稱(中) 臨床藥學與藥物科技研究所
系所名稱(英) Institute of Clinical Pharmacy and Pharmaceutical sciences
學年度 103
學期 2
出版年 104
研究生(中文) 沈敬堯
學號 S66021044
學位類別 碩士
語文別 中文
口試日期 2015-07-16
論文頁數 115頁
口試委員 指導教授-鄭靜蘭
共同指導教授-莊喬雄
口試委員-高雅慧
召集委員-陳炯瑜
口試委員-許美英
關鍵字(中) 發炎性腸道疾病
克隆氏症
潰瘍性大腸炎
處方型態分析
疾病風險因子
關鍵字(英) Inflammatory bowel disease
Crohn’s disease
Ulcerative colitis
Prescribing pattern
Risk factors
學科別分類
中文摘要 研究背景
發炎性腸道疾病 (Inflammatory bowel disease, IBD) 為自體免疫慢性疾病,分為克隆氏症 (Crohn's disease, CD) 以及潰瘍性大腸炎 (Ulcerative colitis, UC)。此疾病主要發生在西方國家以及已開發國家,然而亞洲和開發中國家在近幾年IBD的發生率與盛行率亦有增加的趨勢。治療藥品分為四大類,包含Aminosalicylates (5-ASA)、類固醇、免疫抑制劑以及近年來開始核准使用的生物製劑。
亞洲國家對於IBD的治療趨勢在近幾年有改變此外關於治療效果的研究相當的少,而台灣的研究也僅止於疾病的流行病學調查,因此本研究目的在討論台灣IBD的治療趨勢、藥品使用情況、共病症以及疾病復發相關因子。

研究方法
由1998年到2010年全民健康保險資料庫之重大傷病證明明細檔,擷取診斷代碼為「555」克隆氏症或「556」潰瘍性大腸炎,且重大傷病申請時間介於2000/1/1至2008/12/31之病患。將其重大傷病申請日定為「指標日期」,追蹤各病患的就醫紀錄以及IBD相關藥品的處方紀錄,分別進行下列分析。
1.藥品使用與疾病復發的累積機率百分比。
2.重大傷病申請前、後藥品使用與疾病復發的比例。
3.疾病復發風險因子的探討。

研究結果
本研究收入1,872位病患,332位為CD病患,其餘1540位罹患UC。CD與UC的平均年齡分別為37.12歲以及44.28歲,男女比為2.19:1及1.54:1。CD與UC病患中,口服5-ASA是疾病確診早期會使用的藥品而且使用比例最高,其第一年、五年及十年的累積機率百分比分別為71.4%、84.9%以及93.0%與68.4%、83.7%以及79.8%。口服類固醇也在疾病早期就開始使用,累積機率百分比分別是37.1%、66.7%以及74.4%與33.1%、51.1%以及61.4%,其中長時間類固醇使用的比例分別為23.5%、39.7%以及44.7%與14.0%、22.8%以及27.4%。Thiopurine類的藥品在台灣的使用比例比其他國家低,其累積機率百分比則為6.9%、16.9%以及21.1%與2.7%、8.0%以及9.7%。不同世代藥品使用的比較裡無論何種藥品,新世代 (2005-2008) 的使用比例都比舊世代 (2000-2004) 高而且使用時間提早,整體治療越趨積極。
大多數的病患主要在重大傷病前、後半年內藥品使用的比例最高,然而在後續的追蹤時間內藥品使用比例則緩慢下降。疾病復發事件的發生比例最高存在於重大傷病申請前半年。
無論是CD或是UC病患,重大傷病申請前有使用過高劑量類固醇或在重大傷病申請後曾經住院者,在未來兩年內都有2.3-2.7倍發生須以高劑量類固醇來控制的疾病嚴重復發。CD病患如果在重大傷病申請之後有使用高劑量類固醇,也能反應出未來疾病嚴重復發增加的風險。UC病患中門診就醫次數較高、重大傷病申請後合併多種藥品治療及重大傷病申請後使用過任何類固醇者,出未來疾病復發風險都會增加,而年齡越大的組別有降低疾病復發的產生。

研究結論
由本研究發現,5-ASA在台灣IBD病患的使用比例遠高於其他國家,類固醇使用情況並無差異,但Thiopurine的使用卻低於其他國家。台灣藥品的使用比其他國家保守,藥品使用趨勢與西方國家十年前的情形相似。因此建議未來台灣地區IBD病患,特別是類固醇依賴性病患,Thiopurine的使用可以更加積極以降低疾病再復發。重大傷病申請前曾使用高劑量類固醇、申請後曾住院、多次就醫以及合併多種藥品的病患,建議選擇比較積極的疾病治療。年齡的增加、手術及Thiopurine的使用則有降低IBD復發的趨勢。
英文摘要 SUMMARY
The incidence and prevalence of inflammatory bowel disease (IBD) in Taiwan was increased in recent year. However, the information of use of medication and disease flare up in Taiwan is still limited. Thus, we conducted a longitudinal study by National Health Insurance Research Database (NHIRD).
The study included the patients who applied catastrophic illness certificate between 2000 and 2008 and analyzed the cumulative probabilities of medication and disease flare up in follow-up period. We also analyzed the risk factors of disease flare up within the 2 year follow-up period.
This current study showed that 5-ASA was the most used medication in Taiwan and the proportion of 5-ASA was higher than the use in other countries. Systemic steroid use in Taiwan has the similar pattern with other studies. However, thiopurine use in Taiwan is less than in other countries. The risk factors of disease flare up were similar in Crohn’s disease (CD) and ulcerative colitis (UC) patients. High dose steroid use before the CIC being applied and hospitalization after CIC being applied would predict the disease flare up in both CD and UC. More clinic visits, combination medication therapy and younger age group would also increase the flare up in UC patient.
Thiopurine use is rare in Taiwan so it should be recommended only in severe patients who need to maintain disease remission. Besides, the patients who had the risk factors would had higher risk of disease severe flare up and need more aggressive strategies for maintaining disease remission.
論文目次 第一篇、 台灣發炎性腸道疾病之處方型態分析 P.1
第一章、 研究背景 P.1
第二章、 文獻回顧 P.2
第一節、 發炎性腸道疾病簡介 P.2
第二節、 流行病學 P.5
第三節、 發炎性腸道疾病治療 P.8
第四節、 處方型態分析 P.13
第五節、 疾病復發 P.16
第三章、 研究目的與重要性 P.17
第四章、 研究方法 P.18
第一節、 研究設計 P.18
第二節、 研究變項與操作定義 P.24
第三節、 研究結果測量 P.25
第四節、 資料處理流程 P.30
第五節、 統計分析 P.31
第五章、 研究結果 P.33
第一節、 研究對象納入與排除 P.33
第二節、 研究對象之人口學特性 P.34
第三節、 藥品使用、疾病復發的累積機率百分比 P.36
第四節、 重大傷病申請前後藥品使用、疾病復發的比例 P.49
第五節、 疾病復發風險因子的探討 P.55
第六章、 研究討論 P.60
第一節、 研究對象納入與排除之分析 P.60
第二節、 研究對象之人口學特性 P.61
第三節、 藥品服用與疾病復發的累積機率百分比分析 P.62
第四節、 重大傷病申請前後藥品使用、疾病復發的比例 P.78
第五節、 重大傷病申請期間疾病復發風險因子 P.79
第六節、 研究優勢與限制 P.82
第七章、 結論與建議 P.83
第八章、 未來研究方向 P.84
第二篇、 臨床藥事服務:多重激脢抑制劑衛教計畫 P.85
第一章、 服務背景 P.85
第二章、 服務目的與重要性 P.86
第三章、 服務方法 P.87
第一節、 服務流程 P.87
第二節、 藥品衛教單張設計 P.87
第三節、 病患衛教計畫 P.88
第四章、 服務結果 P.90
第一節、 衛教單張與問卷設計 P.90
第二節、 病患衛教計畫 P.91
第五章、 討論與建議 P.94
第三篇、 參考文獻 P.97
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系統識別號 U0026-2208201422185600
論文名稱(中文) 台灣低體重兒出生後使用類固醇與神經發育副作用之相關性研究
論文名稱(英文) Association of Postnatal Corticosteroids and Effects of Neurodevelopment in Low Birth Weight Infants in Taiwan
校院名稱 成功大學
系所名稱(中) 臨床藥學與藥物科技研究所
系所名稱(英) Institute of Clinical Pharmacy and Pharmaceutical sciences
學年度 102
學期 2
出版年 103
研究生(中文) 郭姿伶
學號 S66014013
學位類別 碩士
語文別 中文
口試日期 2014-07-24
論文頁數 169頁
口試委員 指導教授-鄭靜蘭
口試委員-高雅慧
口試委員-林永傑
口試委員-高淑敏
關鍵字(中) 早產
低體重兒
出生後使用類固醇
處方型態
腦性麻痺
神經發育
全民健康保險研究資料庫
台灣
關鍵字(英) Low birth weight infants
postnatal corticosteroid
prescribing patterns
neurodevelopment
Taiwan
學科別分類
中文摘要 研究背景
研究發現類固醇的抗發炎作用,可以預防以及治療早產兒肺支氣管發育不全(bronchopulmonary dysplasia, BPD)。早產兒投予出生後類固醇(postnatal corticosteroids)的治療,在1990年左右最廣為使用,除增加BPD的治療成效,也降低了早產兒死亡率。不過,隨著早產兒的存活率上升,出生後類固醇對日後腦部發育的影響逐漸顯現,統計發現,曾經使用過出生後類固醇的早產兒,在腦性麻痺或神經發育異常的比例皆高於未使用者,因此,美國小兒科醫學會針對早產兒使用出生後類固醇的安全性及有效性提出建議:將類固醇用於出生7天以上且無法脫離機械性呼吸器的早產兒,使用前需仔細評估類固醇帶來的效益及風險。2002年公告使用建議之後,各國研究顯示,出生後類固醇的處方盛行率有下降趨勢,但台灣對早產兒出生後類固醇的處方型態變化卻知之甚少。
研究目的
希望藉由台灣健保資料的分析,對於台灣低體重兒使用類固醇的處方型態以及與神經發育相關性做初步的探討,期望提供第一線臨床醫護人員使用出生後類固醇之實證參考。
研究方法
本研究使用1999年至2010年全民健康保險資料庫,由於台灣並未有出生週數相關的診斷碼,故研究對象選定以ICD-9診斷碼有765.XX代表出生小於37週之早產低體重兒,分析1999年至2010年間,台灣醫師處方出生後類固醇的處方型態變化,分析處方盛行率、肺支氣管發育不良與處方盛行率之關係、類固醇投予途徑、成分、使用天數分析等。另外,追蹤1999年至2009年曾經使用過上述藥物的低體重兒,觀察24個月,分析類固醇的使用與腦性麻痺以及神經發育異常的關聯性。
研究結果
自1999年至2010年共73,606位符合收錄及排除條件的研究對象,共5,325人在出生後處方過類固醇,整體台灣在低體重兒處方盛行率有下降趨勢,1999年處方率平均為9.2%,至2010年則降為5.5%。肺支氣管發育不良的患者,類固醇處方盛行率亦有下降變化,由1999年65.0%降至2010年48.5%。分析使用途徑及成分,全身性投予以dexamethasone為主要處方成分,不過hydrocortisone的使用近年有增加現象。途徑方面,吸入性類固醇近年使用增加。
追蹤研究對象24個月的門診紀錄,觀察發現,使用過出生後類固醇,比未使用組在腦性麻痺發生風險比值為6.28倍[95%CI:5.73-6.90, P<0.0001],校正危險因子後風險為1.65倍[95% CI:1.48-1.84, P<0.0001]。存活曲線分析也達統計差異(log rank P<0.0001)。敏感性分析針對嚴格條件定義腦性麻痺、BPD患者、極低體重之BPD患者、追蹤72個月至學齡前的腦性麻痺存活曲線分析,排除出院後24個月內死亡者,合併出院後24個月內死亡或是腦性麻痺風險皆是相同結果。另外,本研究head-to-head比較吸入性類固醇與全身性類固醇,以及dexamethasone與hydrocortisone使用在腦性麻痺的診斷風險比值。結果顯示,使用吸入性類固醇者發生腦性麻痺的風險低於全身性類固醇。然而,與dexamethasone相較之下,使用hydrocortisone者日後被診斷腦性麻痺的風險則未達統計學差異HR 0.86 [95% CI: 1.63-1.18, P=0.3398]。
結論
台灣低體重兒使用出生後類固醇的處方盛行率有下降趨勢,顯示類固醇的使用趨向保守,符合國際治療趨勢。在類固醇的使用與神經發育也觀察到相關聯性,處方出生後類固醇的研究對象,在24個月內被診斷腦性麻痺、神經發育異常之比例皆高於未使用組。
英文摘要 The American Academy of Pediatrics recommended that use of postnatal corticosteroid treatment with bronchopulmonary dysplasia (BPD) in preterm infants should be judgment on the potential side effect of impaired neurodevelopment. The aim of this study was to analyze the trend in the use of postnatal corticosteroid over a 12-year period in preterm infants in Taiwan, and discuss the relationship between postnatal corticosteroids use and neurodevelopment. We used population-based nationwide claim database from 1999 to 2010 as materials. The data were analyzed using the Cochran-Armitage trend test, chi-square for categorical variable, t-test for continuous variable, cox proportional hazard model for risk adjustment and statistical significance was indicated by a p-value < 0.05.
A total of 73,606 infants with 5,325 postnatal corticosteroid prescriptions were analyzed. The overall prescription rate of steroids for infants decreased from 9.2% in 1999 to 5.5% in 2010 (P<0.0001). The overall prescription trend were similar in subgroup analysis. The use of postnatal corticosteroid did had a 1.65 times increased risk of cerebral palsy event compared to non-users. Inhaled steroid has 52% less risk than systemic steroid in cerebral palsy rate, adjusted HR 0.48 [95% CI: 0.32-0.74], P=0.0007. There was no statistically significant difference in safety of hydrocortisone use when compared to dexamethasone, adjusted HR 0.86 [95% CI: 0.63-1.18], P=0.3398.
The prevalence of postnatal steroid prescriptions in Taiwan had decreased. There did has some relationship between the use of postnatal corticosteroid and increase cerebral palsy risk.
論文目次 中文摘要 II
Extended Abstract IV
誌謝 VII
目錄 IX
表目錄 XV
圖目錄 XVIII
附件目錄 XX
縮寫與全名對照表 XXI
第一篇、台灣低體重兒出生後使用類固醇與神經發育副作用之相關性研究 1
第一章、研究背景 1
第二章、文獻回顧 2
第一節、低體重兒與早產兒 2
一、 低體重兒的定義 2
二、 早產兒的定義 2
三、 流行病學 2
四、 早產兒常見的問題 5
第二節、肺支氣管發育不良(bronchopulmonary dysplasia, BPD) 5
一、 流行病學 5
二、 診斷條件 6
三、 致病機轉 6
四、 皮質性類固醇(corticosteroids)的藥理機轉與藥物動力學 7
五、 皮質性類固醇使用於肺支氣管發育不良之臨床治療建議 8
六、 早產兒出生後使用dexamethasone的副作用 9
七、 Dexamethasone替代療法的相關研究 10
八、 早產兒出生後使用類固醇之處方型態變化 15
第三節、早產兒出生後使用皮質性類固醇與長期神經發育異常 17
一、 腦性麻痺簡介 17
二、 早產兒使用類固醇對神經發育影響的機轉 20
三、 早產兒使用dexamethasone與腦性麻痺或神經發育的相關研究 20
四、 早產兒使用hydrocortisone與腦性麻痺或神經發育相關研究 21
五、 出生後使用類固醇與長期神經發育相關的系統性文獻回顧 22
六、 吸入性類固醇與腦性麻痺或神經發育的相關研究 22
第四節、文獻回顧總結 23
第三章、研究目的與重要性 24
第一節、研究目的 24
第二節、研究重要性 24
第四章、研究方法 25
第一節、研究設計 25
一、 研究類型 25
二、 研究材料與工具 25
三、 研究對象 27
四、 研究分組 30
五、 研究結果變項(outcome) 30
六、 研究流程 30
第二節、研究變項與操作定義 32
一、 研究名詞定義 32
二、 研究變項與排除條件之操作定義 34
三、 研究族群基本資料之操作定義-處方型態分析 37
四、 研究族群基本資料定義-神經發育追蹤 42
五、 觀察終止之操作定義 43
第三節、資料處理流程 44
第四節、統計方法 45
一、 統計軟體 45
二、 統計模式設定 45
三、 資料分析 45
第五節、敏感性分析 47
一、 改變定義之追蹤對象 47
二、 改變追蹤時間 48
第六節、次族群分析(subgroup analysis) 48
一、 比較投予途徑對腦性麻痺的影響 48
二、 比較不同成分之全身性類固醇 48
第五章、研究結果 49
第一節、研究對象的身份辨識 49
第二節、台灣出生後使用類固醇之處方型態分析 49
一、 研究對象的納入與排除 49
二、 納入處方型態分析者的身份確認比例 51
三、 納入處方型態分析者依附申報的比例分布 51
四、 低體重兒出生後使用類固醇之處方盛行率變化 54
五、 BPD與出生後類固醇之關聯性分析 55
六、 類固醇之使用分析 59
七、 醫學中心及區域醫院出生後類固醇處方盛行率變化 67
八、 醫學中心以就醫地區劃分之處方盛行率分析 69
第三節、次族群處方型態分析 71
第四節、研究對象背景資料 84
第五節、神經發育追蹤 86
一、 研究對象的納入與排除 86
二、 門診神經發育分析 87
三、 出生後類固醇使用與腦性麻痺之相關性分析 88
第六節、敏感性分析 91
一、 較嚴謹的腦性麻痺定義之存活曲線分析 91
二、 BPD診斷者發生腦性麻痺之存活曲線分析 94
三、 極低體重且診斷為BPD發生腦性麻痺之存活分析 97
四、 追蹤72個月至學齡前發生率存活分析 99
五、 排除出院後2年內死亡研究對象後發生腦性麻痺之存活分析 102
六、 使用類固醇者出院後兩年內死亡或是腦性麻痺之存活分析 105
七、 依使用天數分組之存活分析 108
第七節、次族群分析 110
一、 不同類固醇使用途徑發生腦性麻痺之存活分析 110
二、 比較不同成分之全身性類固醇與發生腦性麻痺之存活分析 113
第六章、研究討論 116
第一節、處方型態分析 116
一、 處方盛行率變化 116
二、 BPD診斷與處方盛行率變化之關聯性 119
三、 出生後類固醇處方品項分析 120
四、 研究對象背景分析 123
第二節、神經發育副作用分析 124
一、 出生後類固醇使用與神經發育的關聯性 124
二、 吸入性類固醇的安全性與腦性麻痺之關聯性討論 125
三、 使用dexamethasone或 hydrocortisone之腦性麻痺發生率存活分析 126
第三節、本研究的限制與優勢 128
一、 資料庫的限制 128
二、 執業習慣的改變:腦性麻痺重大傷病卡的開立 130
三、 本研究的優勢 131
第七章、結論與建議 132
第八章、未來研究方向 133
第二篇、臨床藥事服務:小兒溶液劑劑量對照表 135
第一章、緣起 135
第二章、目的與方法 138
第一節、目的 138
第二節、方法 138
第三章、結果 139
第一節、抗組織胺溶液劑對照表 140
第二節、止痛退燒溶液劑對照表 141
第三節、抗生素溶液劑對照表 142
第四節、呼吸道用藥溶液劑對照表 146
第五節、腸胃道用藥溶液劑對照表 149
第六節、癲癇用藥溶液劑對照表 152
第七節、利尿劑之溶液劑對照表 155
第八節、類固醇之溶液劑對照表 155
第九節、強心劑之溶液劑對照表 156
第十節、腦波(EEG)檢查前使用之溶液劑對照表 157
第四章、討論 158
第五章、未來建議 160
參考文獻 161

表目錄
表 2-1台灣活產新生兒之懷孕週數年度分布表 4
表 2-2台灣活產新生兒之出生體重年度分布表 4
表 2-3 Hydrocortisone用於BPD治療的研究 11
表 2-4吸入性類固醇與系統性類固醇療效比較 13
表 2-5腦性麻痺危險因子 19
表 4-1各檔案間串檔變項內容說明 26
表 4-2雙胞胎診斷碼 28
表 4-3產科相關診斷碼 28
表 4-4產科相關術式代碼 29
表 4-5本研究定義之早產兒診斷碼對照表 33
表 4-6全身性類固醇及吸入性類固醇之ATC代碼對照表 38
表 4-7本研究之併用藥物ATC代碼對照表 39
表 4-8本研究之共病症診斷碼對照表 40
表 4-9醫療院所所在之地理區域 41
表 4-10醫院特約類別對照 41
表 4-11神經發育異常疾病與ICD-9對照表 43
表 5-1低體重兒身份辨識人數分布 53
表 5-2納入處方盛行率之低體重兒身份校正人數分布 53
表 5-3納入處方型態分析者依附申報的人數分布 53
表 5-4台灣低體重兒出後類固醇之處方人數年度分布 54
表 5-5低體重兒BPD診斷人數年度分布 56
表 5-6 BPD診斷者出生後類固醇使用年度人數分布 57
表 5-7出生後類固醇使用者為BPD患者的比例 58
表 5-8未使用類固醇者為BPD者的人數年度分布 58
表 5-9年度出生後類固醇使用途徑分析 61
表 5-10全身性類固醇使用成分年度人數分布 62
表 5-11所有全身性類固醇使用成分比例分布 63
表 5-12全身性類固醇平均使用天數變化 65
表 5-13使用3個劑量以上者全身性類固醇平均使用天數 65
表 5-14吸入性類固醇使用成分分析 66
表 5-15醫學中心及區域醫院處方盛行率變化 67
表 5-16以區域劃分之醫學中心年度出生後類固醇使用人數分布 70
表 5-17次族群類固醇年度處方人數 73
表 5-18次族群BPD診斷年度人數 74
表 5-19次族群BPD者使用類固醇年度處方人數變化 75
表 5-20次族群類固醇使用途徑比例分布 76
表 5-21使用全身性Dexamethasone之次族群分析 77
表 5-22使用全身性Hydrocortisone之次族群分析 78
表 5-23出生體重小於1,000公克者,醫學中心及區域醫院處方盛行率變化 81
表 5-24出生體重1,000-1,499公克者,醫學中心及區域醫院處方盛行率變化 82
表 5-25出生體重≥1,500公克者,醫學中心及區域醫院處方盛行率變化 83
表 5-26門診神經發育分析 87
表 5-27發生腦性麻痺之存活分析 88
表 5-28較嚴謹的腦性麻痺定義之存活分析分析 91
表 5-29 BPD診斷者之存活分析 94
表 5-30極低體重BPD診斷者發生腦性麻痺之存活分析 97
表 5-31追蹤72個月至學齡前危險因子之存活分析 99
表 5-32排除出院後2年內死亡者發生腦性麻痺之存活分析 102
表 5-33使用類固醇出院後兩年內死亡或腦性麻痺之存活分析 105
表 5-34依使用天數分組之存活分析 108
表 5-35不同類固醇使用途徑發生腦性麻痺之存活分析 110
表 5-36不同成分之全身性類固醇與發生腦性麻痺之存活分析 113
表 6-1各國處方盛行率比較 118

圖目錄
圖 4-1研究流程 31
圖 5-1研究族群的納入與排除 50
圖 5-2納入處方型態分析者的身份辨識率 52
圖 5-3納入處方型態分析者依附申報的比例分布 52
圖 5-4台灣低體重兒出生後類固醇之處方盛行率變化 54
圖 5-5 BPD診斷年度比例分布 56
圖 5-6 BPD診斷者出生後類固醇處方盛行率年度分布 57
圖 5-7出生後類固醇使用途徑變化趨勢 61
圖 5-8全身性類固醇使用成分比例分析 62
圖 5-9所有全身性類固醇使用成分分析圖 64
圖 5-10吸入性類固醇使用成分比例分析 66
圖 5-11醫學中心及區域醫院處方盛行率趨勢變化 68
圖 5-12醫學中心就醫地區的處方盛行率分析 69
圖 5-13次族群類固醇處方盛行率分布變化 73
圖 5-14次族群BPD診斷分布變化 74
圖 5-15次族群BPD者處方類固醇比例變化 75
圖 5-16次族群類固醇使用途徑分析 76
圖 5-17 Dexamethasone次族群使用比例分布 77
圖 5-18 Hydrocortisone次族群使用比例分布 78
圖 5-19出生體重小於1,000公克者使用吸入性類固醇成分比例分布 79
圖 5-20出生體重1,000-1,499公克者使用吸入性類固醇成分比例分布 79
圖 5-21出生體重≥1,500公克者使用吸入性類固醇成分比例分布 80
圖 5-22出生體重<1,000公克,醫學中心及區域醫院類固醇處方盛行率變化 81
圖 5-23出生體重1,000-1,499公克,醫學中心及區域醫院類固醇處方盛行率變化 82
圖 5-24體重≥1,500公克者,醫學中心及區域醫院類固醇處方盛行率變化 83
圖 5-25門診神經發育追蹤納入與排除結果 86
圖 5-26出生後類固醇使用與腦性麻痺之存活曲線分析 90
圖 5-27較嚴謹的腦性麻痺定義之存活曲線分析 93
圖 5-28 BPD診斷者發生腦性麻痺之存活曲線分析 96
圖 5-29極低體重BPD診斷者發生腦性麻痺之存活分析 98
圖 5-30追蹤72個月至學齡前腦性麻痺診斷存活曲線 101
圖 5-31排除2年內死亡之門診腦性麻痺診斷存活曲線 104
圖 5-32出院後兩年內死亡或是腦性麻痺之存活分析 107
圖 5-33不同類固醇使用途徑發生腦性麻痺之存活分析 112
圖 5-34比較不同成分之全身性類固醇與發生腦性麻痺之存活分析 115



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系統識別號 U0026-2401201312074900
論文名稱(中文) 臺灣類風濕性關節炎病患使用DMARDs之處方型態分析
論文名稱(英文) Prescribing Pattern of Disease-Modifying Anti-rheumatic Drugs in Established Rheumatoid Arthritis Patients in Taiwan
校院名稱 成功大學
系所名稱(中) 臨床藥學與藥物科技研究所
系所名稱(英) Institute of Clinical Pharmacy and Pharmaceutical sciences
學年度 101
學期 1
出版年 102
研究生(中文) 黃昱穎
學號 S66991045
學位類別 碩士
語文別 中文
口試日期 2013-01-11
論文頁數 109頁
口試委員 指導教授-高雅慧
口試委員-嵇允嬋
口試委員-劉明煇
口試委員-張慧真
口試委員-翁孟玉
關鍵字(中) 疾病修飾抗風濕病藥物
類風濕性關節炎
處方型態
關鍵字(英) DMARDs
Rheumatoid arthritis
Prescribing patterns
學科別分類
中文摘要 研究背景
類風濕性關節炎為慢性、發炎性的疾病,以侵犯關節為主,未接受治療常導致患者疼痛、關節破壞變形、失能、早發性死亡,也明顯增加心血管疾病、感染、骨質疏鬆罹病率和死亡率。及早開始、適時調整傳統DMARDs與生物製劑使用證實可顯著改善類風濕性關節炎病患的預後。目前類風濕性關節炎無法治癒,持續的疾病活性和關節破壞的進展有直接相關性。因此,使疾病達到緩解或低疾病活性是治療努力的目標。然而,DMARDs治療選擇與策略使用在臺灣類風濕性關節炎病患常規照護之相關研究仍屬少數。本研究之目的即在於瞭解臺灣類風濕性關節炎患者DMARDs治療型態及近幾年臨床治療的趨勢變化。

研究方法
利用2001年至2010年全民健保資料庫,研究對象納入2002/01/01 -2009/12/31間新通過類風濕性關節炎重大傷病卡申請的患者,申請者必須符合1987年ACR類風濕性關節炎分類標準。以重大傷病卡申請日期當作指標日期,於病患確診時、確診後第30天、第90天、第180天、第365天五個不同時間點觀察DMARDs使用情形。另外,同時亦針對確診後一年內TNF-α inhibitors新使用者進行分析,評估TNF-α inhibitors和傳統DMARDs合併治療情形。

研究結果
經由納入、排除條件篩選後,研究對象共21,196人,平均年齡54歲,女性佔77.4%。病患確診時,82.5%RA患者接受DMARDs治療,未接受DMARDs治療的病患有逐年下降趨勢,2002年到2009年,從22.1%下降至13.3%。48.8% RA患者接受DMARDs合併治療且逐年明顯增加,DMARDs單一治療則呈現逐年下降趨勢,合併口服類固醇治療比率約51.6%。Hydroxychloroquine、sulfasalazine、methotrexate是三種最常被開立的DMARDs,MTX的使用率在不同觀察時間點逐漸超越sulfasalazine、hydroxychloroquine。在確診後一年,TNF-α inhibitors的使用明顯逐年增加,2002年到2009年,從0.1%上升至7.6%。84%TNF-α inhibitor使用者至少合併一種以上傳統DMARDs,與MTX併用比率約74%。

研究結論
本研究顯示臺灣對於類風濕性關節炎患者傾向採取越來越積極的治療。DMARDs使用、DMARDs合併治療皆有明顯逐年增加趨勢,特別是MTX為主的治療組合。整體上,臺灣類風濕性關節炎患者的治療與國際治療趨勢一致。
英文摘要 Background
Rheumatoid arthritis (RA) is a chronic inflammatory condition affecting the joints most. When untreated, RA causes pain, continuing joints damage and deformity, disability, and premature mortality in most patients. RA also increases disease morbidity and mortality, especially cardiovascular disease, infection and osteoporosis. Early initiation and timely escalation of treatment with conventional disease-modifying anti-rheumatic drugs(DMARDs) and the initiation of treatment with biologic DMARDs can significantly improve the prognosis. For now, RA can’t be cured and disease activity is thought to be related to radiologic progression. The goal of treatment is to achieve a state of clinical remission or low disease activity. However, little is known of the extent to which treatment options and strategies have entered routine care in Taiwan. Therefore, this study was aimed to investigate the prescribing pattern of DMARDs in established RA patients and the changes in patterns of DMARDs utilization.

Methods
We conducted a cross-sectional study by using 2001-2010 Taiwan’s National Health Insurance Research Database. We identified patients who was issued a catastrophic illness certificate for RA (ICD code: 7140) for the first time during the period from January 1, 2002 through December 31, 2009 and patients must fulfill the 1987 ACR criteria. We estimated DMARDs utilization using cross-sectional assessments and defined the date of application for catastrophic illness certificate as index date, and observed DMARDs prescribing patterns at different time point after the index date. In addiction, if patients started their first TNF-α inhibitors prescription after the first year of the index date, we analyzed how TNF-α inhibitors were being used in clinical practice.

Results
During the study period, we identified 21,196 patients with RA. The mean age was 54 years; the average proportion of female patients was 77.4%. Approximately, 82.5% of RA patients received DMARDs on the index date. The proportion of patients without DMARDs prescription on the index date decreased from 22.1% in 2002 to 13% in 2009. A continuous increase in combination DMARDs therapy and a decrease in monotherapy were observed. 51.6% of RA patients were co-prescribing oral steroids.
Hydroxychloroquine, sulfasalazine, methotrexate were the three most prescribed DMARDs. At different observed time point, the utilization of methotrexate had a trend to surpass the utilization of sulfasalazine and hydroxychloroquine during the study period. At the first year after the index date, the use of TNF-α inhibitors increased from 0.1% of patients in 2002 to 7.6% in 2009. The percentage of patients initiated on TNF-α inhibitors in combination with any conventional DMARDs was 84%, while combination with methotrexate was about 74%.

Conclusions
This study showed the utilization of DMARDs increased in Taiwan with RA, especially combination therapy including methotrexate. Overall, there was a trend toward more aggressive management of RA in Taiwan and in accordance with international trends.
論文目次 中文摘要 I
Abstract III
目錄 VII
表目錄 IX
圖目錄 XII
第一篇 臺灣類風濕性關節炎病患使用DMARDs之處方型態分析 1
第一章 研究背景 1
第二章 文獻回顧 3
第一節 類風濕性關節炎簡介 3
第二節 Disease-modifying antirheumatic drugs(DMARDs)藥品 10
第三節 DMARDs處方型態分析與治療趨勢 27
第三章 研究目的 34
第四章 研究方法 35
第一節 研究設計 35
第二節 研究變項與操作定義 40
第三節 研究藥品與研究結果測量 43
第四節 資料處理流程 46
第五節 統計方法 47
第五章 研究結果 48
第一節 研究對象納入與排除 48
第二節 研究對象之人口學特性 50
第三節 DMARDs處方型態分析 53
第六章 研究討論 70
第一節 研究對象納入與排除之分析 70
第二節 研究對象之人口學特性 72
第三節 DMARDs處方型態分析 73
第四節 服藥順從性 79
第五節 研究優勢與限制 83
第七章 結論與建議 84
第八章 未來研究方向 85
第二篇 臨床藥事服務:類風濕性關節炎病患之服藥順從性 86
第一章 服務背景 86
第二章 服務目的與進行方法 88
第一節 服務目的 88
第二節 服務進行方法 88
第三章 服務結果 90
第一節 研究對象之基本資料與DMARDs藥品使用情形 90
第二節 服藥順從性 90
第三節 DMARDs藥物信念 93
第四節 順從性佳與不佳者之比較 95
第四章 討論與建議 96
參考文獻 98
附錄 107

表目錄
第一篇 臺灣類風濕性關節炎病患使用DMARDs之處方型態分析 1
表2-1 2010新類風濕性關節炎的分類準則 4
表2-2 Disease Activity Measures 9
表2-3 Conventional disease-modifying antirheumatic drugs
used in the treatment of rheumatoid arthritis 23
表2-4 Biologic disease-modifying antirheumatic drugs used
in the treatment of rheumatoid arthritis 24
表2-5 傳統DMARDs與生物製劑之使用禁忌 25
表2-6 DMARDs prescribing patterns in different countries
32
表2-7 DMARDs prescribing patterns in different countries
(續) 33
表4-1 各檔案間串檔變項說明 35
表4-2 研究疾病與診斷碼對照 42
表4-3 研究藥品與ATC對照表 45
表5-1 研究對象之基本資料 51
表5-2 研究對象之基本資料(續) 52
表5-3 Proportions of patients using individual DMARDs at
the index date 57
表5-4 Proportions of DMARDs in monotherapy and combination
regimens at the index date 58
表5-5 Proportions of patients using individual DMARDs at
the first month after the index date 59
表5-6 Proportions of DMARDs in monotherapy and combination
regimens at the first month after the index date 60
表5-7 Proportions of patients using individual DMARDs at
three months after the index date 61
表5-8 Proportions of DMARDs in monotherapy and combination
regimens at three months after the index date 62
表5-9 Proportions of patients using individual DMARDs at
six months after the index date 63
表5-10 Proportions of DMARDs in monotherapy and combination
regimens at six months after the index date 64
表5-11 Proportions of patients using individual DMARDs at
one year after the index date 65
表5-12 Proportions of DMARDs in monotherapy and combination
regimens at one year after the index date 66
表5-13 Details of DMARDs therapy at start of TNF-α
inhibitors 67
表5-14 Different DMARDs combination regimens at one year
after the index date 68
表5-15 Different DMARDs combination regimens at one year
after the index date(續)69
表6-1 指標日期接受DMARDs治療的患者,其他觀察時間點上持續使用DMARDs
情形 81
表6-2 Studies reporting rate of medication adherence 82

第二篇 臨床藥事服務 89
Table 3-1 受訪者之基本資料、藥物順從性與藥物信念評估分數 91
Table 3-2 目前受訪者DMARDs藥品使用情形 92
Table 3-3 DMARDs藥物信念評估 93
Table 3-4 服藥順從性佳或不佳者之基本資料 94
Table 3-5 服藥順從性佳或不佳者之藥物信念 95

圖目錄
圖2-1 Algorithm for treating rheumatoid arthritis to
target 8
圖4-1 研究設計 38
圖4-2 研究流程圖 39
圖4-3 研究藥品使用定義 44
圖5-1 研究對象納入與排除 49
圖5-2 指標日期與指標日期後一年TNF-α inhibitors使用率 55
圖5-3 DMARDs combination and observed DMARDs combination
regimens 56
圖6-1 不同觀察時間點未使用DMARDs比率 81
圖6-2 RA病患於五個觀察時間點使用DMARDs的累積百分比 81
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系統識別號 U0026-3107201311024800
論文名稱(中文) 臺灣乾眼症之流行病學與處方型態分析
論文名稱(英文) Epidemiology and Prescribing Pattern of Dry Eye Disease in Taiwan
校院名稱 成功大學
系所名稱(中) 臨床藥學與藥物科技研究所
系所名稱(英) Institute of Clinical Pharmacy and Pharmaceutical sciences
學年度 101
學期 2
出版年 102
研究生(中文) 陳玫潔
學號 S66004034
學位類別 碩士
語文別 中文
口試日期 2013-07-19
論文頁數 115頁
口試委員 指導教授-高雅慧
口試委員-張義昇
口試委員-翁孟玉
口試委員-林文亮
關鍵字(中) 乾眼症
發生率
長期使用
全民健康保險研究資料庫
處方型態
盛行率
臺灣
眼用製劑
類固醇
關鍵字(英) dry eye
incidence
long-term use
NHIRD
prescribing pattern
prevalence
Taiwan
topical steroid
學科別分類
中文摘要 研究背景
乾眼是眼科門診中常見的主訴,各國文獻中的盛行率變異度大,約介於 <0.1~33%,但整體盛行率隨年齡增加而向上攀升,先前的研究顯示亞洲地區有較高盛行率,而目前關於臺灣乾眼症流行病學的研究不多。過去認為乾眼症的治療以給予人工淚液緩解症狀即可,但近年研究發現乾眼症致病機轉與發炎反應有關,因此局部抗發炎藥物在乾眼症的治療中開始佔有一席之地,而臺灣目前缺乏乾眼症處方型態的相關研究。中重度乾眼症患者可能需長期依賴局部抗發炎藥物緩解症狀,目前環孢靈素眼用製劑(cyclosporine)未發現嚴重副作用,但國內價格昂貴且需符合健保給付規定;相對而言,含類固醇眼用製劑則相對便宜且無健保給付限制,因此臨床上醫師有選擇使用後者之可能性,但其潛在副作用風險,通常不建議長期使用。

研究目的
統計臺灣乾眼症的流行病學資料,觀察臺灣乾眼症患者之人口學特性,並分析年齡、性別差異或都市化程度對於發生率之影響,以做為未來乾眼症預防的實證依據。此外,本研究將觀察乾眼症患者的處方型態,並進一步分析患者長期使用含類固醇眼用製劑之相關潛在預測因子。

研究方法
使用臺灣全民健康保險研究資料庫中,2000年與2005年的百萬人承保抽樣歸人檔,共約二百萬人,擷取2000年至2010年的就醫資料。研究對象為2005年至2009年期間於門診紀錄檔中,出現乾眼症診斷碼 (ICD-9 370.33, 375.15, 710.2),且具Schirmer test紀錄者,或經重大傷病檔確認為Sjögren’s syndrome者。新診斷乾眼症為指標日期前五年內未出現乾眼症診斷者。
研究對象自指標日期後追蹤一年,分析臺灣乾眼症患者之處方型態。此外,將指標日期後30天內曾使用含類固醇眼用製劑者,分為長期使用者與非長期使用者,利用單變項與多變項邏輯迴歸,分析臺灣乾眼症患者長期使用含類固醇眼用製劑之潛在預測因子。

研究結果
研究對象共44,501人,平均年齡51.5歲,女性占73.6%,50歲(含)以上占55.7%,僅2.0%為Sjögren’s syndrome。乾眼症平均發生率0.37%,平均盛行率0.86%。研究對象於乾眼症診斷後30天內的乾眼症治療藥物使用率約66.4%,其他眼用製劑約32.5%,未使用眼用製劑約1.1%。研究對象中,於指標日期後365天內再次回診者共23,327人,前30天內的乾眼症治療藥物使用率71.0%,其他眼用製劑占27.6%,未使用眼用製劑占1.4%。就再次回診者的乾眼症治療藥物分組而言,單獨使用人工淚液占19.5%,單獨使用含類固醇眼用製劑占27.6%,其中19.3%患者併用上述二類藥物,單獨使用其他乾眼症治療用藥物僅占4.6%。指標日期後30天到一年,研究對象的乾眼症治療藥物平均使用率為28.5%,僅剩原使用人數的42.9%;再次回診者的平均使用率維持41.8%,為原使用人數的58.9%。
含類固醇眼用製劑的使用者共22,060人,6,338人為長期使用者。長期使用的預測因子,包含年齡、男性、糖尿病、角膜移植術後、青光眼、白內障、結膜炎、眼瞼發炎、眼表受傷或挫傷、人工水晶體置換等,或併服藥物如antihistamines、anticholinergics等,其中角膜移植術後最顯著 (OR 5.95)。

研究結論
臺灣乾眼症的發生率與盛行率有逐年上升的趨勢,其中50歲(含)以上、女性、高度都市化地區的發生率較高。約半數乾眼症患者於指標日期30天後停止使用乾眼症治療藥物,但後續有一定比例的患者會繼續使用藥物緩解乾眼症狀,再次回診者的藥物使用率較高。臨床上的確有長期使用含類固醇眼用製劑的情形,顯示臺灣乾眼症患者長期使用含類固醇眼用製劑符合臨床治療需要,未來可針對此類患者加強類固醇用藥指導,並注意其眼內壓變化,以確保用藥安全。
英文摘要 Background
Dry eye disease (DED) is one of the common chief complaints of the ophthalmologic outpatient. The reported prevalence ranged from <0.1% to 33% based on various definition, and the dry eye disease was more prevalent among the women and the elderly. In addition, the previous studies showed that the prevalence was higher in Asia, and the epidemiology of DED in Taiwan was insufficient. Due to inflammation is a key factor of the pathogenesis for dry eye disease, the anti-inflammatory agents, such as ophthalmologic steroids or cyclosporine, had their place in the treatment of DED other than artificial tears. However, the prescribing pattern of DED in Taiwan was lacking. Topical cyclosporine is the better choice when taking the safety into consideration, but topical steroids are much cheaper and relieve symptoms rapidly with low dose. However, long-term use of steroids is not recommended generally.

Objective
This study aimed to investigate the epidemiology and prescribing pattern of DED in Taiwan. Besides, we analyzed the characteristics of the dry eye patients and identified the predictors associated with the long-term use of topical steroids.

Methods
We conducted a retrospective cohort study based on the Longitudinal Health Insurance Database 2005 and 2010 in National Health Insurance Research Database (NHIRD), and we collected the registration and claims data in the year 2000 to 2010. All patients diagnosed with DED (ICD-9 370.33, 375.15, 710.2) and administered Schirmer test during observation period were included unless patients with Sjögren’s syndrome (SS) as record in the registry for catastrophic illness. Patients without diagnosis of DED prior to five years before the index date would be identified as incident cases. Patients were followed from index date for one year to analyze the prescribing pattern of DED and the status of steroid use in Taiwan. Multiple logistic regression model adjusted by patient demographics, co-morbidities, and co-medications was used to evaluate the predictors of the long-term use of topical steroids.

Results
There were 44,501 patients with mean age of 51.5 years having DED diagnosis during 2005 to 2009. Among them, 32,731 (73.6%) were female, 24,790 (55.7%) were older than 50 years old, only 894 (2.0%) were SS patients, and there were 23,327 patients returning for DED within one year after index date. The average incidence and prevalence of DED in Taiwan was 0.37% and 0.86% respectively, and both of them increased on the yearly basis. Within 30 days after index date, there were 66.4% patients using defined medication for DED, but 71.0% in returned patients. Of the medications for DED in returned patients, 19.5% used artificial tears without ocular steroids, 27.6% used ocular steroids without artificial tears, 19.3% used both, and only 4.6% received other medication for DED.
Among 44,501 patients, 22,060 patients used ocular steroids within 30 days after index date, and 6,338 patients were identified as long-term users. The predictors of long-term use of ocular steroids including age, male, diabetes mellitus, asthma, fracture, cornea transplant, glaucoma, cataract, macular degeneration, keratitis, conjunctivitis, inflammation of eyelids, ocular trauma, pseudophakia, antihistamines, anticholinergics, antidepressants, benzodiazepines, diuretics, vitamins and systemic steroids. The cornea transplant was the most powerful predictor, (OR 5.95) followed by pseukophakia (OR 1.57).

Conclusions
The incidence and prevalence were both increasing during 2005 to 2009, and the incidence of the elderly, women, or high-urbanized area was higher. Half patients discontinued their medications for DED within the first 30 days after index date, but some patients kept using medication to relieve their symptoms in the following days. Long-term use of topical steroids among dry eye patients in Taiwan were reasonable, like the patients with cornea transplant, and the counseling of steroids use should be conducted if ocular steroids is initiated.
論文目次 中文摘要 i
Abstract iii
誌謝 v
目錄 vii
圖目錄 x
表目錄 xi
附錄 xiii
第一篇 臺灣乾眼症之流行病學與處方型態分析
第一章 研究背景 1
第二章 文獻回顧 3
第一節 乾眼症簡介 3
一、 乾眼症的定義 3
二、 乾眼症相關之眼部結構簡介 4
三、 乾眼症的病因 5
四、 乾眼症的致病機轉 10
五、 乾眼症的診斷方法 11
六、 乾眼症的嚴重程度與治療建議 12
第二節 乾眼症的流行病學與危險因子 14
一、 乾眼症的發生率 14
二、 乾眼症的盛行率 14
三、 具統計意義的乾眼症相關危險因子 18
第三節 長期使用含類固醇眼用製劑之安全性探討 19
第四節 文獻回顧總結 20
第三章 研究目的與重要性 21
第一節 研究目的 21
第二節 研究重要性 21
第四章 研究方法 22
第一節 研究設計 22
一、 研究材料與工具 22
二、 研究對象之納入條件與指標日期定義 23
三、 研究對象之排除條件 24
四、 基本資料與分組 24
第二節 研究流程 25
一、 研究變項及操作型定義 27
二、 資料處理流程 33
第三節 統計方法 34
第五章 研究結果 36
第一節 研究對象的納入與排除 36
第二節 研究對象基本資料 38
第三節 臺灣的乾眼症發生率 45
第四節 臺灣的乾眼症盛行率 48
第五節 臺灣乾眼症的處方型態分析 51
第六節 乾眼症患者長期使用含類固醇眼用製劑的潛在預測因子 55
第七節 敏感性分析 59
第六章 研究討論 63
第一節 研究對象的納入與排除分析 63
第二節 研究對象基本資料分析 66
第三節 臺灣乾眼症的發生率分析 67
第四節 臺灣乾眼症的盛行率分析 69
第五節 臺灣乾眼症的處方型態分析 70
第六節 長期使用含類固醇眼用製劑的預測因子分析 73
第七節 研究限制 75
第七章 結論與建議 77
第八章 未來研究方向 78
第二篇 臨床藥事服務:眼科門診用藥指導
第一章 服務背景 79
第二章 服務目的與進行方法 80
第一節 服務目的 80
第二節 服務進行方法 80
一、 服務時間、地點與服務對象 80
二、 標的藥物 80
三、 用藥指導工具與參考資料來源 80
四、 問卷內容之專家效度 82
五、 服務進行流程 83
第三節 服務結果 84
一、 問卷內容的專家效度 84
二、 服務對象的基本特性 86
三、 眼用製劑的了解程度與藥物使用情形 88
四、 服務滿意度與回饋 90
第四節 討論 91
第五節 服務心得與建議 93
參考文獻 110
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