臺灣博碩士論文加值系統

研究背景
非類固醇抗發炎劑（Nonsteroidal Anti-Inflammatory Drugs, NSAIDs）在全球被廣泛地應用在消炎、解熱及鎮痛等治療；但也造成了使用者胃腸道副作用的發生，從輕微的消化不良（10–20%）至胃潰瘍、胃腸道出血（1–4%），甚至引發死亡。兩個大型臨床試驗中，選擇性第二型環氧化酶抑制劑在胃腸道併發症的發生率有低於傳統非類固醇抗發炎劑的趨勢，但在一綜合分析（meta-analysis）試驗結果中卻未證實選擇性第二型環氧化酶抑制劑優於傳統非類固醇抗發炎劑。

研究目的
評估選擇性第二型環氧化酶抑制劑或優先性第二型環氧化酶抑制劑與傳統非類固醇抗發炎劑與嚴重胃腸道副作用之相關性。

研究方法
本研究為回溯性世代追蹤研究法 (retrospective cohort study)，利用2000-2004百萬人抽樣健保資料庫門、住診檔，擷取出2002/1/1至2003/12/31定義新使用非類固醇抗發炎劑者，分析指標日期後第二型環氧化酶抑制劑或優先性第二型環氧化酶抑制劑與傳統非類固醇抗發炎劑使用者上胃腸道出血住院率之關係。

研究結果
主要研究對象共計29,887人，女性占46.77%，平均年齡為48.46歲，60歲以上人口占28.01%。以環氧化酶抑制劑之傾向評分（propensity score）分佈作分層，經由共變項與傾向評分之多變項分析校正後，優先性環氧化酶抑制劑（adjusted HR：0.606；95% CI：0.315-1.164）相較於傳統型非類固醇抗發炎劑並未顯著降低胃腸道出血住院之風險。選擇性環氧化酶抑制劑（adjusted HR：1.473；95% CI：0.872-2.488）相較於傳統型非類固醇抗發炎劑亦未顯著增加胃腸道出血住院之風險。

結論
優先性與選擇性環氧化酶抑制劑使用者普遍顯著比傳統型非類固醇抗發炎劑使用者有較高的危險概況。合併使用共變項與傾向評分分層作校正後，優先性或選擇性環氧化酶抑制劑皆未比傳統型非類固醇抗發炎劑顯著降低上胃腸道出血住院之風險。

Background
NSAIDs (Nonsteroidal Anti-Inflammatory Drugs) are among the most widely used medicines in the world. Unfortunately, they are associated with dose-dependent gastrointestinal adverse events ranging from dyspepsia (10–20%) to symptomatic and complicated ulcers (1–4%). Although clinical trial results suggest that coxibs has less gastrointestinal toxicity than most other non-steroidal anti-inflammatory drugs (NSAIDs), but not in meta-analysis.

Objective
To estimate whether preferential and selective coxibs have been channeled towards high risk patients, and to estimate the risk of hospitalisation for gastrointestinal haemorrhage associated with the use of these drugs, allowing for the effects of channelling.

Method
This was a retrospective cohort study using National Health Insurance databases. The study included only new episodes of prescribed NSAID or coxib use between 2002 and 2003 and controlled for multiple baseline risk factors for upper gastrointestinal disease. We compared gastrointestinal haemorrhage hospitalization rates among patients taking NS-NSAIDs, preferential and selective coxibs.

Result
There are total 29,887 people as the object of study of which female accounts for 46.77%. The average age is 48.46 year-old and the percentage of people above 60 is 28.01. Analyses stratified by propensity score with individual covariate adjustments, the adjusted HRs of gastrointestinal haemorrhage for preferential coxibs compared with older non-specific NSAIDs are 0.606 (95% CI: 0.315-1.164). The adjusted HRs of gastrointestinal haemorrhage for selective coxibs compared with older non-specific NSAIDs are 1.473 (95% CI: 0.872-2.488). There was no significant difference in the HRs for preferential and selective coxibs compared with older non-specific NSAIDs.

Conclusion
Channelling towards high risk gastrointestinal patients occurred in the prescribing of preferential and selective coxibs. After attempting to correct for channelling bias, preferential and selective coxibs exposure was not associated with a significantly lower risk of gastrointestinal haemorrhage than older
non-specific NSAID exposure.

第一章 研究背景 1
第二章 文獻回顧 3
第一節 非類固醇抗發炎藥引起之胃腸道副作用簡介 3
2.1.1 流行病學 3
2.1.2 致病機轉 4
2.1.3 危險因子與相對風險 5
2.1.4 個別非類固醇抗發炎劑嚴重胃腸道副作用之比較 5
2.1.5 急性出血之藥物治療方式 6
2.1.6 預防方法與建議 6
第二節 環氧化酶抑制劑簡介 8
2.2.1 環氧化酶（cyclooxgenase）理論 8
2.2.2 環氧化酶-2選擇性 8
2.2.3 藥物特性 9
2.2.4 臨床療效 12
2.2.5 安全性 13
第三節 環氧化酶抑制劑對胃腸道不良反應之影響 17
2.3.1 胃腸道症狀 17
2.3.2 上胃腸道安全性 17
第四節 胃腸保護劑簡介 20
2.4.1 氫離子幫浦阻斷劑（proton pump inhibitors，PPIs） 20
2.4.2 前列腺素劑（misoprostol） 20
2.4.3 乙型組織胺受體阻斷劑（H2 receptor antagonists） 21
第五節 其它影響非類固醇抗發炎劑相關胃腸道不良反應之因素 22
2.5.1 Aspirin 22
第三章 研究目的及方法 33
第一節 研究目的 33
第二節 研究型態 33
第三節 研究材料 33
第四節 研究對象 35
3.4.1 納入條件 35
3.4.2 排除條件 35
第五節 研究變項及操作定義說明 36
3.5.1 研究對象定義 36
3.5.2 研究事件 37
3.5.3 病患基本特質 37
第六節 資料處理 40
3.6.1 資料處理流程 40
3.6.2 指標日期前之患者基本特性分析 41
3.6.3 指標日期後之患者基本特性分析 41
第四章 統計分析 42
第一節 資料分析方法 42
4.1.1敘述性統計 42
4.1.2推論性統計（以傳統型非類固醇抗發炎劑為參考值） 42
第二節 統計模式設定 43
第三節 統計工具 43
第五章 研究結果 44
第一節 病患基本特性分佈 44
第二節 病患之共病症與其它合併用藥 46
5.2.1 非類固醇抗發炎劑組別與基本特質分佈 46
第三節 影響胃腸道出血相關因子與上胃腸道出血住院之關聯性 49
5.3.1影響胃腸道出血疾病與上胃腸道出血住院之關聯性 49
5.3.2影響胃腸道出血藥品與上胃腸道出血住院之關聯性 49
第四節 非類固醇抗發炎劑與上胃腸道出血住院之關聯性 51
5.4.1 優先性環氧化酶抑制劑與上胃腸道出血住院之關聯性 51
5.4.2 選擇性環氧化酶抑制劑與上胃腸道出血住院之關聯性 51
5.4.3傾向評分（propensity score）分析 51
5.4.4敏感度分析 52
第六章 研究討論 81
第一節 研究族群人口特性 81
第二節 影響胃腸道出血相關因子與上胃腸道出血住院之關聯性 84
第三節 非類固醇抗發炎劑與上胃腸道出血住院之關聯性 85
第七章 研究限制 89
第八章 結論與建議 90
第九章 未來研究方向 90
臨床藥事服務 91
第一章 服務背景 91
第二章 衛教方式 92
第三章 服務結果 93
第四章 服務心得與建議 94
參考文獻 97
附錄 106

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