臺灣博碩士論文加值系統

研究背景：國人服用安眠藥的狀況，逐年增加，根據衛福部食藥署統計發現，民國99至102年國人每年服用安眠藥依序為3億粒、3.24億粒、3.33億粒、3.27億粒。服用安眠藥常見的副作用為噁心、嘔吐、健忘、頭痛、幻覺、短期記憶喪失，安眠藥僅是短期治療失眠的不宜長期使用。由於民眾服用安眠藥的狀況是無法做隨機分派，而服用安眠藥的族群與一般族群有些許差異，這可能會導致研究上的偏差。本篇目的為藉由控制相關干擾因子，探討民眾使用安眠藥物是否與對於死亡有影響。
材料與方法：研究對象為2006~2009年40歲以上參加基隆市社區整合式篩檢的民眾，共44163人，並追蹤至2010年12月31日。該社區篩檢以結構式問卷進行個人病史及生活習慣資料收集，生化檢驗資料以8小時禁食後血清進行檢測並記錄。安眠藥服用頻率則以問卷進行收集，問卷回答選項分為『從不』、『每天』、『每週1~2次』、『每週3~4次』、『每週5~6次』。本研究考量追蹤人年後進行統計方法使用Poisson方法進行總死亡率計算。本研究以三種模式進行安眠藥服用頻率對於總死亡影響分析：包括(1)Cox比例風險模型、(2)傾向分數存活模型、(3)傾向配對存活模型進行分析，以考量相關干擾因子後，探討服用安眠藥頻率對於死亡影響。其中傾向分數存活模型及傾向配對存活模型的傾向分數，以logistic regression model進行個人特質與安眠藥頻率相關因素探討，再以多變項logistic regression model進行傾向變項選取及分數計算並作為該兩項模型分析及調整用。
結果：本研究結果顯示，有服用安眠藥物者男性佔8.3%及女性佔11.2%，其中每週服用五次以上男性佔5.1%及女性佔5.7%，顯示我國40歲以上有5-6%民眾幾乎天天服用安眠藥，且高頻率服用狀況隨著年齡增加而增加。經過中位數4.18年追蹤後，共計有617位男性及341位女性死亡。利用傳統Cox regression進行其他干擾因素調整後，與從未服用者比較，一週服用1-4次及服用5次以上安眠藥之死亡危險比分別為0.97倍(95%信賴區間0.73, 1.30)及1.40倍(95%信賴區間1.12, 1.74)。使用傾向分數調整方法，將相關干擾因子以一傾向分數直接進行調整後，與從未服用者比較，一週服用1-4次及服用5次以上安眠藥之死亡危險比分別為1.01倍(95%信賴區間0.74, 1.37)及1.35倍(95%信賴區間1.06, 1.73)。以傾向配對存活模型進行分析結果顯示，與從未服用者比較，一週服用1-4次及服用5次以上安眠藥之死亡危險比分別為0.91倍(95%信賴區間0.62, 1.32)及1.42倍(95%信賴區間1.02, 1.98)。
結論：本研究利用三種統計模式進行安眠藥服用頻率對於全死因影響分析，控制相關潛在干擾因子後，三種結果顯示服用安眠藥高頻率民眾與死亡呈現顯著的相關，與從不服用者比較，安眠藥高頻率服用者(每週服用5次以上)高出1.35-1.42倍之死亡危險。

Background: Hypnotics are widely used by the general population in Taiwan. According to the statistics by Ministry of Health and Welfare, the overall prevalence of using Hypnotics is dramatically increasing from 2010 (300 million/per year) to 2013 (327 million/per year). Because of the side effects and potential risks of hypnotics, some studies indicated that using hypnotics has relationship to mortality. In practice, it is hard to evaluate the impact of people taking hypnotics situation using randomized controlled trial, but mostly previous studies were design by cross-sectional study. On the other hand, the characteristics in people who trend to use hypnotics are also lack to consider, might affect the analysis result of mortality. The aim of our study is to examine the effect and impact of hypnotics use on mortality based on general population, after controlling potential confounding factors using propensity score approach.
Methods: Our study population enrolled 17,123 men and 27, 040 women aged over 40 years who participated Keelung Community-Based Integrated Screening Program between 2006 to 2009. Those disease history and life styles were collected by structural questionnaire. The frequencies of hypnotics use were collected by 5 categories, including never, 7, 1-2, 3-4, and 5-6 times per week. Mortality outcomes were ascertained by linking to Taiwan Death Registry Database till the end of 2010. In our analysis, those who having hypnotics intake with 1-4 times or ≧5 times per week were defined as low and high frequency, respectively. Logistic regression was applied to calculate the propensity score based on the parsimonious model. We conducted Cox regression model to estimate the effect of different frequencies of hypnotics use on the all-cause mortality, based on traditional multivariable model to adjust propensity score directly or propensity score matching approach.
Results: The prevalence of low combined high frequency hypnotic use was 8.3% of men and 11.2% of women, respectively. Furthermore, the prevalence of high frequency were 5.1% and 5.7% for men and women, respectively, which significantly increased by age. After the median 4.18 years follow-up, there were 617 men and 341 women died. After adjusted for potential confounding factors using conventional Cox regression model, compared with no hypnotics intake, high frequency hypnotic use was significantly increased risk on all-cause mortality (adjusted Hazard Ratio (aHR)= 1.40, 95% CI= 1.12 to 1.74). Adjustment for propensity score, high frequency hypnotic use was significantly increased risk on mortality (aHR= 1.35, 95% CI= 1.06 to 1.73). For the propensity-score matching approach, high frequency hypnotic use significantly increased risk on mortality (aHR= 1.42, 95% CI= 1.02 to 1.98).
Conclusion: Our study revealed the subjects having high frequency use of Hypnotics significantly increased the risk of all-causes mortality with 1.35-1.42 times compared with no hypnotics use. The results were consistent regardless conventional or propensity score approach.

指導教授推薦書
口試委員會審定書
致謝..................................iii
摘要..................................iv
Abstract..............................vii
目錄.................................ix
圖目錄.................................xi
表目錄.................................xii
第一章、研究背景與目的...................1
第二章、文獻探討........................3
第一節、安眠藥的簡介...................3
第二節、各國安眠藥服用狀況..............5
第三節、服用安眠藥者族群特性............6
第四節、服用安眠藥導致的風險............8
第五節、服用安眠藥物與死亡的關聯.........10
第三章、材料與方法........................14
第一節、研究族群........................14
第二節、資料來源........................15
第三節、統計方法........................19
第四章、結果與分析........................23
第一節、研究對象服用安眠藥狀況...........23
第二節、研究樣本之死亡率................23
第三節、死因統計.......................25
第四節、Cox比例風險模型.................26
第五節、序位邏輯斯迴歸檢定...............28
第六節、服用安眠藥族群的特性.............29
第七節、廣義邏輯斯迴歸模型...............29
第八節、傾向分數配對法...................36
第五章、討論..............................38
第一節、安眠藥族群服用情形................38
第二節、安眠藥之死因探討..................39
第三節、傾向分數配對法與傳統調整方法之比較..40
第四節、本研究的優勢......................41
第五節、研究限制.........................41
第六章、結論...............................43
參考文獻...............................45


圖目錄
圖 3-1 研究架構流程圖.........................................................................49
圖 4-1 比例風險假設檢定 ...................................................................50
圖 4-2 調整前傾向分數分佈圖.............................................................51
圖 4-3 調整後傾向分數分佈圖.............................................................52


表目錄
表 4-1 整體樣本服用安眠藥頻率之分布情形......................................53
表 4-2 社會人口學變項及臨床特徵導致死亡的風險..........................57
表 4-3 樣本死亡人口之死因統計..........................................................59
表 4-4 各種因素導致死亡的風險 (Cox regression).............................60
表 4-5 服用安眠藥頻率變項序位邏輯斯迴歸檢定..............................62
表 4-6 整體樣本民眾服用安眠藥頻率的分佈情形..............................64
表 4-7 個人特質與服用安眠藥之單變項廣義邏輯斯迴歸..................67
表 4-8 個人特質與服用安眠藥之多變項廣義邏輯斯迴歸..................69
表 4-9 調整前各組別傾向分數分布......................................................71
表 4-10 調整後各組別傾向分數分布....................................................71
表 4-11 經傾向分數調整過後，安眠藥導致死亡的風險程度............72
表 4-12 使用傾向分數配對後，安眠藥導致死亡的風險程度............73

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