摘要:台灣是C型肝炎感染高盛行率的區域,而且近20年C型肝炎導致的肝癌人數漸增。目前干擾素 (peginterferon ) 及抗病毒藥物 (Ribavirin) 之合併治療是目前慢性C型肝炎病患最主要的治療方式; 然而,此合併治療造成病患經歷許多的身心症狀,包括嚴重的疲倦、沮喪及出現自殺的想法,進而影響病患對治療的遵從性而影響療效。身體活動對於改善身體功能降低心理困擾及增加抗發炎的細胞激素(anti-inflammatory cytokines),例如干擾素。但是,目前並未有全面的身體活動及衛教照護計畫,協助慢性C型肝炎病患在治療期間處理面臨的身心困擾。因此,此四年期之研究以運動之生物行為模式為架構發展之研究目的,包括:(1) 瞭解接受長效型干擾素與ribavirin 之合併治療期間之慢性C 型肝炎病患運動現況及其喜好,以發展此族群可行的運動計畫建議;(2) 探討合併治療期間之慢性C 型肝炎病患體適能(肌力、心肺功能)、疲倦、憂鬱、睡眠困擾、生活品質之改變情形及其相關性;(3) 發展及測試個別化運動及衛教計畫於接受合併治療期間之慢性C 型肝炎病患改善體適能疲倦、憂鬱、睡眠困擾、生活品質之成效;(4) 評估個別化之運動及衛教計畫於合併治療期間之慢性C 型肝炎病患於治療遵從性、以及治療結束24週之持續病毒反應率(sustained virological response)之成效。研究假設為個別化運動及衛教計畫可 (1) 改善病患的體適能(肌力、心肺功能);(2) 降低疲倦、憂鬱及睡眠困擾並進而改善生活品質;(3) 增加治療遵從性及治療結束24週後之持續病毒反應率。第一階段(1-2年)採縱貫式相關性研究設計,針對接受長效型干擾素(peginterferon α) 與Ribavirin 之合併治療期間之慢性C 型肝炎病患進行問卷訪談及6分鐘走路測試、手部握力及下肢肌力(膝伸直及髖屈曲)之測量,以瞭解病患之運動習慣、疲倦、憂鬱、睡眠困擾、生活品質、心肺適能、及上下肢肌力現況,同時分析影響治療24週內之生活品質影響因素。問卷使用自擬之基本屬性及運動習慣、癌症疲倦量表、醫院焦慮與憂鬱量表及SF 36生活品質量表,評估病患之運動習慣、疲倦、症狀困擾、焦慮及憂鬱。收案時間為治療前、治療第8、16、24週。使用描述性統計、Pearson’s 相關性分析及概化估計方程式(generalized estimating equations; GEE),以瞭解肌力、心肺功能之改變及生活品質之重要預測因子。預估第一階段完成150位。第二階段(3-4年)採隨機臨床試驗,於台北市某一醫學中心內科門診,選取接受長效型干擾素(peginterferon α) 與ribavirin 之合併治療期間之慢性C 型肝炎病患為研究對象,隨機分配至對照組或實驗組。對照組接受常規照護,而實驗組則給予24週之個別化身體活動及衛教計畫,衛教諮詢於門診進行,介入時間為治療前、治療第2, 4, 6, 8, 12, 16, 20, 24週,每次20-30分鐘。此衛教計畫內容大剛包括: (1) 治療相關資訊; (2) 身體活動諮詢; (3) 身體症狀之自我處理; (4)營養自我準備; (5) 心理困擾之自我調適技巧學習; (6) 溝通技巧之學習。將以第一階段之量表及自擬之自我效能及治療遵從性量表進行資料收集,同時進行6分鐘走路測試、手部握力及下肢肌力之測量。測量時間共計5次,分別於治療前、治療第12, 24, 36, 及48週以瞭解執行12週、24週之立即效果及維持3、6個月之效果。長期持續病毒反應率(sustained virological response) 之成效將以治療完成後半年之HCV RNA 結果判讀。資料將以描述性統計以及概化估計方程式進行分析,以瞭解個別化身體活動及衛教計畫之成效。此階段實驗組與對照組各需60位,考量流失率30%,預計共需徵求156位病患。 預期結果: 預期本研究可以暸解病患於治療期間之心肺適能、及上下肢肌力與疲倦、憂鬱、睡眠及生活品質之相關性及個別化身體活動於治療期間的成效,以及發展適合治療期間之慢性C 型肝炎之照護模式,以作為未來臨床照護之參考。
Abstract: Taiwan is an area with the highest prevalence rate of hepatitis C virus (HCV) infection. Peglated interferon α plus ribavirin is the current mainstay of treatment for these patients. However, the therapy requires weekly subcutaneous injections, twice-daily oral dosing and frequent blood tests over a period of several months. Most patients experience multiple symptom distress including severe fatigue and depression, and even suicidal ideation during the course of treatment. Experiencing those side effects could affect patients’ adherence to therapy. However, physical activity has been found to increase physical function, decrease psychological distress and most importantly increase anti-inflammatory cytokines such as interferon. To date, there are very few studies that have examined the exact role of physical activity and the establishment of a comprehensive care program to manage fatigue and treatment-related symptoms in this population. This 4-year project will be guided by a biobehavioral model for the study of exercise interventions in two phases. The four aims of this study are to (1) explore the patients’ physical activity preferences and develop feasible activity lists during treatment period; (2) examine the changes of health-related physical fitness component (i.e., muscular strength and cardiopulmonary) during combined therapy; (3) develop the Personalized Physical Activity and Psycho-Education (PPAPE) Program and test its effects on decreasing fatigue, physical and psychological distress, and improving their physical fitness and quality of life in patients with HCV infection receiving 48 weeks of Interferon with Ribavirin Combination Therapy; and (4) evaluate the outcome of the PPAPE program on increasing adherence to therapy and the sustained virological response (SVR) in 24 weeks after the end of treatment. We hypothesize that our PPAPE program can (1) improve the physical fitness (i.e., muscle strength and cardiopulmonary), decrease the level of fatigue and symptom distress, and improve quality of life during treatment; and (2) increase the rate of adherence to therapy and SVR. Phase I of this project, the first and second years, will examine the research aims (1) and (2). A prospective correlational longitudinal design will be conducted. The patients with HCV infection who plan to receive peginterferon alpha and Ribavirin combined therapy in an outpatient setting will be recruited. A set of questionnaire will be used to collect data. Cardiopulmonary fitness and muscular strength (grip strength, knee extension and hip flexion) will be examined using 6-minute walk test, hand dynamometer, and hand-held dynamometer. The data will be collected at baseline (before treatment, T0), at weeks 8 (T1), 16 (T2), and 24 (T3) during treatment. A total of 150 patients will be recruited. The longitudinal data will be analyzed by descriptive statistics and generalized estimating equations. Phase II of this project, the third and fourth year, will examine the research aims (3) and (4). A randomized control clinical trial will be conducted to test the effects of the PPAPE program. The waiting list group will consist of the patients receiving usual care. The experimental group will receive the following major components of the PPAPE program: (1) treatment-related information support; (2) physical activity consultation; (3) self-management of treatment-related physical distress; (4) nutrition support: how to eat during treatment; (5) self-management of psychological distress (i.e., anxiety, depression, and uncertainty); and (6) managing social or communication problems with health care providers and families. The PPAPE group will receive 6 months of consultation and education with eight sessions: before treatment and at weeks 2, 4, 6, 8, 12, 16, 20, 24 during treatment. Each session will last 20-30 minutes in the outpatient setting. An exercise diary (exercise mode, intensity and duration) and adherence to therapy will be recorded during treatment. The effects of PPAPE program will be examined at weeks 12, 24, 36, and 48 during treatment with a set of questionnaires and a physical fitness examination. Data will be analyzed by descriptive, Pearson’s correlation, student t-test and generalized estimating equations to examine the effects of the PPAPE program. In total, 156 subjects will be interviewed in the second phase. We expect this project will lead to develop a comprehensive care model for patients with HCV infection and improve the understanding of the role and function of physical activity during the combined therapy.