PDF 國立臺北護理健康大學護理系博士論文

國立臺北護理健康大學護理系博士論文 School of Nursing National Taipei University of Nursing and Health Sciences Doctoral Dissertation 運動介入計畫對血液透析病人身體功能、 心理與生活品質相關變項之成效. Effect of exercise on physical function, psychological factors and health-related quality of life in patients during hemodialysis. 研究生:劉月敏 撰 Graduate student：Yueh-Min Liu. 指導教授:葉美玲 教授 Advisor：Professor, Mei-Ling Yeh. 中華民國 104 年 7 月 July, 2015.

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ACKNOWLEDGEMENTS 工作數年之餘，可以重拾課本繼續求學是一種幸福，又能夠得到明師的指導 與鼓勵更是可遇不可求的幸運。 本論文之所以完成，首先，要感謝我的指導教授葉美玲博士，承蒙教授的悉 心指導，在這五年的學習過程，獲益匪淺。每當我在論文上有迷惑、瓶頸，甚至 想要放棄時，葉老師總能及時透過Facebook不斷的給予肯定和鼓勵，亦不斷地鞭 策，讓我可以在學習道路上更加進步與精進的成長，老師對學問的嚴謹更是我學 習的典範。還有，感謝健康事業管理系林寬佳教授，在兼任系主任繁忙之餘，總 能撥冗時間討論論文統計並指點我正確的方向。感謝臺北榮民總醫院護理部主任 王桂芸教授，給予學生在論文方面上的建議與指導，使得研究論文更加完整。感 謝高雄醫學大學醫學院張榮参副教授，從遙遠的高雄前來鼎力協助，總是提供諸 多寶貴意見，使本篇論文更加周延。感謝耕莘醫院血液透析中心主治醫師盧國城 教授，在百忙之中，撥空給予學生學業與專業上的協助，分享寫論文的技巧，傾 囊相授許多專業的知識，讓學生在各方面的專業得以更上一層樓。 感謝鄭彩梅醫師、Mark Wisemantel、與蔡屬娥老師在英文上的修正，讓此 論文撰寫更加流暢。感謝耕莘醫院整個家族的支持與肯定，得以順利在職進修。 感謝所有的腎友，無條件的配合，以及感謝腎友雷玉梅在運動器材上給予援助， 收案得以順利完成。感謝我的同學怡人、怡娟、如文、麗雲姐、英芬姐、紫娟姐、 桂芬、慧芬、朱岑、安奇和秀玫，難得緣份，我們在校園共聚一堂，求學的階段 互相加油打氣，彼此鼓舞奮進，謝謝妳們陪伴，讓我的人生留下美好的回憶。還 有感謝玉珠、靜修、和惠卿學姐，始終不斷的鼓舞與勉勵。 感謝姐姐月惠、弟弟坤宗和坤祥，無私的付出。感謝我的大寶貝子毅，總會 自己獨立完成學校的功課，不讓媽媽有後顧之憂;小寶貝苡甄，總會陪著爸爸到 廟裡祈求保佑媽媽能順利畢業，工作順利。最重要的還有一路在我身後無怨無悔 支持我的外子慶昌，感謝你總是容忍我面對到論文壓力時的無理取鬧，感謝你不 時給予我支持、關懷和諒解。最後，我將來能有所成就，這都要要感謝曾經協助 我和支持我的這些貴人。要感謝的人實在太多，只有真心誠意地感謝天。 劉月敏 謹誌於 2015 年 6 月. i.

ABSTRACT Background Patients with end-stage renal disease under hemodialysis (HD) are associated with dramatically impaired physical function, depression, fatigue, and finally with decreased health-related quality of life (HRQoL). Exercise may be effective in improving physical function, psychological factors and health-related quality of life in these patients. Previous studies have concluded that regular exercise might improve individual’s exercise self-efficacy and resilience, which could play an important role in improving the physical, psychological factors and health-related quality of life in these patients. Purpose This study aimed to evaluate the effects of intra-dialytic aerobic and resistance cycling exercise program (ARCEP) on physical function, depression, fatigue, and HRQoL in HD patients, and further confirmed the mediator effects of exercise self-efficacy and resilience in the exercise group. Methods This was randomized controlled trial. Data were collected from June, 2013 to August, 2014. Seventy-six maintenance HD patients were included and randomly assigned into control and exercise group, with 38 participants each group. The control group received nursing routine care (n= 31), whereas the exercise group received not only nursing routine care but also a 3-month ARCEP (30 minutes per session, 3 times a week) (n= 27). Data were collected at baseline, 1st month, 2nd month, and 3rd month. Outcome measures include 6 minutes’ walk test (6MWT), time taken to complete 10 sit-to-stand-to-sit cycles (STS-10), and number of sit-to-stand-to-sit cycles in 60 seconds (STS-60), Beck Depression Inventory, fatigue scale, and quality. ii.

of life scale (WHOQOL-BREF). Mediation effects were measured by the exercise self-efficacy, outcome expectations and resilience scale. Data were analyzed by SPSS 20.0 software. Descriptive statistics were calculated for basic characteristics. The independent t-test and Chi-square test were identically distributed to homogeneity of demographic characteristics. Generalized estimating equation (GEE) examined the repeated measurements data, and difference-in-differences estimation (DID) explored the impact of exercise program on physical function, depression, fatigue, and HRQoL scores in the exercise group. Results The data shown, firstly, the score of 6MWT was significantly improved in change over-time between groups in each testing month, i.e. baseline, 1st month, 2nd month, and 3rd month (p= .004, p< .001, p< .001) compared with baseline, respectively, the score of STS-10 was significantly improved in change over-time between groups in each testing month (p= .002, p< .001, p< .001), the score of STS-60 was significantly improved in change over-time between groups in each testing month (p= .01, p< .001, p< .001), the depression score was significantly improved over-time between groups in the second and third month (p= .21, p= .003, p< .001), the fatigue score was significantly improved over-time between groups in each testing month (p= .03, p= .02, p= .001), the HRQoL score was significantly improved over-time between groups in third month (p= .68, p= .66, p= .01). Secondly, significant differences were noted in depression (p= .02), and fatigue (p= .04), using exercise self-efficacy as a mediator in the exercise group, but not significantly differed in physical function (6MWT, p= .62; STS-10, p= .18; STS-60, p= .86), and HRQoL (p= .60) between the groups. Moreover, significant differences over-time noted in depression (p= .001), fatigue (p= .03), and HRQoL (p< .001) with resilience. iii.

as an effect in the exercise group, but no significant difference was noted with physical function (6MWT, p= .78; STS-10, p= .96; STS-60, p= .17). Conclusion The 3-month ARCEP revealed improved physical function, reduced depression, improved fatigue and increased HRQoL. Exercise self-efficacy significantly improves depression and fatigue; and resilience improved depression, fatigue and HRQoL. Thus, HD patients are recommended for regular exercise. Future studies might implement this ARCEP in various medical settings, and examining the longitudinal effects of this intervention.. Keywords: hemodialysis, exercise program, physical function, depression, fatigue, health-related quality of life, exercise self-efficacy, resilience. iv.

中文摘要 背景 末期腎臟疾病病人接受血液透析治療，與身體功能衰退，憂鬱和疲憊有關， 進而降低健康相關生活品質。規律運動訓練有助於提高血液透析病人的身體功 能、心理健康與生活品質。研究指出，規律運動有助於提高運動自我效能和復原 力，這可能在改善這些患者的身體功能、心理健康與生活品質變項中發揮重要作 用。 目的 血液透析病人接受透析中有氧運動和阻力腳踏車運動計劃（ARCEP）對身 體功能、憂鬱、疲憊和健康相關生活品質之成效。並進一步驗證運動自我效能感 和復原力在運動組的中介效果。 方法 本研究採隨機對照試驗。收集資料期間從 2013 年 6 月至 2014 年 8 月，總共 76 位血液透析病人被納入，並隨機分派二組各有 38 位。對照組接受常規護理， 而運動組接受常規護理及 3 個月的運動計劃（ARCEP）（每次 30 分鐘，每週 3 次）。資料收集時間為前測、運動後 1 個月、2 個月和 3 個月。主要測量項目包 括 6 分鐘的步行試驗（6MWT） 、一次完成 10 次坐到站姿到坐的時間（STS-10）、 採取 60 秒坐到站姿到坐的次數（STS-60） 、貝克憂鬱量表、疲憊量表及生活品質 問卷。中介效果是由運動自我效能、結果期望量表和復原力量表測定。資料由 SPSS 20.0 軟體進行分析。描述性統計檢定基本特性，獨立 t 檢定和卡方檢定檢 驗二組人口特徵的同質性，廣義估計方程（GEE）檢驗重複測量資料，和差異中 的差異估計（DID）檢驗運動組內的身體功能、憂鬱、疲憊和健康相關生活品質 之影響。 結果 運動介入後，首先，實驗組與時間交互作用在主要成果測量上達顯著差異， 六分鐘步行試驗實驗組與 1 個月，2 個月，3 個月介入後時間交互作用達顯著差 異（p= .004, p< .001, p< .001） ；STS-10 的檢驗在每一個月的介入後交互作用都達 顯著差異（p= .002, p< .001, p< .001） ，STS-60 的檢驗在每一個月的介入後時間交 互作用都達顯著差異（p= .01, p< .001, p< .001），憂鬱的測量僅有在第二和第三. v.

個月介入後時間交互作用達顯著差異（p= .21, p= .003, p< .001），疲憊的測量在 每一個月介入時間後交互作用都達顯著差異（p= .03, p= .02, p= .001） ，對健康相 關生活質量僅有在第三個月介入後時間交互作用達顯著差異（p= .68, p= .66, p= .01） 。其次，運動自我效能只有對憂鬱（p= .02） ，和疲憊（p= .04）有顯著差 異，對身體功能（6MWT, p= .62; STS-10, p= .18; STS-60, p= .86） ，以及健康相關 生活質量（p= .60）無顯著差異。此外，復原力只有對憂鬱(p= .001） 、疲憊（p= .03） 及健康相關生活品質（p< .001）達顯著差異，對身體功能（6MWT, p= .78; STS-10, p= .96; STS-60,. p= .17）無顯著差異。. 結論 三個月的運動計劃顯著改善身體功能，減少憂鬱，改善疲憊和提高健康相關 生活品質。運動自我效能顯著改善憂鬱和疲憊；復原力改善憂鬱，疲憊和健康相 關生活品質。因此，建議所有的血液透析病人，應鼓勵定期參與運動，以及未來 的研究，能在不同的醫療機構宣導血液透析中運動及追縱長期效果。. 關鍵詞：血液透析，運動計劃，身體功能，憂鬱，疲憊，健康相關生活品質，運 動自我效能，復原力. vi.

CONTENTS Page ACKNOWLEDGEMENTS. i. ABSTRACT. ii. ABSTRACT IN CHINESE. v. CONTENTS. vii. LIST OF TABLES. ix. LIST OF FIGURES. x. 1. INTRODUCTION. 1. 1.1. General Background Information. 3. 1.2. Literature Review. 8. A. End Stage of Renal Disease and Hemodialysis. 8. B. Principles of Exercise Implementation. 13. C. Effects of Exercise Program on Physical function,. 19. Depression, Fatigue and HRQoL D. The Mediator Effects of Exercise Program on Exercise. 25. Self-efficacy and Resilience 1.3. Research Purpose. 27. 1.4. Research Questions. 28. 1.5. Research Hypotheses. 29 30. II. METHOD 2.1. Research Design. 30. 2.2. Subjects/ Materials. 30. A. Subjects. 30. B. Instruments. 33. C. Exercise program. 40. 2.3. Data Collection Procedure. 42. 2.4. Ethical Considerations. 44. 2.5. Statistical Analysis. 45 46. III. RESULTS 3.1. Demographic and clinical characteristics. 46. 3.2. Differences in physical function. 49. 3.3 Differences in depression. 55 vii.

3.4. Differences in fatigue. 57. 3.5. Differences in the HRQoL. 59. 3.6. Differences in physical function, depression, fatigue, and the. 61. HRQoL with exercise self-efficacy-mediator 3.7. Differences in physical function, depression, fatigue, and the. 61. HRQoL with resilience-mediator 63. IV. DISCUSSION 4.1. Demographic and clinical characteristics. 63. 4.2. Effects on Physical Function. 64. 4.3. Effects on Depression. 67. 4.4. Effects on Fatigue. 69. 4.5. Effects on HRQoL. 70. 4.6. Mediator Effects of Exercise Self-Efficacy. 72. 4.7. Mediator Effects of Resilience. 73 75. V. CONCLUSIONS 5.1. Conclusions. 75. 5.2. Application in Nursing. 76. VI. LIMITATIONS/ RECOMMENDATIONS. 78. REFERENCES. 79. APPENDICES. 98. viii.

LIST OF TABLES Table 3-1-1. Demographic variables. 47. Table 3-1-2. Clinical characteristics. 48. Table 3-2-1-1. GEE model on the effects of the 6MWT. 49. Table 3-2-1-2. DID on the effects of the 6MWT in the exercise group. 50. Table 3-2-2-1. GEE model on the effects of the STS-10. 51. Table 3-2-2-2. DID on the effects of the STS-10 in the exercise group. 52. Table 3-2-3-1. GEE model on the effects of the STS-60. 53. Table 3-2-3-2. DID on the effects of the STS-60 in the exercise group. 54. Table 3-3-1. GEE model on the effects of depression. 55. Table 3-3-2. DID on the effects of depression in the exercise group. 56. Table 3-4-1. GEE model on the effects of the fatigue. 57. Table 3-4-2. DID on the effects of the fatigue in the exercise group. 58. Table 3-5-1. GEE model on the effects of HRQoL. 59. Table 3-5-2. DID on the effects of the HRQoL in the exercise group. 60. Table 3-6-1. GEE on the mediated effects of exercise self-efficacy and. 62. resilience with exercise on outcomes Table 3-6-2. The mediated effects of exercise self-efficacy and resilience on relationships between exercise and outcomes. ix. 62.

LIST OF FIGURES Figure 1. Flow chart of research design and participants. 32. Figure 2. Conceptual framework of exercise on HD participants. 35. x.

1. INTRODUCTION End-stage renal disease (ESRD) patients receiving hemodialysis (HD) therapy lead both physically and mentally poor life. Reduced physical activity, depression and fatigue are closely associated with poor health-related quality of life (HRQoL) (Moug, Grant, Creed, & Boulton Jones, 2004; Greenwood et al., 2012; Yurtkurana, Alp, Yurtkuran, & Dilekb, 2007). Poor functional capacity and physical limitations lead to cardiovascular diseases, which are responsible for higher morbidity and mortality in these patients (Sarnak, & Levey, 1999; Kouidi, 2004；McIntyre, Selby, Sigrist, Pearce, Mercer, & Naish, 2006；Kosmadakis et al., 2010). Regular exercise program has been shown to benefit for dialysis patients and could play an important role in their rehabilitation (Painter, Carlson, Carey, Paul, & Myll, 2000a; Yurtkuran et al., 2007; Capitanini et al., 2008; Huang, 2009). Exercise program during dialysis improves patients’ physical activity (Parsons, Toffelmire, & King–Van Vlack, 2006; Greenwood et al., 2012; Huang, 2009) and enhances psychological status (Ouzouni, Kouidi, Sioulis, Grekas, & Deligiannis, 2009; Greenwood et al., 2012), and consequently improves their HRQoL (Ouzouni et al., 2009; Chan, 2011; Huang, 2009). Exercise program during HD also improves therapeutic intervention in these HD patients (Konstantinidou, Koukouvou, Kouidi, Deligiannis, & Tourkantonis, 2002; Parsons et al., 2004; Johansen, Doyle, Sakkas, & Kent–Braun, 2005; Ouzouni et al., 2009; Segura-Ortí, Kouidi, & Lisón, 2009). Exercise plays a critical role in physical activity performance and improves depression (Liu, Chung, Chang, & Yeh, 2014). Although some well-established health mediators of exercise program were known, exercise self-efficacy and resilience are not determined as beneficial mediators for health. Exercise self-efficacy has been shown as an important mediator of health behavior (Everett, Salamonson, & Davidson, -1-.

2009). Self-efficacy acknowledges the individual’s ability for self-regulation and develops competencies in particular behavioral domains. Perceived self-efficacy is not only the measure of a person's skills, but also a belief that which people can do different sets of conditions with whatever skills the one possesses (Bandura, 1997). Moreover, resilient individuals tend to have an adaptive behavior, especially as relevant to social functioning, morale and somatic health (Wagnild, & Young, 1993). Thus, a significant relationship exists between exercise self-efficacy, resilience and exercise behavior (Resnick, & Inguito, 2011). Although the health benefits of regular exercise program has been reported, it is not yet integrated into regular hemodialysis therapy effectively. Exercise program should be considered as a possible therapeutic method for improving physical function, psychological factors and thus HRQoL in ESRD populations and should be encouraged during HD therapy in dialysis centers.. -2-.

1.1. General Background Information ESRD is an irreversible, life-threatening disease, ultimately requiring renal replacement therapy (RRT). According to United States Renal Data System (USRDS) data, U.S., Taiwan and Japan continue to have the highest "incidence" rates of ESRD with 371, 347, and 287 per million of population in 2009, respectively. In addition, Taiwan has the highest "prevalence" rates of 2,447, Japan and the U.S, were 2,205 and 1,811 per million of population in 2009 (USRDS, 2011). Further, incidence rate increased to 457.3 per million of population, and prevalence rate to 2927.2 per million of population recently (National Health Insurance Administration Ministry of Health and Welfare, 2015). 76,957 patients with ESRD were estimated in April, 2015 (National Health Insurance Administration Ministry of Health and Welfare, 2015). ESRD is a major cost driver for health care systems, with annual growth of dialysis programs ranging between 6% and 12% over the past two decades and continue to increase annually (Couser, Remuzzi, Mendis, & Tonelli, 2011). Most HD patients in Taiwan have been effectively treated and reimbursed by the National Health Insurance Administration Ministry of Health and Welfare. Around NT$81.6 billion (9.8% of the National Health Insurance Administration Ministry of Health and Welfare annual outpatient budget) was spent on HD in the first quarter of 2015 (National Health Insurance Administration Ministry of Health and Welfare, 2015). As a result, ESRD in Taiwan not only adversely affects public health but also inflicts huge medical expenses, and is a heavy burden both socially and economically. In Taiwan, 95% of ESRD patients are on long-term HD, due to easily accessible dialysis centers (Kuo, Tsai, Tiao, & Yang, 2007). Most ESRD patients receive maintenance HD with 2 to 3 sessions per week, average 4 hours per each session. At the end of dialysis, inevitably frequent and severe physical symptoms, including. -3-.

hypotension, spasm and exhaustion are noted. These patients might suffer from the decrease of red blood cell production to have generalized fatigue and lower physical activity (Jhamb et al., 2009; Johansen, & Painter, 2012). Many studies reported that poorly active or inactive lifestyle mainly contributed to impaired physical activity with ultimately muscle wasting in dialysis patients (Tawney, Tawney, & Kovach, 2003; Johansen, Doyle, Sakkas, & Kent-Braun, 2005; McIntyre et al, 2006). In an analysis done by Painter et.al, (2011) on 1,323 ESRD patients revealed 57% had regular physical activity; however, based on frequency, duration, and intensity of physical activity, only 13.2% completed the recommended levels. In these circumstances, a vicious circle occurs, weakness-inactivity-weakness. A vicious cycle exists between inactivity, disuse muscle atrophy/weakness, changes in body composition and metabolic disturbances including increase the risk of coronary heart disease, diabetes, certain cancers, obesity, hypertension, etc. which negatively impact health and well-being, finally increased mortality (US CDC, 1996; Beddhu, Pappas, Ramkumar, & Samore, 2003; Karatzaferi, & Chase, 2013). ESRD patients have a higher risk for cardiovascular disease whose mortality rate is 15 times higher than in general population (Sud, Tangri, Pintilie, Levey, & Naimark, 2014; National kidney Foundation, 2005). Furthermore, compare with more active HD patients, sedentary patients have 62% higher mortality rate at 1 year (O’Hare, Tawney, Bacchetti, & Johansen, 2003). Most commonly observed mental health problem in HD patients is depression (Hedayati, & Finkelslein, 2009), with incidence ranging from 27.9% to 40.2% (Keskin, & Engin, 2011; Ugurlu, Bastug, Cevirme, & Uysal, 2012). Depression is, however, underrecognized and undertreated in this population and markedly increased their mortality rate (Hedayati et al., 2008). In the past decade, nephrologists. -4-.

recognized depression as an important factor influence HD patients' overall health status and survival (Rosenthal Asher, Ver Halen, & Cukor, 2012), and ≤ 1-year mortality is doubled among HD patients hospitalized with depression as one of their comorbidities (Busko, 2008). Thus, depression is significantly correlated with mortality in these patients. Fatigue is one of highest incidence among the symptoms in HD patients (Mollaoglou, 2009). Numbers of studies reported that 53 to 97% of those HD patients experienced fatigue (Lee, Hicks, & Nino-Murcia, 1991; Jhamb et al., 2009; Georgios, Victoria, Evangelos, Savvas, & Sofia, 2015; Curtin, Bultman, Thomas-Hawkins, Walters, & Schatell, 2002; Jablonski, 2007), one third of the patients reported that they felt worse in the immediate hours after the dialysis session while one out of four reported severe or very severe intensity of fatigue after dialysis (Gordon, Doyle, & Johansen, 2011). Fatigue can have widespread effects including reduced survival, decreased physical function, decreased ability to perform daily activities and QoL (Astroth, Russell, & Welch, 2013). While long-term HD maintenance therapy can prolong the patients’ lives, QoL is also a consideration and is an important indicator of the effectiveness of the medical care (Valderrábano, Jofre, & López-Gómez, 2001). The QoL for ESRD patients has been shown lower than that of the general public (Cleary, & Drennan, 2005). Furthermore, the ESRD patients even have a lower QoL than other chronic illnesses persons (Loos, Briancon, Frimat, Hanesse, & Kessler, 2003). Regular exercise program improves general health in many chronic diseases (Johansen et al., 2012; Johansen, 2005; Pedersen, & Saltin, 2006). Exercise is traditionally to prescribe the evidence based treatment known to be the most effective and the fewest side effects or risks (Painter et al., 2000a; Greenwood et al., 2012).. -5-.

Exercise programs among HD patients have resulted in a significant increase in aerobic capacity and peak oxygen (VO2 peak), have increased physical functional, have reduced cardiovascular risk (Headley et al., 2002; Parsons et al., 2006; Huang, 2009; Heiwe, & Jacobson, 2011; Eriksson, & Gard, 2011; Liu et al., 2014), have decreased depression (Ouzouni et al., 2009; Stavroula, Evangelia, Athanasios, Dimitrios, & Asterios, 2009), have decreased fatigue (Yurtkurana et al., 2007; Astroth et al., 2013), and have improved QoL (Ridley, Hoey, & Ballagh–Howes, 1999; Capitanini et al., 2008; Ouzouni et al., 2009). The Kidney Disease Outcomes Quality Initiative (K/DOQI) published that clinical practice guidelines focusing on the control of cardiovascular disease and stated that, “all dialysis patients should be counselled and regularly encouraged by nephrology and dialysis supervise to increase their level of physical activity” (guideline 14.2) (National Kidney Foundation, 2005). Therefore, the majority of ESRD patients receiving long-term HD therapy have the physiological problems or psychological distress (Ugurlu et al., 2012; Hedayati et al., 2008), which are the leading causes for their sedentary lifestyle and muscle wasting which further increase the risk of mortality (Tawney, Tawney, & Kovach, 2003; Johansen et al., 2005; McIntyre et al, 2006). Exercise program is a promising non-pharmacological intervention that can safely and effectively improve physical function, reduce depression and fatigue, and increase the QoL (Ouzouni et al., 2009; Goldstein, & Montgomery, 2009; Parsons et al., 2006; Keskin et al., 2011). Besides, self-efficacy theory is one of the most widely applied theories in predicting health behavior. Self-efficacy, a central and an important concept of Bandura’s social learning theory (Bandura, 1977), incorporates self-efficacy expectations. It can be used as a judgment of one's personal efficacy. Self-efficacy expectations are an individual’s beliefs in their capabilities to perform an action to. -6-.

attain a desired outcome. The theory of self-efficacy proposes that the stronger the individual’s self-efficacy and outcome expectations, the more likely to perform a behavior successfully (Bandura, 1977; Gecas, 1989). A study reported that selfefficacy is a mediator of the effects of stressful events on depression (Maciejewski, Prigerson, & Mazure, 2000). The resilient and self-efficacy are similar in coping mechanisms, while the resilient and competent patients scored higher when face their adversity (Hamill, 2003). Resilience is defined in spite of the presence of risk factors, in terms of factors that contribute to good psychological outcomes (Rutter, 2006). Resilient individuals tend to have apparent adaptive behavior, particularly relevant to social functioning, morale, and somatic health (Wagnild et al., 1993). As the result, there was a clear relationship between resilience and self-efficacy, outcome expectations, and exercise behavior (Resnick et al., 2011).. -7-.

1.2. Literature Review A. End Stage of Renal Disease and Hemodialysis Kidneys are responsible for maintaining fluid, electrolyte and acid-base balance of the body; excreting metabolic waste; manufacturing and secreting hormones. Secreted hormones include renin which controls blood pressure and aldosterone production; erythropoietin stimulates red blood cell production and activated vitamin D to maintain bone density and health in the body. ESRD is the last stage of chronic kidney disease (CKD), and at that time most of the body’s metabolic status deranged. The guidelines define ESRD as either (1) a GFR falls to less than 15 mL/min per 1.73 m2, it means that they have less than 15% kidney functions, in the National Kidney Foundation (NKF) Kidney Disease Outcomes Quality Initiative (KDOQI) guidelines (Clinical practice guidelines for chronic kidney disease, 2002) or (2) starts kidney replacement therapy (dialysis or transplantation). Approximately 98% of patients with kidney failure in the United States undergo dialysis when their GFR is less than 15 mL/min per 1.73 m2 (Obrador et al., 1999; Smeltzer, & Bare, 2000). With an irreversible, typically chronic course, ESRD patients may survive longer than expected by receiving renal replacement therapy (RRT), such as hemodialysis (HD), peritoneal dialysis (PD), or kidney transplantation. Approximately 95% of ESRD patients in Taiwan are on HD (Kuo et al., 2007). The most common causes of ESRD individuals were diabetes mellitus (DM) (43%), hypertension (28%), unknown etiology (15%) and obstructive uropathy (14%) (Afshar, Shegarfy, Shavandi, & Sanavi, 2010). Roughly two thirds of all patients with ESRD suffer from dyslipidemia (Liu, & Rosner, 2006), a common risk factor for cardiovascular disease (Junyent et al., 2010), and also responsible for mortality in nearly 50% of HD patients (AlWakeel et al., 2002). HD patients would face many. -8-.

stressful problems in every aspect of their life including physical changes, emotional problems for the uncertain future, conflicts in social roles and responsibilities; psychological and metabolic problems including dependency on the HD therapy machine (Heidarzadeh, Atashpeikar, & Jalilazar, 2010; Yodchai, Dunning, Hutchinson, Oumtanee, & Savage, 2011). HD is a long-term therapy typically prescribed to be performed 3 times per week, 3-6 hours per each session, for the rest of a patient’s life or until successful kidney transplantation (Cheema, & Singh, 2005). ESRD patients receiving maintenance HD have a lower exercise tolerance, functional activity, endurance and strength, and more muscle wasting than healthy subjects (McIntyre et al., 2006; Johansen et al., 2005). About one third of HD patients are incapable to perform the normal daily activities without assistance (Parsons, Toffelmire, King-Van Vlack, 2004; Johansen, Chertow, Silva, Carey, & Painter, 2001). ESRD patients assessed by subjective reporting found that they have limited physical functioning (Lowrie, Curtin, LePain, & Schatell, 2003). HD patients suffer from muscle weakness and lacks of energy as the most common distress (Storer, 2009). The physical inactivity in HD patients is also related to increase obesity and mortality (Kosmadakis et al., 2010). Aside from the suffering and helplessness, HD patients also encounter challenges including role change, physical degeneration, difficulties in daily living activities and self-care, which gradually deteriorate their physiological and psychosocial conditions. The severe interference of living capabilities caused by a negative symptom might lead to depression (Chilcot, Wellsted, Da Silva-Gane, & Farrington, 2008). Depression is the most commonly observed emotional disorder in HD patients (Keskin et al., 2011; Ugurlu et al., 2012). Based on cross-national epidemiologic surveys on rates and patterns of major depression and bipolar disorder, prevalence of. -9-.

major depression is nearly 1.1%-15% for men and 1.8%-23% for women in general population (Weissman et al. 1996); versus the prevalence of depression in HD patients with nearly 20% (Lopes et al., 2002) and which might be high as 44% (Watnick, Kirwin, Mahnensmith, & Concato, 2003). Researchers found a significant positive correlation between depression and death in HD patients (Troidle et al., 2003). Depression and anxiety were the indicators of suicidal ideation (Chen et al., 2010). A 16-month follow-up study reported that the comorbidities of depression increased over time in HD populations (Cukor, Cohen, Peterson, & Kimmel, 2007). Depression markedly increased the hospitalization and mortality rate (Lopes et al., 2002; Hedayati et al., 2008). In the first year of HD, the hospitalization and mortality rates for patients with depression were more than twice higher than those without depression. Jhamb et al. (2009) reported that ESRD patients experience extreme levels of fatigue. Bonner, Wellard, & Caltabiano (2008) also revealed ESRD experienced more fatigue than the normal population. Fatigue was the most common symptom noted by HD patients (Mollaoglou, 2009). Roughly 53%-97% of HD patients experience fatigue (Lee, Hicks, & Nino-Murcia, 1991; Jhamb et al., 2009; Georgios et al., 2015). Fatigue is associated with poor QoL on HD patients (Mollaoglou, 2009; Chang, Hung, Huang, Wu, & Tsai, 2001). The concept of fatigue is unclear while it is too difficult to be defined and assessed both qualitatively and quantitatively (Georgios et al., 2015). Fatigue is described as a subjective and invisible symptom characterized by tiredness, weakness, decreased energy and performances lower than expected (Danquah, Zimmerman, Diamond, Meininger, & Bergstrom, 2010; McCann, & Boore, 2000), which might be easily neglected by caregivers (McCann et al., 2000). The causes of fatigue in HD patients are not well understood but it has been shown that these should include both muscular and central activation failures. - 10 -.

(Johansen et al., 2005). The patients with maintenance HD might suffer from weakness, nausea, cramps, itching, and pain which are related to varying levels of fatigue everyday (Yong et al., 2009). A study reported that physiological factors such as receiving long-term dialysis treatment, restricted daily dietary and fluid intake, nausea and loss of appetite make HD patients prone to protein and energy malnutrition, which in turn causes fatigue (McCann et al., 2000). A study showed that the patients with non-diabetic, under 70 years of age experienced low level of fatigue, whereas women experienced lightly higher fatigue than men (p< .005) (Georgios et al., 2015). In another study, age served as an important variable predicting fatigue; a significant positive correlation exists between age and total fatigue scores (p= .006, r= 0.33), however, no significant relation exists between patient’s sex and fatigue (Motedayen, Nehrir, Tayebi, Ebadi, & Einollahi, 2014). According to Letchmi’s study, a significant correlation was noted between fatigue and dialysis duration (Letchmi et al., 2011). However, Liu’s study reported no correlation between fatigue and dialysis duration (Liu, 2006). Interestingly, a study reported that patients with less than 24 months since their start dialysis showed greater fatigue (Motedayen et al., 2014). Probably, patients receiving HD less than two years were not yet capable of developing coping behavioral strategies to deal with HD treatment. Studies reported that HD patients who experienced higher rates of fatigue, decreased the daily life activities, seem to have worse QoL (p< .005) (Heidarzadeh et al., 2010; Georgios et al., 2015). Over the past few decades, QoL is usually used as a tool to measure the outcome of therapeutic intervention in chronic diseases (Kaufman, 2001). WHO defines QoL as a broad-ranging concept and an individual’s perception of their position in life in the context of culture and value systems, and in relation to their goals, expectations,. - 11 -.

standards and concerns (WHOQOL Group, 1994; 1995). Different concepts of QoL were defined by many scholars from different fields; philosophers focused on the nature of human existence and defined QoL as a “good life”, psychologists concerned the human needs, physicians focused on wellbeing- and illness-related problems (Anderson, & Burckhardt, 1999; Bubloz, Eicher, Evers, & Sontag, 1980). HRQoL was defined as a multi-dimensional concept that usually encompasses a range of subjective evaluations in response to positive and negative life experiences (Haas, 1999). QoL includes physical, mental, emotional and social functioning domains and ultimately focuses on the impact of health (McHorney, 1999; Selim et al., 2009). Although HD treatment has extended the lifespan for ESRD patients, many patients have a low QoL attributable to both physical and psychological problems (Finkelstein, & Finkelstein, 2000; Cheema et al., 2005). Patients suffer from loss of freedom, dependency, disrupt marital, family, and social life, and reduce financial income from impair occupational roles since HD therapy itself is time-intensive, expensive, requires daily dietary and fluid restrictions (Lin, Lee &, Hicks, 2005). HD patients commonly accrue as a consequence of biological aging, catabolic illness and inactive lifestyle; all of these factors may contribute to the progressive decline of QoL (Cheema et al., 2005). Numerous studies have reported that HD patient suffer from impairments of QoL than healthy control (Gorodetskaya et al., 2005; Loos-Ayav, Frimat, Kessler, Chanliau, Durand, & Briançon, 2008) or patients who successful received kidney transplants (Cheema et al., 2005). Sex is a factor which affects QoL in general population as well as HD patients (Santos, Daher, Jr Silva, Libório, & Kerr, 2009). Females have poor QoL as compared to males in social relationship dimension (Anees et al., 2014). In contrast, a study showed women have higher interpersonal relationship scores than male (Georgios et al., 2015). A lower QoL was found to be. - 12 -.

associated with hospitalization and mortality (DeOreo, 1997). B. Principles of Exercise Implementation Planned exercise includes aerobic and resistance modalities. Exercise becomes recognized as a therapeutic intervention that can increase physical activity and improve psychological deterioration (Cheema et al., 2005). Principles of exercise program implementation describe by FITT factors (frequency, intensity, time and type), benefits of exercise on HD session, and risks of exercise. B.1. FITT Factors -Frequency and Time Painter (1993) recommended that exercise frequency needed for ESRD patients is between 2 and 6 days a week. Thompson, Gordon, & Pescatello, (2009) thought exercise frequency needed to improve health should be 5-7 days a week for 30 minutes. Ouzouni et al., (2009) revealed the exercise program needed for HD patients is about 3 times a week for 60-90 minutes. Cho, & Sohng’s (2014) study showed the exercise program for HD patients should be performed about 3 times a week for 40 minutes. A study carried out by Parsons et al., (2006) found HD patients should meet about 3 times a week exercise for 30 minutes. Yurtkuran et al., (2007) worked out as 2 times a week for 30 minutes is enough for dialysis patients. A study showed the exercise program for stable HD patients should be performed about 3 times a week for 15 minutes (Makhlough, Ilali, Mohseni, & Shahmohammadi, 2012). Moreover, American College of Sports Medicine (ACSM) in 2007 reported that regular exercise for poor physical functional individuals were 3-5 times a week for 30 minutes. Although a wide variation in frequency of exercise exists in these previous studies, it is generally accepted as at least 3 times a week is needed. Thus, in this study, we determined the exercise program for these HD patients 3 times a week during dialysis sessions, 30 minutes per each session, for 3 months totally.. - 13 -.

Many advantages exist for exercise during HD. Firstly, exercise during HD is time-efficient, and with the possibility of better participant to an exercise program with doesn’t need extra visit (Konstantinidou et al., 2002). Secondly, exercise during HD provides an active opportunity during inactive therapy (Parsons et al., 2006). Finally, other advantages have been reported, including good compliance, adherence, and sustainable for exercise program by the patients (Yurtkurana et al., 2007; Konstantinidou et al., 2002). Moreover, intradialytic exercise improves fluid control in these high-risk patients (Daul et al. 2004). According to many studies, exercise is better performed within the first 2 hours of HD (Parsons et al., 2004; Banerjee, Kong, & Farrington, 2004), since exercise related vascular hypovolemia and hypotension occurs after the second hour, resulting from microvascular to interstitial fluid shifts. Therefore, this study performs the exercise program within the first 2 hours of HD. B.2. FITT Factors -Intensity The intensity for exercise is an important issue for achieving higher ranges of cardiorespiratory fitness. The intensity at a level 40-60% of heart rate reserve can be beneficial for management of body weight (target heart rate= [(HR max–HR rest)] x percent intensity] + HR rest) (Howe, & Jarvis, 2008). However, HD patients should not rely only on heart rate assessed during the exercise performance to monitor the intensity, since these patients are commonly prescribed with anti-chronotropic medications such as beta blockers and antiarrhythmic agents, which usually impairs autonomic heart rate control. Subjective intensity of patient evaluates by Rating of Perceived Exertion (RPE) scale, which is created by Swedish psychologist Gunnar Borg in 1962. RPE estimates the exercise intensity by patients’ feelings of exercise (heart rate, breathing, sweating, muscle fatigue, etc.). The range of RPE is rating form a level of 6-20, for example. - 14 -.

level 7 (very, very light), level 11 (fairly light), level 13 (somewhat hard), and level 19 (very, very hard). Day, McGuigan, Brice, & Foster (2004), defined the value of RPE rating form 11-13, individual could choose an intensity level (e.g., RPE 7) to start the exercise. Many studies have reported the intensity of all exercises was adjusted via the RPE scale, at a level between 12 to 16 is the most appropriate level (Ouzouni et al., 2009; Segura-Ortí et al., 2009; Verschell, 2009). The regular exercise of moderate intensity can be applied in ESRD patients without a serious risk (Suh, Jung, Kim, Park, & Yang, 2002). In this study, taking into consideration of age and disease severity, the level of RPE between 11 and 13 was defined during exercise program. B.3. FITT Factors -Type A number of studies reported that exercise interventions, including aerobic exercise program, resistance exercise program, and combined aerobic and resistance program have benefits in physical activity and psychosocial effects on HD patients (Konstantinidou et al., 2002; painter et al., 2002; Koufaki, Mercer, & Nash, 2002; Ouzouni et al., 2009; Segura-Ortí et al., 2009; Koh, Fassett, Sharman, Coombes, & Williams, 2010; Makhlough et al., 2012; Cho, & Sohng, 2014). A number of studies have been stated that aerobic exercise improves peak VO2 consumption in dialysis patients (Konstantinidou et al., 2002; Painter et al., 2002; Koufaki et al., 2002; Johansen, 2007). An 8-week to 6-month aerobic exercise program improves VO2 peak by approximately 17% (Johansen, 2007). Resistance exercise has been shown increased muscle mass, strength, reduction of muscle weakness and frailty in HD population (Headley et al., 2002; Segura-Ortí et al., 2009). The resistance exercise was a powerful stimulating effect on muscle strength by increasing oxygen consumption in HD patients (Ikizler, 2011). Muscle strength was an important predictor of gait speed in HD patients (Johansen, Shubert,. - 15 -.

Doyle, Soher, Sakkas, & Kent-Braun, 2003). Resistance exercise could be of beneficial to these patients and few studies have been focused on resistance exercise or included resistance training as part of the exercise program. In a 12-week resistance exercise program including eight to nine weight-machine exercises per week with exercise bands (Theraband, Hygenic Corp., Akron, OH, U.S.A.), improvement in strength and functional capacity is noted in stable HD patients (Headley et al., 2002). A 24-week resistance training program using weights and elastic bands compared to low-intensity aerobic bicycle training during dialysis improves physical functioning effectively (Segura-Ortíet al., 2009). In combined aerobic and resistance programs, an aerobic exercise on a cycle ergometer and a local muscular endurance circuit of eight exercises included in a 12-week sessions (Mercer, Crawford, Gleeson, & Naish, 2002). A 12-week combined exercise program include weight training (before or after dialysis) and a cycle ergometer training (during HD) (DePaul, Moreland, Eager, & Clase, 2002). A 6-month aerobic and strengthening exercise program (3 times a week, 90 min per each session) include the training routine (on non-dialysis days) with a 10-min warm-up followed by 50 min of aerobic exercise, 10 min of low-weight resistance exercise, 10 min of stretching exercise, and 10 min of cool-down (Kouidi et al., 1998). A 6-month exercise program consisted of pre-dialysis stretching classes (stretching tubes) and resistance exercises (dumb bells) for 10 min and 15-20 min of exercise while on the dialysis machine (Bennett, Breugelmans, Agius, Simpson-Gore, & Barnard, 2007). The combined exercise resulted in a greater improvement difference than any program involving aerobic exercise alone (Johnsen et al., 2007). In summary, types of exercise adopted by HD patients including walking, swimming, cycling, and aerobic dancing (National kidney foundation, 2005). Besides,. - 16 -.

a number of studies have confirmed cycle ergometer, mini-stepper, Taijiquan, yoga program, Qigong, thera-band exercise, weight lifting, and speed walking on treadmill. Based on these findings, any type of exercise modality could be a health promotion program for HD patients (Parsons et al., 2006, Wu et al., 2014; Yurtkuran et al., 2007; Ouzouni et al., 2009; Huang, 2009). Researchers showed that stationary cycling exercise was adequate equipment during HD (Liu, & Chen, 2002; Miller, Cress, Johnson, Nichols, & Schnitzler, 2002; Parsons et al., 2006; Ouzouni et al., 2009; Koh et al., 2010). Therefore, the horizontal electromagnetic cycle ergometer (Medical Exercise Peddler 3000, Medi-Bike, Taiwan) which involves aerobic and resistance exercise modalities was used in this study. B.4. Benefits of Exercise during HD Sessions Despite the well-established health benefits of exercise program, survey suggests that HD population rarely or unwillingly participate in exercise programs during non-dialysis days (Jang, & Kim, 2009; Konstantinidou et al., 2002). Many studies have pointed out the most suitable time of exercise programs was during HD sessions (Daul, Schafers, Daul, & Philipp, 2004; Vaithilingam, Polkinghorne, Atkins, & Kerr, 2004; Kouidi, 2004; Kouidi, 2002; Konstantinidou et al., 2002; Parsons et al., 2004). Exercise during HD has reported to be more popular and safe, mainly due to under monitoring by clinicians and nurses (Daul et al., 2004), improved dialysate phosphate removal (Vaithilingam et al., 2004), as well as due to its convenience, timeeffectiveness, higher compliance (Kouidi, 2004; Kouidi, 2002; Konstantinidou et al., 2002; Parsons et al., 2004). A randomized controlled study compared designed exercise during HD versus home-based exercise program or usual care, revealed that exercise during HD improved physical function (14%) better than home-based exercise (11%) or usual care (5%) (Koh et al., 2010).. - 17 -.

Bennett et al. (2010) analyzed 171 articles revealed several elements needed to be considered for exercise during HD: (1) Require exercise professionals, (2) Better exercise during HD, (3) Support from dialysis team members, (4) Adequate physical requirements of equipment and space. (5) Create interesting and stimulating exercise programs (6) Feasible cost of the exercise program. (7) Exercise is not for everyone and requires individual prescription. (8) Age is not barrier to implement exercise. Thus, the effectiveness of exercise program critically depends on the exercise professionals involved, individual acceptance and participation, acceptable equipment, feasible cost and cooperation among HD groups. However, due to high benefits of exercise in these patients, it is encouraged to develop although with great barriers to overcome. B.5. Risks of Exercise The most common exercise risk in general population is musculoskeletal injury; with most serious risks related to cardiac origin, ranging from dysrhythmia, ischemia, eventually to sudden death (Copley, & Lindberg, 1999). CKD patients have hyperparathyroidism and related bone disorders, thus, musculoskeletal problems and bone fractures increased during exercise (Alem et al., 2000). For HD patients, from a meta-analysis study showed hypotension is the commonest complication during exercise (Cheema et al., 2005). Exercise during HD in Germany, after more than 50,000 individual exercise sessions, revealed no severe cardiovascular complications, although some cases of leg cramps (cited in Kosmadakis et al., 2010) were noted. A number of exercise studies have not reported serious injuries in this HD population (Johansen, 2007; Moug et al., 2004; Capitanini et al., 2008). However, a case of clinically severe autonomic dysregulation was noted in a study of more than 4,000 individual exercises during HD and over 300 peak exercise tests, in North. - 18 -.

Staffordshire, UK (cited in Kosmadakis et al., 2010). C. Effects of Exercise Program on Physical function, Depression, Fatigue and HRQoL A number of studies have reported that exercise has great benefits for HD patients, including reduction in risk for cardiovascular mortality, achievement of better blood pressure and diabetic control, improvement in physical functioning, depression, fatigue, and better QoL (Cho et al., 2014; Greenwood et al., 2012; Ouzouni et al., 2009; Sato, Nagasaki, Nakai, & Fushimi, 2003). Therefore, exercise program for HD patients is of great important. C.1. Effects of Exercise Program on Physical Function Skeletal muscles move the human body by using a large number of energy through complex metabolic pathways. Muscle activities keep the whole body movement and energy balance. However, people may due to lifestyle choices, injury or chronic disease, cause inactivity, and muscle fatigue. People can fall because of weakness, which may result in endangering situation or loss of independence (Karatzaferi et al., 2013). Chronic illness might also affect any one or two of muscle mass, including protein and fat. In ESRD patients, Harter (1994) proposed the uremic toxin is the mediator to accelerate muscle protein catabolism, so that muscle fiber degenerates and changes the tolerance to the oxidative enzyme. This will then result in muscle diseases, muscle loss or weakness. Muscle wasting, decreased visceral protein stores, and reduced physical functioning attribute to uremic myopathy and neuropathy (Kosmadakis et al., 2010; Beddhu et al., 2003). Exercise training could reduce muscle protein catabolism in uremic patients (Davis, Karl, Goldberg, & Harter, 1983). During oxidative stress after exhaustive aerobic and isometric exercise, lipid hydroperoxides, protein carbonyls, and total. - 19 -.

antioxidants were increased due to a mass effect of oxygen consumption (VO2) (Alessio et al., 2000). Hambrecht et al. (1997) pointed out that exercise program can also increase the number of muscle fibers, mitochondria density in the muscle cells and oxidative activity. It also changes muscle composition from anaerobic metabolism type II muscle fibers into the aerobic metabolism type I muscle fibers. Resistance and isotonic exercise program during a prolonged training period has a strong stimulatory effect on muscle protein synthesis (Phillips, Tipton, Ferrando, & Wolfe, 1999) which results in muscle fiber hypertrophy (Andersena et al., 2005) and gains strength (Aagaard et al., 2000). A number of studies reported the exercise program significantly improved physical function (Liu et al., 2014; Huang, 2009; Parsons et al., 2006; Headley et al., 2002; Segura-Ortí et al., 2009) and increased peak VO2, and reduced cardiovascular risk (Heiwe et al., 2011). However, the peak VO2 measurement is not suitable for the elderly or weak people (Guyatt et al., 1985; Painter, Stewart, & Carey, 1999). The 6MWT is a practical simple test that requires no exercise equipment or advanced training for technicians. In some clinical studies, the 6MWT reflects information that may be a better index than peak VO2 uptake in the patient’s ability to perform daily activities (Guyatt, Townsend, Keller, Singer, & Nogradi, 1991; Niederman et al., 1991). STS-10 is to measure the muscle power, and STS-60 is to measure the muscular endurance (McIntyre et al., 2006). A 12-week exercise program (30 min per session, 3 times a week) resulted in improved physical performance (Liu et al., 2014). A 12-week exercise program, by using therabands (The Hygenic Corporation, Akron, OH, U.S.A.), on 10 stable HD patients, improved on physical performance tests include 6MWT, normal and maximum gait speed, and time to complete a STS-10 times (Headley et al., 2002). A. - 20 -.

12-week speed walking on treadmill exercise program (20-30 min per session, 3 times a week) resulted in improving the STS-5 and STS-10 times, STS-60, and 6MWT (Huang, 2009). A 5-month cycle ergometer, mini-stepper exercise program (30 min per session) resulted in increasing 6MWT (Parsons, Toffelmire, & King-VanVlack, 2006). A 24-week intradialytic resistance program (30 min per session) resulted in improved physical function, physical performance, and exercise capacity (Segura-Ortí et al., 2009). A 6-month on dialysis days, stationary bike, dumbbells, dynaband and exercise tubes (60-90 min per session, 3 times a week) resulted in improved physical function (Bennet et al., 2007). A 10-month exercise program (60-90 min per session) during HD improved functional capacity (Ouzouni et al., 2009). A 16-week of aerobic exercise (8-week of individually prescribed independent at home, followed by 8-week of cycling during HD), the Medical Outcomes Study Short Form 36-Item questionnaire (SF-36) was used to assess self-reported health status in 286 HD patients and found improvement in the SF-36 physical scale (Painter et al., 2000a). In summary, a well-planned exercise program could safely increase physical function for HD patients. C.2. Effects of Exercise Program on Depression A number of factors lead to depression (Eriksson et al., 2011) among which serotonin deficiency in the central nervous system is the most common cause. Serotonin deficiency can not only reduce norepinephrine production in depression, but also cause less neural activity in the hippocampus with increase in hypothalamuspituitary-adrenocortical axis activity that will finally affect mood and memory. Therefore, serotonin partially plays a role between sedentary life style and depression (Wipfli, Landers, Nagoshi, & Ringenbach, 2011). Vaynman et al. (2006) reported mice after exercise expressed increased hippocampal plasticity, which may affect the. - 21 -.

cognitive skills such as learning and memory that are related to depression (Vaynman, Ying, Wu, & Gomez-Pinilla, 2006). Moreover,. Solomon's. opponent-process. theory. of. acquired. motivation. conceptually explains the exercise-induced mood change (Solomon, 1980; Solomon, & Corbit, 1973, 1974). Solomon reports a model which utilized a physiological mechanism (e.g. endorphins) to explain psychological change. Solomon (1980) proposes that endorphins, body's natural opioid peptides (i.e. endogenously produced), might be an important mediator of the opponent-process sequence. Specifically, he also reveals that endorphins could be the major substrate for the opponent-process which is responsible for development of affective habituation to aversive stimuli (e.g. feeling better following repeated exposure to exercise) (cited from Petruzzello, Landers, Hatfield, Kubitz, & Salazar, 1991). There were several previous studies that mentioned the effects of exercise training on the psychological status in HD patients. A 6-month vigorous aerobic exercise program (3 times a week), reduced self-reported Beck Depression Index scores by an average of 4.3 points compared with an increase of 2.5 points in patients who did not exercise (n= 7; P< .05) (Carney et al., 1987). A 10-month exercise program (60-90 min per session) during HD therapy on ESRD patients could improve depression (Ouzouni et al., 2009; Stavroula et al., 2009). A systematic review of seven of the eight studies, examined in revealed positive effects of exercise on depression, concluded that more highly controlled studies on the effect of physical exercise on depression, focusing on the type, intensity, and frequency of exercise are still needed (Eriksson et al., 2011). On the contrary, a 6-week cycling ergometer, (45-60 min per session, 2 times a week), resulted no statistical significance in depression (Moug et al., 2004). A. - 22 -.

12-week moderate-intensity aerobic exercise training composed of bicycle ergometer, treadmill or upper limb ergometer (60 min per session, 3 times a week), resulted no statistically significant reduction in depression, but a decreased trend was noted (from 44.8 ± 8.4 to 39.7 ± 6.4) (Suh et al., 2002). C.3. Effects of Exercise Program on the Fatigue Two kinds of treatment exists for fatigue, both pharmacologically and non-pharmacologically (Bossola, Vulpio, & Tazza, 2011). Pharmacological treatment includes L-carnitine-, vitamin C, and prescription of erythropoietin (EPO) and medications for anemia (Mahrova, & Svagrova, 2013; Bossola et al., 2013). The non-pharmacological treatment includes cycle ergometer, yoga-based, relaxation exercises and virtual reality exercise program (Ridley et al., 1999; Liu et al., 2002; Yurtkuran et al., 2007; Motedayen et al., 2014; Cho, 2014). Various exercises were performed to improve fatigue in HD patients. A database from 1999 through 2011 retrieved 25 articles of 1,388 citations resulted exercise interventions in improved fatigue (Astroth et al., 2013). An 8-week off-dialysis stationary bicycle exercise program (30 to 50 min per session, 3 times a week), resulted in improved exercise capacity, reduced fasting plasma TG and total cholesterol level, and decreased fatigue (Liu et al., 2002). An 8-week virtual reality exercise program while waiting for their dialyses (40 min per session, 3 times a week), resulted in improved physical fitness, body composition, and decreased fatigue (Cho et al., 2014). A 3-month yoga program (30 min per session, 2 times a week) resulted in improved fatigue (Yurtkuran et al., 2007). A 2-month intradialytic physical and mental exercises (20 min per session, 2 times a week), resulted in improved fatigue (Motedayen et al., 2014). A 6-month qigong exercises (10 min per session, 3 times a week on HD day and 2 times a day on non-HD days at home), proved that fatigue was. - 23 -.

significantly lower in the qigong group than in the control group (Wu et al., 2014). C.4. Effects of Exercise Program on the HRQoL A few studies have done regarding the effects of exercise on QoL among HD patients (Capitanini et al., 2008; Suh et al., 2002; Bennet et al., 2007; Capitanini et al., 2008). A 12-week moderate intensity bicycle ergometer, treadmill or upper limb ergometer exercise training (60 min per session, 3 times a week), resulted significant improvement in QoL (Suh et al., 2002). A 6-month program of stationary bike, dumbbells, dynaband and exercise tubes on dialysis days (60-90 min per session, 3 times a week) resulted in improved QoL (Bennet et al., 2007). A 12-month exercise program of mild to moderate cycling (20-50 min per session, 2 times a week) on non-dialysis days also revealed improved QoL (Capitanini et al., 2008). On the contrary, after a 16-week of aerobic exercise, Medical Outcomes Study Short Form 36-Item questionnaire (SF-36) (Painter et al., 2000a), which assess self-reported health status, found no differences over time compared with those without exercise in 286 HD patients. A 24-week intradialytic resistance training program, using weights and elastic bands compared with low intensity aerobic exercise using the lowest level bicycles (30 min per session, 3 times a week), revealed no significant improvement in HRQoL (Segura-Ortí et al., 2009). An 8-week cycle ergometry (15 min per session, 3 times a week) had no effect on QoL scores (Parsons et al., 2004). A 6-month, stationary bike, dumbbells, dynaband and exercise tubes (60-90 min per session, 3 times a week) on dialysis days, resulted no improvement on QoL, but an improving trend (Bennett, et al., 2007).. - 24 -.

D. The Mediator Effects of Exercise Program on Exercise Self-efficacy, and resilience D.1. The Mediator Effects of Exercise Program on Exercise Self-efficacy Bandura investigated the concept of the self-efficacy based on two theories; efficacy expectancy affected the outcome expectancy. Two types of expectancies are included in this theory, which powerfully influences on behavior change. “Self-efficacy expectancy” is the belief that individual can successfully perform the behavior; and “outcome expectancy” is the effectiveness of the behavior in producing a desired outcome. Moreover, the results of the outcome would feedback to the individual to improve the self-efficacy constantly (Bandura, 1977). Exercise self-efficacy is defined as participants’ confidence in their ability to exercise regularly (most days of the week) (Bandura, 2006). “Exercise self-efficacy expectancy” refers to the individual’ attitude to perform a particular behavior, i.e., the individuals could overcome the environmental problems and self-contributing barriers in order to go for exercise. For example, I will still go to exercise in bad weather. “Exercise outcome expectancy” pertains to the belief for the individual to anticipate the outcome from the completion of exercise, i.e., whether the outcome achieved from the individual’s completion of the exercise meets his/her anticipation. For example, I believe exercise allows me to be in a good body or mood. Several studies examined associations of exercise improved physiological function, psychological changes and HRQoL, as well as exercise self-efficacy. A 12-month exercise programs induced changes in cardiopulmonary fitness and body composition may lead to greater improvements in HRQoL and self-efficacy that could promote exercise maintenance (Imayama et al., 2013). A study supported the role of self-efficacy in the relationship between physical activity and QoL (McAuley et al.,. - 25 -.

2008). A study identified the exercise self-efficacy; depression and stress were significant variables to explain a possible relationship with exercise stages of middle aged women in the community (Lee, & Park, 2004). A study showed that was significant correlation between exercise self-efficacy and exercise benefits (Hwang, & Chung, 2008). Resnick et al. (2011) pointed that there was a significant relationship between self-efficacy outcome expectations, exercise behavior and resilience. Clinically, this is relevant in older adults who have lower resilience, since they might benefit from exposure to self-efficacy based interventions, which is associated with exercise related strengthening self-efficacy and outcome expectations. Exercise increases exercise self-efficacy and health-related quality of life (HRQoL); however, the mechanisms are unknown. We examined the associations of exercise adherence and physiological improvements with changes in exercise self-efficacy and HRQoL self-efficacy that could promote exercise maintenance (Imayama et al., 2013). D.2. The Mediator Effects of Exercise Program on Resilience Wagnild et al. (1993) reported that resilience was the personal trait which moderated negative impacts, the ability of “standing against the storm” and making appropriate adaptation. Resilience has thus caused great concern, as it is also the ability of an individual to successfully endure and adapt to stress, challenges or environmental changes (Rutter, 1999, Cicchetti, & Cohen, 1995). Luthar, Cicchetti, & Becker (2000) and Masten (2001) also described resilience as a “dynamic process” involving the ability to develop competency and adaptive strategies for coping with difficulties using resources in a tough environment. Wagnild et al. (1993) reported the resilience operationally defined five traits including: (1) Equanimity: ability to find the equilibrium state in one’s life, (2) Meaningfulness: ability to explore the goals in. - 26 -.

one’s life, (3) Perseverance: ability to eliminate frustrations in one’s life, (4) Existential aloneness: ability to identify one’s own unique path and accept life, (5) Self-reliance: ability to maintain confidence of self and abilities. Resilience thus has caused great concern, as it is also the ability for an individual to successfully endure and adapt to pressure, challenges or environmental changes (Cicchetti et al., 1995; Rutter, 1999). In summary, when facing adverse events, those who keep the belief that they can control their thoughts are more likely to persist in their efforts. Those who are self-efficacious or high-resilience are also more likely to reject negative thoughts about themselves or their abilities than those with a sense of personal inefficacy.. 1.3. Research Purpose Although the health benefits of exercise program has been reported, it is not yet integrated into regular HD therapy effectively; exercise self-efficacy and resilience are not also determined as beneficial mediators for health in these patients. This study aimed to evaluate the effects of 3-month intra-dialytic ARCEP on physical function, depression, fatigue, and HRQoL in HD patients, and further confirmed mediator effects of exercise self-efficacy and resilience in the exercise group.. - 27 -.

1.4 Research Questions 1. Does the exercise program improve the physical function over-time between the control and exercise groups? 2. Does the exercise program improve the depression over-time between the control and exercise groups? 3. Does the exercise program improve the fatigue over-time between the control and exercise groups? 4. Does the exercise program improve the HRQoL over-time between the control and exercise groups? 5. Does the exercise program affect the change of exercise self-efficacy as a mediator over-time in the physical function, depression, fatigue, and HRQoL in the exercise group? 6. Does the exercise program affect the change of resilience as a mediator over-time in the physical function, depression, fatigue, and HRQoL in the exercise group?. - 28 -.

1.5 Research Hypotheses 1. After the exercise program, there is significant change over-time in the physical function between two groups. 2. After the exercise program, there is significant change over-time in depression between two groups. 3. After the exercise program, there is significant change over-time in the fatigue between two groups. 4. After the exercise program, there is significant change over-time in HRQoL between two groups. 5. After the exercise program, there is significant change over-time in the physical function, depression, fatigue, and HRQoL with exercise self-efficacy as a mediator in the exercise group. 6. After the exercise program, there is significant change over-time in the physical function, depression, fatigue, and HRQoL with resilience as a mediator in the exercise group.. - 29 -.

II. METHOD 2.1. Research Design This was randomized controlled trial. The procedure of randomization was done by using a computer generated random numbers. All participants who met the inclusion criteria were assigned into two groups. The control group received nursing routine care. The exercise group received not only nursing routine care but the 3-month exercise program. Data were repeatedly collected at baseline, Mon 1, Mon 2, and Mon 3. At the end of each monthly exercise routine, the control and exercise group underwent physical function measurements, which involved 6MWT, STS-10, and STS-60. Totally, four measurement periods were conducted. 2.2. Subjects/ Materials A. Subjects ESRD participants were recruited from a 50-bed HD center in 872-bed northern regional hospital in Taiwan. This study was a randomized controlled trial design and includes repeatedly measured outcomes. Data were collected over a 14 months from June, 2013 to August, 2014. A total of 79 participants who were eligible, 76 participants met inclusion criteria and signed the consent form. To estimate the number of samples, the effect size was set at 0.3, α value was set at 0.05, and power set 0.08 for the analysis by G-power software (Faul, Erdfelder, Lang, & Buchner, 2007). The estimated number of samples was 58. According to the pertinent literature, the dropout rate was about 7- 40% (Segura-Orti, 2009; Miller et al., 2002; Parsons et al., 2006). The anticipated dropout rate of the pilot study was 30% (Liu et al., 2014), then the sample size of 76 was statistically meaningful. In the relevant studies, the number of participant was 20-75 (Ouzouni et al., 2009; Goldstein et al., 2009; Miller et al., 2002; Segura-Orti, & Johansen, 2010; Yurtkuran et al., 2007; Liu et al., 2002). - 30 -.

Based on the aforementioned sample size calculation and dropout rate estimation, the total recruitment number in this study was determined to be 76, with 38 participants each in the control and exercise group respectively. The inclusion criteria were as follows: (1) age above 20 years old and consented to join the study; (2) receive HD 3 times a week at least 3 months; (3) not miss more than two dialysis sessions in the prior month; (4) Kt/V (dialysis efficacy) ≧1.2 and stable on HD; (5) ambulatory with or without using the assistance device, can walk for at least 50 meters; (6) have arteriovenous grafts or native fistulas; and (7) basic comprehension and communication in Chinese or Taiwanese. The exclusion criteria were as follows: (1) active infection or inflammation; (2) autoimmunity disorders; (3) cerebrovascular accidents within prior 6 months; (4) presence of severe muscle weakness or interfering skeletal deformity; (5) history of repeated episodes of hypoglycemia; (6) cardiopulmonary contraindications to resistance exercise such as myocardial infarction within prior 6 months, unstable angina, and uncompensated congestive heart failure; (7) lower limb amputation; and (8) history of prior regular exercise program. All participants who met the inclusion criteria were assigned into two groups. The control group received routine nursing care. The exercise group received not only routine nursing care but also the 3-month intradialytic ARCEP. At the end of each monthly routine exercise, control group and exercise group underwent physical function measurements, including 6MWT, STS-10, and STS-60 scales and completing a questionnaire. Of the 18 participants who declined participation at the end of this study. The reasons were lower limb weakness (n= 5), knee pain (n= 1), foot injury (n= 2), hip fracture (n= 1), arteriovenous fistula failure (n= 2), appendix surgery (n= 1), unstable blood pressure (n= 1), fatigue (n= 2), abroad (n= 1) and unable to cooperate. - 31 -.

(n= 2). 58 (76.4%) participants were included in the final analysis with a dropout rate of 23.6%. Figure 1, presents the flow chart of research design and participants.. Assessed for eligibility (n= 79) Not met inclusion criteria (n= 2) Refused to participate (n= 1) Met inclusion criteria (n= 76) Randomized. Characteristics of demography& Physical function, and questionnaire were assessed before exercise program. Exercise group (n= 38). Control group (n= 38). Month 1 (1st) after HD session (n= 30). Month 1 (1st) after HD session (n= 32). Physical function and questionnaire were assessed after the exercise program. Exercise program for 1 month. Month 2 (2nd) after HD session (n= 27). Month 2 (2nd) after HD session (n= 31). Physical function and questionnaire were assessed after the exercise program. Exercise program for 1 month. Month 3 (3rd) after HD session (n= 27). Month 3 (3rd) after HD session (n= 31). Physical function and questionnaire were assessed after the exercise program. Exercise program for 1 month. Figure 1. Flow chart of research design and participants. - 32 -.

B. Instruments B.1 Demographic Data The demographic variables included age, sex, marital status, education level, employment, reasons not exercising; clinical characteristics variables included causes of renal failure, comorbidity (Charlson comorbidity score), and duration of HD (months). B.2. The Safety Monitoring Instruments Before prescribing any physical activity regimen, all participants were assessed for cardiac and other medical contraindications to exercise by using physical activity readiness questionnaire scale. The exercise intensity level of each participant was determined by Borg Rate of Perceived Exertion Scale. B.2.1. Physical activity readiness questionnaire (PAR-Q) PAR-Q is a simple and pre-evaluation assessment instrument for the moderate intensity physical activity programs. PAR-Q is also used to assess each participant’s medical risk (Thomas, Reading, & Shephard, 1992). PAR-Q involves seven questions regarding heart trouble, chest pain, high blood pressure, dizzy spells, joint problems, and other problems that may prevent participants from participating in physical activities. Participants, who answered “yes” to any of the questions on the PAR–Q, or those in need of rehabilitation, should be referred to the exercise physiologists and rehabilitation specialists for further evaluation. A study has reported that PAR-Q might be a useful instrument to identify older adults for whom low to moderate physical activity participation is safe (Cardinal, 1997). B.2.2. Borg Rate of Perceived Exertion (Borg’s RPE) Scale Borg (1982) developed a RPE scale for ratings of perceived exertion. The concept of perceived exertion as an indicator of physical strain mainly refers to the. - 33 -.

heavy muscular work involving a relatively great strain on the musculoskeletal, cardiovascular, and respiratory systems. The rating scale valued from 6 to 20, with 6 means "no exertion at all" and 20 means “maximal exertion” (Borg, 1998). Although RPE Scale is a subjective evaluation, a high correlation exists between RPE and actual heart frequency (Borg, 1998). The RPE scale range of 6 to 20 corresponds to heart rates of 60 to 200 beats per minute (Borg, 1998). For example, if a person’s RPE is 14, then 14 x 10 = 140; so the heart rate should be nearly 140 beats per minute. Based on this estimate, RPE is commonly used to assess exercise tolerance and to prescribe and regulate therapeutic training intensity (Noble & Robertson, 1996). A study showed that the RPE scale was a reliable and useful tool to assess exercise intensity during resistance exercise programs (Mauger, Huntley, & Fletcher, 2014). The scale was designed to grow linearly with exercise intensity and heart rate for bicycle ergometer exercise (Borg, 1990). B.3. Outcome Measures Based on the conceptual framework of exercise on HD participants in Figure 2, the independent variable was exercise program. The dependent variables were physical function estimated by 6MWT, STS-10, STS-60, depression, fatigue, HRQoL, and the mediator variables were resilience and exercise self-efficacy.. - 34 -.

Exercise Self-Efficacy. Physical Function Depression. Exercise Program. Fatigue. Quality of Life Resilience. Figure 2. Conceptual framework of exercise on HD participants. - 35 -.

B.3.1. Physical function The physical function included 6MWT, STS-10 and STS-60 in this study. Since review of renal failure patients’ functioning and well-being was limited to questionnaire data, it was recommend that performance-based assessments should also be used for a better representation of patients’ abilities (Kutner, 1994). Huang (2009) pointed out in their study that STS-60 and 6MWT were favorable indicators to monitor physical functions. Cheema, O’Sullivan, & Chan (2006) revealed that 6MWT assessment is easy, simple and safe as they don’t require special equipment or expert patients. Reboredo et al (2010) shown that 6MWT is frequently used to measure physical function in HD patients. In this study, the participants performed 6MWT along a 20-m long and 2-m wide walkway in a quiet hospital corridor. In this study, markers were placed every 5 m along the length of the corridor. Participants were instructed to walk as far as they could in 6 min. They were allowed to stop and rest if needed but were instructed to resume walking when they felt able to do so. Reasons for immediately stopping a 6MWT included chest pain, dyspnea, leg cramp, or pale appearance. In HD patients, the 6MWT value has been reported to be highly positively correlated with peak VO2 during the cardiopulmonary test (Reboredo et al., 2007). Sit-to-stand test (STS) is an indirect measure of lower limb muscle strength and endurance (McIntyre et al., 2006). The STS-10 test measures in the time of 10 numbers, a participant gets up from a chair of standardized height and sits down again during a 10 numbers. The STS-60 test measures the number of times a participant gets up from a chair of standardized height and sits down again during a 60-second period. The STS-60 is a feasible way to measure changes in physical function resulting from exercise (Segura-Ortí et al., 2009). On the basis of the assessment from 2 raters (Liu and Hsieh), the intra-class correlation of the inter-rater reliability was high for 6MWT. - 36 -.