京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第20669号 / 医博第4279号 / 新制||医||1024(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 林 康紀, 教授 渡邉 大, 教授 高橋 淳 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

付記する学位プログラム名: 充実した健康長寿社会を築く総合医療開発リーダー育成プログラム / 京都大学 / 0048 / 新制・課程博士 / 博士(薬科学) / 甲第21046号 / 薬科博第89号 / 新制||薬科||10(附属図書館) / 京都大学大学院薬学研究科薬科学専攻 / (主査)教授 金子 周司, 教授 竹島 浩, 教授 髙倉 喜信 / 学位規則第4条第1項該当 / Doctor of Pharmaceutical Sciences / Kyoto University / DFAM

京都大学 / 新制・課程博士 / 博士(薬学) / 甲第24564号 / 薬博第862号 / 新制||薬||243(附属図書館) / 京都大学大学院薬学研究科薬学専攻 / (主査)教授 金子 周司, 教授 竹島 浩, 教授 生田 宏一 / 学位規則第4条第1項該当 / Doctor of Pharmaceutical Sciences / Kyoto University / DFAM

健康相關生活品質越來越重視病人主觀的感受，然而將這個部分納入測量之後，許多研究結果卻出現殘疾悖論(disability paradox)的現象，也就是重度疾病病人的自評生活品質並不比程度輕微或甚至健康的人差。反應轉移理論認為，造成這個現象的原因在於個人的自評生活品質會受到個體對於生活品質定義的改變（重新構念）、內在測量尺度標準的改變（重新校準）、以及價值的改變（重新權重）的影響，到目前為止，反應轉移尚未發展出合適的測量工具。 SEIQoL-DW (Schedule for the Evaluation of Individual Quality of Life- direct weighting)做為一個生活品質測量個人化的代表，其評估分成三個步驟，分別是提名重要的生活領域、評估提名領域的滿意程度、以及評估提名領域的相對權重，許多研究者嘗試用SEIQoL-DW在兩點間的領域變化做為重新構念，權重變化做為重新權重，重新校準則需要搭配then test來測量，then test是在第二個測量點時邀請受試重新對第一個時間點的提名領域進行評估，然而這三個成分指標的操作型定義不一，then test也有使用上的不便，同時過去這些指標對生活品質的效用檢驗也都未達顯著。本研究分認為，若能解決上述的問題，將有助於解釋殘疾悖論，同時可以區辨不同類別病人的反應轉移模式，並運用在臨床來幫助病人進行調適。 本研究以立意取樣招募3期以上之慢性腎臟病患者、以及血液透析、腹膜透析未滿一年以上之三組病患共85名，除了背景和臨床資料外，在間隔三個月的兩點分別填寫SEIQoL-DW、ideal scale（評估期待）、生活滿意問卷、正負向情緒問卷，並在後測時填寫then test。研究結果顯示，三組病人的生活品質符合殘疾悖論，並無顯著差別。重新構念、重新校準、和重新權重當中，僅重新校準有助於生活品質的提升，並能夠顯著解釋生活品質的改變。 對腎臟病患者來說，期待越高，生活品質提升得越多，進一步的分析顯示，受試會捨棄相對權重較低的領域，新提名領域的滿意程度、期待、和相對權重都顯著高於捨棄的舊領域，這可以作為臨床上協助病人調適的策略。雖然then test的結果顯著，但實證結果和理論卻相當混亂，尚待未來研究釐清。 / Health-related quality of life (HRQoL) is increasingly recognized as being subjective, which emphasized patient-reported outcomes. Many HRQoL studies reported that people with serious illness perceived no less quality of life (QoL) than those without such illness. This phenomenon is labeled as disability paradox. Response shift theory provides an explanation for it and refers to a change in the meaning of one’s self-evaluation of QoL as a result of changes in internal standards (recalibration), values (reprioritization), and reconceptualization of QoL. It is these changes that will influenced perceived QoL. Current methods to detect Response Shift are still evolving. SEIQoL-DW (Schedule for the Evaluation of Individual Quality of Life- direct weighting) is one of individualized QoL instruments and measures three elements of QoL, including five important aspects of life, current satisfaction with each aspect, and relative importance of each aspect. Many researchers tried to use SEIQoL-DW to detect response shift. Changes in the content of aspects of life between two time points reflect reconceptualization. Changes in the relative weighting between two time points reflect reprioritization. Recalibration is measured by then test, which is a method by asking respondents at time two to provide a renewed rating of their aspects of life given at time one. However, there are no consensus operational definition of indices of reconceptualization , reprioritization, and recalibration. The examination between indices and improvements in QoL was not significant, either. Besides, then test with SEIQoL-DW has a disadvantage when aspects nominated between time one and two are different. This study tried to resolve issues above. If these issues are resolved, disability paradox will be explained. Response Shift will possibly differentiate patients of various disease, and provide ideas to help patients adjust to illness. 85 patients were recruited, including those with renal disease stage 3-5, and those undergoing hemodialysis or peritoneal dialysis within one year. All patients completed SEIQoL-DW, ideal scale, Satisfaction with Life Scale, the Positive And Negative Affect Scale at time one and three months after , except questionnaire on personal background and biological information (at time one) and then test (at time two). Results indicated that the QoLs of these three groups of patients showed no different, which confirmed disability paradox. Only recalibration showed helpful. Regression analyses also showed that recalibration indices were better predictors in QoLs. For End-stage Renal Disease patients, higher expectation suggested higher QoL improvement. Further analysis showed that patients would abandon lower-weighted aspect of life. Compared to the abandoned aspects, higher satisfaction, expectation and weighting were seen in new-nominated aspect. This finding could be useful in helping patients adjust. Although then test also reached significance, evidences was contradicted to its prediction. More research is needed in the future.

研究目的 失眠的過度激發是目前最廣為接受的失眠病因之一。無論在生理、認知、行為三不同層面上，多可觀察到失眠者有身心過度激發的狀態。根據失眠三因子模式，不同失眠病程階段，影響過度激發的背後成因有所差異。在慢性失眠部分，過 去累積了相當多的實證研究證實其過度激發的現象，但尚未進入慢性病程前之過度激發相關機轉，仍有待研究進一步探討。本研究嘗試以橫斷式的研究方法，並依據過去失眠病因發展推導，選擇從壓力反應特性 (包含壓力操弄後的壓力反應強度和 消退速度)、注意力偏誤 (包含警覺性注意力和注意力移除困難)、與睡前的睡眠監控行為三個面向切入，探討不同病程階段個體過度激發的背後機轉，並進一步檢驗上述之差異是否可用以預測在壓力操弄情境下，不同病程個體睡前的激發反應變化，藉此檢驗失眠病程發展之病因假說，並希望未來可據此發展有效之失眠防治與介入策略。 研究方法 本研究共計招募受試者 58 人，年齡介於 24-48 歲，包含符合 ICSD-3 慢性失眠者 18 人，以及以壓力下失眠反應量表( Ford Insomnia Response to Stress Test; FIRST)區分出急性失眠高危險組 19 人與低危險組 21 人。每位受試者皆需到睡眠實驗室進行兩階段的實驗，第一階段包含晤談評估、問卷填答、壓力反應的生理測量(以指溫與膚電為指標)、與包含威脅與睡眠刺激之點偵測注意力作業，之後需配戴腕錶與記錄睡眠日誌配合充足且規律作息一週後，再到睡眠實驗室進行第二階段的評量，包含睡前 2 小時、1 小時、關燈前生理指標 (指溫、膚電) 與腦波的測量和主觀身心激發狀態 (Pre-Sleep Arousal Scale, 簡稱 PSAS) 評量，於睡前填寫睡眠相關監測指標 (Sleep Associated Monitoring Index，簡稱 SAMI)，並完成一晚的 PSG 測量以排除其他睡眠相關疾患。 研究結果 首先，以單因子變異數分析比較不同組別間在壓力反應與回復和二因子變異數分析注意力警覺/移除困難指標的差異。在壓力生理反應表現上，慢性失眠組與高危險組在接受壓力操弄後的激發消退時間較低危險組來得長。在注意力層面，高危險組對壓力(威脅圖片) 刺激有顯著的警覺與移除困難注意力偏誤，慢性失眠組則是對睡眠刺激有顯著的移除困難注意力偏誤。在行為層面，慢性失眠組與高危險組睡前的注意力監控行為 (包含監測自身身體感覺訊息是否與入睡狀態不一致、鬧鐘 時間、環境) 均顯著較低危險組來得多。再者，以皮爾森相關探討注意力偏誤與睡前激發反應之關聯性，結果顯示高危險組的注意力偏誤現象與睡前高頻腦波與主觀生理激發的降幅呈現顯著負相關; 而慢性失眠組的注意力偏誤指標卻與膚電、主觀認知激發的降幅呈顯著正相關。 結論 本研究結果支持不同失眠病程背後的過度激發影響機制有所差異，生理層面較慢的激發消退能力與對壓力源的認知偏誤的前置因子，可能為急性失眠者易受日常壓力源誘發睡眠困擾之原因；而影響慢性失眠族群的持續因子主要在於其將睡眠視 為壓力源的認知歷程與行為轉變。此外，研究更進一步發現兩組分別對於壓力與睡眠的注意力轉移困難，使其在覺察壓力後易持續表現出過度激發現象。本研究結果除支持失眠過度激發理論之外，更釐清不同階段失眠的認知歷程的機制，並彰顯不 同失眠病程介入策略應有所差異，和急性失眠高危險族群及早介入預防之重要性。 / Introduction Hyperarousal has been recognized to be a major etiological factor of chronic insomnia. Cumulated research evidences have demonstrated that chronic insomnia patients are hyperaroused in somatic, cognitive, and behavioral aspects. According to Spielman’s 3P Model of Insomnia, there were different factors are involved at different points during the course of insomnia. However, there are seldom study to investigate the difference mechanism of hyperarousal in the course of the development of insomnia. The present study used cross-sectional design to compare the difference of good sleeper (low sleep vulnerability, LV), acute insomnia (high sleep vulnerability, HV), and chronic insomnia (CI) in stress reaction (eg. reactivity and recovery), attentional bias (eg. vigilance and disengagement), and sleep associated monitoring behaviors to investigate the underlying mechanism of hyperarousal. Furthermore, the study examined the correlation between attentional bias indices and subsequent pre-sleep arousal to investigate the impact of attentional bias on sleep in different groups. Method The present study recruited fifty-eight subjects, aged between 24-48. They included eighteen chronic insomniacs (CI) diagnosed ICSD-3, nineteen healthy individuals scoring high (HV) and twenty-one healthy individuals scoring low (LV) on the Ford Insomnia Response to Stress Test (FIRST). All subjects visited sleep lab twice. During the first visit, the subjects filled in a package of questionnaires, and went through psychophysiological recording (including) of stress reaction, and a visual dot-probe task. They then were required to keep a sleep log and wear actigraphy at home for one-week to make sure they followed a regular sleep schedule. During the second visit, subjects went through a pre-sleep physiological recording (including peripheral temperature, skin conductance, and EEG) and filled in two questionnaires (Pre Sleep Arousal Scale [PSAS] and Sleep Associated Monitoring Index[SAMI]) at three time points and had a PSG recording to screen for sleep disorders. Result One-way ANOVAs were conducted to compare the differences of stress reaction/recovery among three groups. Two-way ANOVAs were used to compare the differences in attentional bias (vigilance/ disengagement) of threatening and sleep-related stimulus among three groups. In stress related physiological activity, CI and HV showed slower recovery rate than LV. Considering attentional bias, HV had significant vigilance and disengagement bias to threatening pictures, and CI had significant disengagement bias to sleep-related pictures. CI and HV also showed more prevalent sleep-associated monitoring behaviors than LV. Furthermore, Spearman’s correlation was used to examine the association between attentional bias and pre-sleep arousal. The result shows the attentional bias of HV had negative correlation with reduction of high frequency EEG and somatic sub-score on the PSAS. In contrast to our prediction, CI showed positive correlation between decrease of skin conductance and the cognitive sub-score on the PSAS. Conclusion The study showed that stress recovery ability and stress-related attentional bias were the major differences between individuals with low and high sleep vulnerability, indicating that increased information processing to threats and stress-related stimulus as well as decreased recovery ability of autonomic arousal in reacting to stress may predisposed an individual to stress-related sleep disturbances. On the other hand, the attention shift from threat toward sleep can differentiate chronic insomnia from those individual with frequent acute insomnia. Moreover, the difficulty in disengagement from sleep-related stimulus, rather the vigilance, might explain the cause of hyperarousal that perpetuate insomnia. The results support the transition of arousal from general treat to sleep-related stimulus in the development of chronic insomnia. The study not only further the understanding of the etiological mechanism of insomnia, but also imply that different strategies should be applied in the treatment of acute and chronic insomnia. It also highlights the importance of preventive intervention for individuals with high sleep vulnerability

本文以流行病學法探討空氣污染物對人體健康影響之研究，主要有3個研究重點： 　　1.採用probit模型分析空氣污染物造成的慢性與急性健康效果：實證結果發現懸浮微粒及二氧化硫對慢性支氣管炎、肺氣腫與氣喘三種慢性病組合之罹患，有顯著的正向效果；懸浮微粒、臭氧及PSI對15種急性病症組合有顯著的促發作用。 　　2.運用兩階段估計法，將急性計量反應函數中之慢性疾病變數內生化：估計結果顯示懸浮微粒、臭氧及PSI對急性病症仍有顯著的促發作用，而慢性疾病變數之顯著性則大幅提高。急性健康效益的估計顯示，如果沒有將慢性疾病變數內生化，可能會造成效益的低估。 　　3.利用隨機效果模型分析急性panel資料：此部分以Limdep軟體進行估計，結果發現懸浮微粒、臭氧及PSI對急性病症亦有顯著的促發作用，抽煙、運動、所得與工作或學校環境有無污染等解釋變數則不顯著，與前述研究之結果不同。

本論文研究專注於研究穿戴科技對於銀髮族遠距照護服務創新的可能性，利用系統思維與設計思維的研究方法來進行服務設計。研究問題設定為”一個罹患慢性病並獨自在家生活的銀髮族,如何自主健康生活，並能讓家人感到安心呢” 。透過顧客驅動價值共創的服務設計模型，確認利害關係人，並實際訪談利害關係人後深入分析使用者潛在問題及需求，以不同視角來找出創新的洞見。依據此洞見來發展可行的方案，並展開成為完整的服務系統，再將此服務系統雛型具體化產出後進行風險分析。最終的研究結果以商業模式草圖來呈現完整的商業模式。 / The aim of this thesis is to study the possibility of the wearable technology and to create a service innovation toward the tele-health for elders. The research method of the service design is based on the design thinking and the system thinking.We set up a hypothetical situation as follows: A solitary elder who has chronic diseases knows to how to manage her/ his life well without making the family worry. Through the service design models from the co-creation of the customer empowerment, we affirm the stakeholder at the beginning and then interview her/ him to get to know more about the needs and some main details. The purpose is to look for the insight into the innovation in different aspects. Based on this insight, we start a feasible plan and develop the integrity of the service design. Next thing we externalize the service design prototype and provide the follow-up risk assessment.As the final result, we use business model canvas to bring out the coherence and the integrity to our business models.

全球遠端醫療產業蓬勃發展，各國家的法規也越來越明朗化，未來醫療需求將隨人口老化而大幅上升，如何利用新型態的醫療方式來解決醫療問題，便成為國際上討論的趨勢。本文以遠端藥事做為研究目標，透過「iHealth政昇處方宅配藥局」服務全台的經營模式，以及「春森藥局」服務社區式的經營模式，比較兩家藥局的施行歷程，如何以不同的形態達成遠端藥事。 本研究以Osterwalder提出之經營模式圖(Business Model Canvas)做為基礎，論文以商業畫布、市場機會的發掘與辨識、興業的商業概念、興業的執行、興業的成果呈現，探討機構的獲利方式、民眾的營收方式、藥事服務的形式、慢性病照護，以及政策性的醫療網絡建構等…議題，皆可做為政府規劃醫療政策之參考，本研究有別於其他遠端醫療研究多半選擇科技之論述，以藥局經營做為研究對象，探討產業商機所在。 研究結果顯示，台灣遠端藥事可以符合在現有的法規之上，藥局經由的通訊科技聯繫到病患，提供連續處方箋獲利，不需要依靠業外收入，達成藥事服務營利。比較特別的事，不同藥局要施行遠端藥事的動機不同，分別有企業藥局的經營導向，協助機構評鑑、提供民眾的宅配，此模式下的遠端藥事僅為企業願景的一部分，最終以平台建製作為目標；另一種模式為個人藥局的經營導向，藥師透過政策接觸到社區病患，提供居家服務、甚至安寧服務，實現全人照護之目標。 本研究認為，台灣的遠端藥事尚有發展之潛能。企業經營的方向，需要以機構做為穩定現金流的基礎；個人經營的方向，依然以自身的使命感為主，然而配合「遠端醫療法案」鬆綁、「居家照護政策」的補助，建製完善的社區醫療網絡，將有助於提升社區藥局參與遠端藥事服務之意願，形成新型的產業模式。 / As the telemedicine industry flourishing, the regulations became clear among the countries, the medical needs will also increase in the future. As the goal of the research, this dissertation focused on telepharmacy, the research compared two pharmacies with two different models: serves-the-entire-Taiwan bussiness model from 「iHealth政昇處方宅配藥局」, and serves-the-community bussiness model from 「春森藥局」, hoping to be able to present the telepharmacy with different forms and conditions. This research used the Business Model Canvas which was presented by Osterwalder as the foundation, Unlike other telemedicine researches, this research explored the industry opportunities, and focused on the pharmacy management perspective, instead of the science perspective. The result shows that the telepharmacy in Taiwan can be consistent with the existing regulations. What is more special is that, different pharmacies have different motivations for telepharmacy, and the telepharmacy under this model is only part of the enterprise vision, and creates Platform as the final goal; another model is the business directoin of personal pharmacy, pharmacist contacts patients in the communities through policies, provide home services, and hospice home care to achieve the goal of holistic care. This study considers that telepharmacy still has the potential for development. The direction of enterprise management needs to be based on institutions as the basis of stable cash flow; the direction of personal management sill based on their sense of mission. However, with the help of telepharmacy laws and home care policies, through building the well rounded community medical network, can help increasing the wills of the community pharmacies to participate in telepharmacy.