血液透析病患的生活品質：從測量方法的發展到運用

Quality of Life in End-Stage Renal Disease Patients Undergoing Maintenance Hemodialysis: from Mesaurement to Implication

楊樹昌(Shu-Chang Yang)

指導教授 ： 蘇喜 ； 王榮德

國立臺灣大學/公共衛生學院/醫療機構管理研究所/博士(2006年)

https://doi.org/10.6342/NTU.2006.02997

摘要

近年來生活品質的探討已漸受重視，有關的文獻探討無論是基礎、公共衛生或臨床運用的領域皆快速增加。生活品質除了本身是一項重要的健康結果(health outcome)，也和其他的健康結果如死亡率、罹病率、及後遺症/併發症(complication/ cormobidity)有密切相關，是此等健康結果的指標(indicator)。
慢性腎衰竭進行到最後叫做末期腎病(end-stage renal disease)，大部分需要接受長期血液透析(maintenance hemodialysis)。末期腎病接受血液透析是單一疾病耗用全民健保醫療費用第一大原因。雖然透析治療延長了末期腎病患者的生命，末期腎病本身及血液透析治療都會影響腎病患者的生活品質。我們就以此等患者為例，探討生活品質這一重要的健康結果。
大家常常提生活品質，但是各學者、各個研究對於生活品質的概念、定義很紛雜而不一致。世界衛生組織（Word Health Organization, WHO）於1991年起開始著手發展生活品質測量的研究。他們集合專家學者詳細討論，把生活品質定義為「individuals’ perceptions of their position in life in the context of the culture and value systems in which they live , and in relation to their goals , expectations , standards and concerns. It is a broad ranging concept, incorporating in a complex way the persons’ health, psychological state, level of independence, social relations, personal beliefs and relationship to salient features of the environment 」 其意思是：「生活品質是指個人在所生活的文化價值體系中，對於自已的目標、期望、標準、關心等方面的感受程度，其中包括生理健康、心理狀態、獨立程度、社會關係、個人信念以及環境顯著特點等六大方面」。這個定義強調生活品質是處於生活中之主觀感受，且論及多種層面。很久以前健康(health)就是由WHO所定義出來，指出健康是一個舒適、安寧的狀態，且有生理、心理、社會等三項層面。健康狀態因之可以是較客觀狀況的描述，如血壓、心跳、臨床表徵，也可以是主觀的感受；層面上之探討則一般不出生理、心理及社會等三層面。雖然許多的學者專家對於生活品質有不同定義，我們採用WHO對生活品質的定義，認為生活品質是主觀感受，至少在問卷架構中生活品質有生理、心理、社會、環境四範疇。WHO發展了供實際臨床使用的世界衛生組織問卷簡明版(WHOQOL-BREF)。此問卷有兩題整體性的題目(global items)及四範疇(domains)，每一範疇再包含4至9個層面或題目(facet/items)。我們採用WHO生活品質的定義理由是WHO可說是全世界的健康主管部門，從各個國家、社會、文化的角度出發，如此產生的生活品質可以跨越國家比較，而且涵蓋項目可能較為廣泛周延。但是WHOQOL-BREF是一般性問卷(generic questionnaire)，使用於特殊的疾病群，例如此血液透析病患群時，可以發展特別的題目再加上去形成某一特別疾病的模組(module)。第一章的主題就是發展透析模組問卷(dialysis module questionnaire)，以WHOQOL-BREF(TW)為核心，加上透析病患特別的題目。我們驗證此模組問卷之信、效度，並以此問卷和常被用來代表生活品質的SF-36問卷做比較。SF-36問卷也是一般性問卷，偏重生理及心理功能，缺乏環境及社會範疇的項目。我們的「WHOQOL-BREF(TW)透析模組問卷」的信、校度都符合標準，不遜於其他華人地區一般族群或特殊疾病群使用之WHOQOL-BREF，但有較為廣泛之內容效度。WHOQOL-BREF(TW)和SF-36相較，天花板效應(ceiling effect)及地板效應(floor effect)較少，而包含範圍明顯較多。
第二章以WHOQOL-BREF(TW)評估其鑑別臨床變項之敏感度(sensitivity)，並且探討影響各範疇及層面/題目之決定因素。統計學顯示各範疇及整體性題目的分數可以鑑別末期腎病透析患者的症狀/問題(symptom/problem)及每週紅血球生成素(erythropoietin)注射量多或少。影響各範疇及各題目比較顯著的因素是「基隆或台北地區別」、血紅素(hemoglobin)濃度、蛋白質代謝率(protein catabolic rate)、及症狀//問題等項目。
第三章是生活品質的運用。將生活品質和存活結合而成為「品質調整後存活函數」 (quality adjusted survival function, QAS function)，可以計算「品質調整後終生存活預期」(quality-adjusted life expectancy, QALE)及「預期健康存活期損失」(loss of healthy life expectancy, LHLE)。此兩者對應於一般族群的「健康預期」(health expectancy)和「健康差距」(health gap)，這兩個名詞見於WHO曾贊助研究且提倡的「族群健康之總結測量」(summary measures of population health)一書中。我們使用黃景祥及王榮德提出之簡易方法，結合(integrate)生活品質函數和存活函數，成為「品質調整後存活」。此一函數是以生活品質為權重來調整之存活函數，也就是是以存活為權重來調整之生活品質函數。我們指出「一個族群之平均生活品質」就是仍存活者之生活品質乘上此一族群之存活率。使用黃景祥及王榮德首創之Monte Carlo外推方法，外推存活或品質調整後存活函數至終生，此函數積分而得之曲線下面積就是「品質調整後終生存活預期」(QALE)。和血液透析病患群的年齡、性別配對，從一般族群隨機抽樣而成之正常對照群，也可以形成此對照群的存活或「品質調整後存活」函數並計算「品質調整後終生存活預期」；血液透析病患群和正常對照群兩者「品質調整後終生存活預」的差就是血液透析病患的「預期健康生活期損失」(LHLE)。我們計算出血液透析病患的「終生存活預期」，「品質調整後終生存活預期」，及「預期健康生活期損失」分別是125.5±21.3月，100.0±21.9月及152.7±21.3月。此處之生活品質數值是由標準賭博(standard gamble, SG)效用方法(utility method)而得的。另外由健保局支付費用的資料，我們計算出台灣血液透析病患從開始透析後每月的血液透析費用，乘上預期終生存活期後可以估計血液透析病患預期終生之透析費用，以2002年資料計算平均數及中位數分別是127,256及177,365美元，以2003年資料計算則分別是128,507及175,682美元。相較於未做透析迅速死亡者，透析之成本效果評估C/E值在2002及2003年分別為12,167及12,286美元，成本效能評估C/U值在2002及2003年分別為15,178及15,327美元。這些數值是標竿值，適用於健康之決策分析或醫療之經濟評估。
中文所寫之相關文章1是比較WHOQOL-BREF(TW)和兩種效用測量「標準賭博法」(SG)及「視覺類比法」(visual analogue scale, VAS)。SG法之效用值高於其他測量值，VAS法之效用值和心理計量分數相似。一樣是測量血液透析病患的整體性生活品質，SG法卻和VAS法或其他心理計量方法所測是有所不同，且影響因素也較複雜。
上述血液透析病患的「預期終生存活期」、「品質調整後終生存活預期值」、及「預期健康生活期損失」，也可以由WHOQOL-BREF(TW)各種生活品質分數做品質調整而計算其數值。中文所寫之相關文章2就是這一方面的研究，此時「品質調整後終生存活預期值」的單位是「心理記量分數－時間」(score-time)而非「品質權重值－時間」(quality-adjusted life months or quality-adjusted life years, QALM or QALY)。各種不同生活品質測量值來調整存活估計出來的「品質調整後終生存活預期」、及「預期健康生活期損失」並不一致，其代表意義如何值得進一步探討。

關鍵字

末期腎病 ； 血液透析 ； 生活品質 ； 世界衛生組織生活品質問卷 ； 世界衛生組織生活品質問卷台灣簡明版 ； 透析模組 ； 決定因素 ； 校度 ； 信度 ； 敏感度 ； 品質調整後存活 ； 品質調整後存活預期 ； 健康存活預期損失 ； 健康預期 ； 健康差距

並列摘要

The thesis was comprised of three main papers and some related papers. In the first paper, we developed the dialysis module of the brief form of “World Health Organization Quality-of –Life Questionnaire Taiwan Version” [WHOQOL-BREF(TW)] and assessed its psychometric properties including reliability, validity, and sensitivity in patients undergoing regular hemodialysis (HD). QOL survey was administered to 283 regular HD patients in metropolitan Taipei. Instruments used included (1) the proposed module: composed of the core part, the WHOQOL-BREF(TW), and the six specific items; (2) the symptom/problem (S/P) scale: composed of 12 items specific for dialysis patients; (3) utility measurement which was performed with standard gamble (SG) method; and (4) rating scale (RS). Based on the 6 criteria of validity, reliability, and variance of the items, 4 HD-specific items were selected. Reliability study showed that the Cronbach’s alphas, composite reliability, and test-retest reliability (intraclass correlation at average 4-8 weeks retest interval) of the four domains, physical, psychological, social relationship, and environment, ranged from 0.74-0.82, 0.79-0.84, and 0.61-0.79, respectively. Validity study showed that all the correlations between an item and its corresponding domain were highly significant (r>0.4, p <0.01) and larger than the correlations between the item and other domains. SG and psychometric measures showed relatively low correlations (0.12-0.26). The module showed the same construct as the WHOQOL-BREF(TW) under confirmatory factor analysis, whereas the exploratory factor analysis showed mild variation. Convergent and discriminant validity were good. Global QOL, physical, psychological, and environment domains had some sensitivity to differentiate the severity of the condition of patients receiving HD. Clinical validity was demonstrated in global QOL, physical, and psychological domains to have significant correlations with S/P scores. We concluded that besides broader coverage than the core WHOQOL-BREF(TW), the dialysis module of the WHOQOL-BREF(TW) is a valid, reliable and sensitive QOL instrument for the assessment of HD patients in Taiwan.
In the second paper, We administered again WHOQOL-BREF(TW) and symptom/problem scale to 376 end-stage renal disease patients on regular hemodialysis in Metropolitan Taipei and Kee-lung City. WHOQOL-BREF(TW) was reliable and valid from various validation studies. Reliability and validity of WHOQOL-BREF(TW) in HD patients were verified and compared with those in a sample of general population of Taiwan. All four domains (physical, psychological, social, and environment) and global items (overall quality of life and general health) of WHOQOL-BREF(TW) each differentiated symptom/problems of HD patients from age-, gender-, and education-matched healthy referents. All four domains except environment and global items of WHOQOL-BREF(TW) each differentiated erythropoietin dosage from age-, gender-, and education-matched healthy referents. Analysis with multiple stepwise regressions was conducted to study determinants of QOL domains and items. After adjusting age, gender, marriage and education, the prominent associated factors of various QOL domains and items were age, area (Taipei or Keelung), hemoglobin level, normalized protein catabolic rate (nPCR); and symptom/problem scale. We concluded that the WHOQOL-BREF (TW) is reliable and valid for long term study of HD patients, and HD had negative impacts on QOL, especially in more severe patients with greater symptom/problems scores, lower hemoglobin levels, and lower nPCR values.
In the third paper, we applied the QOL to form a composite outcome indicator- “quality-adjusted life expectancy” in maintenance hemodialysis (MHD) patients. The objective of this study was to determine the cost of maintenance hemodialysis (MHD), including loss of healthy life expectancy and lifetime financial burden to the NHI (National Health Insurance) in Taiwan. Survival data were collected from 746 consecutive patients on MHD in Keelung-ChangGung Memorial Hospital from 1996 to 2003. The health expenditure data were collected from reimbursement file of National Health Insurance (NHI) in 2002 and 2003.The survival function was estimated and extrapolated throughout lifetime based on logit transform of survival ratio between the patients’ cohort and age-, gender-matched general population from vital statistics. The quality-of-life (QOL) data of MHD patients were measured by standard gamble (SG) and rating scale (RS) methods, which were integrated with survival to estimate quality-adjusted life expectancy (QALE). The QOL of general population was assumed as one. The results showed that life expectancy in MHD patients was 141.3±27.1 months (mean±standard deviation) with an expected loss of 111 months. After adjusted for QOL, the QALE were 113.3±19.8 and 80.2±15.7 quality-adjusted life months, respectively for SG and RS measurements, while those of loss of healthy life expectancy were 139.6±19.8 and 172.3 ±15.7 months, respectively. Estimated lifetime financial burden for a case of MHD were 143,307 and 144,715 USD in 2002 and 2003, respectively, while the corresponding incremental cost per quality-adjusted life years (QALY) for SG method would be 15,178 and 15,327 USD. The estimation based on extrapolation of survival and integration with QOL can be used as bench mark values for financial planning and comparative outcome evaluation of health services in the future.

並列關鍵字

end-stage renal disease ； hemodialysis ； quality of life ； WHOQOL ； WHOQOL-BREF(TW) ； dialysis module ； determinants ； validity ； reliability ； sensitivity ； quality-adjusted survival ； quality-adjusted life expectancy ； loss of healthy life expectancy ； health expectancy ； health gap

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