【作者】 张兴文；

【导师】 崔丽英； 朱以诚；

【作者基本信息】 中国协和医科大学 ， 神经病学， 2008， 博士

【摘要】 第一部分缺血性脑卒中直接医疗成本及其与预后关系研究背景:从上世纪七十年代起,临床经济学已经深入到临床医学的各个角落,通过研究医疗资源配置和医疗支付制度中存在的问题,为消除潜在的资源浪费提供有力的数据支持。脑血管病直接医疗成本占医疗卫生总费用的2～4%,给家庭和社会带来长期而沉重的负担。在目前,结合国外的研究经验,分析我国卒中诊疗自身特点的研究较少,对长时间的输液治疗、传统中医中药的广泛应用、转诊机制的不健全等情况的深入探讨尚未见相关报道。目的:(1)通过建立急诊卒中登记,前瞻性研究脑梗死患者的直接医疗成本构成;(2)探讨影响住院费用的相关因素;(3)分析卒中预后和费用的关系,比较住院与非住院的轻中度卒中患者的预后和成本效果比,从卫生经济学角度评价轻中度脑梗死患者住院治疗的费效比,探寻优质低耗的脑梗死治疗模式。方法:研究对象为151例北京协和医院急诊就诊的脑梗死患者,收集相关临床及费用资料,随诊患者的预后和花费情况。(1)分析住院患者的费用构成;(2)对住院费用的相关因素进行线性回归分析;(3)将轻症患者分成住院组和非住院组,对NIHSS评分≤10分的轻症患者的预后相关因素进行Logistic回归分析,比较两组患者的预后和成本效果比。结果:(1)住院组患者住院费用的中值为11282.9元(相当于28.3%的人均年工资),日均住院费用为488.6元。和以往的研究比较,年度分布似有卒中费用占人均年工资的比例逐渐下降的趋势。住院费用占12个月费用的54.06%。(2)费用构成比中,占前几位的分别为药费、影像费、材料费、化验费(32.80%、16.66%、13.83%、12.42%)。医疗服务费(诊疗费+护理费+治疗费)占住院费用的5.42%,药费(包括西药费及中药费)占住院费用的32.80%,康复费用占住院费用的1.12%。(3)住院费用的主要影响因素为输液天数、监护、在院天数、卒中的严重程度(来诊时NIHSS评分)。(4)Logistic回归分析的结果显示直接医疗成本并不是轻症患者预后的相关因素。(5)成本效果分析显示,非住院组成本效果比优于住院组患者。结论:1.与发达国家相比,我们的卒中花费处于较低水平,占人均收入的比例处于可负担的合理水平,但对于低收入群体是一个沉重的负担。2.脑梗死的主要费用构成为药费、影像费、材料费、化验费。医疗服务费用比例低、药费比例相对偏高,卒中患者恢复期的康复和护理费用所占比例低,应提高对恢复期治疗的重视。3.住院费用的主要影响因素为输液天数、监护、在院天数、卒中的严重程度。合理地控制输液天数和选择监护措施的应用可能成为有效减少卒中费用的重要手段。患者住院时间长,在建立合理的转诊制度、完善社区医院功能等方面我们还有许多工作尚需加强。4.轻症患者中,非住院组和住院组患者比较,预后和复发无显著差异,非住院组成本效果比优于住院组,按疾病诊断相关分组(Diagnosis Related Groups,DRGs)进行分级管理的制度是可借鉴的减少卒中费用的方法。第二部分血浆金属蛋白酶9对动脉粥样斑块相关的脑血管事件的预测研究背景:动脉粥样硬化斑块是心脑血管病的重要致病因素,炎症反应在动脉粥样硬化形成的各个环节起关键作用。人们通过对血液中多种炎症因子和炎症标记物进行研究,期望发现这些标记物与心脑血管卒中的相关性,并用其来预测血管事件。目前研究显示金属蛋白酶-9(Matrix metalloproteinases,MMPs-9)是其中最有希望的指标之一,但是针对脑血管动脉粥样斑块稳定期的血浆MMPs-9水平研究目前尚无相关报道。目的:通过对头颈部动脉粥样斑块患者稳定期血浆MMPs-9水平的检测,旨在了解在病情稳定期血浆MMPs-9水平的差异,分析MMPs-9在患者中的变化规律,探讨MMPs-9在临床中的应用价值。方法:本研究采用病例对照研究方法,研究对象为122例动脉粥样斑块患者和43例健康对照组,病例组分为无症状脑血管狭窄、长期稳定和反复复发的脑梗死三个亚组。收集相关临床资料、头颈部血管检查情况、采集卒中事件稳定期血浆,采用双抗夹心法酶联免疫吸附试验测定血浆MMPs-9浓度。结果:(1)病例组血浆MMPs-9水平显著高于健康对照组(P＜0.001)。(2)复发组、稳定组、无症状组患者之间的血浆MMPs-9水平无显著差异,但有复发组＞无症状组＞稳定组的趋势。(3)MMPs-9水平和头颈部血管病变范围之间并无显著相关性。(4)脑血管病的危险因素、他汀类药物、ACEI类药物等均不是血浆MMPs-9水平的影响因素。结论:1.病例组血浆MMPs-9水平显著高于健康对照组。2.在血管事件稳定期患者中,MMPs-9的水平有复发组＞无症状组＞稳定组的趋势,但结果有待进一步证实。3.MMPs-9水平和头颈部血管病变范围之间无显著相关性,这一研究结论需要更深入的研究预以证实。4.影响脑血管病的危险因素、他汀类药物、ACEI类药物等均不是血浆MMPs-9水平的影响因素,这和以往的结论不一致,由于样本量小,需要大样本量的研究进一步证实。更多还原

【Abstract】 Part One The direct medical costs and prognosis of cerebral ischemiaBackground:Economic evaluation has permeated through every corner of health service research since the 1970s.It would be beneficial to optimizing the allocation of health care resource reasonably and improving the payment system of medical service.Stroke is a heavy economic burden on the individuals,society and health service,accounting for 2～4%of the direct costs of healthcare.At present,there is no study concerned with the features of diagnosis and treatment of stroke in our country,such as long-term venous transfusion,widely application of traditional chinese medicine,lack of referral system.Based on foreign experience,we will analyse this features in our study.Objectives:(1) Set up the stroke data bank of the emergency,and prospective study the direct medical costs of stroke.(2) Discuss the factors that influence the direct medical costs.(3) Assess the outcome and cost-effectiveness ratio of mild or moderate patients based on inpatients versus no inpatients.Methods:Data were obtained from the stroke data bank of emergency in peking union hospital, we identified 151 patients with a first or recurrent stroke during may 1,2006,to March 31,2007. Univariate and multivariate analyses were performed to identify the main predictors of resource use and costs.Logistic regression analysis were applied to examine the main predictors of prognosis in the mild or moderate patients.Compare the cost-effectiveness ratio of mild inpatients versus no inpatients.Results:(1) By the 12th month after stoke,the median hospital cost per patient was 11282.9 yuan(equal to 28.3 percent per capita annual net income of urban residents),488.6 yuan per day. Of the first year stroke costs 54.06%accounts for the inpatient costs.(2) The largest contributors to the the inpatient costs were medication(32.80%),image studies(16.66%),medical material(13.83%),laboratory tests(12.42%).5.42%attribut to the costs for staff.(3) The significant variables associated with the inpatient costs on multiple linear regression analysis were:(ⅰ) length of venous transfusion,(ⅱ) intentive care,(ⅲ) length of stay,(ⅳ) stroke severity(NIHSS),(4) In mild or moderade patient,the direct medical costs wasn’t associated with the outcomes of prognosis based on logistic regression analysis,(5) Inpatient is not a cost-effective choice for the mild and moderade patients.Conclusions:(1) Compare with developed country,our expenditure of stroke is still at a low level stage.The ratio of stroke costs accounting for per capita annual net income of urban residents is in rational range that can be burdened.But it is a heavy burden to the low-income groups.(2)The main components to the the inpatient costs were medication,image studies,medical materials,laboratory tests.(3) The hospital costs are significantly determined by length of venous transfusion,intentive care, length of stay and stroke severity(NIHSS).It may be the effective method to reduce the discharge of stroke by reasonably controlling the length of venous transfusion and intentive care.(4) Inpatient is not a cost-effective choice for the mild and moderade patients.Diagnosis Related Groups System may provide a good reference to cutting down the costs of stroke. Part Two Predictive value of plasma matrix metalloproteinase-9 for atherosclerotic cerebrovascular eventsBackground:Rupture of atherosclerotic plaque is the main trigger of acute cardiovascular and Cerebrovascular events.Inflammatory response play a crucial role in every session of atherosclerosis.Through the study of inflammation factors people expect to find the markers that related to vascular events.Matrix metalloproteinases 9(MMPs-9) is one of the most promising markers.But the plasma levels of MMPs-9 of atherosclerotic cerebrovascular patients in the stable period have not been reported.Objectives:To study the differences of the MMPs-9 levels of the atherosclerotic cerebrovascular patients in the stable period,and to approach the clinical application values of this detection.Methods:Recruit 122 cerebrovascular atherosclerotic patients and 43 normal subjects.All patients were divided into 3 groups according to symptomatology(group 1,asymptomatic;group 2,recurrent;group 3,without recurrence).Plasmas MMPs were measured quantificatly during the stable period were subjected by ELISA.Results:(1) The plasma MMPs-9 levels of patients were significantly higher than that of the normal subjects.(2) There were no statistical significance differences among subgroups of patients in the levels of MMPs.But the trend of the levels was asymptomatic＞recurrent＞stable patients.(3) There is no significant correlation between the MMPs-9 level and the extent of cerebrovascular lesions.(4) No significant increase was observed for MMPs-9 level according to the risk factors,and the using of medications(angiotensin-converting enzyme inhibitors and statin) as well.Conclusions:(1).The plasma MMPs-9 levels of patients were significantly higher than that of the normal subjects. (2).There was a gradually rising trend of the MMPs-9 levels in the asymptomatic,recurrent and stable patients.But this results needs further investigation.(3).There is no significant correlativity between the MMPs-9 levels and the extent of cerebrovascular lesions.(4).the risk factors of cerebrovascular disease do not affect the MMPs-9 level,so do ACEI and statin drugs.These conclusions were inconsistent with the reports of foreign authors’.更多还原