尿激酶静脉溶栓治疗急性缺血性卒中/短暂性脑缺血发作的院内死亡率及相关影响因素的多中心分析

目的 探讨尿激酶静脉溶栓治疗急性缺血性卒中/TIA患者的院内死亡率及其影响因素。
方法 回顾性分析2013年1月-2016年5月河南省11家市级、县级医院神经内科连续收治的发病6 h内
接受尿激酶静脉溶栓治疗的急性缺血性卒中和TIA患者的临床资料，统计院内全因死亡率，采用多因
素Logistic回归分析院内死亡的相关影响因素。
结果 共入组444例患者，平均年龄60.19±11.61岁，男性296例（66.7%），院内死亡25例（5.6%）。多
因素Logistic回归分析显示，发病至溶栓时间3～6 h（OR 3.006，95%CI 1.120～8.071，P =0.029）、溶栓前
NI HSS评分（OR 1.130，95%CI 1.079～1.183，P＜0.001）及心房颤动病史（OR 3.671，95%CI 1.282～10.511，
P =0.015）是尿激酶静脉溶栓治疗急性缺血性卒中/TIA患者院内死亡的独立影响因素。
结论 发病至溶栓时间3～6 h、严重神经功能损害、心房颤动病史是尿激酶静脉溶栓治疗急性缺
血性卒中/TIA患者住院期间死亡的独立危险因素。     

脑梗死静脉溶栓后24 h内选择性双联 抗血小板治疗的安全性观察

目的 探讨阿替普酶（alteplase,rt-PA）静脉溶栓治疗缺血性卒中后1 h内选择性早期使用口服抗血
小板药物治疗的安全性。
方法 本研究为前瞻性研究,通过多模影像和溶栓后出血风险（hemorrhage after thrombolysis,
HAT）评分连续入选了第三军医大学第三附属医院神经内科2011年1月～2014年4月期间出血性转化
（hemorrhagic transformation,HT）风险较低（HAT评分≤2分或者HAT评分3～5分但多模影像提示侧支循
环良好）的急性脑梗死静脉溶栓住院病例（n =112）。根据患者或家属是否同意早期使用口服抗血小
板药物（阿司匹林100 mg联合氯吡格雷75 mg）治疗分为溶栓后1 h内的早期使用治疗组（n =66）和溶
栓24 h后的标准治疗组（n =46）;观察溶栓后1 d内的再闭塞发生率、3 d内颅内及其他部位出血的发生
率、溶栓7 d后的美国国立卫生研究院卒中量表（National Institutes of Health Stroke Scale,NIHSS）评
分和死亡率。
结果 两组的性别构成、年龄分布、高血压病史、2型糖尿病病史、高胆固醇血症病史、冠状动脉粥
样硬化性心脏病病史、短暂性脑缺血发作病史、心脏瓣膜病史、心房颤动病史、收缩压、舒张压、血糖、
溶栓前NIHSS评分、发病到溶栓时间、HAT评分、责任血管的构成比等基线情况比较差异无显著性（P＞
0.05）;早期使用治疗组的HT发生率与标准治疗组比较差异无显著性（7.6% vs 6.5%,P =1.000）;两
组的症状性脑出血（symptomatic intracerebral hemorrhage,sICH）和死亡数均为0;早期使用治疗组再闭塞
发生率有低于标准治疗组的趋势,但差异无显著性（4.5% vs 15.2%,P =0.107）;早期使用治疗组溶
栓7 d后NIHSS评分也有低于标准治疗组的趋势,但差异也无显著性（NIHSS=6 vs NIHSS=7,P =0.143）。
结论 通过多模影像和HAT评分选择HT风险较低的rt-PA静脉溶栓患者在溶栓后1 h内使用口服抗血
小板药物治疗并不增加溶栓后出血风险。     

个体化静脉溶栓治疗的研究进展

缺血性卒中严重影响着人类的生活。静脉重组组织型纤溶酶原激活剂（intravenou s
recombinant tissue plasminogen activator,rt-PA）溶栓治疗是目前被循证医学证明缺血性卒中急性期唯
一有效的方法。然而,在临床实施中,存在一些问题,如时间窗问题、伴随意识障碍问题、年龄问题、
剂量问题等等,提示在规范的基础上需进行个体化治疗,从而提高溶栓的有效性和安全性。本文就
静脉溶栓中涉及个体化方案临床研究的最新进展做一综述。     

卒中单元对急性缺血性卒中患者医疗质量和在院预后的影响

目的 调查中国卒中单元对缺血性卒中患者收治的现况，并探索卒中单元对改善卒中医疗质量绩效
指标及患者在院预后的影响。
方法 本研究数据来自中国多中心缺血性卒中住院患者登记研究。按照是否进入卒中单元，将
研究对象分为卒中单元组与非卒中单元组。比较两组间患者的卒中医疗质量关键绩效指标（key
performance index，KPI）和在院预后（卒中复发、联合血管事件、全因死亡）的差异，并采用多因素回归，
分析与卒中单元相关的KPI及卒中单元与缺血性卒中患者在院预后的相关性。
结果 本研究共纳入了全国1374家医院的269 428例急性缺血性卒中住院患者。其中，63 548例
（23.6%）患者纳入卒中单元组。卒中单元与较高比例的rt-PA静脉溶栓（OR 1.48，95%CI 1.43～1.53）、
早期抗栓治疗（OR 1.13，95%CI 1.10～1.17）、深静脉血栓预防（OR 1.19，95%CI 1.16～1.22）、吞
咽功能筛查（OR 1.36，95%CI 1.32～1.39）、康复评估（OR 1.31，95%CI 1.28～1.34）、出院抗栓治疗
（OR 1.12，95%CI 1.08～1.15）、合并心房颤动患者抗凝治疗（OR 1.13，95%CI 1.08～1.19）、戒烟宣教
（OR 1.22，95%CI 1.20～1.25）独立相关，与较低的在院卒中复发率（HR 0.79，95%CI 0.75～0.82）和
联合血管事件发生率（HR 0.80，95%CI 0.77～0.84）独立相关（均P <0.001）。
结论 进入卒中单元的缺血性卒中患者，卒中医疗质量KPI完成较好，在院卒中复发率及联合血管事
件率较低。     

中国七城市卒中患者急诊溶栓情况分析

目的 超早期重组组织型纤溶酶原激活剂（recombinant tissue plasminogen activator,rt-PA）溶栓治疗是缺血性卒中有效的治疗方法,但目前缺血性卒中救治过程中存在溶栓率偏低的问题,本调查的目的在于了解实际溶栓状况及未溶栓原因。方法 本调查在中国的7个城市31家中心展开前瞻性调查,调查采用标准的登记数据,内容包括患者的一般人口学信息、院前卒中急救信息、院前院内关键延误时间、溶栓信息等。结果 在研究期间,共有1091例患者确诊符合入选标准,其中754例（69.6%）急性缺血性卒中患者中共有20例（2.7%）患者溶栓,其中静脉rt-PA15例、动脉rt-PA2例、静脉尿激酶（Urokinase,UK）3例。在静脉rt-PA中,93.3%（14/15）存在方案违背。大部分病例（17/20）在2 h内就到达了医院,院前延迟平均中位时间为1.17 h。急诊接诊到获得检查（CT或磁共振）平均中位时间为0.67 h。未进行溶栓的主要原因除年龄（>80岁或<18岁）（28.9%）、卒中症状太轻（24.0%）、病情迅速恢复（16.5%）、CT影像已有病灶（15.7%）、时间>3 h（15.7%）、卒中症状太重（7.4%）等因素外,患者/家属主观拒绝仍占了18.2%。结论 急性缺血性卒中溶栓比例偏低,溶栓药物使用不规范且存在方案违背,存在院前延迟问题,亟待整合院前急救中心与医院间医疗资源,规范院前转运途径,缩短延误时间,提高溶栓率。     

磁共振灌注成像－弥散成像不匹配对指导超时间窗急性缺血性卒中患者溶栓的价值

目的 探讨磁共振灌注成像－弥散成像（perfusion weighted imaging-diffusion weighted imaging,PWI-DWI）不匹配对指导超时间窗（>6h）的急性缺血性卒中患者溶栓的价值。方法 选择在发病12h内完成磁共振检查,且（PWI-DWI）/DWI×100%>30%的40例急性缺血性卒中患者,分为溶栓组和对照组,溶栓组给予重组组织型纤溶酶原激活剂（recombinant tissue plasminogen activator,rt-PA）0.6～0.9mg/kg静脉溶栓治疗,对照组常规治疗。两组患者在溶栓前、溶栓后1周、2周、3个月分别行美国国立卫生院卒中量表（National Institutes of Health Stroke Scale,NIHSS）评分,溶栓前、溶栓后2周、3个月分别行日常生活能力量表（activities of daily living,ADL）评分。结果 溶栓组在溶栓后1周、2周、3个月NIHSS评分均较对照组降低（P<0.01）;在2周和3个月,溶栓组ADL评分较对照组明显升高（P<0.01）。结论 在PWI>DWI影像学模式指导下,适当延长急性缺血性卒中的溶栓时间窗具有可行性。     

影像学指导扩大时间窗急性缺血性卒中溶栓治疗的进展

1996年美国食品及药物管理局（food and drug administration,FDA）规定缺血性卒中静脉应用重组组织型纤溶酶原激活剂（recombinant tissue type plasminogen activator,rt-PA）的时间窗为3 h,但越来越多的证据表明,先进的影像学指导扩大时间窗静脉溶栓治疗具有安全性和有效性。本文将对影像学指导扩大时间窗急性缺血性卒中溶栓治疗的进展进行综述。     

三维动脉自旋标记评价丁苯酞注射液对急性缺血性卒中患者脑血流的影响

目的 采用MRI 三维动脉自旋标记（3-dimensional arterial spin labeling，3D-ASL）技术观察急性缺血
性卒中患者使用丁苯酞注射液对脑血流灌注的影响。
方法 纳入60例非大动脉狭窄或闭塞性急性缺血性卒中患者，随机分为观察组（30例）和对照组
（30例）。对照组采用常规治疗，观察组在对照组治疗基础上加用丁苯酞注射液，疗程为14 d。治疗前
后均进行头颅3D-ASL检查来测量梗死灶相对脑血流量（relative cerebral blood flow，rCBF）的变化。
结果 观察组和对照组治疗前rCBF差异无统计学意义，治疗后观察组rCBF高于对照组（0.97±0.45
vs 0.35±0.15，P =0.003）。
结论 丁苯酞注射液可以提高急性缺血性卒中患者梗死病灶区域的脑血流灌注水平。     

缺血性卒中患者静脉溶栓后不良预后危险因素的研究现状

急性缺血性卒中静脉溶栓的患者临床预后可受疾病严重程度、发病到溶栓的时间、脑小
血管病、血糖水平、中性粒细胞计数、血小板计数、溶栓后再灌注损伤及出血转化等多种因素的影响。
本文从流行病学、溶栓前后影响缺血性卒中静脉溶栓预后的危险因素及相关预测模型进行文献复习,
旨在加强对缺血性卒中患者静脉溶栓后不良预后危险因素及相关预测模型的认识,为其防治提供理
论依据和临床指导。     

急性缺血性卒中静脉溶栓桥接血管内治疗的疗效和安全性

目的 观察rt-PA静脉溶栓桥接血管内治疗急性缺血性卒中的临床疗效和安全性。 方法 回顾性纳入2017年1-12月郑州市第一人民医院神经重症科收治的前循环急性缺血性卒中患 者,按rt-PA静脉溶栓后是否桥接血管内治疗分为单纯静脉溶栓组和桥接治疗组。主要疗效结局为治 疗后3个月mRS评分,次要疗效结局为24 h、3 d和30 d的NI HSS评分。安全性结局为2 d症状性颅内出血及 其他部位出血、10 d全因死亡。 结果 共入组56例患者,平均年龄60.77±12.72岁,男性35例（62.5%）。单纯静脉溶栓组39例,桥接 治疗组17例。桥接治疗组3个月mRS评分≤2分比例高于单纯静脉溶栓组（88.2% vs 56.4%,P =0.021）。 两组治疗后24 h、3 d和30 d NIHSS评分差异无统计学意义。两组2 d症状性颅内出血率及其他部位出血 率、10 d全因死亡率差异无统计学意义。 结论 rt-PA静脉溶栓桥接血管内治疗可改善急性缺血性卒中患者3个月预后。     

Cost-effectiveness analysis of mechanical thrombectomy plus tissue-type plasminogen activator compared with tissue-type plasminogen activator alone for acute ischemic stroke in France

Background and purpose

Recent studies demonstrated the benefit of mechanical thrombectomy (MT) plus intravenous tissue-type plasminogen activator (IV-tPA) (MT-IV-tPA) in acute ischemic stroke. This study aimed to estimate the cost-utility of MT-IV-tPA compared with IV-tPA alone from the perspective of the French National Health Insurance.

Intravenous rt-PA for acute ischemic stroke: 69 consecutive patients managed in an emergency stroke centre

INTRODUCTION: After the 2002 European agreement on the use of rt-PA for fibrinolysis within less than 3 hours after ischemic stroke, we designed a specific patient management scheme for patients referred to our center. METHODS: We report the activity of the "stroke emergency" pathway in the Purpan Hospital (Toulouse) for 4 years. We wanted to evaluate our daily practice and to confirm that the results obtained in the randomized clinical trials with rt-PA can be reproduced in routine practice. RESULTS: Among all stroke patients treated in the Neurology Department, 10.2 per cent were managed via this new pathway, in order to receive a fibrinolytic treatment. Amongst these, 25.6 per cent were treated with rt-PA (2.6 per cent of all ischemic and hemorrhagic strokes, with an average NIHSS score of 15.8 at admission [5; 25]. In 90 per cent of the cases, potential patients for thrombolysis were selected by CT-scan. Time from onset to treatment averaged 2 h 25 min, whilst door-to-treatment time averaged 40 minutes. Two patients (3 percent) showed a symptomatic intra-cerebral hemorrhage. Death rate was 18.8 per cent. After 3 months, 53.5 per cent of patients were regarded as functionally "independent" (Rankin scale<3). CONCLUSION: These results in our unit confirm the feasibility, reproducibility, efficacy and safety of the rt-PA fibrinolytic treatment for ischemic stroke of less than 3 hours. A "Stroke emergency" pathway appears to be a helpful option to treat as many patients as possible with the shortest possible lead times.     

Cost-effectiveness of Apixaban versus Warfarin and Aspirin in Sweden for Stroke Prevention in Patients with Atrial Fibrillation

Introduction

Atrial fibrillation (AF), one of the major risk factors for stroke, imposing a substantial burden to the Swedish health care system. Apixaban has demonstrated superiority to warfarin and aspirin in stroke prevention amongst patients with AF in two large randomised clinical trials. The aim of this study was to assess the economic implications of apixaban against warfarin and aspirin in these patients from a Swedish societal perspective.

Materials and Methods

A Markov cohort model was constructed to characterise the consequences of anticoagulant treatment with regards to thromboembolic and bleeding events, as well as the associated health care costs, life-years and quality-adjusted life years (QALYs) for patients with AF treated with apixaban, warfarin or aspirin. Incremental cost-effectiveness ratios (ICERs) per QALY gained of apixaban relative to warfarin (among patients suitable for warfarin treatment) and aspirin (among patients unsuitable for warfarin treatment) were calculated. Costs (in 2011 SEKs) and QALYs were discounted at 3% per annum.

Results

The model estimated the ICER of apixaban versus warfarin amongst patients who are suitable for warfarin therapy to be SEK 33,458/QALY gained and that of apixaban versus aspirin amongst those unsuitable for warfarin therapy to be SEK 41,453/QALY gained. Probabilistic sensitivity analyses indicate that apixaban is an optimal treatment option compared with warfarin and aspirin, when the willingness-to-pay is above SEK 35,000 and SEK 45,000 per QALY, respectively.

Conclusions

Apixaban was found to be a cost-effective alternative to warfarin and aspirin for stroke prevention in patients with AF in Sweden.     

急性脑梗死患者多模式CT指导下的静脉溶栓治疗

目的 对发病3～9 h内的急性脑梗死患者,应用多模式CT指导下静脉rt-PA溶栓治疗,研究其疗效.方法 2007年8月至2009年5月于我院就诊,经多模式CT筛选出符合溶栓的患者27例.分为＞3～6 h组及7～9 h组,记录溶栓前、后的NIHSS、mRS及BI评分,症状性出血率和病死率.结果 27例样本中20例(74.1%)患者溶栓治疗有效,11例(40.7%)临床结局良好,5例(18.5%)血管完全再通,症状性出血1例(3.7%).其中＞3～6 h组有效率为92.3%(12/13,χ~2=4.34,P=0.037),血管冉通率38.5%(5/13,χ~2=6.608,P=0.010).结论 多模式CT指导下＞3～9 h溶栓是超过常规溶栓时间窗患者的一种可选择的治疗方法.     

Antithrombotic treatments in acute ischemic stroke

A therapeutic role for antiplatelet agents and anticoagulants within 6 hours of the onset of ischemic stroke symptoms has not been tested. With one exception, their use in early stroke (< 48 hours) did not produce a favorable outcome. The use of rt-PA in appropriate patients presenting with ischemic stroke within 3 hours of symptom onset has been accompanied by significant benefit, which has exceeded the risk of intracerebral hemorrhage in one trial. The recent group of clinical studies has provided evidence for factors which may contribute to hemorrhagic transformation. These studies also demonstrate the following: i) recanalization of carotid and vertebrobasilar artery territory occlusions is technically feasible within 3 to 6 hours of symptom onset, ii) the frequency of hemorrhage is increased in ischemic stroke patients receiving PAs, iii) the interval from symptom onset to treatment to achieve clinical improvement varies individually and contributes to hemorrhagic risk, and iv) the optimal PAs, their dose-rate, and delivery systems have not yet been defined in either the carotid or vertebrobasilar territory. Taken together, the NINDS trial, ECASS, and ECASS II indicate the enormous importance of patient selection to reduce the hemorrhagic risk which accompanies the use of PAs in stroke. However, it is currently not possible to separate benefit from hemorrhagic risk in a given patient based upon simple clinical criteria, although contributors to this risk have been identified. Clearly, attempts to reduce the risk of hemorrhage should contribute to the overall benefit of selected ischemic stroke patients treated with rt-PA and with other PAs. This experience may also provide a clinical basis for the prospective study of antiplatelet agents and anticoagulants in acute ischemic stroke.     

Admission glucose level and clinical outcomes in the NINDS rt-PA Stroke Trial

BACKGROUND: Hyperglycemia during acute ischemic stroke may augment brain injury, predispose to intracerebral hemorrhage (ICH), or both. METHOD: To analyze the relationship between admission glucose level and clinical outcomes from acute ischemic stroke, the authors performed multivariate regression analysis with the National Institute of Neurological Disorders and Stroke recombinant tissue plasminogen activator (rt-PA) Stroke Trial data. Neurologic improvement was defined as improvement on the NIH Stroke Scale by 4 or more points from baseline to 3 months, or a final score of zero. Favorable outcome was defined as both Glasgow Outcome score of 1 and Barthel Index 95 to 100 at 3 months. Symptomatic ICH was defined as CT-documented hemorrhage temporally related to clinical deterioration within 36 hours of treatment. Potential confounding factors were controlled, including acute treatment (rt-PA or placebo), age, baseline NIH Stroke Scale score, history of diabetes mellitus, stroke subtype, and admission blood pressure. RESULTS: There were 624 patients enrolled within 3 hours after stroke onset. As admission glucose increased, the odds for neurologic improvement decreased (odds ratio [OR] = 0.76 per 100 mg/dL increase in admission glucose, 95% CI 0.61 to 0.95, p = 0.01). The relation between admission glucose and favorable outcome depended on admission mean blood pressure (MBP): as admission MBP increased, the odds for favorable outcome related to increasing admission glucose levels progressively decreased (p = 0.02). As admission glucose increased, the odds for symptomatic ICH also increased (OR = 1.75 per 100 mg/dL increase in admission glucose, 95% CI 1.11 to 2.78, p = 0.02). Admission glucose level was not associated with altered effectiveness of rt-PA. CONCLUSIONS: In patients with acute ischemic stroke, higher admission glucose levels are associated with significantly lower odds for desirable clinical outcomes and significantly higher odds for symptomatic ICH, regardless of rt-PA treatment. Whether this represents a cause and effect relationship remains to be determined.     

Cost-utility analysis of Parkinson's disease

Many expensive treatments have been developed for Parkinson's disease (PD), and a good cost-utility analysis is required. Quality-adjusted life-years (QALY) allows comparison of the cost-utility of different medical conditions. If a treatment strategy gives a patient an extra but unhealthy year, the QALY he obtained will be less than one. When a therapeutic strategy is more effective, but causes higher costs, it is mandatory to calculate the incremental cost-effectiveness ratio (ICER). In keeping with guidance from the UK National Institute for Health and Clinical Excellence (NICE), a therapy that deliver QALYs of ￡20,000 or less are likely to be approved. The threshold used by NICE for the maximum it is prepared to pay for a QALY, which lies between ￡20,000 and ￡30,000, will be reviewed case by case. Subthalamic deep brain stimulation (STN-DBS) is an effective therapy, which can improve the quality of life in PD patients immediately, but has not been approved by the Bureau of National Health Insurance here. It has been estimated that the ICER/QALY in STN-DBS patients was of 34,389C= , which is within appropriate limits to consider STNDBS as an efficient therapy. We expect that we can have a decision-making mechanism similar to that of NICE that, according to the ICER of each medical condition, medical resource can be redistributed openly and justly.     

Acute ischemic stroke therapy

Acute ischemic stroke is a medical emergency that requires rapid evaluation and treatment. Prehospital and emergency department care can be streamlined to meet those goals. Intravenous rt-PA therapy improves outcome in selected patients with ischemic stroke if given within 3 hours of stroke onset, but offers no benefit beyond that time window. Intra-arterial thrombolytic therapy and intravenous defibrogenating agents may also be beneficial in selected patients. Newer thrombolytic agents such as aspirin and heparin in acute ischemic stroke treatment have been clarified by recent trials.     

急性脑梗死超早期重组组织型纤溶酶原激活物溶栓治疗的临床研究

目的:探讨发病6h内急性脑梗死给予重组组织型纤溶酶原激活物(rt-PA)溶栓治疗的疗效及并发症,并分析预后相关因素。方法:共收集本院2001-2005年70例溶栓治疗的急性脑梗死病例,其中52例静脉溶栓,18例动脉溶栓,分析比较两组病例溶栓前后及3个月随访的ESS评分及Barthel指数结果;同时分析与预后相关的因素。结果:静脉和动脉溶栓组溶栓前及溶栓30min后ESS评分及Barthel指数迅速增加,溶栓前后分值有显著差异。1个月内颅内出血率为5.77%(静脉组)和16.67%(动脉组)。3个月时ESS评分及Barthel指数较溶栓后30min的评分有显著改善。结论:6h内动脉、静脉溶栓治疗均安全有效。