缺血性卒中二级预防后复发的危险因素及药物干预对4-HNE浓度的影响

目的:探讨缺血性卒中二级预防后复发的危险因素,并观察谷胱甘肽对4-HNE浓度的影响。方法:以2017年10月-2019年10月于山东第一医科大学第二附属医院等3家医院因脑血栓或脑栓塞住院治疗的97例缺血性卒中1年内复发患者为观察组,以同期97例未复发患者为对照组并进行配对。观察组患者按分层随机抽样法又分为常规治疗组(49例)和药物干预组(48例)。常规治疗组患者于住院期间进行脑血流再通、改善循环、控制血压、维持血糖、治疗高脂血症和心律失常等常规治疗,药物干预组患者在常规治疗组治疗的基础上加用注射用谷胱甘肽1.8 g,每天1次,静脉注射;疗程均为14天。均于入院时及治疗14天后测定血浆中4-HNE浓度,均于入院时检测ALDH2基因分型和TOAST分型。采用多元线性回归分析探讨4-HNE升高的相关因素;采用条件Logistic分析探讨缺血性卒中二级预防后复发的独立危险因素。结果:观察组患者入院时血浆中4-HNE浓度、大动脉粥样硬化患者比例均显著高于对照组(P<0.05)。两组患者的ALDH2各基因型分布均符合Hardy-Weinberg遗传平衡定律(P>0.05)。观察组携带ALDH2*2等位基因的患者比例(50.50%)显著高于对照组(36.08%)(P<0.05)。携带ALDH2*2等位基因[B=2.33,95%CI(1.35,5.50),P=0.03]和大动脉粥样硬化[B=1.90,95%CI(1.29,3.74),P=0.04]与4-HNE浓度升高显著相关;大动脉粥样硬化[OR=2.93,95%CI(1.84,4.67),P<0.01]、卒中家族史[OR=1.50,95%CI(1.18,1.90),P=0.04]、血浆中4-HNE浓度升高[OR=1.34,95%CI(1.11,1.62),P=0.04]是缺血性卒中二级预防后复发的独立危险因素。干预后,药物干预组和常规治疗组患者血浆中4-HNE浓度均显著低于同组干预前(P<0.05);而两组组间比较,差异均无统计学意义(P>0.05)。结论:卒中家族史、大动脉粥样硬化、血浆中4-HNE浓度升高是缺血性卒中二级预防后复发的独立危险因素;尽管药物干预能降低患者血浆中4-HNE浓度,但加用谷胱甘肽的效果并不比常规治疗显著。     

伴凝血障碍的隐源性脑缺血患者的预后分析

目的探讨凝血障碍的隐源性脑缺血患者在二级预防措施下卒中复发的风险。方法对286例诊断为急性隐源性缺血性卒中或短暂性脑缺血发作(TIA)患者,进行遗传学和特殊的凝血检查,包括凝血因子Ⅴ基因突变、抗活化蛋白C、凝血酶原突变、抗凝血酶Ⅲ、蛋白S、抗心磷脂IgG抗体和狼疮类抗凝物。61例(21.3%)有凝血障碍的患者为凝血障碍组,225例(78.7%)患者检查无凝血障碍者作为对照组。平均随访3年,观察二级预防治疗与缺血性卒中或TIA的发病率。随访3年后对复发性缺血性卒中或TIA的Kapaln-meier风险估计。结果凝血障碍组复发风险为14.1%(95%CI 5.3²1.6),而对照组为9.7%(95%CI 4.921.6),而对照组为9.7%(95%CI 4.9¹6.1)。Cox回归分析发现两组间无显著性差异(P>0.05),但发病前的脑缺血事件是凝血障碍组和对照组患者复发危险的独立预测因素。结论伴有凝血障碍的隐源性脑缺血患者与对照组相比,没有增加复发的风险,对二级预防治疗也无明显影响。     

缺血性小卒中患者两年复发卒中的危险因素分析

目的探讨缺血性小卒中患者两年复发卒中的危险因素。方法纳入我院神经内科2013年1月~2015年1月入院确诊为缺血性小卒中患者474例,共随访两年,以脑卒中复发为终点访视事件。收集复发及未复发患者各项临床资料,采用Log-rank检验进行单因素分析,Cox回归模型进行多因素分析。结果两年内复发缺血卒中患者68例,复发率为14.35%。多因素Cox回归分析结果显示年龄≥65岁(HR 1.877,95%CI 1.159~3.072,P=0.011)、既往脑卒中或短暂性脑缺血发作(transient ischemic attack,TIA)史(HR1.851,95%CI 1.096~3.126,P=0.021)、糖尿病(HR 2.186,95%CI 1.350~3.541,P=0.001)、大动脉狭窄(HR1.789,95%CI 1.079~2.966,P=0.024)是缺血性小卒中两年内再发脑卒中的危险因素。结论年龄≥65岁、既往脑卒中或TIA史、糖尿病、大动脉狭窄是影响缺血性小卒中复发的危险因素,给予合理正确的二级预防,可以减少卒中复发。     

标准二联止吐方案预防中致吐风险药物所致恶心呕吐的成本-效果分析

目的:对预防中致吐风险药物所致恶心呕吐的标准二联止吐方案进行经济学评价.方法:回顾性分析我院2018–2019年采用标准二联止吐方案预防中致吐风险药物所致恶心呕吐的住院患者资料,采用决策树模型,对使用昂丹司琼8 mg+地塞米松5 mg(A组)、格拉司琼3 mg+地塞米松5 mg(B组)、托烷司琼5 mg+地塞米松5 m...     

阿司匹林联合双嘧达莫预防缺血性卒中复发的临床观察

缺血性卒中是一组临床症候群，主要表现为脑梗死、短暂性脑缺血发作（TIA），具有较高的病死率和致残率，对人类健康危害较大。约20％～40％的缺血性卒中患者在其发病后5年内会复发。因此临床对缺血性卒中的二级预防十分重要。我们对部分脑梗死恢复期患者联合应用阿司匹林加双嘧达莫预防治疗，现报告如下。     

《2021 AHA/ASA指南:卒中和短暂性脑缺血发作患者的卒中预防》解读

2021年5月24日,美国心脏协会和美国卒中协会(AHA/ASA)发布《2021AHA/ASA指南:卒中和短暂性脑缺血发作患者的卒中预防》。该指南内容涉及继发性卒中预防的诊断评估、血栓风险因素的管理、病因学管理以及继发性卒中的系统护理等。该文拟对指南中药物治疗相关部分进行解读,并对抗栓药物与既往版本指南进行比较,以期为我国缺血性卒中和短暂性脑缺血发作生存者卒中的二级预防提供参考。     

临床药师参与1例非心源性脑卒中合并CKD 4期患者卒中二级预防治疗的病例分析

目的 探讨临床药师在非心源性卒中合并慢性肾功能不全4期(CKD4)患者个体化卒中二级预防中的作用。方法 临床药师通过调研文献及查阅指南,为1例非心源性卒中合并CKD4期患者制定个体化的卒中二级预防方案。结果 临床药师通过查阅文献,配合临床医生为非心源性脑卒中合并CKD4期患者制定了个体化的抗血小板治疗方案、他汀类药物治疗方案及口服降糖、降压药物方案,患者依从性高。经过精细化的药物治疗后,该患者血压及血糖水平较入院前明显改善,头晕及行走不稳较入院前明显好转。结论 临床药师在个体化的药物治疗中起着至关重要的作用,通过一系列药物重组方案,可进一步规范临床合理用药。     

新型抗凝药与华法林用于非瓣膜性房颤患者卒中防治的成本效果分析

目的:评估中国非瓣膜性房颤患者使用新型抗凝药预防卒中的成本效果,为中国房颤患者抗凝治疗药物的合理选用提供理论依据。方法:基于全球性临床试验ARISTOTLE、RE-LY及ROCKET-AF的研究数据及我国目前医疗成本,建立一年期决策树及长期外推Markov模型的方法,通过分别计算3种新型口服抗凝药物阿哌沙班(5 mg bid)、达比加群(150 mg bid、110 mg bid)、利伐沙班(20 mg qd)和华法林的调整质量生命年(QLAYs)及治疗成本,对新型抗凝药物用于中国房颤患者卒中预防的成本效果进行了分析和研究。结果:NOACs治疗的总成本为163586~582710元,使用NOACs患者可获得的质量调整生命年为6.812~7.010。以华法林为参考的增效成本效果分析显示,成本效果比(ICER)为177271~739480元/QLAY,ICER_利伐沙班> ICER_阿哌沙班> ICER_{达比加群150 mg}> ICER_{达比加群110 mg}。3种抗凝药物与华法林比较的ICER均大于我国人均国民生产总值(GDP)的3倍,但小于部分城市人均GDP的3倍。一维敏感度分析显示该成本效果分析结果稳定可靠。结论:目前在我国,与华法林相比,使用新型抗凝药物预防非瓣膜性房颤患者卒中不具备成本效果优势。目前仅在我国经济发达的某些城市,可推荐阿哌沙班或达比加群用于房颤卒中的治疗。     

脑卒中二级预防,双抗不优于单用阿司匹林

2012年国际卒中大会上,来自加拿大的皮质下卒中二级预防(SPS3)试验中期结果表明,不支持阿司匹林联合氯吡格雷治疗对皮质下小卒中二级预防的益处,联合抗血小板治疗被提前终止。皮质下小卒中是超过25%脑梗死的致病原因,也是导致血管性痴呆的最常见原因。SPS3试验是在8个国家进行的一项随机多中心临床试验,旨在为减少卒中复发、认知能力的下降和严重血管事件制定策略。研究采用磁共振成像(MRⅠ)确诊,受试者在180d内无颈动脉狭窄或心脏来源的严重栓塞。采用析因设计,     

他汀类药物预防缺血性卒中患者复发的疗效观察

<正>随着我国人口老年化的到来及高血压病患病率的升高,缺血性卒中已成为我国居民导致死亡疾病之一。缺血性卒中复发加重了残疾程度,增加患者病死率,延长了患者住院时间。因此,对于卒中的二级预防具有非常重要的意义。1资料与方法1.1一般资料:选择2008年7月至2010年7月我院内科     

泛基因型直接抗病毒药物治疗慢性丙型肝炎的成本-效用分析

目的:评价泛基因型直接抗病毒药物(DAAs)治疗慢性丙型肝炎患者的成本-效用,为相关医疗卫生决策提供药物经济学证据。方法:从全社会角度出发,以中国初治慢性丙型肝炎患者为目标人群,参考文献资料建立Markov模型,以索磷布韦维帕他韦为对照,分析格卡瑞韦派伦他韦、索磷布韦+可洛派韦治疗慢性丙型肝炎患者的质量调整生命年(QALYs)和增量成本-效用比(ICERs);采用敏感性分析验证结果的稳健性。结果:与索磷布韦维帕他韦相比,格卡瑞韦哌仑他韦增加了0.0021 QALYs,成本增加25021元,ICERs为12129031元/QALY(意愿支付阈值为70892元/QALY),不具有成本-效用;当其单价下降至1679元时(降价64.65%)将具有成本-效用。索磷布韦+可洛派韦增加了0.0020 QALYs,成本减少515元,是成本节约的绝对优势方案。敏感性分析显示,持续病毒学应答率和药品价格对结果的影响最大,索磷布韦+可洛派韦具有成本-效用的概率高于格卡瑞韦哌仑他韦。结论:格卡瑞韦哌仑他韦需大幅降低价格,才可达到更好的可负担性;索磷布韦+可洛派韦具有良好的经济性。     

Drug treatments for maintaining remission in Crohn's disease. A lifetime cost-utility analysis

A recent literature overview has estimated the long term frequency of the main outcomes of Crohn's disease (e.g. relapses, hospitalisations and surgery). Using these frequency data, we defined a model for the long term course of the disease. In this model, the quality-of-life (QOL) scores for the main levels of disease severity were determined by a panel of expert gastroenterologists. We conducted a combined analysis of these long term clinical data and of this QOL information to determine the cost-utility ratio of long term maintenance therapy with mesalazine (mesalamine) in patients with inactive Crohn's disease. After obtaining the cost-of-illness data needed for this analysis from a recent study conducted in the UK, we completed our incremental cost-utility analysis, in which mesalazine was compared with no maintenance treatment, using 2 hypothetical groups of 100 patients. These 2 groups were assumed to have the same general characteristics as those found in a group of 583 patients included in a recent meta-analysis. Our cost-utility evaluation included 5% annual discounting. In the mesalazine group, the overall lifetime costs for the 100 patients were around $US5 100,000 with an overall utility value of about 1700 quality-adjusted life years (QALYs). Both the lifetime costs and the utility values for the placebo (no treatment) group were very similar to those calculated for the mesalazine group. Our cost-utility analysis showed that mesalazine maintenance therapy was associated with a cost of about $US5000 per QALY gained. There was, therefore, a small incremental benefit obtained, albeit with a very small incremental cost. Sensitivity analyses confirmed these results. In conclusion, our study showed that long term maintenance therapy with mesalazine in patients with inactive Crohn's disease should not be discouraged on the basis of preliminary cost-utility considerations. However, long term placebo-controlled studies of mesalazine are urgently needed to better define the long term prognosis of these patients.     

依替巴肽与替罗非班在急性非ST段抬高型心肌梗死患者介入治疗中的药物经济学研究

目的:本研究旨在对比依替巴肽与替罗非班在急性非ST段抬高型心肌梗死(NSTEMI)患者介入治疗中的成本-效果分析,为中国NSTEMI患者经皮冠状动脉介入治疗(PCI)抗栓药物的选用提供依据及参考.方法:基于Markov数学模型,以国内医疗成本为成本数据,以国内外临床研究结果为疗效指标,利用Treeage软件模拟计算使用...     

Cost–utility analysis of reslizumab for patients with severe eosinophilic asthma inadequately controlled with high-dose inhaled corticosteroids and long-acting β2-agonists in South Korea

Objectives: We aimed to assess the cost-utility of reslizumab for patients with severe eosinophilic asthma uncontrolled with high-dose inhaled corticosteroids and long-acting β₂-agonists (ICS/LABAs) in Korea.

Methods: A Markov model with limited societal perspective was used to compare the costs and quality-adjusted life years (QALYs) of reslizumab add-on therapy with standard-of-care (high-dose ICS/LABA) and standard-of-care alone. The model adopted a 4?week cycle with the following six health states over a lifetime (60?years): controlled asthma, uncontrolled asthma, moderate exacerbation, severe exacerbation, all-cause death and asthma-related death. The population comprised adult patients (age ≥18?years) with severe eosinophilic asthma (eosinophils ≥400 cells/μL) at Global Initiative for Asthma (GINA) step 4 or 5 who had experienced at least three exacerbations in the preceding year. Model inputs were sourced from individual patient-level data from two 52?week randomized controlled trials of reslizumab (NCT01287039, NCT01285323). The model included discontinuation rules where patients uncontrolled with reslizumab add-on therapy were transitioned to the standard-of-care arm. Costs and QALYs were annually discounted at 5%. Deterministic and probabilistic sensitivity analyses were performed.

Results: Reslizumab add-on therapy was associated with increased cost (US$119,394) and improved QALYs (5.17) compared with standard-of-care alone, resulting in an incremental cost-effectiveness ratio of US$23,081 per QALY gained. Body weight, time horizon and discount rate were influential factors in the model.

Conclusions: The addition of reslizumab to high-dose ICS/LABA was cost-effective in Korean patients with severe eosinophilic asthma uncontrolled with high-dose ICS/LABA, based on the threshold of 1 gross domestic product in Korea.     

脾多肽注射液联合化疗治疗中晚期非小细胞肺癌的药物经济学评价

目的:评估脾多肽注射液联合化疗相比单独化疗治疗中晚期非小细胞肺癌患者的经济性。方法:基于中国卫生体系角度,构建分区生存模型模拟脾多肽注射液联合化疗与单独化疗的长期健康产出与成本。临床疗效来源于已发表的基于中国人群的真实世界队列研究。直接医疗费用包括一线化疗费用、维持治疗费用、二线治疗费用等。健康效用值来源于最新发表的相关文献。采用单因素敏感性分析和概率敏感性分析验证结果稳健性。结果:基础分析显示,脾多肽注射液联合化疗组的质量调整生命年(1.892 QALYs)比单独化疗组(1.597 QALYs)高0.295 QALYs,脾多肽注射液联合化疗组和单独化疗组的总成本分别为143 724元和126 004元。脾多肽注射液联合化疗组相比单独化疗组的增量成本效果比为60 130元/QALY。概率敏感性分析结果显示,当以中国2021年3倍人均GDP作为阈值时,脾多肽注射液联合化疗具有成本效果的概率为79.26%。结论:相比单独化疗,脾多肽注射液联合化疗治疗中晚期非小细胞肺癌患者更具经济性。     

Cost utility of maintenance treatment of recurrent depression with sertraline versus episodic treatment with dothiepin

The objective of this study was to model, for patients at risk of recurrent depression, the cost-utility of maintenance therapy with sertraline compared with treatment of acute episodes with dothiepin ('episodic treatment'). Using clinical decision analysis techniques, a Markov state-transition model was constructed to estimate the lifetime costs and quality-adjusted life-years (QALYs) of the 2 therapeutic strategies. The model follows 2 cohorts of 35-year-old women at high risk for recurrent depression over their lifetimes. Model construction and relevant data (probabilities) for performing the analysis were based on existing clinical knowledge. Two physician panels were used to obtain estimates of recurrence probabilities not available in the literature, health utilities, and resource consumption. Costs were obtained from published sources. The baseline analysis showed that it costs 2172 British pounds sterling ($US3692, 1991 currency) to save an additional QALY with sertraline maintenance treatment. Sensitivity analysis showed that the incremental cost-utility ratio ranged from 557 British pounds sterling to 5260 British pounds sterling per QALY. Overall, the resulting ratios are considered to be well within the range of cost-utility ratios that support the adoption and appropriate utilisation of a technology. Based on the study assumptions, long term maintenance treatment with sertraline appears to be clinically and economically justified choice for patients at high risk of recurrent depression.     

Modelling the cost effectiveness of antidepressant treatment in primary care

The aim of this study was to estimate the cost effectiveness of nefazodone compared with imipramine or fluoxetine in treating women with major depressive disorder. Clinical decision analysis and a Markov state-transition model were used to estimate the lifetime health outcomes and medical costs of 3 antidepressant treatments. The model, which represents ideal primary care practice, compares treatment with nefazodone to treatment with either imipramine or fluoxetine. The economic analysis was based on the healthcare system of the Canadian province of Ontario, and considered only direct medical costs. Health outcomes were expressed as quality-adjusted life years (QALYs) and costs were in 1993 Canadian dollars ($Can; $Can1 = $US0.75, September 1995). Incremental cost-utility ratios were calculated comparing the relative lifetime discounted medical costs and QALYs associated with nefazodone with those of imipramine or fluoxetine. Data for constructing the model and estimating necessary parameters were derived from the medical literature, clinical trial data, and physician judgement. Data included information on: Ontario primary care physicians' clinical management of major depression; medical resource use and costs; probabilities of recurrence of depression; suicide rates; compliance rates; and health utilities. Estimates of utilities for depression-related hypothetical health states were obtained from patients with major depression (n = 70). Medical costs and QALYs were discounted to present value using a 5% rate. Sensitivity analyses tested the assumptions of the model by varying the discount rate, depression recurrence rates, compliance rates, and the duration of the model. The base case analysis found that nefazodone treatment costs $Can1447 less per patient than imipramine treatment (discounted lifetime medical costs were $Can50,664 vs $Can52,111) and increases the number of QALYs by 0.72 (13.90 vs 13.18). Nefazodone treatment costs $Can14 less than fluoxetine treatment (estimated discounted lifetime medical costs were $Can50,664 vs $Can50,678) and produces slightly more QALYs (13.90 vs 13.79). In the sensitivity analyses, the cost-effectiveness ratios comparing nefazodone with imipramine ranged from cost saving to $Can17,326 per QALY gained. The cost-effectiveness ratios comparing nefazodone with fluoxetine ranged from cost saving to $Can7327 per QALY gained. The model was most sensitive to assumptions about treatment compliance rates and recurrence rates. The findings suggest that nefazodone may be a cost-effective treatment for major depression compared with imipramine or fluoxetine. The basic findings and conclusions do not change even after modifying model parameters within reasonable ranges.     

阿替利珠单抗联合标准化疗方案治疗广泛期小细胞肺癌的成本-效用分析

目的:从卫生体系角度评价阿替利珠单抗联合标准化疗方案对比单用化疗方案一线治疗广泛期小细胞肺癌(ES-SCLC)的经济性.方法:参考一项Ⅲ期临床试验数据(IMpower133研究)及其他文献数据构建ES-SCLC患者分区生存模型,评价阿替利珠单抗联合标准化疗方案(依托泊苷+卡铂)对比单纯化疗方案(依托泊苷+卡铂)一线治疗...     

A cost--utility analysis comparing second-line chemotherapy schemes in patients with metastatic breast cancer.

A cost-utility analysis has been performed comparing taxanes, vinorelbine and standard therapy for metastatic breast cancer considering clinical efficacy, quality-adjusted-life-years (QALYs) and costs. A decision model has been built. Clinical efficacy data were collected by literature review. Utility data and cost data were collected from previous studies and Dutch wholesale prices. Except for the MV standard therapy, VM has the lowest C/E ratio of $17,114/QALY, followed by paclitaxel ($30,270/QALY) and docetaxel ($49,739/QALY). VM yields the highest number of QALYs (0.47), compared to paclitaxel (0.35), docetaxel (0.34) and MV (0.29). Compared to the MV standard therapy, the incremental C/E of VM is $23,046/QALY, which is the lowest of all alternatives. We conclude that compared to paclitaxel, docetaxel and MV standard chemotherapy, VM is the most cost-effective second-line chemotherapy for metastatic breast cancer patients. There is a considerable variation in utility scores, depending on the methods or the data sources used. The C/E ratios were influenced most strongly by drug prices, utility and efficacy (in descending order of importance).