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阿司匹林作为结核性脑膜炎辅助治疗的疗效与安全性:一项系统评价与荟萃分析

Efficacy and safety of aspirin as an adjunctive therapy in tubercular meningitis: A systematic review and meta-analysis.

作者信息

Rohilla R, Shafiq N, Malhotra S

机构信息

DM-Resident Clinical Pharmacology, Department of Pharmacology, PGIMER, Chandigarh, India.

Department of Pharmacology, PGIMER, Chandigarh, India.

出版信息

EClinicalMedicine. 2021 Apr 17;34:100819. doi: 10.1016/j.eclinm.2021.100819. eCollection 2021 Apr.

Abstract

BACKGROUND

Tubercular meningitis (TBM) is associated with high mortality and stroke with chronic neurological sequelae even with best of care and antitubercular therapy. Studies have shown that aspirin as an adjunctive therapy might play some role in management of TBM. This systematic review and meta-analysis has been planned to evaluate the efficacy and safety of aspirin as an adjunctive therapy in TBM patients.

METHODS

We conducted a systematic search of randomized controlled trials in patients with tubercular meningitis published till October 2019 in all major clinical journals. Study was registered with PROSPERO with registration number: CRD42019136689. Articles were tested for eligibility and assessed for quality and various bias. Data synthesis and analysis was done using Review manager 5.3. The primary end point for assessment of efficacy was mortality at three months. The secondary end point was stroke or composite outcome of stroke and mortality at three months. Adverse effects were also assessed as secondary safety end point.

FINDINGS

Overall, three eligible randomized controlled trials with 365 participants were included that provided quantitative data for this meta-analysis. The analysis of primary and secondary end points was done using fixed effect model. There was not significant reduction in mortality [hazard ratio 0.78 (95% CI 0.45-1.35,  = 0.37)] and composite outcome of mortality and new onset stroke [hazard ratio 0.86 (95% CI 0.60-1.24,  = 0.43)] in aspirin group as compared to placebo. However, aspirin as compared to placebo significantly reduced new onset stroke [hazard ratio of 0.51 (95% CI 0.29-0.87,  = 0.01)].

INTERPRETATION

We did not find significant reduction in mortality and composite outcome (mortality and new onset stroke) with aspirin as compared to placebo but there was significant reduction in new onset stroke in aspirin group as compared to placebo with Number Needed to Treat (NNT) = 10, which might be of clinical importance since stroke is responsible for high mortality and morbidity in these subset of patients. However, a large well conducted randomized controlled trial is required to put more light on the available evidence.

摘要

背景

结核性脑膜炎(TBM)即便接受了最佳治疗和抗结核治疗,仍与高死亡率以及伴有慢性神经后遗症的中风相关。研究表明,阿司匹林作为辅助治疗可能在TBM的管理中发挥一定作用。本系统评价和荟萃分析旨在评估阿司匹林作为TBM患者辅助治疗的疗效和安全性。

方法

我们对截至2019年10月在所有主要临床杂志上发表的结核性脑膜炎患者的随机对照试验进行了系统检索。该研究已在国际前瞻性注册系统(PROSPERO)注册,注册号为:CRD42019136689。对文章进行合格性测试,并评估其质量和各种偏倚。使用Review manager 5.3进行数据合成和分析。评估疗效的主要终点是三个月时的死亡率。次要终点是三个月时的中风或中风与死亡率的综合结局。不良反应也作为次要安全终点进行评估。

结果

总体而言,纳入了三项符合条件的随机对照试验,共365名参与者,为该荟萃分析提供了定量数据。使用固定效应模型对主要和次要终点进行分析。与安慰剂相比,阿司匹林组的死亡率[风险比0.78(95%可信区间0.45 - 1.35,P = 0.37)]以及死亡率和新发中风综合结局[风险比0.86(95%可信区间0.60 - 1.24,P = 0.43)]没有显著降低。然而,与安慰剂相比,阿司匹林显著降低了新发中风[风险比为0.51(95%可信区间0.29 - 0.87,P = 0.01)]。

解读

与安慰剂相比,我们发现阿司匹林在降低死亡率和综合结局(死亡率和新发中风)方面没有显著效果,但与安慰剂相比,阿司匹林组的新发中风有显著降低,需治疗人数(NNT)= 10,这可能具有临床意义,因为中风是这些患者亚组中高死亡率和高发病率的原因。然而,需要进行一项大型、精心设计的随机对照试验来进一步阐明现有证据。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a255/8080028/0a8e972ad8e7/gr1.jpg

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