Kai Michael Schubert, Johan Zelano, David J Seiffge, Francesco Brigo, Eugen Trinka, Nishant K Mishra, Emilio Russo, Marian Galovic
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引用次数: 0
摘要
直接口服抗凝剂（DOACs）和抗癫痫药物（asm）同时使用越来越普遍，特别是在房颤、中风和癫痫患者中。某些asm可能通过酶诱导或p -糖蛋白调节影响DOACs的药代动力学，可能改变其有效性和安全性。然而，关于这些相互作用及其对临床结果的影响的证据仍然有限，异质性和不一致的报道。本系统综述的目的是综合目前关于DOACs和asm同时治疗患者的脑血管结局、出血风险和药代动力学效应的证据。方法：本方案概述了随机对照试验、观察性研究、病例对照研究和药代动力学调查的系统综述和荟萃分析，这些研究涉及8岁或以上接受DOACs联合asm治疗的患者。检索数据库包括MEDLINE、Embase、Cochrane CENTRAL、Web of Science和临床试验注册（ClinicalTrials.gov、WHO ICTRP），不受语言限制。其他研究将通过参考筛选、专家联系和人工智能辅助证据发现（Elicit）来确定。研究选择、数据提取和使用经过验证的工具（Newcastle-Ottawa Scale （NOS）、预后质量研究（QUIPS）工具和Cochrane risk of bias 2.0工具）进行偏倚风险评估将采用双重独立审查。在适当的情况下，将使用随机效应模型进行meta分析；否则，结果将按照SWiM（综合无荟萃分析）指南进行叙述性综合。计划结局：主要有效结局：缺血性卒中和全身性栓塞（IS/SE）的组合。次要结局：单独缺血性脑卒中、单独全身性栓塞、短暂性脑缺血发作（TIA）、大出血、颅内出血、药代动力学测量和癫痫发作。亚组分析将根据ASM类型、药代动力学相互作用潜力、年龄组（8-17岁，≥18岁）和DOAC适应症（如非瓣膜性心房颤动、静脉血栓栓塞、左室血栓）进行分层。如果有足够的合格数据，计划进行个体参与者数据（IPD）荟萃分析。提供了结果和定义的汇总表（表1）和计划过程的概述流程图（图1）。系统评价注册：PROSPERO CRD4201050986。
Safety and Effectiveness of Direct Oral Anticoagulants in Combination with Antiseizure Medications: Protocol for a Systematic Review and Meta-analysis.
Introduction: The concurrent use of direct oral anticoagulants (DOACs) and antiseizure medications (ASMs) is increasingly common, particularly among patients with atrial fibrillation, stroke, and epilepsy. Certain ASMs may affect the pharmacokinetics of DOACs through enzyme induction or modulation of P-glycoprotein, potentially altering their effectiveness and safety. However, evidence regarding these interactions and their impact on clinical outcomes remains limited, heterogeneous, and inconsistently reported. The objective of this systematic review is to synthesize current evidence on cerebrovascular outcomes, bleeding risk, and pharmacokinetic effects in patients treated concurrently with DOACs and ASMs.
Methods: This protocol outlines a systematic review and meta-analysis of randomized controlled trials, observational studies, case-control studies, and pharmacokinetic investigations involving patients aged 8 years or older treated with DOACs in combination with ASMs. Databases including MEDLINE, Embase, Cochrane CENTRAL, Web of Science, and clinical trial registries (ClinicalTrials.gov, WHO ICTRP) will be searched without language restrictions. Additional studies will be identified via reference screening, expert contact, and AI-assisted evidence discovery (Elicit). Dual independent review will be applied for study selection, data extraction, and risk of bias assessment using validated tools (Newcastle-Ottawa Scale (NOS), the Quality In Prognosis Studies (QUIPS) tool, and the Cochrane Risk of Bias 2.0 tool). Where appropriate, meta-analysis will be performed using random-effects models; otherwise, results will be synthesized narratively in accordance with SWiM (Synthesis Without Meta-analysis) guidelines.
Planned outcomes: Primary effectiveness outcome: composite of ischemic stroke and systemic embolism (IS/SE).
Secondary outcomes: ischemic stroke alone, systemic embolism alone, transient ischemic attack (TIA), major bleeding, intracranial hemorrhage, pharmacokinetic measures, and seizure occurrence. Subgroup analyses will stratify by ASM type, pharmacokinetic interaction potential, age groups (8-17, ≥ 18 years), and DOAC indications (e.g., non-valvular atrial fibrillation, venous thromboembolism, left ventricular thrombus). An individual participant data (IPD) meta-analysis is planned if sufficient eligible data are available. A summary table of outcomes and definitions (Table 1) and an overview flow diagram of the planned process (Fig. 1) are provided.
期刊介绍：
Aims and Scope
Neurology and Therapy aims to provide reliable and inclusive, rapid publication for all therapy related research for neurological indications, supporting the timely dissemination of research with a global reach, to help advance scientific discovery and support clinical practice.
Neurology and Therapy is an international, open access, peer reviewed, rapid publication journal dedicated to the publication of high-quality clinical (all phases), observational, real-world and health outcomes research around the discovery, development, and use of neurological and psychiatric therapies, (also covering surgery and devices). Studies relating to diagnosis, pharmacoeconomics, public health, quality of life, and patient care, management, and education are also welcomed.
The journal is of interest to a broad audience of healthcare professionals and publishes original research, reviews, case reports, trial designs, communications and letters. The journal is read by a global audience and receives submissions from all over the world. Neurology and Therapy will consider all scientifically sound research be it positive, confirmatory or negative data. Submissions are welcomed whether they relate to an international and/or a country-specific audience, something that is crucially important when researchers are trying to target more specific patient populations. This inclusive approach allows the journal to assist in the dissemination of all scientifically and ethically sound research.
Rapid Publication
The journal’s rapid publication timelines aim for a peer review decision within 2 weeks of submission. If an article is accepted, it will be published online 3-4 weeks from acceptance. These rapid timelines are achieved through the combination of a dedicated in-house editorial team, who closely manage article workflow, and an extensive Editorial and Advisory Board who assist with rapid peer review. This allows the journal to support the rapid dissemination of research, whilst still providing robust peer review. Combined with the journal’s open access model, this allows for the rapid and efficient communication of the latest research and reviews to support scientific discovery and clinical practice.
Open Access
All articles published by Neurology and Therapy are open access.
Personal Service
The journal’s dedicated in-house editorial team offer a personal “concierge service” meaning that authors will always have a personal point of contact able to update them on the status of their manuscript. The editorial team check all manuscripts to ensure that articles conform to the most recent COPE and ICMJE publishing guidelines. This supports the publication of ethically sound and transparent research. We also encourage pre-submission enquiries and are always happy to provide a confidential assessment of manuscripts.
Digital Features and Plain Language Summaries
Neurology and Therapy offers a range of additional features designed to increase the visibility, readership and educational value of the journal’s content. Each article is accompanied by key summary points, giving a time-efficient overview of the content to a wide readership. Articles may be accompanied by plain language summaries to assist readers who have some knowledge of, but not in-depth expertise in, the area to understand the scientific content and overall implications of the article. The journal also provides the option to include various types of digital features including animated abstracts, video abstracts, slide decks, audio slides, instructional videos, infographics, podcasts and animations. All additional features are peer reviewed to the same high standard as the article itself. If you consider that your paper would benefit from the inclusion of a digital feature, please let us know. Our editorial team are able to create high-quality slide decks and infographics in-house, and video abstracts through our partner Research Square, and would be happy to assist in any way we can. For further information about digital features, please contact the journal editor (see ‘Contact the Journal’ for email address), and see the ‘Guidelines for digital features and plain language summaries’ document under ‘Submission guidelines’.
For examples of digital features please visit our showcase page https://springerhealthcare.com/expertise/publishing-digital-features/
Publication Fees
Upon acceptance of an article, authors will be required to pay the mandatory Rapid Service Fee of €5250/$6000/£4300. The journal will consider fee discounts and waivers for developing countries and this is decided on a case-by-case basis.
Peer Review Process
Upon submission, manuscripts are assessed by the editorial team to ensure they fit within the aims and scope of the journal and are also checked for plagiarism. All suitable submissions are then subject to a comprehensive single-blind peer review. Reviewers are selected based on their relevant expertise and publication history in the subject area. The journal has an extensive pool of editorial and advisory board members who have been selected to assist with peer review based on the afore-mentioned criteria.
At least two extensive reviews are required to make the editorial decision, with the exception of some article types such as Commentaries, Editorials and Letters which are generally reviewed by one member of the Editorial Board. Where reviews conflict, an Editorial Board Member will be contacted for further advice and a presiding decision. Manuscripts are then either accepted, rejected or authors are required to make major or minor revisions (both reviewer comments and editorial comments may need to be addressed. Once a revised manuscript is re-submitted, it is assessed along with the responses to reviewer comments and if it has been adequately revised, it will be accepted for publication. Accepted manuscripts are then copyedited and typeset by the production team before online publication. Appeals against decisions following peer review are considered on a case-by-case basis and should be sent to the journal editor, and authors are welcome to make rebuttals against individual reviewer comments, if appropriate.
Preprints
We encourage posting of preprints of primary research manuscripts on preprint servers, authors'' or institutional websites, and open communications between researchers whether on community preprint servers or preprint commenting platforms. Posting of preprints is not considered prior publication and will not jeopardize consideration in our journals.
Please see here for further information on preprint sharing: https://www.springer.com/gp/authors-editors/journal-author/journal-author-helpdesk/submission/1302#c16721550
Copyright
Neurology and Therapy is published under the Creative Commons Attribution-Noncommercial License, which allows users to read, copy, distribute, and make derivative works for non-commercial purposes from the material, as long as the author of the original work is cited. The author assigns the exclusive right to any commercial use of the article to Springer. For more information about the Creative Commons Attribution-Noncommercial License, click here: http://creativecommons.org/licenses/by-nc/4.0.
Contact
For more information about the journal, including pre-submission enquiries, please contact managing editor Lydia Alborn at lydia.alborn@springer.com.
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