Faculty of Medicine, University of Ottawa, 451 Smyth Rd #2044, Ottawa, ON, K1H 8M5, Canada.
Clinical Epidemiology Program, Blueprint Translational Group, Ottawa Hospital Research Institute, 501 Smyth Box 511, Ottawa, ON, K1H 8L6, Canada.
Syst Rev. 2023 Mar 21;12(1):50. doi: 10.1186/s13643-023-02189-2.
The importance of investigating sex- and gender-dependent differences has been recently emphasized by major funding agencies. Notably, the influence of biological sex on clinical outcomes in sepsis is unclear, and observational studies suffer from the effect of confounding factors. The controlled experimental environment afforded by preclinical studies allows for clarification and mechanistic evaluation of sex-dependent differences. We propose a systematic review to assess the impact of biological sex on baseline responses to disease induction as well as treatment responses in animal models of sepsis. Given the lack of guidance surrounding sex-based analyses in preclinical systematic reviews, careful consideration of various factors is needed to understand how best to conduct analyses and communicate findings.
MEDLINE and Embase will be searched (2011-present) to identify preclinical studies of sepsis in which any intervention was administered and sex-stratified data reported. The primary outcome will be mortality. Secondary outcomes will include organ dysfunction, bacterial load, and IL-6 levels. Study selection will be conducted independently and in duplicate by two reviewers. Data extraction will be conducted by one reviewer and audited by a second independent reviewer. Data extracted from included studies will be pooled, and meta-analysis will be conducted using random effects modeling. Primary analyses will be stratified by animal age and will assess the impact of sex at the following time points: pre-intervention, in response to treatment, and post-intervention. Risk of bias will be assessed using the SYRCLE's risk-of-bias tool. Illustrative examples of potential methods to analyze sex-based differences are provided in this protocol.
Our systematic review will summarize the current state of knowledge on sex-dependent differences in sepsis. This will identify current knowledge gaps that future studies can address. Finally, this review will provide a framework for sex-based analysis in future preclinical systematic reviews.
PROSPERO CRD42022367726.
主要资助机构最近强调了研究性别差异的重要性。值得注意的是，生物学性别对脓毒症临床结局的影响尚不清楚，且观察性研究受到混杂因素的影响。临床前研究提供的受控实验环境允许阐明和评估性别依赖性差异的机制。我们提出了一项系统评价，以评估生物学性别对疾病诱导时的基线反应以及脓毒症动物模型中治疗反应的影响。鉴于临床前系统评价中缺乏有关基于性别的分析的指导，需要仔细考虑各种因素，以了解如何最好地进行分析和交流研究结果。
将在 MEDLINE 和 Embase 中进行检索（2011 年至今），以确定已发表的任何干预措施均已实施且报告了性别分层数据的脓毒症临床前研究。主要结局将是死亡率。次要结局将包括器官功能障碍、细菌负荷和 IL-6 水平。研究选择将由两名独立评审员进行，并进行重复。将由一名评审员进行数据提取，并由另一名独立的评审员进行审核。从纳入的研究中提取的数据将进行汇总，并使用随机效应模型进行荟萃分析。主要分析将按动物年龄分层，并将评估以下时间点的性别的影响：干预前、治疗反应时和干预后。使用 SYRCLE 的风险偏倚工具评估风险偏倚。本方案提供了分析性别差异的潜在方法的说明性示例。
我们的系统评价将总结脓毒症中性别差异的现有知识状态。这将确定未来研究可以解决的当前知识差距。最后，本综述将为未来临床前系统评价中的基于性别的分析提供框架。
PROSPERO CRD42022367726。
