Extending Safe and Effective Thrombolysis for Stroke

描述(由申请人提供)：静脉溶栓治疗(TT)改善了急性缺血性中风(AIS)的预后，如果在症状出现后3小时内进行静脉溶栓治疗，尽管总体上有好处，但即使在3小时的时间框架内，仍存在显著的溶栓相关性颅内出血(ICH)风险。包括超过这一时间窗口的患者在内的多项试验都未能在AIS中发现TT的益处。部分由于治疗机会的狭窄时间窗口，目前只有不到5%的AIS患者接受TT治疗。 我们的初步工作表明，在症状出现3小时后给药时，TT没有总体好处，这掩盖了这样一个事实，即一些患者仍然可能受益，而另一些患者更有可能受到伤害。此外，这些患者亚组可以根据治疗前的临床特征来识别，但只有在同时考虑多种特征的情况下才能识别。 基于我们的数学模型，确定了哪些AIS患者具有良好的TT风险-收益特征，并与经验丰富的人为因素工程师和最终用户(即中风神经科医生和急诊医生)密切合作，我们建议开发一套工具，整合到基于计算机的决策支持工具(CDS1)中，以供实时使用。CDSI的核心组件是患者选择模块，以帮助选择具有良好的TT风险-收益概况的患者。 因此，该项目的具体目标是： 1.将我们开发的用于患者选择的数学模型整合到可用的CDSI中。 2.通过迭代设计周期，包括几个阶段的可用性测试，将这个原型开发成一个全面的决策支持工具，具有设计良好的用户界面，很好地集成到通常的工作流程中，并支持对急性中风护理至关重要的一系列功能。 3.计划开展一项先导性研究，以评估“实时辅助多维患者选择”的可行性，以选择在发病3小时以上治疗时可能受益于TT的AIS患者。 虽然这项研究的结果应该对在AIS中使用TT有重要的意义，但我们预计这种“辅助多维患者选择”的新方法可能会在许多领域产生深远的影响，特别是对于风险和收益得到很好平衡的治疗。

DESCRIPTION (provided by applicant): Intravenous thrombolytic therapy (TT) improves outcomes in acute ischemic stroke (AIS), when delivered within 3 hours of symptom-onset Yet, despite the overall benefits, there remains a significant risk of thrombolytic-related intracranial hemorrhage (ICH), even within the 3-hour time frame. And multiple trials including patients beyond this time-window have failed to find benefit for TT in AIS. In part because of the narrow time-window of therapeutic opportunity, less than 5% of all AIS patients are currently treated with TT. Our preliminary work has demonstrated that the absence of overall benefit from TT when administered after 3 hours from symptom-onset obscures the fact that some patients are still likely to benefit, while others are more likely to be harmed. Further, these patient sub-groups can be identified on the basis of pre-treatment clinical characteristics, but only when multiple characteristics are considered simultaneously. Based on our mathematical models that identify patients with AIS who have a favorable risk-benefit profile for TT, and working closely with experienced human factors engineers and the ultimate end-users (ie stroke neurologists and emergency physicians), we propose to develop a set of tools incorporated into a computer-based decision-support instrument (CDS1) for use in real time. The core component of this CDSI is the patient-selection module, to help select patients with a favorable risk-benefit profile for TT. Thus, the specific aims of this project are: 1. To incorporate our developed mathematical models for patient-selection into a usable CDSI. 2. Through an iterative design cycle, including several phases of usability testing, to develop this prototype into a comprehensive decision-support instrument with a well-designed a user interface, well-integrated into usual work-flow, and supporting a range of functions important for acute stroke care. 3. To plan a pilot study to evaluate the feasibility of "real-time assisted multi-dimensional patient selection" to select AIS patients who may benefit from TT when treated more than 3 hours from symptom-onset. While the results of this study should have important implications for the use of TT in AIS, we anticipate that this new method of "assisted multi-dimensional patient-selection" may have profound implications in many areas, especially for treatments in which the risks and the benefits are finely balanced.