Extending Safe and Effective Thrombolysis for Stroke

描述（由申请人提供）：静脉溶栓治疗（TT）在急性缺血性卒中（AIS）发作后3小时内给药可改善结局。然而，尽管总体获益，但即使在3小时内，仍存在溶栓相关颅内出血（ICH）的显著风险。包括超过这个时间窗的患者在内的多项试验未能发现TT在AIS中的益处。部分由于治疗机会的时间窗较窄，目前所有AIS患者中只有不到5%接受TT治疗。 我们的初步工作已经证明，当在发病3小时后给药时，TT没有总体获益，这掩盖了一个事实，即一些患者仍然可能受益，而另一些患者更可能受到伤害。此外，这些患者亚组可以根据治疗前的临床特征进行识别，但仅当同时考虑多种特征时。 基于我们的数学模型，识别出具有良好TT风险-获益特征的AIS患者，并与经验丰富的人为因素工程师和最终用户（即卒中神经学家和急诊医生）密切合作，我们建议开发一套纳入基于计算机的决策支持工具（CDS 1）的工具，以供真实的使用。该CDSI的核心组件是患者选择模块，以帮助选择具有良好TT风险-获益特征的患者。 因此，该项目的具体目标是： 1.将我们开发的患者选择数学模型纳入可用的CDSI。 2.通过迭代设计周期（包括几个可用性测试阶段），将该原型开发为具有精心设计的用户界面的综合决策支持工具，该工具可很好地集成到日常工作流程中，并支持急性卒中护理的一系列重要功能。 3.计划一项试点研究，以评估“实时辅助多维患者选择”的可行性，以选择在发病后超过3小时接受治疗时可能从TT中获益的AIS患者。 虽然这项研究的结果应该对TT在AIS中的使用具有重要意义，但我们预计这种“辅助多维患者选择”的新方法可能在许多领域产生深远的影响，特别是对于风险和获益得到精细平衡的治疗。

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.