Dose-Response of Movement Practice During Stroke Rehabilitation

描述（由申请人提供）：剂量已成为促进卒中后功能恢复的关键因素。目前，缺乏关于剂量-反应关系的数据阻碍了中风康复领域的进展。该项目的目标是确定运动练习的剂量范围，以最大限度地改善慢性中风患者的预后。借用中风的动物模型，人类的剂量可以通过特定任务练习的重复次数来量化。我们的中心假设是，中风患者存在一个剂量范围，低于该范围，益处最小，高于该范围，进一步的实践不会产生进一步的益处。有益剂量的范围可能会根据运动缺陷的严重程度和其他领域中存在的非运动缺陷而有所不同。采用随机、平行剂量-反应设计，我们将在100名慢性卒中患者中评估四种不同剂量的任务特异性上肢训练的益处，这些训练具有匹配的时间表，1小时训练，4次/周，持续8周。待评估的总重复剂量（3200、6400、9600和个体化最大剂量）基于我们的初步数据。个体化最大值组可将其疗程延长至8周以上，直至达到规定的停药标准。我们的主要目标是测试较大的总剂量是否比较小的总剂量产生更好的结果。四种剂量的益处将在损伤、活动和参与水平上进行评估，因为了解所有测量水平上的剂量反应关系对于推进康复研究至关重要。我们假设9600和个体化最大剂量组的改善最大，其次是6400，然后是3200重复剂量组。我们的第二个目标是描述上肢特定任务练习的剂量-反应关系。使用来自多个评估点的数据，将使用个体曲线建模来估计剂量范围，低于该剂量范围，获益最小，高于该剂量范围，进一步的实践不会产生进一步的获益。此外，我们将确定各种因素如何修改剂量估计值。我们假设运动缺陷的严重程度将是剂量-反应关系的主要修正因素，对于那些运动缺陷较轻的患者，需要更大的剂量。我们进一步预计，对于那些患有抑郁症和半侧空间忽视的人来说，所需的剂量将更大。我们的团队能够很好地调查剂量的关键问题，因为我们在中风康复研究和测量方面的专业知识，我们对临床实践和临床研究挑战的理解，以及我们随时可以接触到这一患者群体。该项目的预期结果是由患者驱动的估计值，表明驱动最大改善所需的运动练习剂量，以及如何针对接受卒中康复的患者单独修改这些估计值。我们的估计将立即影响康复研究和临床实践。该项目的重要性超越了中风康复;我们的主要结果对许多其他康复人群也具有很高的价值，这些人群也受到缺乏剂量-反应关系知识的阻碍。

DESCRIPTION (provided by applicant): Dose has emerged as a key factor promoting functional recovery after stroke. Currently, a lack of data on the dose-response relationship impedes progress in the field of stroke rehabilitation. The goal of the proposed project is to define the range of doses of movement practice that produce the greatest improvements in outcomes in people with chronic stroke. Borrowing from animal models of stroke, dose in humans can be quantified by the number of repetitions of task-specific practice. Our central hypothesis is that there exists a range of doses for people with stroke, below which, there is minimal benefit, and above which, further practice does not result in further benefit. The range of beneficial doses is likely to vary based on the severity of motor deficits and the presence of non-motor deficits in other domains. Using a randomized, parallel dose-response design, we will evaluate the benefits of four different doses of task-specific upper extremity training with matched schedules of 1 hr sessions, 4 sessions/wk for 8 wks, in 100 people with chronic stroke. Total repetition doses to be evaluated (3200, 6400, 9600, & individualized-maximum) are based on our preliminary data. The individualized-maximum group may extend their sessions beyond 8 wks until meeting defined stop criteria. Our primary aim will test whether larger total doses result in better outcomes than smaller total doses. Benefits of the four doses will be evaluated at the impairment, activity, and participation levels, since understanding the dose-response relationship at all levels of measurement is critical for advancing rehabilitation research. We hypothesize that improvements will be greatest in the 9600 and individualized-maximum, followed by the 6400, and then the 3200 repetition dose groups. Our secondary aim is to characterize the dose-response relationship of upper extremity task-specific practice. With data from multiple assessment points, individual curve modeling will be used to estimate dose ranges, below which, there is minimal benefit, and above which, further practice does not result in further benefit. Furthermore, we will determine how various factors modify the dose estimates. We hypothesize that the severity of motor deficits will be the primary modifier of the dose- response relationship, with larger doses needed for those with more mild motor deficits. We further expect that needed doses will be larger for those with depression and hemispatial neglect. Our team is well-positioned to investigate the critical issue of dose because of our expertise in stroke rehabilitation research and measurement, our understanding of the challenges of clinical practice and clinical research, and our ready access to this patient population. Expected outcomes from this project are empirically-driven estimates indicating the dose of movement practice required to drive maximal improvements and how these estimates can be individually modified for people undergoing stroke rehabilitation. Our estimates will immediately impact rehabilitation research and clinical practice. The importance of this project transcends stroke rehabilitation; our primary results will be of high value to many other rehabilitation populations also impeded by the lack of knowledge regarding dose-response relationships.