Therapies to Restore Consciousness in Patients with Severe Brain Injuries: A Gap Analysis and Future Directions.
Therapies to Restore Consciousness in Patients with Severe Brain Injuries: A Gap Analysis and Future Directions.
复制标题
DOI：
10.1007/s12028-021-01227-y
复制
发表时间：
2021-07
影响因子：
3.5
通讯作者：
Curing Coma Campaign and its contributing members
中科院分区：
文献类型：
--
作者：
Edlow BL;Sanz LRD;Polizzotto L;Pouratian N;Rolston JD;Snider SB;Thibaut A;Stevens RD;Gosseries O;Curing Coma Campaign and its contributing members
对于意识障碍（DoC）患者及其家属来说，寻找新的治疗方法一直是希望和挫折的源泉。几乎所有针对DoC患者的临床试验都受到样本量小、缺乏安慰剂组和使用异质性结果测量的限制。因此，很少有疗法有强有力的证据支持其使用；金刚烷胺是目前临床指南中唯一推荐的治疗方法，特别是对于严重创伤性脑损伤引起的DoC患者。为了促进和推进对DoC患者的意识促进疗法的发展，治愈昏迷运动召集了一个昏迷科学工作组来进行差距分析。我们考虑了五类治疗方法：(1)药理学；(2)电磁;(3)机械;(4)感觉;(5)再生。对于每一类治疗，我们总结了科学的现状，确定了知识上的差距，并提出了治疗发展的未来方向。所有五个治疗类别的知识差距可归因于缺乏：(1)评估治疗作用机制的统一概念框架；(2)大规模随机对照试验；(3)在早期试验中测量亚临床治疗效果的药效学生物标志物。为了解决这些差距，我们提出了一种精准医学方法，在这种方法中，临床试验根据患者对靶向治疗的生理接受度选择性地招募患者，并通过补充行为、神经成像和电生理终点来测量治疗效果。这种个性化的方法可以通过严格的临床试验设计和国际合作来实现，这两者对于推进新疗法的发展并最终改善DoC患者的生活至关重要。在线版本包含补充材料，可在10.1007/s12028-021-01227-y获得。
For patients with disorders of consciousness (DoC) and their families, the search for new therapies has been a source of hope and frustration. Almost all clinical trials in patients with DoC have been limited by small sample sizes, lack of placebo groups, and use of heterogeneous outcome measures. As a result, few therapies have strong evidence to support their use; amantadine is the only therapy recommended by current clinical guidelines, specifically for patients with DoC caused by severe traumatic brain injury. To foster and advance development of consciousness-promoting therapies for patients with DoC, the Curing Coma Campaign convened a Coma Science Work Group to perform a gap analysis. We consider five classes of therapies: (1) pharmacologic; (2) electromagnetic; (3) mechanical; (4) sensory; and (5) regenerative. For each class of therapy, we summarize the state of the science, identify gaps in knowledge, and suggest future directions for therapy development. Knowledge gaps in all five therapeutic classes can be attributed to the lack of: (1) a unifying conceptual framework for evaluating therapeutic mechanisms of action; (2) large-scale randomized controlled trials; and (3) pharmacodynamic biomarkers that measure subclinical therapeutic effects in early-phase trials. To address these gaps, we propose a precision medicine approach in which clinical trials selectively enroll patients based upon their physiological receptivity to targeted therapies, and therapeutic effects are measured by complementary behavioral, neuroimaging, and electrophysiologic endpoints. This personalized approach can be realized through rigorous clinical trial design and international collaboration, both of which will be essential for advancing the development of new therapies and ultimately improving the lives of patients with DoC. The online version contains supplementary material available at 10.1007/s12028-021-01227-y.
登录
查看更多内容
DOI：
10.1017/s1472928807000325
发表时间：
2008-03
期刊：
Thalamus & related systems
影响因子：
--
作者：
Blethyn, Kate L;Hughes, Stuart W;Crunelli, Vincenzo
通讯作者：
Crunelli, Vincenzo
影响因子：
4.2
作者：
Baguley, Ian J.;Perkes, Iain E.;Hendricks, Henk T.
通讯作者：
Hendricks, Henk T.
影响因子：
3.1
作者：
Battistella G;Najdenovska E;Maeder P;Ghazaleh N;Daducci A;Thiran JP;Jacquemont S;Tuleasca C;Levivier M;Bach Cuadra M;Fornari E
通讯作者：
Fornari E
影响因子：
9.9
作者：
Baloh, RW
通讯作者：
Baloh, RW
探索人类大脑功能的科学
DOI：
10.1073/pnas.0911855107
发表时间：
2010-03-09
影响因子：
11.1
作者：
Biswal, Bharat B.;Mennes, Maarten;Milham, Michael P.
通讯作者：
Milham, Michael P.