Intracerebral hemorrhage (ICH) is a form of stroke characterized by uncontrolled bleeding into the parenchyma of the brain. There is no approved therapy for ICH and it is associated with very poor neurological outcomes with around half of subjects dying within 1 month and most subjects showing complete or partial disability. A key challenge is to identify subjects who could benefit from intervention using characteristics such as baseline hemorrhage volume and the increase in hemorrhage volume in the first few hours, which have been correlated with final outcomes in ICH. Combined longitudinal models were developed to describe stroke scales using categorical data (Modified Rankin Scale, mRS), continuous bounded data (National Institutes of Health Stroke Scale, NIHSS), and time to death. Covariate effects for baseline hematoma volume and maximum increase in hematoma volume were incorporated to assess the improvement in outcome when hematoma volume increase would be reduced by a potential treatment. The combined model provided an adequate description of stroke scales, with patients split into a Non-survival and a High-survival sub-population, and dropout due to death was well described by a constant hazard survival model. Models were compared indicating that the combined mRS/NIHSS model provided the most information, followed by the NIHSS-only model, and the mRS-only model, and finally the traditional statistical analysis on dichotomized response at 90 days. Simulations showed that substantial reductions in hematoma volume increase were required to increase the probability of a favorable outcome.

中文翻译：

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对脑出血中的改良兰金量表和美国国立卫生研究院卒中量表神经系统终点进行建模和仿真。

脑出血（ICH）是中风的一种形式，其特征是无法控制的出血进入脑实质。尚无批准的ICH治疗方法，它与非常差的神经系统结局有关，约一半的受试者在1个月内死亡，大多数受试者表现出完全或部分残疾。一个关键的挑战是使用基线出血量和前几个小时的出血量增加等特征来识别可从干预中受益的受试者，这些特征与ICH的最终结局相关。开发了组合纵向模型，以使用分类数据（改良的Rankin量表，mRS），连续有界数据（美国国立卫生研究院卒中量表，NIHSS）和死亡时间来描述卒中量表。纳入基线血肿量和血肿量最大增加的协变量效应，以评估当潜在治疗可减少血肿量增加时的预后改善。组合模型提供了对卒中量表的充分描述，将患者分为非存活和高存活亚人群，而恒定危险生存模型很好地描述了由于死亡而导致的辍学。比较模型表明，组合的mRS / NIHSS模型提供最多的信息，其次是仅NIHSS模型和仅mRS模型，最后是传统的90天二分法反应统计分析。模拟显示血肿体积增加的实质性减少需要增加有利结果的可能性。