Computerized Cognitive Rehabilitation in Children after Severe Malaria

描述（由申请人提供）：研究主题：我们在乌干达之前的工作中记录了四分之一的脑疟疾（CM）学龄幸存者在患病两年后仍有持续的注意力、记忆或学习障碍。目前没有可行的治疗方法来预防这些残疾，每年在撒哈拉以南非洲有数十万儿童受到影响。150名严重疟疾幸存者（5至12岁）和150名从其家庭中招募的健康社区对照（CC）儿童将成为我们的研究参与者。其中50名儿童将被随机挑选出来，接受名为“船长日志”（Captain’s Log）的电脑认知康复治疗（CCRT）项目的24次培训，该项目主要面向有注意力和/或学习问题的美国儿童。主动控制组将使用船长日志的锁定版本，该版本没有以渐进的方式指导孩子的训练，而被动控制组则不进行干预。孩子们将在家中或附近的诊所接受训练，由现场教练监督。研究目的1：评估CCRT在改善乌干达严重疟疾存活儿童的神经心理表现和精神预后方面的有效性。研究目的2：评估疟疾疾病的严重程度（例如，免疫性脑炎、脑电图异常）是否可预测CCRT的神经心理学益处。结果评估：在8周训练前后和1年随访时，采用考夫曼儿童评估量表第2版（kbc -2）、视觉和听觉注意变量测试（TOVA）、CogState计算机化神经心理筛查测试、bruinink - oseretsky运动能力测试（第2版）和Achenbach儿童行为检查表（CBCL）。学业成绩的改善也将被评估。我们以前曾对患有慢性脊髓炎或艾滋病毒的乌干达儿童进行所有这些评估，以有效地评估神经心理和精神问题，并记录CCRT的有效性。船长日志有一个内部评估器功能，它将帮助我们监控孩子们对具体训练任务的最佳反应。根据我们之前对CM幸存者和HIV儿童的CCRT干预研究，我们期望CCRT在改善注意力、记忆和学习方面有效；我们的评估将足够敏感，以记录神经心理学和精神病学的益处。分析：我们将比较在8周的CCRT和1年的随访中，我们的干预组在严重疟疾和对照儿童（3 × 2 ANCOVA控制家庭环境质量）中的神经心理学和精神病学的收益。对于接受CCRT干预的儿童，这些收益将显著增加（研究目标1）。疟疾疾病期间更严重的免疫和脑电图指标将显示更需要改进CCRT（研究目标2）。结论：CCRT在重症疟疾康复治疗中具有良好的效果和可持续性。CCRT和计算机认知测试将证明在资源贫乏环境中治疗儿童是可行的。

DESCRIPTION (provided by applicant): Research Topic: We have documented in our prior work in Uganda that 1 out of 4 school-age survivors of cerebral malaria (CM) has persisting attention, memory, or learning impairment two years after illness. No viable treatment presently exists to prevent these disabilities, and hundreds of thousands of children are affected each year in sub-Sahara Africa. One hundred and fifty severe malaria survivors (5 to 12 yrs of age), and 150 healthy community control (CC) children recruited from their households will be our study participants. Fifty of these children will be randomly selected to receive 24 training sessions of a computerized cognitive rehabilitation therapy (CCRT) program called Captain's Log, marketed mostly for American children with attention and/or learning problems. A locked version of Captain's Log which does not direct the child's training in a progressive manner will be administered to an active control group, and no intervention for the passive control group. Children will undergo training in their homes or in a nearby clinic supervised by a field trainer. Study Aim 1: To evaluate the effectiveness of CCRT in improving neuropsychological performance and psychiatric outcomes in Ugandan children who survive severe malaria. Study Aim 2: To evaluate whether severity of malaria illness (e.g., immunological brain inflammation, EEG abnormalities) is predictive of neuropsychological benefit from CCRT. Outcome Assessments: The Kaufman Assessment Battery for Children, 2nd ed. (KABC-2), visual and auditory Tests of Variables of Attention (TOVA), CogState computerized neuropsychological screening test, Bruininks-Oseretsky Test of Motor Proficiency (2nd edition), and Achenbach Child Behavior Checklist (CBCL) will be administered before and after the 8-week training period and at 1-yr follow-up. Improvements in academic performance will also be evaluated. We have previously used all these assessments with Ugandan children surviving CM or with HIV to effectively evaluate neuropsychological and psychiatric problems, and to document the effectiveness of CCRT. Captain's Log has an internal evaluator feature which will help us monitor the specific training tasks to which the children best respond. Based on our prior research with CCRT intervention with CM survivors and in children with HIV, we expect CCRT to be effective in improving attention, memory, and learning; and that our assessments will be sensitive enough to document neuropsychological and psychiatric benefit. Analyses: We will compare neuropsychological and psychiatric gains over the 8-weeks of CCRT and at 1-yr follow-up for our intervention groups across the severe malaria and control children (3 by 2 ANCOVA controlling for quality of home environment). These gains will be significantly greater for the CCRT intervention children (Study Aim 1). More severe immunological and EEG indicators during malaria illness will show greater need for an improvement from CCRT (Study Aim 2). Conclusion: CCRT will prove effective and sustainable in rehabilitation for severe malaria. CCRT and computerized cognitive tests will prove viable for treating children in resource-poor settings. PUBLIC HEALTH RELEVANCE: Severe malaria is the single greatest cause of mortality and morbidity in African children less than 5 yrs and malarial illness as a leading cause of neurodisability leaves 1 in 4 survivors with cognitive impairment at some level. Therefore, severe malaria as a disease provides a rich source of attention and working memory impairment upon which to evaluate computerized cognitive rehabilitation training (CCRT) programs specifically designed and prescribed to treat these needs in American children. Furthermore, our CCRT clinical study has overarching scientific value in allowing us to differentiate cognitive performance domains more proximal to CNS disease and amenable to CCRT treatment, from the more pervasive and distal brain/behavior developmental effects of impoverishment in general.