Enriching Clinical Trials Enrolling Children With Cerebral Malaria Using Admission Demographics, Physical Examination and Point-of-care Testing Results.

IF 2.9 4区 医学 Q3 IMMUNOLOGY
Rami Imam, Kennedy M Chastang, Ronke Olowojesiku, Meredith G Sherman, Amina M Mukadam, John R Barber, Alice M Liomba, Karl B Seydel, Douglas G Postels
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Abstract

Background: Multiple clinical trials evaluating therapies for cerebral malaria (CM) have failed to demonstrate improved outcomes. This may derive from inclusion of children at all risk levels, including those at low risk of mortality or neurologic morbidity, limiting power to detect significant differences between intervention arms. One solution is enrichment, enrolling clinical trial participants at higher risk of adverse outcomes. We assessed if demographic, physical examination and point-of-care laboratory testing results in combination could identify children with CM at higher risk of death or neurologic disability.

Methods: Retrospective case-control study of 1674 children hospitalized with CM in Blantyre, Malawi. We used univariate and multivariate analyses of admission factors to find the most parsimonious model associated with death or neurologic disability. To assess the clinical utility of the models, we evaluated derived probability density curve separation.

Results: Blantyre Coma Score (BCS), deep breathing and high blood lactate were independently associated with mortality. The derived receiver operating curve yielded an area under the curve of 0.7118. There was poor separation of derived probability density curves predicting death or survival, indicating limited clinical utility of this model. On multivariate modeling of neurologic sequelae in CM survivors, only BCS was associated with adverse outcomes (area-under-the-curve = 0.6151). Probability density curves again largely overlapped, demonstrating limited utility of BCS alone in outcome prediction.

Conclusions: Combinations of admission demographic, clinical and point-of-care laboratory factors are inadequate to predict prognosis in children with CM. Higher technology assessment methods are necessary for clinical trial enrichment.

利用入院人口统计学数据、体格检查和床旁检测结果丰富脑疟疾患儿的临床试验。
背景:评估脑型疟疾(CM)疗法的多项临床试验均未能证明疗效有所改善。这可能是因为纳入了所有风险水平的儿童,包括死亡率或神经系统发病率较低的儿童,从而限制了检测干预措施之间显著差异的能力。解决方法之一是丰富临床试验,即纳入不良后果风险较高的临床试验参与者。我们评估了将人口统计学、体格检查和护理点实验室检测结果结合在一起能否识别出死亡或神经系统残疾风险较高的儿童慢性阻塞性肺病患者:方法:对马拉维布兰太尔市住院的 1674 名儿童进行回顾性病例对照研究。我们对入院因素进行了单变量和多变量分析,以找到与死亡或神经系统残疾相关的最合理模型。为了评估这些模型的临床实用性,我们对衍生的概率密度曲线分离进行了评估:结果:布兰太尔昏迷评分(BCS)、深呼吸和高血乳酸与死亡率密切相关。推导出的接收者操作曲线的曲线下面积为 0.7118。推导出的预测死亡或存活的概率密度曲线分离度较差,表明该模型的临床实用性有限。在对 CM 幸存者的神经系统后遗症进行多变量建模时,只有 BCS 与不良后果相关(曲线下面积 = 0.6151)。概率密度曲线在很大程度上再次重叠,这表明仅用BCS预测结果的作用有限:结论:入院人口学、临床和护理点实验室因素的组合不足以预测CM患儿的预后。有必要采用更高的技术评估方法来丰富临床试验。
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来源期刊
CiteScore
6.30
自引率
2.80%
发文量
566
审稿时长
2-4 weeks
期刊介绍: ​​The Pediatric Infectious Disease Journal® (PIDJ) is a complete, up-to-the-minute resource on infectious diseases in children. Through a mix of original studies, informative review articles, and unique case reports, PIDJ delivers the latest insights on combating disease in children — from state-of-the-art diagnostic techniques to the most effective drug therapies and other treatment protocols. It is a resource that can improve patient care and stimulate your personal research.
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