Sepsis online: learning while doing to understand biology and treatment

项目概要/摘要 每年有超过100万美国人因败血症住院，近1/ 五个人不能活下来大多数减少败血症死亡的努力开始的前提是， 患者在很大程度上是相似的，乙醚移动治疗早期或靶向 单一机制的治疗将改善结果。在以前的工作中， NIGMS R35奖，我们使用一套机器学习来推导脓毒症内型 电子健康记录（EHR）在一个大型的综合卫生系统内的方法。 这些内型在生物学、结果和治疗反应方面不同， 在成千上万的患者中重现。但是，它们将如何实现精准护理？在这 更新，我们将利用我们的临床转化实验室和残余血液 收集，以更好地了解脓毒症内源性的生物学，并探索新的 与病原体、微生物组和分子机制相关的领域。我们将使用 贝叶斯因果网络和强化学习优化治疗策略， 超过1000万次EHR遭遇中的内型。最后，我们将把学习搬到网上 并在护理点将内型嵌入EHR中。这些步骤将使 脓毒症内型科学，并在时间压力下做出临床决策， 不确定性通过在“活边”测试内型治疗政策，我们将加强 因果推理，机械洞察力，边做边学。我的计划将是 由外部顾问委员会监督，他们在机器学习，炎症， 免疫学，计算和系统生物学，因果方法，人工智能， 和健康信息技术。这项工作将进一步发展我的临床翻译 实验室和跨领域指导初级科学家。

PROJECT SUMMARY / ABSTRACT More than 1 million Americans are hospitalized with sepsis each year, and nearly one in five don’t survive. Most efforts to reduce sepsis deaths begin with the premise that patients are largely similar, and that ether moving treatment earlier or targeting therapeutics to a single mechanism will improve outcomes. In prior work funded by a NIGMS R35 award, we derived sepsis endotypes using a suite of machine learning methods inside the electronic health records (EHR) in a large integrated health system. These endotypes differed in biology, outcomes, and treatment response, and were reproduced in thousands of patients. But how will they lead to precision care? In this Renewal, we will leverage our clinical translational laboratory and remnant blood collection to better understand the biology of sepsis endotypes and explore new domains related to pathogen, microbiome, and molecular mechanisms. We will use Bayesian causal networks and reinforcement learning to optimize treatment policies over endotypes in more than 10 million EHR encounters. Finally, we will move learning online and embed endotypes inside the EHR at the point-of-care. These steps will take the science of sepsis endotypes and inform clinical decisions made under time pressure and uncertainty. By testing endotype treatment policies at the “live-edge”, we will strengthen causal inference, mechanistic insight, and learn while doing. My program will be supervised by external advisory boards with expertise in machine learning, inflammation, immunology, computational and systems biology, causal methods, artificial intelligence, and health information technology. This work will further develop my clinical-translational laboratory and cross-cutting mentorship of junior scientists.