Mentoring patient-oriented researchers in pediatric diarrhea

项目摘要 腹泻是全球幼儿非新生儿死亡的第二大常见原因， 也是发病的主要原因。目前腹泻的病原学诊断依赖于微生物检测，并且 抗生素的决定通常是经验性的。然而，大多数腹泻病例并没有受益于 抗生素的使用和对所有潜在病原体的检测在财务上和后勤上都是不可行的。因此， 改进小儿腹泻病的临床治疗方法，包括抗菌药策略 和诊断管理，是必要的。临床预测规则是满足这一需求的潜在工具，并且 在K24应用程序中，我们的总体目标是探索改善腹泻临床决策的策略 通过使用时空数据和生物标志物进行管理。私人侦探梁博士是一位内科科学家 接受临床传染病、免疫学、微生物学和流行病学方面的培训，重点是 肠道感染，特别是那些在资源有限的环境中导致儿童腹泻的感染。他有 自年开始独立研究计划以来，指导了40多名以患者为导向的研究人员(PORS) 2014年；此外，他还与科学家和临床医生合作指导了许多Pors 在低收入和中等收入国家。利用NIH资助的三个正在进行中的基础设施 奖项(R01AI130378，R01AI135114，R01AI135115)，以及盖茨基金会资助的研究，他 建议通过解决以下目标来扩大他目前的POR：1)审查空间- 儿童腹泻的个体水平临床预测的时间数据，其中使用A)血清监测， B)分子诊断，以及C)将探索来自地球观测的数据，以及2)确定临床用途- 补充临床决策支持工具的粪便生物标记物的病例和潜在候选者 儿童腹泻的管理，使用两种定性方法来检查最终用户的观点和 确定用例，以及代谢组学和转录组学方法，以确定候选生物标记物。至 为了实现这些目标，他建立了一支由经验丰富的调查人员组成的共同指导团队，他们具有不同的 在统计方法、生物标记物发现和指导POR调查人员方面的专业知识。这一奖项将 为梁博士提供有保障的时间，以改善和增加他对POR学员的指导能力，扩大 他在生物信息学方面的专业知识和经验，并为未来的项目生成数据，以改善 儿童腹泻感染的管理和知识。

Project Summary Diarrheal illness is the second most common cause of non-neonatal death among young children worldwide, and is a major cause of morbidity. Current etiologic diagnosis of diarrhea relies on microbial detection, and decisions for antibiotics commonly empiric. However, the majority of cases of diarrhea do not benefit from antibiotic use, and testing for all potential pathogens is neither financially nor logistically feasible. Thus, methods to improve the clinical management of pediatric diarrheal illness, including strategies for antimicrobial and diagnostic stewardship, are needed. Clinical prediction rules are potential tools to address this need, and in this K24 application, our overall goal is to explore strategies to improve clinical decision-making for diarrhea management, through use of spatial-temporal data and biomarkers. Dr. Leung, the PI, is a physician-scientist with training in clinical infectious diseases, immunology, microbiology, and epidemiology, with a focus on enteric infections, especially those that cause diarrheal illness in children in limited-resource settings. He has mentored over 40 patient-oriented researchers (PORs) since the start of his independent research program in 2014; additionally, he has co-mentored numerous PORs in collaboration with scientists and clinicians working in low- and middle-income countries. Leveraging infrastructure already in place from three ongoing NIH-funded awards (R01AI130378, R01AI135114, R01AI135115), as well as Gates Foundation-funded studies, he proposes to augment his current POR by addressing the following aims: 1) To examine the use of spatial- temporal data for individual-level clinical prediction of pediatric diarrhea, where the use of A) serosurveillance, B) molecular diagnostic, and C) earth observation-derived data will be explored, and 2) To identify clinical use- cases, and potential candidates, of fecal biomarkers that complement clinical decision support tools for management of pediatric diarrhea, using both qualitative methods to examine end-user perspectives and identify use-cases, and metabolomics and transcriptomics methods to identify candidate biomarkers. To accomplish these aims, he has established a co-mentoring team of experienced investigators with diverse expertise in statistical methods, biomarker discovery, and mentoring of POR investigators. This award will provide protected time for Dr. Leung to improve and increase his mentoring capacity of POR trainees, expand his expertise and experience in bioinformatics, and generate data for future projects to improve the management and knowledge of pediatric diarrheal infections.