Assessment of Dehydration in Children with Diarrhea in Resource-Limited Settings

描述(申请人提供)：腹泻每年导致近200万五岁以下儿童死亡，占全球儿童死亡总数的五分之一。由于疾病的严重程度取决于液体丢失的程度，准确评估脱水状态仍然是预防发病率和死亡率的关键步骤。虽然严重脱水的儿童需要立即静脉输液治疗，以防止血液动力学损害和死亡，但与昂贵的静脉输液治疗相比，轻度至中度脱水的儿童住院时间显著缩短，不良事件也较少。虽然世界卫生组织(WHO)建议使用四分临床评分来确定儿童脱水的严重程度，但该评分从未根据生理学金标准(如公认的补充水分后体重变化百分比标准)进行验证。虽然之前的几位作者已经开发了儿童严重脱水的替代临床预测规则，但这些量表尚未在发展中国家进行过生理学黄金标准的外部验证，因为绝大多数儿童腹泻死亡发生在发展中国家，临床医生的专业知识和不同的疾病模式可能会影响发达国家得出的任何临床量表的准确性。迫切需要研究新的临床工具，能够在资源有限的情况下准确和可靠地评估脱水情况。作为K01奖项的一部分，我们将进行一系列三项研究，以推导、验证和评估发展中国家腹泻儿童严重脱水的新临床预测规则的可靠性。此外，我们将验证和评估下腔静脉(IVC)超声预测发展中国家腹泻儿童严重脱水的可靠性。最后，我们将把每一种新诊断工具的准确性与世界卫生组织的标准进行比较，使用体重变化百分比和再水化作为我们所有脱水措施的黄金标准，以确定这些新方法中的任何一种是否可以改善目前的护理标准。我之前的培训和研究经验为我获得这个职业发展奖奠定了坚实的基础。我在加州大学旧金山分校获得了医学博士学位，在加州大学伯克利分校获得了国际卫生公共卫生硕士学位。我还拥有设计和管理两项在资源有限的情况下进行的小型研究的经验，其中一项研究为国际研究科学家发展奖(IRSDA)的申请提供了初步数据。然而，我将受益于特定领域的其他有针对性的培训，包括高级回归分析和递归分区、临床试验设计和管理、成本效益分析、腹泻和营养不良的病理生理学，以及在资源有限的情况下进行研究的伦理，这些培训将在K01奖的五年期间通过正式课程、研讨会、定向阅读和个性化教程完成。我还将受益于在三位在进行公共卫生和全球卫生研究方面拥有丰富经验的科学家的指导下管理大型前瞻性研究的额外经验，这些科学家包括布朗医学院的Jennifer Friedman博士、孟加拉国国际腹泻病和研究中心(ICDDRB)的Nur Haque Alam博士和哈佛大学公共卫生学院的Earl F.Cook博士。在K01获奖后，我计划申请R01赠款，以资助一项随机对照试验，将这些诊断和管理腹泻儿童脱水的新方法与当前的护理标准进行比较，分析与健康相关的结果，如不良事件和总成本。改进的评估严重脱水的方法有可能帮助发展中国家的临床医生识别最需要紧急干预的腹泻儿童，同时还可以防止与不适当使用静脉输液相关的不良事件和资源浪费。这些新方法有可能改善发达国家和发展中国家医院和诊所以及在腹泻疾病暴发常见的难民营环境中提供护理的情况。除了资助开发这些新方法的研究外，IRSDA还将为我提供必要的支持，以启动我作为一名独立资助的全球卫生研究领域的内科科学家的职业生涯。利用作为IRSDA一部分获得的知识和技能，我致力于一项旨在改善在资源有限的情况下诊断和管理脱水的证据基础的职业，从而提高护理的效力和成本效益，并可能每年挽救数千人的生命。

DESCRIPTION (provided by applicant): Diarrhea causes nearly two million deaths annually in children under five, or one fifth of all child deaths worldwide. As the severity of the disease depends on the degree of fluid loss, accurately assessing dehydration status remains a crucial step in preventing morbidity and mortality. While children with severe dehydration require immediate treatment with intravenous fluids to prevent hemodynamic compromise and death, children with mild to moderate dehydration have a significant reduction in hospital length of stay and fewer adverse events when treated with relatively inexpensive oral rehydration solution (ORS) as compared to treatment with costly intravenous fluids. While the World Health Organization (WHO) recommends using a four-point clinical scale for determining the severity of dehydration in children, this scale has never been validated against a physiologic gold standard (such as the accepted standard of percent weight change with rehydration). While several prior authors have developed alternative clinical prediction rules for severe dehydration in children, these scales have not been externally validated against a physiologic gold standard in a developing country, where the vast majority of pediatric deaths from diarrhea occur, and where clinician expertise and varying disease patterns may affect the accuracy of any clinical scale derived in a developed country. There is an urgent need for research into new clinical tools that can accurately and reliably assess dehydration in a resource-limited setting. As part of this K01 award, we will conduct a series of three studies that will derive, validate, and assess the reliability of a new clinical prediction rule for severe dehydration in children with diarrhea in te developing world. In addition, we will validate and assess the reliability of ultrasound of the inferior vena cava (IVC) for predicting severe dehydration in children with diarrhea in the developing world. Finally, we will compare the accuracy of each of these new diagnostic tools to that of the WHO scale, using percent weight change with rehydration as the gold standard for all of our measures of dehydration, in order to determine whether either of these new methods may improve upon the current standard of care. My prior training and research experience have provided me with a solid foundation for this career development award. I have completed a Doctorate of Medicine at the University of California, San Francisco and a Masters of Public Health in International Health at the University of California, Berkeley. I also have experience designing and managing two small research studies conducted in resource-limited settings, including one study providing preliminary data for this International Research Scientist Development Award (IRSDA) application. However, I would benefit from additional targeted training in specific areas, including advanced regression analysis and recursive partitioning, clinical trial design and management, cost- effectiveness analysis, the pathophysiology of diarrhea and malnutrition, and the ethics of conducting research in resource-limited settings, which will be completed during the five years of this K01 award through formal coursework, seminars, directed reading, and individualized tutorials. I will also benefit from the additional experience of managing large, prospective studies under the mentorship of three scientists with extensive experience in conducting public health and global health research, including Dr. Jennifer Friedman of Brown Medical School, Dr. Nur Haque Alam of the International Center for Diarrheal Disease and Research, Bangladesh (ICDDRB), and Dr. Earl F. Cook of the Harvard School of Public Health. After this K01 award, I plan to apply for an R01 grant to fund a randomized controlled trial comparing these new methods for diagnosing and managing dehydration in children with diarrhea to the current standard of care, analyzing both health-related outcomes, such as adverse events, and total costs. Improved methods for assessing severe dehydration have the potential to help clinicians in the developing world identify the children with diarrhea at greatest need for emergent intervention, while also preventing the adverse events and wasted resources associated with the inappropriate use of intravenous fluids. These new methods have the potential to improve the delivery of care in both developed and developing country hospitals and clinics, as well as in refugee camp settings where outbreaks of diarrheal disease are common. In addition to funding research into the development of these new methods, the IRSDA will also provide me with the support necessary to launch my career as an independently funded physician-scientist in translational global health research. Utilizing the knowledge and skills gained as part of the IRSDA, I am committed to a career aimed at improving the evidence base for the diagnosis and management of dehydration in resource-limited settings, thereby improving both the effectiveness and cost- effectiveness of care and potentially saving thousands of lives each year.