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

Summary

Principal Investigator: ADAM CARL LEVINE
Abstract: 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. PUBLIC HEALTH RELEVANCE: Nearly two million children in developing countries die each year from severe dehydration due to diarrhea. This research aims to develop new and improved clinical and ultrasound-based methods for diagnosing severe dehydration in children with diarrhea. These new methods will help doctors and nurses in the developing world identify those children at greatest need for emergent intervention, prevent adverse events, and improve health outcomes, all while conserving scarce healthcare resources.
Funding Period: 2012-09-20 - 2017-06-30
more information: NIH RePORT

Detail Information

Research Grants30

  1. CANCER CENTER SUPPORT GRANT
    TONY R HUNTER; Fiscal Year: 2013
    ....
  2. BIOLOGY OF NEUROENDOCRINE PEPTIDES
    Marc R Montminy; Fiscal Year: 2013
    ..Specifying the contributions of the CRF family of ligands and receptors to the maintenance of homeostasis and to stress-linked allostasis may improve our ability to manage diseases, including mood and metabolic disorders ..
  3. Malaria Transmission and the Impact of Control Efforts in Southern Africa
    Peter C Agre; Fiscal Year: 2013
    ....
  4. Utility of Contact Investigation of Drug Susceptible and Resistant TB in Tanzani
    Elizabeth Fair; Fiscal Year: 2013
    ..The research will form the basis for a future R01 grant application to address the scientific basis of TB transmission and pathogenicity, specifically of drug-resistant M.tb strains. ..
  5. Maternal and Child Health Benefits from Reducing Household Air Pollution
    Patricia L Hibberd; Fiscal Year: 2013
    ..The goal of this proposal is to participate in the Global Network for Women's and Children's Health Research and to study whether cook stoves and fuel that reduce HAP can improve pregnancy outcomes and child health. ..
  6. University of Maryland Greenebaum Cancer Center Support Grant
    Kevin J Cullen; Fiscal Year: 2013
    ..Reflecting our remarkable and continued growth, UMGCC seeks to renew its CCSG to enhance and expand its efforts in high-quality and clinically relevant cancer research. ..
  7. Patient-oriented Research in Pediatric Diarrheal Diseases
    Christopher P Duggan; Fiscal Year: 2013
    ..This mid-career investigator award is needed to protect Dr. Duggan's time to mentor beginning investigators in patient-oriented nutrition research and to expand his research in diarrheal diseases.) ..
  8. The Role of Economic Evaluation in Translating HIV/AIDS Behavioral Interventions
    Jose Luis Burgos; Fiscal Year: 2013
    ..Moreover, the candidate's binational and ethnic minority background combined with the proposed training and research will support a career trajectory focused on vulnerable, underserved populations at risk for HIV infection. ..
  9. COBRE Center for Central Nervous System Function
    Jerome N Sanes; Fiscal Year: 2013
    ..The COBRE Center will leverage the administrative resources available through the Brown Institute for Brain Science to ensure efficient operation and coordinate with other brain science research activities at Brown. ..
  10. Pacific NorthWest Regional Center of Excellence (PNWRCE)
    Jay A Nelson; Fiscal Year: 2013
    ..pseudomallei host pathogen response during both the septicemic as well as the intracellular phases of the disease. ..
  11. Southeast Regional Centers of Excellence for Biodefense &Emerging Infectious Di
    Philip Frederick Sparling; Fiscal Year: 2013
    ..SERCEB brings new investigators to the biodefense effort through a combination of educational programs, support of innovative new projects, and the synergistic interactions among its world-class investigators. ..
  12. NUCLEAR STRUCTURE AND GENE EXPRESSION
    Janet L Stein; Fiscal Year: 2013
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  13. Rocky Mountain Regional Center of Excellence or Biodefense and Emerging Infectiou
    John T Belisle; Fiscal Year: 2013
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  14. Notch-Mediated Expansion of Cord Blood Progenitors for Stem Cell Transplant
    Colleen Delaney; Fiscal Year: 2013
    ..Our goal is to now determine the clinical efficacy of this approach in a phase II clinical trial. ..