Improving Diagnosis and Care for Critically-Ill Children: CTSA Connects the Dots

Mayo Clinic CTSA links key staff, lab and electronic resources

It's 2 a.m. in the neonatal intensive care unit (NICU). A three-pound, premature newborn suddenly spikes a high fever, signaling an inflammatory response. Pediatricians and nurses confer about the cause: is it sepsis, a life-threatening infection spreading through the baby's bloodstream, or is it a non-infectious cause? Sepsis calls for a course of high-powered intravenous antibiotics, while a non-infectious inflammation would be best treated with steroids. For this fragile infant, a timely diagnosis is essential — but standard blood cultures to diagnose sepsis take up to 48 hours to yield reliable results.

What if there was a way to rule out sepsis quickly and reliably? Enter Justin Juskewitch, a CTSA-sponsored M.D.-Ph.D. student at Mayo Graduate School. Juskewitch and his mentors, W. Charles Huskins, M.D., M.Sc., a pediatric infectious disease specialist, and Joseph Grande, M.D., Ph.D., a pathologist specializing in acute and chronic inflammation, are conducting clinical studies comparing standard blood cultures with a new test for sepsis that yields results in hours.

"We don't have a good idea of what pediatric sepsis looks like and this research will help address that issue," says Dr. Grande. "This research will yield more understanding of the underlying disease process in these patients. Moreover, individual immune markers have not proven useful to detect infection in these patients but multi-marker testing could meet this need."

Armed with an accurate diagnosis, doctors could treat sick infants and children with the most effective medications earlier, improving outcomes and avoiding unnecessary side effects.

Mayo Clinic's Center for Translational Science Activities (CTSA) has provided invaluable resources at every step in the translational chain from developing the biomarkers in mouse models to ongoing studies in the NICU. "Having an accurate set of biomarkers would allow physicians to target therapies only to the patients who need them, as well as identify patients who might benefit from new treatments for sepsis," says Dr. Huskins. "We believe the methods used in this study are applicable to other research projects involving the study of labile biomarkers in hospitalized children."

Patient-Centered Research: The Heart of Translation

Juskewitch's team seeks to ensure the best possible care for patients, and the test they are evaluating uses very small quantities of blood — as little as one-quarter teaspoon — to look for the biomarkers they are measuring. This is especially important for infants and children due to their small blood volumes. Additionally, the researchers wanted to minimize the amount of times that blood needed to be collected. They developed their study in a way that would allow the collection of their samples concurrent to other clinical samples — requiring no additional needle sticks for the patient.

CTSA Resources Facilitate Process Improvements

Gathering blood at the same time as regularly scheduled blood draws requires extensive coordination between the research team and the patient's medical team. In this research project, the researchers developed a novel alert system, linking a physician's order for a blood culture in a patient's electronic medical record directly to a research study pager. This allows the researchers to be instantly notified of tests being ordered for sepsis. This page sets the research team into motion to determine if the patient is enrolled in the study and if so, to input the additional blood collection order before the phlebotomist draws the sepsis lab tests. Speed is imperative, since time between the initial blood workup order and collection can be as little as a few minutes, and the research samples must be drawn at the same time.

Once collected, the samples need to be processed.

CTSA's Extended Clinical Research Unit (CRU) provides an especially useful service in that its personnel are able to go to patients throughout the hospital, at any hour of the day or night, to collect and process samples immediately.

This timely service is necessary for Juskewitch and Huskins' research.

"This study looks at labile biomarkers involving critically-ill infants and children, including premature, low birth weight infants in the neonatal intensive care unit," says Juskewitch. "The blood needs to be rapidly separated into testable components and put in cold storage — something we can only accomplish because of the 24/7 presence of the Mobile CRU."

The short timeframe between the collection order and actual blood draw also required the researchers to consider the logistics of the process for obtaining consent to participate in their research project.

They developed a process that involves obtaining consent from parents of patients in the neonatal and pediatric intensive care units when their child is admitted to the unit. This relieves the ethical and practical burden of trying to obtain consent from concerned parents in the midst of their child's medical crisis. The consent documents are then stored for reference of research personnel when determining whether they can collect research samples from a particular individual or not.

Unique Data Management System

Another CTSA resource, REDCap — the Research Electronic Data Capture system — enabled an additional process improvement that has also proved invaluable.

"REDCap allows us to work together efficiently, and for all the members of the research team to be able to access the study information they need — any time, anywhere — including copies of the consent documents," says Juskewitch. "Additionally, it safeguards research participant information, allowing customizable, limited access rights."

REDCap enables Mobile CRU personnel to quickly access only one part of a research participant's information — the informed consent documents, which they must see before collecting and processing the research samples. It also provides the researchers with more comprehensive data entry, storage, manipulation and reporting capabilities than are available in the commonly-used Microsoft Access or Excel.

"Without CTSA resources such as the Mobile CRU and REDCap, this study would not have been possible," says Juskewitch.

Because of the novel processes and tools he incorporated into his research project, Juskewitch was selected as one of two national Clinical and Translational Science Awards — Child Health Research Fellows. He has been invited to present at the 2010 Pediatric Academic Societies meeting and the concurrent Child Health CTSA Consortia Meeting.

Other researchers involved with this project include Swati Prasad, M.B.B.S., Roshini Abraham, Ph.D., and Melissa R. Snyder, Ph.D.

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* The largest research-related center at Mayo Clinic, the Center for Translational Science Activities (CTSA) supports the "infrastructure" that enables Mayo investigators to perform cutting-edge clinical research. In 2006, Mayo Clinic became one of the first 12 institutions in the nation to receive a Clinical and Translational Science Award from the National Institutes of Health (NIH). This five-year, $72.5 million grant seeks to improve the health of our communities by accelerating the translation of laboratory discoveries into improved patient care.

* Mayo Clinic's two hospital-based Clinical Research Unit (CRU) locations, as well as the Mobile CRU and its accompanying research vehicle, offer flexible options for clinical researchers. CRU staff conduct protocols, secure specimens, administer medications and gather critical data from research participants — onsite, in the hospital, or out in the community.

* REDCap (Research Electronic Data Capture) is a secure, web-based application designed exclusively to support data capture for research studies. REDCap provides: 1) an intuitive interface for data entry (with data validation); 2) audit trails for tracking data manipulation and export procedures; 3) automated export procedures for seamless data downloads to common statistical packages (SPSS, SAS, Stata, R); 4) procedures for importing data from external sources; and 5) advanced features, such as branching logic and calculated fields. REDCap was developed by Vanderbilt University within the national CTSA program, and they continue to oversee the implementation of new features. The REDCap Consortium is comprised of 68 active institutional partners and is utilized on five continents. Currently over 1,000 studies spanning numerous research areas utilize REDCap.

• May 4, 2010
• NEW791795