Use of the Electronic Medical Record and Clinical and

Use of the Electronic Medical Record and Clinical and Translational Science Award

Resources for Research Involving Biomarkers of Sepsis in Critically Ill

Neonates and Children

Use of the Electronic Medical Record and Clinical and Translational Science Award

Resources for Research Involving Biomarkers of Sepsis in Critically Ill

Neonates and Children

Justin E. Juskewitch1

Swati Prasad MBBS2

Joseph P. Grande MD, PhD3,4

Roshini Abraham PhD5

W. Charles Huskins MD, MSc2

Justin E. Juskewitch1

Swati Prasad MBBS2

Joseph P. Grande MD, PhD3,4

Roshini Abraham PhD5

W. Charles Huskins MD, MSc2

1Medical Scientist Training Program, Mayo Clinic, Rochester, MN2Department of Pediatric Infectious Disease, Mayo Clinic, Rochester, MN

3Department of Nephrology, Mayo Clinic, Rochester, MN4Department of Pathology and Laboratory Medicine, Mayo Clinic, Rochester, MN

5Department of Clinical Immunology, Mayo Clinic, Rochester, MN

I have documented that I have no relevant financial relationships

to disclose or COIs to resolve.

I have documented that my presentation will not involve

discussion of unapproved or off-label, experimental or investigational use.

SIRS = systemic inflammatory response syndrome

Management different for sepsis versus other forms of SIRS

Identifying infection requires microbial culture

1. 48 hours incubation time2. Volume and access issues

(neonates)

SIRS = systemic inflammatory response syndrome

Management different for sepsis versus other forms of SIRS

Identifying infection requires microbial culture

1. 48 hours incubation time2. Volume and access issues

(neonates)

Sepsis = SIRS + infectionSepsis = SIRS + infection

Critical Care Medicine (1992) 20: 864-874

Need: More rapid, low volume assayNeed: More rapid, low volume assay

Immune Signature for Infection?Immune Signature for Infection?New technologies allow for simultaneous measurement of

multiple immune markers1. Cell surface molecules (flow cytometry)2. Plasma cytokines (Luminex assay)

Advantages: 1. Multimarker panel vs. individual markers2. Low blood volume (1 – 2 cc total)3. Faster turnaround time

New technologies allow for simultaneous measurement of multiple immune markers1. Cell surface molecules (flow cytometry)2. Plasma cytokines (Luminex assay)

Advantages: 1. Multimarker panel vs. individual markers2. Low blood volume (1 – 2 cc total)3. Faster turnaround time

CD64, HLA-DR, CD163 on neutrophils and monocytesIL-1, IL-1ra, IL-2, IL-4, IL- 5, IL-6, IL-8, IL-10, IL-12 p40, IL-

12 p 70, TNF-, and INF-

Study ChallengesStudy Challenges

1. Sepsis episodes are acute, unpredictable events → prospective subject screening and enrollment

2. Lab tests to diagnose sepsis including blood cultures involve STAT orders (sepsis work-ups) → instantaneous notification and rapid study sample ordering

3. Biomarkers are labile → rapid collection, processing, and storage (< 1 hr)

1. Sepsis episodes are acute, unpredictable events → prospective subject screening and enrollment

2. Lab tests to diagnose sepsis including blood cultures involve STAT orders (sepsis work-ups) → instantaneous notification and rapid study sample ordering

3. Biomarkers are labile → rapid collection, processing, and storage (< 1 hr)

Study DesignStudy Design

Pediatric and Neonatal ICU Cohort

May 1, 2009

Collectadditional

study samples

Evaluate subject

eligibility

Obtain informed consent and

baseline samples

Clinically ordered sepsis work-up

for enrolled patient

Jan 31, 2011

Methods Data SetMethods Data Set

Pediatric and Neonatal ICU Cohort

July 1, 2009 Jan 31, 2011 Oct 15, 2009 May 1, 2009

369 admissions62 eligible23 enrolled

33 flow cytometry samples32 plasma cytokine samples

• 16 baseline samples• 9 sepsis work-up samples• 8 follow-up samples

Subject Screening & Enrollment Subject Screening & Enrollment

Subjects screened for eligibility using EMR

Approached for enrollment

Baseline study samples are arranged with next clinical draw

Need: Instantly accessible research database to house enrollment information and signed consent forms

Subjects screened for eligibility using EMR

Approached for enrollment

Baseline study samples are arranged with next clinical draw

Need: Instantly accessible research database to house enrollment information and signed consent forms

Screen & consent patients

Notification of sepsis work-up

Order study samples

Sample processing & storage

REDCap REDCap Developed by Vanderbilt CTSA;

hosted by Mayo CTSA Screen & consent patients


Order study samples


REDCap REDCap

Online signed parental permission and assent forms for rapid access

(NIH regulations)



Order study samples


Sepsis Work-Up Study SamplesSepsis Work-Up Study Samples

Need: System to notify study staff of these orders quickly and consistently

Need: Rapid way to arrange study samples along with sepsis work-up

Need: System to notify study staff of these orders quickly and consistently

Need: Rapid way to arrange study samples along with sepsis work-up



Order study samples


0 10 20 30 40 50 60 70 80 90 100 110

Time between BC order and collection (minutes)

Median = 25 min(n = 9)

Study PagerStudy Pager

Paged when blood culture ordered in NICU and PICU

Paged when blood culture ordered in NICU and PICU

96% capture rate (107/112)



Order study samples


Electronic Study Sample OrderElectronic Study Sample Order

Clinical order for STAT blood culture

Directly into hospital order system Screen & consent patients


Order study samples


Patient Information


Electronic order form for study samples



Order study samples



Electronic study sample order alongside STAT blood culture order



Order study samples


Patient Information

Processing & Storage of Study Samples

Processing & Storage of Study Samples

Analytical validation → labile markers (< 1 hr)

Refrigeration (flow cytometry)

Frozen plasma (cytokines)

Need: 24/7 rapid processing and storage of all research samples

Analytical validation → labile markers (< 1 hr)

Refrigeration (flow cytometry)

Frozen plasma (cytokines)

Need: 24/7 rapid processing and storage of all research samples



Order study samples


Mobile Clinical Research UnitMobile Clinical Research Unit

24/7 laboratory collection and

processing services at the

patient’s bedside



Order study samples


0

10

20

30

40

50

60

Tim

e be

twee

n S

ampl

e C

olle

ctio

n an

d S

tora

ge (

min

)

Flow cytometry Plasma cytokine

End ResultEnd Result

MaximumAcceptableProcessing

Time



Order study samples


(n = 33) (n = 32)

SummarySummary

EMR and CTSA resources addressed all study challenges 1. Acute, unpredictable clinical events2. STAT laboratory orders3. Labile biomarkers

Firsts at Mayo Clinic:1. Use of REDCap for electronic access to signed

study consent forms2. Use of research study pager tied directly into

EMR clinical orders3. Use of an inpatient study sample order in the

EMR

EMR and CTSA resources addressed all study challenges 1. Acute, unpredictable clinical events2. STAT laboratory orders3. Labile biomarkers

Firsts at Mayo Clinic:1. Use of REDCap for electronic access to signed

study consent forms2. Use of research study pager tied directly into

EMR clinical orders3. Use of an inpatient study sample order in the

EMR

Funding

NIH UL1RR024150

NIH F30DK084671

CTSA Child Health Research Fellow Award

Funding

NIH UL1RR024150

NIH F30DK084671

CTSA Child Health Research Fellow Award

AcknowledgementsAcknowledgements

Mayo Collaborators

Mayo CTSA REDCap StaffJoseph WickMichael Lin

Mayo Electronic Ordering StaffRachelle House Mark Foley Munawwar Khan

Mobile CRU StaffNancy HawleyDiane Swanson

Mayo Clinic NICU, PICU StaffSheri Crow, MDWilliam Carey, MDChristopher Colby, MD

Mayo Collaborators

Mayo CTSA REDCap StaffJoseph WickMichael Lin

Mayo Electronic Ordering StaffRachelle House Mark Foley Munawwar Khan

Mobile CRU StaffNancy HawleyDiane Swanson

Mayo Clinic NICU, PICU StaffSheri Crow, MDWilliam Carey, MDChristopher Colby, MD

Health & Medicine

Use of the Electronic Medical Record and Clinical and