Studies - Current
Intravenous Magnesium: Prompt use for Asthma in Children Treated in the Emergency Department (IMPACT-ED)
This pilot trial is a first step to determine if a simple and inexpensive medicine, intravenous magnesium sulfate (IV Mg), can improve outcomes of children treated in emergency departments for severe acute asthma. This pilot trial will enroll 90 children across three hospitals and evaluate giving IVMg or placebo early in ED treatment when the impact on hospitalization would be greatest, characterize changes in blood pressure when IV Mg is given, and collect information necessary to understand what dose of IV Mg is likely to be most effective.
These results will inform the development of a large multicenter trial of IVMg to conclusively answer whether IV Mg given in the ED can prevent hospitalization for these children. If IVMg reduces hospitalization as reported by small prior trials, increased use could reduce hospitalizations by16,500 a year, produce direct cost savings of $60 million yearly, and decrease indirect costs of missed school and work.
Hyperhydration to Improve Kidney Outcomes in Children with Shiga Toxin-Producing E. Coli (HIKO STEC)
This planning study will allow us to finalize RCT design, outcome measures, eligibility criteria, intervention and control arms, sample size, analysis plan and the preparation of study related materials. The CDC estimates that in the U.S., each year, over 175,000 individuals are infected by Shiga toxin-producing Escherichia coli (STEC). A complication of STEC infections is the hemolytic uremic syndrome (HUS). Preliminary data indicates that early volume expansion prior to the development of HUS can mitigate the complications of HUS.
This planning study will facilitate the implementation of a trial which has the potential to save lives, reduce acute and chronic morbidity, shorten length of stay if and when HUS develop in children infected with STEC.
Evaluating Tranexamic Acid (TXA) in Children with Traumatic Injuries (TIC-TOC)
This pilot and feasibility study is a double-blind, randomized controlled trial of 40 patients to provide safety and efficacy data on the use of TXA in severely injured children with torso and/or head injuries. Recent evidence in injured adults indicates that treatment with tranexamic acid (TXA) decreases mortality and blood-transfusion requirements following traumatic hemorrhage; however, TXA has not been appropriately studied in children with hemorrhagic injuries.
May reduce blood transfusions and morbidity in children with head and torso injuries.
The Effect of Emergency Department and After-Emergency Department Analgesic Treatment on Pediatric Long Bone Fracture Outcomes (LongBone) (IMPROVE)
A large multi-center comparative effectiveness study of children with long bone fractures to evaluate the short-term effectiveness of pain treatments during and after ED care. Fracture pain is a common reason for pain in children and the current opioid crisis poses a challenge for ED providers in prescribing analgesic medications. There is currently insufficient evidence to recommend a definitive ED analgesic regimen for children with a fracture.
To identify the most effective method of providing pain relief for children with fracture pain using non opioid analgesic to avoid opioid risk when not necessary.
RNA Biosignatures: A Paradigm Change for the Management of Young Febrile Infants (Biosignatures II)
This study of 2100-2800 infants will refine, validate, and test the clinical utility of RNA biosignatures in practice. Clinicians struggle to differentiate between viral versus bacterial causes for fevers in infants, leading to ineffective or over treatment. RNA bio signatures from a blood sample can distinguish bacterial infections vs. nonbacterial infections.
Could allow early identification of febrile infants with bacterial infections and avoid unnecessary testing, antibiotics and hospitalization for those that do not need it and reduce morbidity and mortality through appropriate and timely treatment.
Pragmatic Pediatric Trial of Balanced Versus Normal Saline (NS) Fluid in Sepsis (PRoMPT BOLUS)
In this pragmatic randomized comparative effectiveness trial that will enroll 8,930 children with suspected septic shock across PECARN hospitals, and will test the hypothesis that resuscitation with lactated Ringer’s (LR) improves hospital mortality, reduces kidney injury, and lowers length of stay compared to resuscitation with normal saline (NS). Sepsis is a leading cause of morbidity and mortality in children, for which crystalloid fluid resuscitation is a critical treatment. Although increasing data supports better efficacy and safety for LR than 0.9% NS, most children are resuscitated with NS and definitive data for the best fluid selection are lacking.
This study will definitively answer which crystalloid fluid is best for resuscitation of children with septic shock. If LR has demonstrably superior efficacy, a relatively cost-neutral paradigm shift to LR-based resuscitation could save hundreds of children’s lives every year in the US and thousands more worldwide.
Pediatric Emergency Care Applied Research Network (PECARN) Registry
An ED visit registry with automated transmission from the electronic health record data for pediatric patients at participating sites. The Registry currently contains data from all ED visits from nine sites with data spanning calendar years 2012 through 2020. Each site transmits data to the DCC monthly. Comprehensive data quality assurance rules have been automated to assess data quality and validation of the transmitted data. The Registry is about to undergo an upgrade to the data collection system and is currently onboarding three new sites. The Registry has data on over 4.4 M visits and 1.6 M unique patients. Data are also used for health services research, comparative effectiveness research, hypothesis generation and grant planning for the network. The Registry is utilized in four other funded PECARN grants.
Report outcomes compared to national standards to identify gaps in ideal care.
Pediatric Sepsis EHR Registry, Clinical Outcomes, and Predictive Model (PED Screen)
Establish a multi-center data registry from electronic health records (EHR) to identify pediatric patients at risk for sepsis, and develop an ED-based prediction model of sepsis-related organ dysfunction. Sepsis is a leading cause of pediatric morbidity and mortality with life-saving treatment dependent on early and accurate identification as children present differently than adults with sepsis.
Develop an ED prediction model to better identify the sickest children early to make sure they get the right treatment and reduce mortality related to sepsis.
Improving Detection of STIs in PEDs ED: A Pragmatic Trial (Adolescent STI)
Determine the most clinically effective and cost-effective sexually transmitted infections (STI) screening approach for adolescents using 3 steps: perform ED workflow evaluations to determine the most efficient way to integrate the screening process; conduct a comparative effectiveness pragmatic trial of targeted STI screening versus universally-offered STI screening through electronic integration of patient reported data for provision of clinical decision support; develop decision analytic models to evaluate the cost-effectiveness of targeted screening compared to universally offered screening. Adolescents are disproportionately affected by sexually transmitted infections and account for 9 million of the 19 million new STI cases annually. The STI epidemic among youth is a national public health priority. Despite established principles for STI control, clinical practices related to screening and diagnosis, treatment, and prevention of STIs among adolescents are suboptimal.
This research shifts the usual clinical practice paradigm in the ED from STI diagnosis in symptomatic adolescents to STI screening and prevention, an approach that is critical to addressing the STI epidemic among adolescents.
Implementation of Evidence Based Care for the Acute Treatment of Sickle Cell Disease Pain (Sickle Cell Improvement: Enhancing Care in the ED) (SCIENCE)
A mixed methods planning study (observational and qualitative) that aims to build the foundation for a future hybrid effectiveness-implementation trial. Guideline-based care, for children with Sickle Cell Disease (SCD), to prevent painful vasooclusive crisis (VOC) and provide treatment in a timely manner is infrequently followed, resulting in more frequent, prolonged pain and higher rates of Emergency Department visits and hospitalizations.
Successful identification of the barriers and facilitators to NHLBI guideline adherent care for pain in SCD will allow for the design of a successful multi-center hybrid effectiveness-implementation trial to improve the experience of children with SCD when they present in acute pain.
Identifying and Understanding Racial/Ethnic Disparities in Pediatric Emergency Care (Disparities)
The goals are to measure racial/ethnic disparities and to examine provider implicit bias. We will develop and validate disparities-sensitive measures. We will use these measures to identify disparities in the quality of pediatric ED using the PECARN Registry. The expected outcomes of our research are an enhanced capacity to capture, analyze, and report performance improvement data to address disparities, and assess for modifiable factors, such as provider implicit racial/ethnic bias. While there is robust evidence of disparities in pediatric emergency care (PEC), accurate and meaningful metrics that allow for measuring and reporting disparities are still needed to promote equity in the ED.
Inform the development of interventions to reduce health care disparities in acutely ill and injured children.
Headache Assessment of Children for Emergent Intracranial Abnormalities (HEADACHE)
This is a prospective observational cohort study of children ages 2 to 17 years old presenting to emergency departments with a headache. The primary aim of the study is to derive and internally validate a risk stratification model that identifies the specific risk of emergent intracranial abnormalities in these children based on clinically sensible and reliable variables. We will also determine whether the prevalence of emergent intracranial abnormalities and association between risk factors and emergent intracranial abnormalities differ based on age.
This research will optimize clinical decision making and use of emergent neuroimaging when evaluating children with headaches, leading to the safe reduction of unnecessary neuroimaging and accurate stratification of children at greater risk of having an emergent intracranial abnormality.
Exclusion of Pulmonary Embolism in Children without Radiation Exposure (BEEPER)
A prospective, observational, cohort study of children ages 4 to 17 years old who have sufficiently high probability of pulmonary embolism (PE). The goal is to measure the diagnostic accuracy of a prediction rule for exclusion of PE (the PERC-Peds rule) and the D-dimer (a lab test used for diagnostic purposes). No study has been performed to prospectively record the presenting complaints, signs, symptoms and comorbidities of children who raised the suspicion of pulmonary embolism (PE) in children. Clinicians must extrapolate what is known about PE in adults to children potentially delaying diagnosis and/or causing unnecessary radiologic testing.
To provide evidence-based guidance on the identification of PE in children to promote timely diagnosis and treatment, while excluding unnecessary radiation testing.
ED-Initiated School-based Asthma Medication Supervision (ED-SAMS)
This planning study will allow us to finalize RCT design, outcome measures, eligibility criteria, intervention and control arms, sample size, analysis plan and the preparation of study related materials for a study evaluating partnership between school based therapy and ED care for children who present with asthma. Approximately 8% of children in the US have asthma. Each year, these children experience 4 million asthma attacks that result in 725,000 ED visits and 100,000 hospitalizations. The total economic burden of asthma is $80 billion annually. Frequent asthma-related school absences impair academic achievement and social functioning. This burden falls disproportionately on minority, low-income, and urban populations. For example, black children have 60% more ED visits and 75% more hospitalizations than white children even though they have similar asthma attack rates.
This planning study will facilitate the implementation of a trial which has the potential to substantially reduce acute asthma related morbidity in underserved at risk children including reduction of missed school days, hospital admissions and ED visits.
Development of computerized clinical decision to combat the overuse of antibiotics in children with pneumonia or urinary tract infections (SPEED)
Our goal is to develop prototype electronic health record-based clinical decision support that will facilitate the appropriate use of antibiotics for children with community-acquired pneumonia or urinary tract infections. The decision support will be scalable across multiple sites. Decision support models will be developed at 3 PECARN sites. Antimicrobial resistance results in patient morbidity and mortality, and increased healthcare costs and is a result of indiscriminate antibiotic prescribing by clinicians. Antimicrobial stewardship programs facilitate appropriate antibiotic prescribing. There is a gap in understanding the optimal strategies to implement ED-based antimicrobial stewardship programs.
After the development of the decision support, we will conduct a multicenter trial to test its effectiveness to decrease the inappropriate use of antibiotics for these t+N2wo common pediatric infections. If successful, we will conduct further antimicrobial stewardship trials to facilitate the proper use of antibiotics for other common pediatric infections in order to minimize antimicrobial resistance.
Development and Testing of a Pediatric Cervical Spine Injury Risk Assessment Tool (C-Spine)
Develop and test a Pediatric CSI Risk Assessment Tool that can be used by EMS and ED providers to determine which children warrant spinal precautions and cervical spine imaging after blunt trauma. Cervical spine injuries (CSI) are serious, but rare events in children. Spinal precautions in the prehospital setting may be beneficial for children with CSI, but are poorly studied. In contrast, spinal precautions for pediatric trauma patients without CSI are common and may be associated with harm.
A rigorously-tested risk assessment tool for CSI in children has the potential for substantially reducing the number of children who receive unnecessary spinal precautions for trauma transport and/or who receive radiographic clearance of their cervical spine. This could lead to significant changes in recommendations for the treatment and transport of injured children worldwide.
Arginine Therapy for Treatment of Pain in Children with Sickle Cell Disease (STArT)
This is a pivotal phase 3 clinical trial using arginine as a novel treatment of pain in children with SCD. Pain in sickle cell disease (SCD) is the leading cause of hospitalizations and ED visits for children with SCD. Arginine has properties that may improve blood flow during these acute occlusion of blood vessels.
SCD is an orphan disease currently lacking treatment options for acute pain beyond opioid analgesics and supportive care. This proposal may change clinical practice in that Arginine may decrease pain in children presenting to the ED with SCD pain crisis.
Studies - Previous
Use Of Lorazepam for the Treatment of Pediatric Status Epilepticus: A Randomized, Double-Blinded Trial of Lorazepam and Diazepam
Textbooks and expert opinion recommend both diazepam and lorazepam as initial therapy for children in status epilepticus (SE) and provide recommended doses that are commonly used. However, unlike diazepam, lorazepam is only FDA-approved for treatment for SE in patients over 18 years of age. Despite this fact, many experts support the use of lorazepam over diazepam in pediatric SE. Increased duration of action, increased effectiveness in terminating SE, and a lower incidence of respiratory depression have been cited as potential advantages of lorazepam over diazepam. However, data to support firm recommendations for one medication over another are lacking. Thus, either diazepam (FDA-approved) or lorazepam can be considered first-line agents for pediatric SE, and the physician’s choice of agent depends on local practice patterns and individual treatment styles.
The purpose of this study is to determine the differences in efficacy and safety between these two commonly used benzodiazepines, as requested by the FDA under the Best Pharmaceuticals for Children Act, using the Exception from Informed Consent provided by the FDA.
Therapeutic Hypothermia After Cardiac Arrest in Children (THAPCA) Trials
Cardiopulmonary arrest (when the heart stops beating) is a tragic event in children that is associated with high rates of death and long term disability. The study, entitled “Therapeutic Hypothermia after Pediatric Cardiac Arrest (THAPCA)”, will evaluate whether regulating the body temperature will improve the outcome for children after cardiac arrest. There is a separate study for children who arrest in the hospital (THAPCA-IH) and children who arrest out of the hospital (THAPCA-OH). The National Heart, Lung, and Blood Institute (NHLBI) is funding the first large scale, multi-center study to help determine the best treatment for children who are successfully resuscitated after a cardiac arrest.
The goal of these two trials is to determine if therapeutic hypothermia improves survival with good neurobehavioral outcome in children who have had a cardiac arrest. About 900 children will be enrolled in this study over 6 years at 30 clinical centers throughout the US and Canada. Enrollment in the THAPCA Trials began in September, 2009.
The THAPCA Trials investigative team has worked collaboratively since 2002 bringing together two federally funded pediatric clinical research networks to study this problem. The two networks are the Pediatric Emergency Care Applied Research Network (PECARN), funded by the Emergency Medical Services for Children (EMSC) program and the NICHD Collaborative Pediatric Critical Care Resesarch Network (CPCCRN).
RNA Biosignatures: A Paradigm Change for the Management of Young Febrile Infants
Every year ~500,000 infants present to EDs in the U.S. with fever as their presenting complaint. Six to 10% of these febrile infants will have invasive bacterial infections. Because there is no single reliable clinical or laboratory predictor of bacterial infections, clinicians depend of varying combinations of blood, urine, and cerebrospinal fluid (CSF) testing. These tests are invasive, often times inaccurate, and do not provide results quickly enough for ED disposition decisions.
The ultimate goal of this study protocol is to develop new, precise diagnostic tools that allow for less invasive, more accurate, and more timely evaluation and diagnosis of young febrile infants in the ED. This will be done by examining the patient’s immune response to bacterial and viral organisms, using RNA microarrays, and identify biosignatures that correctly classify the infants into bacterial, viral, co-infection, or uninfected groups. This study will prospectively gather clinical and RNA data on febrile infants <= 60 days of age who are being evaluated for bacterial infections in all PECARN EDs. Enrollment began in June 2016.
Referral and Utilization Patterns for Psychiatric Related Visits to the Pediatric Emergency Department
Pediatric psychiatric emergencies appear to have reached epidemic proportions over the past 10 years. ED visits related to mental health problems are known to be resource intensive, but data in this area has mainly occurred at individual sites. The aim of this retrospective chart review was to describe the patterns of referral and utilization of ED resources for children with a psychiatric related visit presenting to PECARN EDs. The findings of this study were presented at the Pediatric Ambulatory Society Annual Meeting in 2007. The main manuscript was published in Pediatric Emergency Care (2009).
A Randomized Clinical Trial of Non-operative Management for Acute Uncomplicated Appendicitis
Acute appendicitis is the most common surgical emergency in children. The current standard of treatment of acute appendicitis is appendectomy. With early recognition, increasing diagnostic accuracy and surgical advances, morbidity rates have dramatically lowered. However, surgery remains associated with pain, discomfort, risk of complications, and decreased quality of life. Because of the high incidence in childhood, appendicitis remains a substantial health care and societal burden.
Recently the paradigm for treating acute appendicitis has been challenged, with several randomized control trials (RCT) in adults showing that appendicitis may be safely treated with antibiotics alone. The goal of this multicenter, non-blinded intention-to-treat RCT is to compare the safety of non-operative management of uncomplicated appendicitis in children aged 5 to 18 years compared with urgent appendectomy. Patients will be randomized to either initial treatment with intravenous and oral antibiotics or urgent appendectomy, and followed for up to 4 years. We plan to enroll 1,036 participants in 8 PECARN sites over 3 years. This project is currently funded by a NIDDK planning grant. A U01 application was submitted in February 2018. If awarded, funding may begin as early as Fall 2018.
A Qualitative and Quantitative Evaluation of Patient Safety Issues in Pediatric Emergency Departments: A Pilot Study in New York State
Medical errors are an important cause of morbidity and mortality, causing
the death of between 44,000 and 98,000 patients annually in the United
States. Little is known about medical errors in pediatric patients,
especially in the emergency department (ED) setting. This project, co-funded by the New York Department of Health, evaluated incident reports and medication records in 3 PECARN sites.
To classify and disseminate information from ongoing incident report monitoring, including actual and near-miss medication errors that occurred in the emergency department (i.e. qualitative surveillance).
To monitor medication error rates using systematic sampling and review of emergency department medical records (i.e. quantitative surveillance).
Over 3,000 medical records were reviewed and one year of incident reports were evaluated for this project.
Predicting Cervical Spine Injury (CSI) in Children
Cervical spine injuries (CSI) are serious, but rare events in children. Immobilization of children with CSI in the out-of-hospital setting may be beneficial, but is poorly studied. In contrast, immobilization for transport of pediatric trauma patients without CSI is common and known to be associated with adverse effects. As a result, more than 99% of immobilized children have no CSI and are exposed to harm with no demonstrable benefit. The purpose of this study is to identify a set of variables that separate injured children with negligible risk of CSI from those at non-negligible risk for CSI. Specifically, project goals are to describe CSI and to identify factors associated with increased risk for CSI among a diverse pediatric blunt trauma population. This retrospective study concluded data collection at the end of 2007. Several abstracts have been presented in 2008 and 2009 at national meetings. The main manuscript has been published.
Prospective Yield Study of Children with Severe Traumatic Brain Injury: Pilot Feasibility for a Randomized Controlled Trial of Progesterone for Severe TBI
Traumatic brain injury (TBI) is the leading cause of morbidity from trauma in children, and one of the leading causes of death. Despite the frequency of TBI, its impact on the health of children, and decades of research, no effective treatment exists. For adults, however, there have been several recent phase II studies demonstrating the administration of progesterone to those with moderate-to-severe TBI is safe and may have substantial neuroprotective effects. The PECARN conducted a prospective observational yield study to: demonstrate the number of moderate-to-severely brain injured children presenting to PECARN hospitals, determine time of guardian arrival in order to determine appropriate consent methods, and evaluate fesibility of eligibility criteria. Data from this pilot will also allow us to determine how many clinical sites will be required for an interventional trial. Subject enrollment has concluded and a manuscript is in preparation.
Pediatric Sepsis Registry, Clinical Outcomes, and Prediction Model
This study addresses the critical need to improve pediatric sepsis outcomes by developing methods to accurately identify at-risk children presenting for emergency care. The project will capture electronic health record (EHR) data to create a multi-center registry with the ultimate goal of improving the detection and treatment of pediatric sepsis in the emergency department (ED) setting. To accomplish this, we will automate the determination of organ dysfunction in children with sepsis directly from structured and narrative data in an expanded multicenter EHR patient registry. That data will be used to derive and validate a prediction model of pediatric sepsis that predicts subsequent organ dysfunction within 48 hours using ED EHR data from the first 4 hours of care. Innovative deliverables from this project include the existence of a broad and rich EHR registry, an automated process of outcome determination, and a prediction model of risk of sepsis.
Pediatric Patient Safety in Emergency Departments
This study focused on pediatric patient safety in the emergency department (ED). The first phase involved surveys of pediatric ED staff to assess perceptions of safety. The manuscript for this phase was published in Pediatrics (2009). The second phase of the study involved transmitting incident reports to the data center and classifying and quantifying ED events using a consensus process. Analysis of over 3000 incidents reports was completed and various manuscripts discussing medication errors/events, radiology events, laboratory events, process variance events, and near-miss errors have been published. A newsletter summarizing findings from the medication error review has been distributed to share information on prevention of medication errors in the emergency departments that care for children.
PECARN Core Data Project (PCDP)
This project is a cross-sectional study of all pediatric ED visits from all sites within the network. A database of electronic administrative data is compiled annually from 2002 to the present. This study has several aims:
- to identify the frequency and type of PECARN Emergency Department (ED) visits;
- to identify the availability of data elements from existing electronic databases and chart reviews at each HEDA;
- to identify the availability of clinical parameters collected during usual medical care of patients with selected diagnoses (asthma and long bone fractures);
- to measure the agreement between, and completeness of, data elements collected by electronic methods and chart review.
This study provides important epidemiological information regarding pediatric emergency department visits in the PECARN network. Data are collected annually from all hospital sites. The public use dataset is available on this website.
Intravenous Magnesium for Sickle Cell Vasoocclusive Crisis (MAGIC)
Children with sickle cell disease (SCD) are at risk for acute vasoocclusive crises, the most frequent of which are pain crises. The usual treatment for pain crises, intravenous (IV) fluids and pain medicine, has changed little over the past three decades. The purpose of this study was to determine the safety and efficacy of intravenous magnesium in shortening the duration of a pain crisis and to determine the health-related quality of life and short term outcomes of children treated with intravenous magnesium during an acute pain crisis. This was a multi-center, randomized, double-blind, placebo controlled trial. Patients were randomized to receive either the study drug or placebo every eight hours for a total of six doses, or until discharge, whichever occurred first. Patients were followed up by phone one week after discharge to assess rehospitalization rates, and returned to the sickle cell clinic for follow up within 3 months after discharge. Enrollment began in December 2010 and concluded Dec 2013. This project was co-funded by NICHD and NHLBI. Findings were published in Blood on July 31, 2015. The public use dataset is available on this website.
Implementation of the PECARN Traumatic Brain Injury Prediction Rules for Children Using Computerized Clinical Decision Support: An Interrupted Time Series Trial
Blunt head trauma is a leading cause of mortality and morbidity in children. However, greater than 95% of the more than 450,000 children who present to US emergency departments annually with blunt head trauma have minor head trauma. Although important traumatic brain injuries (TBI) are infrequent, clinicians obtain cranial computed tomography (CT) in up to 50% of children with minor blunt head trauma, exposing them to radiation with its potential to induce malignancies. Given the substantial burden of blunt head trauma to families and society, as well as the importance of minimizing radiation exposure, this study will investigate whether implementation of the recently validated Pediatric Emergency Care Applied Research Network (PECARN) TBI prediction rules using computerized clinical decision support can decrease unnecessary use of CT in children with minor blunt head trauma. The overall goal of this study is to promote the appropriate use of CT for children with blunt head trauma by creating a generalizable model to translate evidence into clinical practice.
The study objectives are:
- To rigorously develop an integrated electronic health record blunt head trauma data collection template and computer-based clinical decision support system to implement the PECARN TBI prediction rules for children; and,
- To assess whether implementing the prediction rules via computerized clinical decision support decreases the number of (unnecessary) cranial CTs in children with minor blunt head trauma at very low risk of traumatic brain injuries.
In order to meet study objective one, we will conduct focus groups of clinicians and perform emergency department workflow evaluations; develop an electronic health record blunt head trauma template that captures patient encounter data; and develop computerized clinical decision support to provide CT recommendations. Subsequently (in order to meet objective two), we will conduct a seven–center prospective, interrupted time series trial with concurrent controls that assesses CT use prior to and after the implementation of the electronic health record-clinical decision support (EHR-CDS) intervention system. We hypothesize that the EHR-CDS intervention system will safely decrease the use of CT compared to passive diffusion. This project is funded by the American Recovery and Reinvestment Act—Office of the Secretary (ARRA OS): Grant #S02MC19289-01-00.
Fluid Therapy and Cerebral Injury in Pediatric Diabetic Ketoacidosis (Fluid Therapy in DKA)
Preliminary data strongly support the concept that diabetic ketoacidosis (DKA) related cerebral injury and subsequent edema may occur as a spectrum of severity. Although only a minority of children develop clinically-overt DKA-related cerebral injury of sufficient severity for obvious, profound neurological dysfunction, a much larger percentage may have subtle cerebral injury. The impact of variation in DKA treatment protocols on this cerebral injury is unknown and arguments for either slower or faster fluid treatment protocols can be made.
This study is a factorial-design, randomized controlled trial comparing four fluid treatment protocols for pediatric DKA. Two rates of rehydration will be compared; a more rapid rate, designed to promote faster reperfusion of brain tissue and a slower rate, geared toward more gradual reperfusion. Within each of these two basic rehydration schemes, we will vary the type of rehydration fluid used (0.9% saline or 0.45% saline). We will compare treatment arms using a comprehensive set of assessments for neurological injury including measurements of subtle neurological dysfunction during DKA treatment (in addition to recording the frequency of acute, clinically-overt cerebral edema) and measures of long-term neurocognitive function. These studies will not only allow us to determine whether variations in fluid treatment protocols affect acute neurological outcomes of DKA, but also will provide important additional data regarding the impact of DKA and DKA treatment on long-term neurocognitive function in children. In this way, we hope to identify a more ideal fluid management strategy for children with DKA. The anticipated enrollment period is from Fall 2010-2015. This project is co-funded by NICHD.
Effectiveness of Oral Dexamethasone in Acute Bronchiolitis
This study assesses the effectiveness and safety of the administration of oral dexamethasone for acute moderate to severe bronchiolitis in children seen in the ED, both with regard to the need for hospitalization (primary outcome), and severity and duration of disease (secondary outcomes). The study hypothesized that dexamethasone would be more effective than placebo in preventing hospital admission of infants with bronchiolitis.
This study was was conducted at selected sites within PECARN for a three-year period (during Bronchiolitis seasons). The study was co-funded by the Health Resources and Services Administration’s (HRSA) Maternal and Child Health Bureau (MCHB) Emergency Medical Services for Children (EMSC) Program and the Research Program. Data collection began in January, 2004. The study concluded in Spring, 2006. We successfully enrolled 600 patients in this study, and we determined that there was no reduction in hospitalizations or improvement in respiratory scores associated with the administration of oral dexamethasone. Findings were published in the New England Journal of Medicine on July 26th, 2007. The public use data set can be requested here.
Emergency Department Screen for Teens at Risk for Suicide (ED-STARS)
The ED-STARS study will develop and test a brief, personalized, computer-based suicide risk screening tool for teenagers. During the first study, over 6,000 youth were screened, and researchers followed up on a subsample of 12-17 year-olds who scored high on suicide risk factors – as well as those who scored low. Their experiences over a 6-month period were used to develop a computerized adaptive screen (CAS) for predicting suicide attempts that adjusts its line of questioning depending on responses to previous questions. The researchers will then compare the sensitivity, specificity, and predictive value of the CAS with the Ask Suicide-Screening Questions (ASQ), a standardized ED youth suicide prevention screening tool. Study Two began the summer of 2017 and will validate the CAS and associated risk stratification algorithm, determining the measure’s ability to predict suicide attempts in a new sample of 4,000 youth. The potential benefit of including a behavioral test of suicidal thoughts, the Implicit Association Test (IAT), as part of the screening process will also be evaluated. This study is funded by the National Institute for Mental Health (NIMH).
Development of Research Partnerships with EMS Agencies and Descriptive Study of EMS Pediatric Population within PECARN
The objective of this protocol was to study pediatric emergency medical services (EMS) within the PECARN network and establish the network’s capability to collect pre-hospital data. This descriptive study initiated data collection from EMS agencies. The project aimed to demonstrate that data transmission from EMS agencies to the data center is feasible. This study established research relationships between PECARN sites and respective EMS agencies and gather data to understand the demographics and disease/injury patterns of the sample that is available to the PECARN network. The data collected will be invaluable in the future for generating hypotheses for pediatric EMS studies and providing preliminary data for grant applications. Data collection and analyses are complete. The main manuscript, Characteristics of the Pediatric Patients Treated by the Pediatric Emergency Care Applied Research Network’s Affiliated EMS Agencies,was published in Pediatric Emergency Care, October 2013.
Childhood Head Trauma: A Neuroimaging Decision Rule
This was a prospective study of children with minor-to-moderate blunt head trauma with a goal of identifying high-risk and low-risk indicators of traumatic brain injury (TBI). The goal was to derive the evidence on which to base appropriate use of head computerized tomography (CT) in children with acute head injury, which will hopefully reduce the number of unnecessary CT scans for children at very low risk for TBI. This will minimize the exposure of these children to the significant drawbacks related to CT (ionizing radiation, transport of children away from the direct observation of the emergency department, pharmacological sedation, and additional health care costs).
The study was co-funded by the Health Resources and Services Administration’s (HRSA) Maternal and Child Health Bureau (MCHB) Emergency Medical Services for Children (EMSC) Program and the Research Program. Data collection began in June, 2004 at all PECARN sites, and concluded in September, 2006. The network successfully enrolled 34,000 patients for the derivation of two clinical decision rules (one for children < 2 years and one for children > 2 years), and an additional 9,000 patients to validate the decision rules. Multiple abstracts from this study have been presented at national emergency medicine and pediatric meetings to date. Several manuscripts have been published including the main prediction rule manuscript which was published in Lancet (October 3, 2009). The public use data set can be requested here.
Clinical Decision Rule to Identify Children with Intra-abdominal Injuries
This was a prospective study of children with blunt torso trauma with a goal of identifying high-risk and low-risk indicators of intra-abdominal injury (IAI). The long term objective of the study is to derive, validate, disseminate and implement decision support tools to optimize the evaluation of children with blunt torso trauma, which will lead to reduced morbidity and mortality. The overall objective of this particular study is to develop a clinical decision rule for appropriate use of abdominal computerized tomography (CT) scanning in children with blunt torso trauma. We will create a decision rule that identifies those children in need of emergent CT scan and treatment, while reducing the use of abdominal CT scans in those children with minimal risk of IAI. The study was funded by the Centers for Disease Control and Prevention. Patient enrollment began in May, 2007 and concluded in January 2010. The main paper, Identifying Children at Very Low Risk of Clinically Important Blunt Abdominal Injuries, was published in Annals of Emergency Medicine, in Feb 2013. The public use data set can be requested here.
ASSESS (Age Specific Screen for Ethanol and Substance Status) aims to validate the newly developed National Institute for Alcohol Abuse and Alcoholism (NIAAA) two-question screen for early detection of alcohol use and problems in 12-17 year olds in 16 PECARN pediatric emergency departments. Approximately 5000 youths presenting to participating PECARN pediatric emergency departments (PED) were enrolled over a 3 year period. Subjects completed the two-question screen along with an alcohol and other drug and behavior assessment battery. The advantage of the PED setting is the ability to capture high risk populations such as school dropouts and those without primary care or insurance, who often use PEDs for their medical care and are missed in other study settings. This study is funded by the National Institute for Alcohol Abuse and Alcoholism (NIAAA).
Arginine Feasibility Project
The Arginine Feasibility project was funded as part of an R34 clinical trials planning grant that will establish a protocol steering committee with expertise in Sickle Cell Disease (SCD) clinical trials, create a clinical network of sites with a strong track record of successful participation in multi-center trials, create an ED-based pain protocol, develop a data coordinating plan, identify safety and clinical endpoints and a completed protocol for a phase III clinical trial of L-arginine for the treatment of vaso-occlusive pain in children with SCD to be submitted for NIH funding. Specifically this study is creating a standardized ED-based pain therapy protocol based on NIH guidelines that will be utilized in the future phase III trial, collecting feasibility data on volume, time of visit and admission rates from high-volume PECARN and non-PECARN sites on all potentially eligible patients with SCD and collecting demographic and clinical data through a 20 patient chart review at each participating site. This study is funded through the NHLBI.
Application of Transcriptional Signatures for Diagnosis of Febrile Infants within the PECARN Network
The ultimate goal of this project is to incorporate a RNA-based diagnostic technology (called transcriptional signatures) to distinguish between bacterial and non-bacterial infections in otherwise well-appearing febrile infants who present to the EDs. The project aims to create a PECARN wide infrastructure for conducting translational genomic research and demonstrate feasibility of screening, consenting, collecting, and processing of small volumes of blood samples to abstract high quality RNA from febrile infants. After initially defining bacterial and non-bacterial biosignatures, we will conduct a limited validation of these diagnostic biosignatures on an independent group of febrile infants. Patient enrollment began in 2008 and continued through May 2013. Analysis is in progress. This project is co-funded by NICHD.
Acute Gastroenteritis-Impact of Emergency Department Probiotic Treatment of Pediatric Gastroenteritis
Acute gastroenteritis (AGE) is a leading cause of malnutrition and death worldwide and affects millions of children in the US each year. Most AGE is viral in origin, and apart from care focused on rehydration and nausea, there are no therapies to reduce the severity of illness. The overall objective of this randomized, placebo-controlled, double-blind, multi-center study is to determine the efficacy and side effect profile of the probiotic, Lactobacillus rhamnosus GG (LGG), in children aged 3 to 48 months presenting to the ED with AGE. Patients were randomized to receive either LGG or placebo twice a day for 5 days, for a total of 10 doses. Nine-hundred and seventy-one children were enrolled in 10 PECARN sites over 4 years. Enrollment completed in Summer 2017. Analysis is in progress. This project is funded by the NICHD.