Internal Research Grant Program (IRGP)  

The Internal Research Grant Program (IRGP) is an annual opportunity that is funded through the generous support of donors. This program funds internal research projects submitted by Children’s staff and professional staff for up to two years.

IRGP is supported by Children’s Hospitals and Clinics of Minnesota’s Education and Research (E&R) Committee. 

2012 Grant Recipients

“Simplified Fetoscopic Tracheal Occlusion for Diaphragmatic Hernia”
 Principal Investigator: Lauren A. Bohm, MD


The high mortality rate of pulmonary hypoplasia associated with congenital diaphragmatic hernia has led to the development of various prenatal surgical interventions. Antenatal tracheal occlusion has recently become a well established method of promoting lung proliferation and pulmonary vascular maturation. Initial surgical approaches to tracheal occlusion involved open procedures. The current operative technique consists of a percutaneous, endoscopic balloon insertion via a series of intrauterine trocars, cannulas and sheaths. However, this technique often requires external fetal version and paralytic administration for direct passage of the flexible endoscope into the fetus’ oral cavity. These supplementary interventions can cause potential harm to the fetus and mother, and may contribute to the significant rate of preterm premature rupture of the membranes associated with this procedure.

This research project is designed as a pilot study to determine the feasibility of a simplified surgical approach to endoscopic tracheal occlusion performed in a fetal sheep model. The proposed technique will only utilize a single transuterine trocar and flexible endoscope. Outcome measures will include sonographic confirmation of tracheal occlusion, operative time and intraoperative complications. It is hypothesized that comparable outcomes can be obtained by a skilled endoscopist using this minimally invasive technique without the need for preoperative fetal version or paralysis. Ultimately, decreasing the amount of intrauterine manipulation and instrumentation may reduce the morbidity of this procedure with less fetal distress, premature membrane rupture and preterm labor.

“Toe walking study: Two pull carbon fiber solid Ankle Foot Orthotics (AFOs) versus
serial casting"
Principal investigator: Nicole Brown, DPT


Background: This study is attempting to garner increased awareness for the importance of early health care intervention in children who toe walk. It is important to gain further understanding of the multi-faceted aspects, which contribute to successful functional outcomes in this population. The use of two-pull carbon fiber solid ankle foot orthotics (AFOs) has not been studied but has shown promise as an intervention for children who toe walk. There is evidence, which demonstrates successful, functional outcomes in dorsiflexion range of motion and improved heel strike at initial contact with serial casting. This study will investigate whether two-pull carbon fiber solid AFOs will have similar outcomes as serial casting, with an improved quality of life, in the treatment of children with a toe walking diagnosis.

Methods/design: Forty children will be randomly placed into two groups, two-pull carbon fiber solid AFOs (n=20) and serial casting (n=20). Both groups will have initial and post assessments to compare outcome measures. Children who successfully meet the discharge criteria will have a follow up assessment to determine retention of skills. Outcomes will assess quality of life, gross motor skills, balance measures and satisfaction in gaining a heel-toe gait pattern.

Results: This study will define whether the use of two-pull carbon fiber solid AFOs is an effective alternative to serial casting in children who toe walk, while comparing quality of life. Results will be used in the development of future research as well as to provide information for improved effectiveness of toe walking physical therapy interventions.

“Deletion and frequency of renal anomalies in 22q11.2 Deletion Syndrome”
Principal investigator: Sarah Dugan, MD


Deletion 22q11.2 is a common genomic condition leading to increased risk of developmental differences, birth defects and medical problems. While the effects of this genetic change on some body systems are well-described, the medical literature contains a relative paucity of information about renal anomalies in this condition. Furthermore, comparison of prenatal ultrasound findings to postnatal renal ultrasound findings among individuals found to have deletion 22q11.2 has not been investigated to our knowledge. We propose to identify patients both retrospectively and prospectively that are followed in our 22q11.2 deletion clinic. We will report type and frequency of renal anomalies. Additionally, we will review prenatal records to determine in what proportion these anomalies were diagnosed by prenatal ultrasound. This study may help elucidate the effects of 22q11.2 deletion on the genitourinary system and result in modification to guidelines for renal ultrasound among individuals with deletion 22q11.2.

 “Gang raped versus sexually exploited girls’ experiences of victimization, risk behaviors, resiliency attributes and legal outcomes”
Principal investigator: Laurel D. Edinburgh, MSN, CNP


The proposed study is a mixed methods analysis of chart records and forensic interview tapes to understand the presenting characteristics, related risk behaviors and resiliency factors of gang-raped and commercially sexually exploited girls seen at the Midwest Children’s Resource Center, and to evaluate their legal outcomes. The mixed-methods qualitative data will be collected from the forensic interview tapes of victims, and quantitative data will be extracted via retrospective review of charts, with linked data of legal outcomes from Ramsey County court records. No other studies to date have investigated how these relatively uncommon but severe abuse experiences are described by victimized girls during their forensic interviews, what injuries, if any, are seen upon exam, whether the antecedent factors and context of the events affect mental health responses, nor have the legal outcomes of these cases been documented and linked to presenting characteristics. The findings will provide important information for child sexual abuse clinical practice, document how clinical treatment needs of these young victims may differ from other forms of abuse, as well as support legal efforts to charge perpetrators for such crimes.

“Decreasing propofol injection pain by pre-treatment with lidocaine in pediatric procedural sedation”
Principal investigator: Didima Mon-Sprehe, M.D.


Propofol is a medication commonly used for procedural sedation in the pediatric population. One of its side effects is pain or burning at the injection site when administered via peripheral intravenous line. While there is variation in the severity of pain, a significant number of children and adults do experience some degree of discomfort. There is not an agreement among providers as to how to best prevent or mitigate this pain, but the administration of 1% lidocaine intravenously immediately prior to the delivery of the propofol is thought to be potentially beneficial. This precise strategy has not been previously studied, but may decrease the pain children experience during their sedation. We propose a double-blinded study in which patients are randomly assigned to receive either 1% lidocaine or placebo (normal saline) intravenously immediately prior to administration of propofol.

Relevance: Several articles have been published discussing premedication with various agents in adult patients receiving general anesthesia,1,2 but there is little literature regarding pediatric patients. In an era in which Children’s has established a commitment to "no needless pain," it is important to establish procedures that will minimize discomfort during the sedation procedure.

We hypothesize that premedication with intravenous 1% lidocaine will decrease the burning sensation during induction of propofol procedural sedation for children.

 “A clinical decision rule for the use of radiography in the evaluation of suspected clavicle fractures”
Principal investigator: Sam Reid, MD


Background: Fractures of the clavicle are among the most common fractures in pediatric patients. Approximately 150 children are diagnosed with a fractured clavicle in the emergency department (ED) at Children’s each year. Because the clavicle lies just beneath the skin and is easily palpable on exam, many clavicle fractures are diagnosed clinically prior to radiography. It may be possible to develop a clinical decision rule with high sensitivity and specificity that would allow the clinician to make an accurate diagnosis of a clavicle fracture without the need for radiography, thereby eliminating unnecessary radiation.

Methods: We will conduct a prospective, un-blinded, observational study to determine whether a group of clinical findings can be identified to predict the presence or absence of clavicular fracture with a high degree of sensitivity and specificity. We will enroll a total of 500 subjects (150 during the pilot stage and 350 during the main study) with a chief complaint of non-penetrating shoulder injury. The decision rule will be developed using observed clinical findings in the pilot stage. Sensitivity and specificity for diagnosis of clavicle will be tested during the main study.

 Relevance: Development of a decision rule for the use of radiography for the clinical evaluation of clavicular injuries could result in decreased radiation exposure, cost and time in the emergency department for affected patients.

“Utility of plasma D-dimer for predicting clinically important intracranial injury in children”
Principal investigator: Sam Reid, MD


Background: Diagnosis of Traumatic Brain Injury (TBI) presents a significant challenge for the treating clinician. While most cases of head injury are minor, delayed diagnosis or misdiagnosis can lead to death or permanent disability. Head Computed Tomography (CT) provides rapid identification of TBI in children, but utilizes ionizing radiation that may increase the risk of cancer. To decrease reliance on head CT, a safe, reliable, rapid and cost effective screening tool is needed to augment the clinical history and physical examination to identify head-injured children at risk for significant intracranial injury and therefore in need of a CT scan. The proposed study aims to determine the utility of plasma D-dimer levels for predicting the presence of clinically important intracranial injury in the traumatically head injured child. 

Methods: We will conduct a prospective, cross sectional observation study to determine the association between D-dimer levels and clinically important intracranial injury as determined by results of CT scans among patients presenting to Children’s emergency department (ED). We will enroll 400 subjects ages 0 and 17 who present with a chief complaint of closed head injury and meet Pediatric Emergency Care Applied Research Network (PECARN) criteria for head CT.  

Relevance: Understanding the utility of D-dimer for identifying clinically important intracranial injury could provide clinicians with a rapid, cost-effective, quantifiable diagnostic tool that is free of the risks of ionizing radiation to make important decisions regarding the clinical management of head injured children. If successful, our study offers the potential to provide a tool that will allow clinicians to identify patients who, despite meeting published criteria indicating a positive need for a CT scan, would likely have normal or non-clinically important CT findings. This would reduce the risks related to unnecessary radiation exposure and decrease medical expense.

 2011 Grant Recipients

“Evaluation of sleep in children and adolescents with Cystic Fibrosis”
Principal investigator: Keith Cavanaugh, MD


Project summary: Cystic fibrosis (CF) is a life-shortening disease that affects primarily the lungs but may also affect other organs. This multi-organ involvement may lead to secondary problems for people with CF. Studies have shown that children with CF experience symptoms of pain, sleep disturbance, anxiety and depression.

Specifically, inefficient sleep may result in decreased quality of life and treatment adherence. To date, little research has been done assessing the quality of sleep in children with CF. We intend to recruit 50 children and adolescents between the ages of six and nineteen who have a confirmed diagnosis of CF. Their sleep habits and patterns will be evaluated through a 14 day wrist actigraphy and sleep log. We will compare these sleep habits and patterns with quality of life, behavioral and emotional functioning, and treatment adherence assessments.

Relevance: In order to provide comprehensive care to patients with CF, it is important to address the less obvious health issues such as inability to achieve adequate sleep. Lack of sleep may reduce quality of life and impair behavioral or emotional functioning. Treatment adherence may also be affected in patients who do not have sufficient sleep, which in turn may result in poor health outcomes. The results of this research, while providing us with a more complete picture of our patients, will enable us to provide optimal all-inclusive care. We will also have the opportunity to disseminate our results to the national CF community.

“Development of a cough reflex sensitivity test for children with motor and/or cognitive delay"
Principal investigator: Stephen Kurachek, MD


Project summary: Cough threshold is breached when a provocative stimulus (inflammation, irritation, secretions) exceeds a specific neurogenic limit, and the mechanical components that constitute cough rapidly ensue. An individual's cough threshold exists along a spectrum but remains relatively constant over time. Cough threshold is delineated through cough reflex sensitivity (CRS) testing, a research tool that has been performed safely in adults and children for decades. Historically, CRS testing has been restricted to subjects six years of age and older who can follow instructions and perform specific breathing maneuvers inherent to the test. Many children with motor and/or cognitive delay have what appears to be an elevated cough threshold. These children cough infrequently, and they suffer the predictable consequences of poor secretion clearance: atelectasis, impaired gas exchange and infection. This population has escaped CRS testing for lack of a suitable methodology that requires minimal subject cooperation or coordination. The primary goal of this study is to develop a safe and reliable CRS test for children with motor and/or cognitive delay. This study promises to lay the scientific foundation for the utilization of a tussive agent employed in CRS testing as a therapeutic agent to promote cough in individuals suffering from the detrimental effects of a high cough threshold.

 Relevance: No prior study has explored the limited cough frequency observed in children with motor and/or cognitive delay. Limited cough frequency results in poor secretion clearance, infection and often hospitalization. A variety of maneuvers to promote cough have been directed at this population with only limited success (see Appendix l). Successful completion of this study will extend our knowledge of cough physiology and posit whether an inhalational tussive agent is an overlooked simple and safe maneuver to promote cough in a vulnerable childhood population.

 “Effects of inspiratory vs. expiratory tidal volume targeting in an animal model of surfactant deficiency”
Principal investigator: Andrea Lampland, MD


Objective: Investigate the physiologic effects of targeting mechanical breath volumes based on inspiratory or expiratory tidal volumes and to investigate the physiologic effects of an endotracheal tube leak on targeted inspiratory and expiratory tidal volumes in both the spontaneously breathing and paralyzed state.

Hypothesis: We hypothesize that in a spontaneously breathing surfactant deficient animal model, volume targeting of the inspiratory tidal volume as well as introduction of an endotracheal tube leak will result in significantly increased respiratory rates. When the animals are paralyzed and respiratory rate is controlled, we anticipate that hypercapnia will be significantly increased in the inspiratory tidal volume targeted group versus the expiratory tidal volume targeted group and further increased with introduction of an endotracheal tube leak

Study design: Randomized, sequential block cross-over study of 20 newborn piglets with saline-lavage induced surfactant deficiency. Physiologic variables (heart rate, respiratory rate, blood pressure and oxygen saturations), arterial blood gases and computerized mechanical ventilator data will be documented throughout the study. Analysis: Continuous variables will be compared using AN OVA with post hoc tests. Dichotomous variables will be compared using Chi-squared analysis or Fisher's exact test as appropriate. P-values of < 0.05 will be considered statistically significant.

“Implementation of a clinical decision rule for children with acute abdominal pain”
Principal investigator: Manu Madhok, MD, MPH


Project summary: We plan to implement an electronic, evidence-based care pathway for the evaluation of pediatric patients presenting to an emergency department (ED) with possible appendicitis, in order to promote standardized, safe and cost-effective care. Utilization of computed tomography (CT), utilization of ultrasound (US), rate of missed appendicitis and direct medical costs will be assessed to determine the efficacy of the pathway.

 Relevance: Immediate and direct benefit of implementation of our pathway could be a reduction in CT scan utilization, a reduction in the misdiagnosis rate and thus more appropriate and efficient care for children with possible appendicitis.

“Cytokines and the effect on sleep in children with Acute Lymphoblastic Leukemia”
Principal investigator: Yoav Messinger, MD


This study, “Cytokines and the affect on sleep in children with Acute Lymphoblastic Leukemia (ALL), proposes to analyze the relationship between sleep or fatigue and cytokines and hormones in children with ALL during maintenance therapy. Sleep and fatigue are common understudied potential adverse effects in Children with ALL. Cytokines and other hormones may be mediators of problems with sleep and fatigue. Pro-inflammatory cytokines have been identified as possible mediators of excessive daytime sleepiness and fatigue. In animals, CNS cytokines and hormones have been identified as mediators of increased sleepiness. No such studies have been reported in children. In a prior study the cytokines IL-6, IL-I 0 and GM-CSF correlate with fatigue and sleep problems. In that study CSF and plasma were stored for additional cytokine and hormone analysis.

 Using stored CSF and plasma samples we propose to evaluate other cytokines, soluble cytokine receptors and hormones that have recently been identified as critical mediators of sleep and fatigue. The following cytokines and hormones known to be involved with sleep regulation will be measured: Cortisol, CRH, BDNF, TNF receptors, IL-6 receptor, GH, GHRH, IL-18, EGF, aFGF, IFN-α, siL-lRI, siL-lR2. This study can contribute significantly to our understanding of the critical role of cytokines and hormones in mediating fatigue, and sleep disorders in children, and in children with ALL. There is exceedingly limited information on CSF cytokine levels in children and this innovative study provides an unprecedented opportunity to correlate CSF cytokine levels with sleep and fatigue in humans: children with ALL.

“Adequacy of pain management in children discharged from the emergency department after treatment for upper extremity fractures”
Principal investigator: Henry Ortega, MD


Project summary: Upper extremity fracture is a common and painful presenting complaint for pediatric emergency department (ED) patients. Treatment approaches vary and lead to discrepancies in the management of post-discharge pain. This prospective, observational study seeks to determine the prevalence of significant post-discharge pain among different racial/ethnic and age groups and to compare pain severity between patients with upper extremity fractures requiring simple splinting to those treated with sedated reduction and splinting.

 Relevance: Determining typical patterns of pain and pain medication administration, while noting any discrepancies among racial/ethnic and age groups, will create a platform to increase awareness of the issue and motivate providers to assess and improve their own performance.

“Probiotics in the treatment of iron deficiency in children with restless leg syndrome: A double-blind, randomized controlled study”
Principal investigator: Gerald Rosen, MD


Project summary: Iron deficiency is the most common micronutrient deficiency in the world and is associated with significant adverse health effects including: cognitive deficits, immune deficiency, anemia, fatigue and increased mortality. Restless leg syndrome (RLS) affects 5 to 10% of adults in the United States and 2% of children. The prevalence of RLS in children with attention deficit hyperactivity disorder (ADHD) is estimated to be 12 to 35%. Iron deficiency has been recognized as an important factor in RLS, and the current recommendation for adults and children with RLS is to maintain serum ferritin level above 50 ng/ml. A common problem in the treatment of iron deficiency is that oral iron is poorly absorbed. Probiotics are a group of microorganisms that benefit the host and are available naturally in fermented foods or as oral supplements. Naturally occurring probiotics, such as yogurt have been used to promote human health for millennia. Probiotic oral supplements have been proven effective and are currently approved for use in pediatrics in the treatment of: acute diarrhea, antibiotic associated diarrhea, and atopy associated with cow milk allergy; and there is some evidence that probiotics may be useful in the treatment of irritable bowel syndrome and necrotizing enterocolitis. In studies in adults, and in cell culture experiments, probiotics have improved iron absorption, but this question has never been studied in children.

Relevance: This study proposes to compare the standard treatment for iron deficiency in children (supplemental iron plus vitamin C) with RLS; to supplemental iron plus vitamin C plus probiotics in a randomized, double-blind randomized controlled trial.

 “Pediatric palliative care service underutilization: A mixed methods study exploring accessibility and caregiver coping”
Principal investigator: Andrea Nugent, MPH, PhD candidate


Pediatric Palliative Care (PPC) is a rapidly growing field, yet data is scarce around referral patterns, parental perspectives or family coping. Children with life-threatening or life-limiting conditions benefit from early referral to PPC services, yet many of these children are referred later in the course of their disease when symptoms are advanced or end of life is near.

Children’s department of homecare, pain medicine, palliative care and integrative medicine cares for a high volume of patients and is uniquely positioned to study these patients to identify barriers to PPC referral. The homecare program provides in-home nursing services to approximately 1,300 infants and children annually, many of whom qualify for, but are not referred for PPC for unknown reasons.

This study will prospectively identify children who meet PPC referral criteria and examine referral patterns to home-based nursing (homecare) and multidisciplinary PPC programs (Karuna and Hospice). Caregivers of children in both programs will be invited to share information about their child’s referral, their knowledge of PPC, and their stress and coping status at the time of enrollment and three months later. New PPC referral criteria will be used to identify eligible families. Questionnaires, chart review, and a validated scale will be used to capture family experiences.

This study is the first to examine caregiver perspectives on PPC under-utilization; to describe associations between caregiver perspectives and institutional, clinical, and family characteristics; and to learn how caregivers handle stress associated with their child’s condition. Information will offer important insights into an under-researched group of children.

 “Animated picture to improve provider adherence to CT scan for head injury rule”
Principal investigator: Olufunmilayo Salami, MD, MSc


Project summary: It is difficult for pediatric emergency department (ED) providers to recognize clinically significant head injuries that are likely to require neurosurgical intervention or close monitoring from those that can be safely discharged. Promising evidence suggests visual cues may prompt providers to more strictly adhere to CT guidelines. This study will explore how visual reminders of the PECARN CT Head Injury rules impact provider compliance with these guidelines.

 Relevance: An animated picture pop-up window with CT guidelines could ultimately reduce the number of unnecessary CT scans while still allowing providers to efficiently recognize clinically significant head injuries.