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Serial plasma and CSF cell-free tumor DNA (CF-TDNA) Tracking in diffuse midline glioma patients undergoing treatment with ONC201 [Meeting Abstract]

Cantor, E; Wierzbicki, K; Tarapore, R S; Thomas, C; Cartaxo, R; Yadav, V N; Ravindran, R; Bruzek, A K; Wadden, J; Babilla, C M; Kawakibi, A R; Ji, S; Ramos, J; Paul, A; Wolfe, I; Leonard, M; Robertson, P; Franson, A; Mody, R; Garton, H; Odia, Y; Kline, C; Vitanza, N A; Khatua, S; Mueller, S; Allen, J E; Gardner, S; Koschmann, C
Diffuse midline glioma (DMG) with the H3K27M mutation is a lethal childhood brain cancer, with patients rarely surviving 2 years from diagnosis. We conducted a multi-site Phase 1 trial of the imipridone ONC201 for children with H3K27M-mutant glioma (NCT03416530). Patients enrolled on Arm D of the trial (n=24) underwent serial lumbar puncture (baseline, 2, 6 months) for cell-free tumor DNA (cf-tDNA) analysis at time of MRI. Additionally, patients on all arms of the trial at the University of Michigan underwent serial plasma collection. CSF collection was feasible in this cohort, with no procedural complications. We collected 96 plasma samples and 53 CSF samples from 29 patients, including those with H3F3A (H3.3) (n=13), HIST13HB (H3.1) (n= 4), and unknown H3 status/not biopsied (n=12) [range of 0-8 CSF samples and 0-10 plasma samples]. We performed digital droplet polymerase chain reaction (ddPCR) analysis and/or ampliconbased electronic sequencing (Oxford Nanopore) of cf-tDNA samples and compared variant allele fraction (VAF) to radiographic change (maximal 2D tumor area on MRI). Preliminary analysis of samples demonstrates a correlation between changes in tumor size and H3K27M cf-tDNA VAF, when removing samples with concurrent bevacizumab. In multiple cases, early reduction in CSF cf-tDNA predicts long-term clinical response (>1 year) to ONC201, and does not increase in cases of later-defined pseudo-progression (radiation necrosis). For example, a now 9-year old patient with thalamic H3K27M-mutant DMG underwent treatment with ONC201 after initial radiation and developed increase in tumor size at 4 months post-radiation (124% baseline) of unclear etiology at the time. Meanwhile, her ddPCR declined from baseline 6.76% VAF to <1%, which has persisted, with now near complete response (15% tumor reduction) at 30 months on treatment from diagnosis. In summary, we present the feasibility and utility of serial CSF/plasma monitoring of a promising experimental therapy for DMG
EMBASE:635831152
ISSN: 1523-5866
CID: 4982472

Impact of a Child Life and Music Therapy Procedural Support Intervention on Parental Perception of Their Child's Distress During Intravenous Placement

Ortiz, Gabriela S; O'Connor, Todd; Carey, Jessa; Vella, Adam; Paul, Audrey; Rode, Diane; Weinberg, Alan
OBJECTIVES/OBJECTIVE:Child life specialists and music therapists have a unique and integral role in providing psychosocial care to pediatric patients and families. These professionals are trained to provide clinical interventions that support coping and adjustment and reduce the risk of psychological trauma related to hospital visits and health care encounters. The researchers devised a multimodal approach using a combined child life and music therapy intervention to address procedure-related distress in patients receiving intravenous (IV) placement in the pediatric emergency department. The aim of this study was to investigate the efficacy of this collaborative intervention by evaluating parental perception of their child's distress. METHODS:This study was a prospective analysis investigating the impact of a child life and music therapy intervention on children aged 4 to 11 years old receiving an IV placement in the pediatric emergency department. Efficacy was evaluated by comparing scores between a 4-question pretest and subsequent 4-question posttest that asked the child's parent to evaluate how they anticipated their child would respond to the procedure, and then to evaluate how they perceived their child to have responded after the procedure. Qualitative data were collected in the form of open-ended comments, which were accommodated at the end of the posttest. Data were analyzed by the Cochran-Mantel-Haenszel method for testing repeated ordinal responses and the PROC GENMOD procedure in the SAS system software. RESULTS:A total of 41 participants were enrolled in this study. Results of the statistical analysis revealed significant differences between all pre- and posttest scores (P < 0.05), and significant likelihood that the patient would improve relative to the 4 questions, as a result of the child life and music therapy intervention. CONCLUSIONS:Improvement was demonstrated across all 4 questions, suggesting that the child life and music therapy intervention supported healthy, adaptive coping and helped to minimize distress experienced by patients during IV placement. These results underscore the importance and potential clinical impact of child life psychological preparation and psychotherapy-based music therapy interventions in reducing distress in pediatric patients during common medical procedures.
PMID: 28225375
ISSN: 1535-1815
CID: 3525912

Consensus Statement on Urgent Care Centers and Retail Clinics in Acute Care of Children

Saidinejad, Mohsen; Paul, Audrey; Gausche-Hill, Marianne; Woolridge, Dale; Heins, Alan; Scott, William Russell; Friesen, Phillip; Rayburn, David; Conners, Gregory; Petrack, Emory; Horeczko, Timothy; Stoner, Michael; Edgerton, Elizabeth; Joseph, Madeline
This article provides recommendations for pediatric readiness, scope of services, competencies, staffing, emergency preparedness, and transfer of care coordination for urgent care centers (UCCs) and retail clinics that provide pediatric care. It also provides general recommendations for the use of telemedicine in these establishments.With continuing increases in wait times and overcrowding in the nation's emergency departments and the mounting challenges in obtaining timely access to primary care providers, a new trend is gaining momentum for the treatment of minor illness and injuries in the form of UCCs and retail clinics. As pediatric visits to these establishments increase, considerations should be made for the type of injury or illnesses that can be safely treated, the required level training and credentials of personnel needed, the proper equipment and resources to specifically care for children, and procedures for safe transfer to a higher level of care, when needed. When used appropriately, UCCs and retail clinics can be valuable and convenient patient care resources.
PMID: 30422946
ISSN: 1535-1815
CID: 3525922

Role of Pediatric Emergency Physicians in Identifying Bullying

Waseem, Muhammad; Paul, Audrey; Schwartz, Gerald; Pauze, Denis; Eakin, Paul; Barata, Isabel; Holtzman, Doug; Benjamin, Lee S; Wright, Joseph L; Nickerson, Amanda B; Joseph, Madeline
BACKGROUND:Bullying is an important public health issue with broad implications. Although this issue has been studied extensively, there is limited emergency medicine literature addressing bullying. The emergency department (ED) physician has a unique opportunity to identify children and adolescents that are victims of bullying, and make a difference in their lives. OBJECTIVE:Our aim is to discuss the role of the emergency physician (EP) in identifying patients who have been victims of bullying and how to provide effective management as well as referral for further resources. DISCUSSION/CONCLUSIONS:This document provides a framework for recognizing, stabilizing, and managing children who have experienced bullying. With the advent of social media, bullying behavior is not limited to in-person situations, and often occurs via electronic communication, further complicating recognition because it may not impart any physical harm to the child. Recognition of bullying requires a high level of suspicion, as patients may not offer this history. After the stabilization of any acute or overt indications of physical injury, along with obtaining a history of the mechanism of injury, the EP has the opportunity to identify the existence of bullying as the cause of the injury, and can address the issue in the ED while collaborating with "physician-extenders," such as social workers, toward identifying local resources for further support. CONCLUSIONS:The ED is an important arena for the assessment and management of children who have experienced bullying. It is imperative that EPs on the front lines of patient care address this public health epidemic. They have the opportunity to exert a positive impact on the lives of the children and families who are the victims of bullying.
PMID: 27693071
ISSN: 0736-4679
CID: 3525902

Evaluation and Monitoring of a Child With Hydrocarbon Pneumonitis Using Point-of-Care Lung Ultrasound in the Pediatric Emergency Department

Vazquez, Michelle; Paul, Audrey Z; Tay, Ee Tein; Tsung, James W
A well-appearing 3-year-old boy presented to the pediatric emergency department 2 hours after a presumed hydrocarbon ingestion. He was referred to the emergency department by his pediatrician after consultation with the local poison control center after possibly ingesting ylang ylang (Cananga odorata) fragrance oil. The child was asymptomatic with a normal physical examination. Point-of-care lung ultrasound identified focal hydrocarbon pneumonitis in the right lung and demonstrated resolution of these findings. Utilization of point-of-care ultrasound resulted in a shorter emergency department length of stay and the avoidance of radiation exposure from serial chest x-rays.
PMID: 26890296
ISSN: 1535-1815
CID: 2045402

Feasibility and Safety of Substituting Lung Ultrasound for Chest X-ray When Diagnosing Pneumonia in Children: A Randomized Controlled Trial

Jones, Brittany Pardue; Tay, Ee Tein; Elikashvili, Inna; Sanders, Jennifer E; Paul, Audrey Z; Nelson, Bret P; Spina, Louis A; Tsung, James W
BACKGROUND: Chest x-ray (CXR) is the test of choice for diagnosing pneumonia. Lung ultrasound (LUS) has been shown to be accurate for diagnosing pneumonia in children and may be an alternative to CXR. Our objective was to determine the feasibility and safety of substituting LUS for CXR when evaluating children with suspected pneumonia. METHODS: We conducted a randomized control trial comparing LUS to CXR in 191 children from birth to 21 years of age with suspected pneumonia in an emergency department. Patients in the investigational arm received a LUS. If there was clinical uncertainty after ultrasound, clinicians had the option to obtain CXR. Patients in the control arm underwent sequential imaging with CXR followed by LUS. Primary outcome was the rate of CXR reduction; secondary outcomes were missed pneumonia, subsequent unscheduled healthcare visits, and adverse events between investigational and control arms. RESULTS: There was a 38.8% reduction (95% CI, 30.0 to 48.9%) in CXR among investigational subjects compared to no reduction (95% CI, 0.0 to 3.6%) in the control group. Novice and experienced clinician-sonologists achieved 30.0% and 60.6% reduction in CXR use, respectively. There were no cases of missed pneumonia among all study participants (investigational arm 0%; 95% CI: 0.0-2.9%; control arm 0%; 95% CI 0.0-3%) or differences in adverse events, or subsequent unscheduled healthcare visits between arms. CONCLUSIONS: It may be feasible and safe to substitute LUS for CXR when evaluating children with suspected pneumonia with no missed cases of pneumonia or increase in rates of adverse events.
PMID: 26923626
ISSN: 1931-3543
CID: 2046112

Point-of-Care Ultrasonography by Pediatric Emergency Medicine Physicians

Marin, Jennifer R.; Lewiss, Resa E.; Shook, Joan E.; Ackerman, Alice D.; Chun, Thomas H.; Conners, Gregory P.; Dudley, Nanette C.; Fuchs, Susan M.; Gorelick, Marc H.; Lane, Natalie E.; Moore, Brian R.; Wright, Joseph L.; Bird, Steven B.; Blomkalns, Andra L.; Carmody, Kristin; Clem, Kathleen J.; Courtney, D. Mark; Diercks, Deborah B.; Fields, Matthew; Hockberger, Robert S.; Holmes, James F., Jr.; Hudak, Lauren; Jones, Alan E.; Kaji, Amy H.; Martin, Ian B. K.; Moore, Christopher; Panebianco, Nova; Benjamin, Lee S.; Barata, Isabel A.; Alade, Kiyetta; Arms, Joseph; Avarello, Jahn T.; Baldwin, Steven; Brown, Kathleen; Cantor, Richard M.; Cohen, Ariel; Dietrich, Ann Marie; Eakin, Paul J.; Gausche-Hill, Marianne; Gerardi, Michael; Graham, Charles J.; Holtzman, Doug K.; Hom, Jeffrey; Ishimine, Paul; Jinivizian, Hasmig; Joseph, Madeline; Mehta, Sanjay; Ojo, Aderonke; Paul, Audrey Z.; Pauze, Denis R.; Pearson, Nadia M.; Rosen, Brett; Russell, W. Scott; Saidinejad, Mohsen; Sloas, Harold A.; Schwartz, Gerald R.; Swenson, Orel; Valente, Jonathan H.; Waseem, Muhammad; Whiteman, Paula J.; Woolridge, Dale
Point-of-care ultrasonography is increasingly being used to facilitate accurate and timely diagnoses and to guide procedures. It is important for pediatric emergency medicine (PEM) physicians caring for patients in the emergency department to receive adequate and continued point-of-care ultrasonography training for those indications used in their practice setting. Emergency departments should have credentialing and quality assurance programs. PEM fellowships should provide appropriate training to physician trainees. Hospitals should provide privileges to physicians who demonstrate competency in point-of-care ultrasonography. Ongoing research will provide the necessary measures to define the optimal training and competency assessment standards. Requirements for credentialing and hospital privileges will vary and will be specific to individual departments and hospitals. As more physicians are trained and more research is completed, there should be one national standard for credentialing and privileging in point-of-care ultrasonography for PEM physicians.
ISI:000353726700039
ISSN: 0031-4005
CID: 3525982

Hip pain and fever: when it's not a septic joint, what's next? [Case Report]

Leuthauser, Amy; Paul, Audrey
Hip pain and fever in children include a broad differential. Most concerning is the possible diagnosis of a septic joint, which carries significant morbidity. We describe the case of a 13-year-old boy with fever and hip pain who was referred to the emergency department with concern for septic hip. The etiology was later discovered to be pyomyositis from methicillin-resistant Staphylococcus aureus. In areas with high prevalence of community-acquired methicillin-resistant Staphylococcus aureus, it is important for physicians to be aware of this rare, but potentially complicated condition.
PMID: 25560620
ISSN: 1535-1815
CID: 3525892

Death of a Child in the Emergency Department

Shook, Joan E.; Ackerman, Alice D.; Chun, Thomas H.; Conners, Gregory P.; Dudley, Nanette C.; Fuchs, Susan M.; Gorelick, Marc H.; Lane, Natalie E.; Moore, Brian R.; Wright, Joseph L.; Benjamin, Lee S.; Barata, Isabel A.; Alade, Kiyetta; Arms, Joseph; Avarello, Jahn T.; Baldwin, Steven; Brown, Kathleen; Cantor, Richard M.; Cohen, Ariel; Dietrich, Ann Marie; Eakin, Paul J.; Gausche-Hill, Marianne; Gerardi, Michael; Graham, Charles J.; Holtzman, Doug K.; Hom, Jeffrey; Ishimine, Paul; Jinivizian, Hasmig; Joseph, Madeline; Mehta, Sanjay; Ojo, Aderonke; Paul, Audrey Z.; Pauze, Denis R.; Pearson, Nadia M.; Rosen, Brett; Russell, W. Scott; Saidinejad, Mohsen; Sloas, Harold A.; Schwartz, Gerald R.; Swenson, Orel; Valente, Jonathan H.; Waseem, Muhammad; Whiteman, Paula J.; Woolridge, Dale; Snow, Sally K.; Vicioso, Michael; Herrin, Shari A.; Nagle, Jason T.; Cadwell, Sue M.; Goodman, Robin L.; Johnson, Mindi L.; Frankenberger, Warren D.; Renaker, Anne M.; Tomoyasu, Flora S.
The American Academy of Pediatrics, American College of Emergency Physicians, and Emergency Nurses Association have collaborated to identify practices and principles to guide the care of children, families, and staff in the challenging and uncommon event of the death of a child in the emergency department in this policy statement and in an accompanying technical report.
ISI:000338774800068
ISSN: 0031-4005
CID: 3525962

Management of acute asthma in the pediatric patient: an evidence-based review

Jones, Brittany Pardue; Paul, Audrey
Asthma is the most common chronic disease of childhood, with asthma exacerbations and wheezing resulting in more than 2 million emergency department visits per year. Symptoms can vary from mild shortness of breath to fatal status asthmaticus. Given the high prevalence of asthma and its potential to progress from mild to moderate to life-threatening, it is vital for emergency clinicians to have a thorough understanding of acute asthma management. Current evidence clearly supports the use of inhaled bronchodilators and systemic steroids as first-line agents. However, in those who fail to respond to nitial therapies, a variety of adjunct therapies and interventions are available with varying degrees of evidence to support their use. This review focuses specifically on evaluation and treatment of pediatric asthma in the emergency department and reviews the current evidence for various modes of treatment.
PMID: 23971269
ISSN: 1549-9650
CID: 3525882