Acute opioid overdose in pediatric patients.

Recent increases in pediatric and adolescent opioid fatalities mandate an urgent need for early consideration of possible opioid exposure and specific diagnostic and management strategies and interventions tailored to these unique populations. In contrast to adults, pediatric methods of exposure include accidental ingestions, prescription misuse, and household exposure. Early recognition, appropriate diagnostic evaluation, along with specialized treatment for opioid toxicity in this demographic are discussed. A key focus is on Naloxone, an essential medication for opioid intoxication, addressing its unique challenges in pediatric use. Unique pediatric considerations include recognition of accidental ingestions in our youngest population, critical social aspects including home safety and intentional exposure, and harm reduction strategies, mainly through Naloxone distribution and education on safe medication practices. It calls for a multifaceted approach, including creating pediatric-specific guidelines, to combat the opioid crisis among children and to work to lower morbidity and mortality from opioid overdoses.

Determinants of Persistent, Multi-Year, Frequent Emergency Department Use Among Children and Young Adults in Three US States.

OBJECTIVE: This study examines the factors associated with persistent, multi-year, and frequent emergency department (ED) use among children and young adults. METHODS: We conducted a retrospective secondary analysis using the 2012-2017 Healthcare Cost and Utilization Project State Emergency Department Databases for children and young adults aged 0-19 who visited any ED in Florida, Massachusetts, and New York. We estimated the association between persistent frequent ED use and individuals' characteristics using multivariable logistic regression models. RESULTS: Among 1.3 million patients with 1.8 million ED visits in 2012, 2.9% (37,558) exhibited frequent ED use (≥4 visits in 2012) and accounted for 10.2% (181,138) of all ED visits. Longitudinal follow-up of frequent ED users indicated that 15.4% (5770) remained frequent users periodically over the next 1 or 2 years, while 2.2% (831) exhibited persistent frequent use over the next 3-5 years. Over the 6-year study period, persistent frequent users had 31,551 ED visits at an average of 38.0 (standard deviation = 16.2) visits. Persistent frequent ED use was associated with higher intensity of ED use in 2012, public health insurance coverage, inconsistent health insurance coverage over time, residence in non-metropolitan and lower-income areas, multimorbidity, and more ED visits for less medically urgent conditions. CONCLUSIONS: Clinicians and policymakers should consider the diverse characteristics and needs of pediatric persistent frequent ED users compared to broader definitions of frequent users when designing and implementing interventions to improve health outcomes and contain ED visit costs.

The Management of Children and Youth With Pediatric Mental and Behavioral Health Emergencies.

Mental and behavioral health (MBH) emergencies in children and youth continue to increasingly affect not only the emergency department (ED), but the entire spectrum of emergency medical services for children, from prehospital services to the community. Inadequate community and institutional infrastructure to care for children and youth with MBH conditions makes the ED an essential part of the health care safety net for these patients. As a result, an increasing number of children and youth are referred to the ED for evaluation of a broad spectrum of MBH emergencies, from depression and suicidality to disruptive and aggressive behavior. However, challenges in providing optimal care to these patients include lack of personnel, capacity, and infrastructure, challenges with timely access to a mental health professional, the nature of a busy ED environment, and paucity of outpatient post-ED discharge resources. These factors contribute to prolonged ED stays and boarding, which negatively affects patient care and ED operations. Strategies to improve care for MBH emergencies, including systems level coordination of care, is therefore essential. The goal of this policy statement and its companion technical report is to highlight strategies, resources, and recommendations for improving emergency care delivery for pediatric MBH.

Emergency department utilization and disposition outcomes by pediatric patients with cancer in Maryland and New York from 2013 to 2017.

BACKGROUND: Pediatric patients with cancer commonly seek emergency department (ED) care, yet there is limited evidence on ED utilization patterns and disposition outcomes among these patients. METHODS: Retrospective analysis of the Healthcare Cost and Utilization Project State Emergency Department Databases and State Inpatient Databases for Maryland and New York from 2013 to 2017. We compared ED visits and disposition outcomes for 5.8 million pediatric patients (<18 years old) with and without cancer, and used multivariable regressions to estimate associations between the number of ED visits, hospital (inpatient) admissions through the ED, and ED or inpatient mortality and sociodemographic and clinical factors within the cancer cohort. RESULTS: Pediatric patients with cancer had more ED visits per year on average (2.4 vs. 1.5, p < .001), higher shares of admissions (56.8% vs. 6.6%, p < .001) and mortality (1.2% vs. 0.1%, p < .001) compared to those without cancer. Among patients with cancer, uninsured pediatric patients had fewer ED visits and lower risk of admission to a hospital through the ED compared to those with Medicaid coverage (total visits: incidence rate ratio [IRR]: 0.82, 95% confidence intervals [CI]: 0.75-0.90; admission: IRR: 0.75, 95% CI: 0.65-0.86). Mortality risks were higher for pediatric patients with cancer residing in areas with the lowest median household income, and with no health insurance coverage (IRR: 2.81, 95% CI: 1.21-6.51) compared to Medicaid. CONCLUSIONS: Our findings emphasize the importance of enhancing health insurance coverage policies and social services for pediatric patients with cancer and their families to address clinical and nonclinical needs.

Molecular insights into the axon guidance molecules Sidestep and Beaten path.

The transmembrane protein Sidestep (Side) functions as a substrate-bound attractant for motor axons in Drosophila. Outgrowing motor axons recognize Side via Beaten path Ia (Beat) and migrate along Side-expressing tissues. Here, we report a structure-function analysis of these guidance molecules using a variety of mutant lines and transgenic constructs. Investigation of Side mutants shows that the exchange of a single amino acid (L241H) in the second immunoglobulin domain disturbs Side function and subcellular localization. Overexpression of Side and Beat deletion constructs in S2 cells and muscles demonstrate that the first Ig domains of both proteins are necessary for their interaction. Furthermore, subcellular distributions of several Beat constructs identify functional domains and suggest a potential posttranslational processing step in ER compartments. In fact, fusing full-length Beat at both the N- and C-terminus with GFP and mCherry, respectively, shows that the N-terminal domain is transported to the plasma membrane and exposed on the cell surface, while the C-terminal domain accumulated in the nucleus. Taken together, these results give insights into the interaction of Side and Beat and imply that Beat might be subject to proteolytic cleavage during maturation.

Marijuana use in children: An update focusing on pediatric tetrahydrocannabinol and cannabidiol use.

Cannabis is the most used recreational drug in the United States, and its use is increasing among children and adolescents.  With the increase in legalized use, there have been increases in intentional and accidental cannabis exposure in the pediatric population. There is also minimized perceived risk.  We review the current use of cannabis and its derivatives, the drug effects and clinical presentation, common misconceptions, pharmacology, and epidemiology. Finally, we review some long-term consequences of cannabis use.

Approach considerations for the management of strangulation in the emergency department.

Patients with a history of strangulation present to the emergency department with a variety of different circumstances and injury patterns. We review the terminology, pathophysiology, evaluation, management, and special considerations for strangulation injuries, including an overview of forensic considerations and legal framework for strangulation events.

Managing acute pain in children presenting to the emergency department without opioids.

Pediatric pain is challenging to assess and manage. Frequently underestimated in children, untreated pain may have consequences including increased fear, anxiety, and psychological issues. With the current opioid crisis, emergency physicians must be knowledgeable in both pharmacologic and non-pharmacologic approaches to address pain and anxiety in children that lead to enhanced patient cooperation and family satisfaction. This document focuses pain management and distress mitigation strategies for the brief diagnostic and therapeutic procedures commonly performed.

Emergency department strategies to combat the opioid crisis in children and adolescents.

The opioid crisis has greatly affected not only adults but also children as well. As clinicians develop effective approaches to minimize pain and distress in children, the risks and benefits of opioids must be carefully considered. Children of parents with opioid use disorder are also at risk of living in unstable environments, performing poorly academically, engaging in future drug use, and having increased stress, which affects their development before entering adulthood. This statement focuses on the effects of the opioid crisis on children and adolescents and is intended to inform institutional policies, improve education, advocate for evidence-informed guidelines, and improve the care of children affected by the opioid epidemic who are seen in the emergency department.

Use of antitussive medications in acute cough in young children.

Acute cough, a common complaint in young children, is often the result of a viral upper respiratory infection. Cough and cold remedies generate billions of dollars in annual sales in the United States, despite a lack of evidence of their efficacy and multiple warnings by the US Food and Drug Administration. The current article begins with the best available evidence for common over-the-counter (OTC) and prescription antitussive remedies in children. The article concludes with a discussion of the pros and cons for the use of antitussives in children with cough. In general, OTC antitussive medications should not be routinely used in children under 2 years of age. In certain cases, antitussives with minimal adverse profile and some evidence of benefit may be recommended after informed counseling.

ACR Appropriateness Criteria® Vomiting in Infants.

Vomiting in infants under the age of 3 months is one of the most common reasons for parents to seek care from their doctor or present to an emergency room. The imaging workup that ensues is dependent on several factors: age at onset, days versus weeks after birth, quality of emesis, bilious or nonbilious vomiting, and the initial findings on plain radiograph, suspected proximal versus distal bowel obstruction. The purpose of these guidelines is to inform the clinician, based on current evidence, what is the next highest yield and most appropriate imaging study to pursue a diagnosis. The goal is rapid and accurate arrival at a plan for treatment, whether surgical or nonsurgical. The following modalities are discussed for each variant of the symptom: plain radiography, fluoroscopic upper gastrointestinal series, fluoroscopic contrast enema, ultrasound of the abdomen, nuclear medicine gastroesophageal reflux scan. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.

A Modified Delphi Study to Prioritize Content for a Simulation-based Pediatric Curriculum for Emergency Medicine Residency Training Programs.

OBJECTIVES: Pediatric training is an essential component of emergency medicine (EM) residency. The heterogeneity of pediatric experiences poses a significant challenge to training programs. A national simulation curriculum can assist in providing a standardized foundation of pediatric training experience to all EM trainees. Previously, a consensus-derived set of content for a pediatric curriculum for EM was published. This study aimed to prioritize that content to establish a pediatric simulation-based curriculum for all EM residency programs. METHODS: Seventy-three participants were recruited to participate in a three-round modified Delphi project from 10 stakeholder organizations. In round 1, participants ranked 275 content items from a published set of pediatric curricular items for EM residents into one of four categories: definitely must, probably should, possibly could, or should not be taught using simulation in all residency programs. Additionally, in round 1 participants were asked to contribute additional items. These items were then added to the survey in round 2. In round 2, participants were provided the ratings of the entire panel and asked to rerank the items. Round 3 involved participants dichotomously rating the items. RESULTS: A total of 73 participants participated and 98% completed all three rounds. Round 1 resulted in 61 items rated as definitely must, 72 as probably should, 56 as possibly could, 17 as should not, and 99 new items were suggested. Round 2 resulted in 52 items rated as definitely must, 91 as probably should, 120 as possibly could, and 42 as should not. Round 3 resulted in 56 items rated as definitely must be taught using simulation in all programs. CONCLUSIONS: The completed modified Delphi process developed a consensus on 56 pediatric items that definitely must be taught using simulation in all EM residency programs (20 resuscitation, nine nonresuscitation, and 26 skills). These data will serve as a targeted needs assessment to inform the development of a standard pediatric simulation curriculum for all EM residency programs.

2018 Academic Emergency Medicine Consensus Conference: A Workforce Development Research Agenda for Pediatric Care in the Emergency Department.

Each year, more than 30 million children visit U.S. emergency departments (EDs). Although the number of pediatric emergency medicine specialists continues to rise, the vast majority of children are cared for in general EDs outside of children's hospitals. The diverse workforce of care providers for children must possess the knowledge, experience, skills, and systemic support necessary to deliver excellent pediatric emergency care. There is a crucial need to understand the factors that drive the professional development and support systems of this diverse workforce. Through the iterative process culminating with the 2018 Academic Emergency Medicine consensus conference, we have identified five key research themes and prioritized a specific research agenda. These themes represent critical gaps in our understanding of the development and maintenance of the pediatric emergency care workforce and allow for a prioritization of future research efforts. Only by more fully understanding the gaps in workforce needs, and the necessary steps to address these gaps, can outcomes be optimized for children in need of emergency care.

Generation of a 3D Liver Model Comprising Human Extracellular Matrix in an Alginate/Gelatin-Based Bioink by Extrusion Bioprinting for Infection and Transduction Studies.

Bioprinting is a novel technology that may help to overcome limitations associated with two-dimensional (2D) cell cultures and animal experiments, as it allows the production of three-dimensional (3D) tissue models composed of human cells. The present study describes the optimization of a bioink composed of alginate, gelatin and human extracellular matrix (hECM) to print human HepaRG liver cells with a pneumatic extrusion printer. The resulting tissue model was tested for its suitability for the study of transduction by an adeno-associated virus (AAV) vector and infection with human adenovirus 5 (hAdV5). We found supplementation of the basic alginate/gelatin bioink with 0.5 and 1 mg/mL hECM provides desirable properties for the printing process, the stability of the printed constructs, and the viability and metabolic functions of the printed HepaRG cells. The tissue models were efficiently transduced by AAV vectors of serotype 6, which successfully silenced an endogenous target (cyclophilin B) by means of RNA interference. Furthermore, the printed 3D model supported efficient adenoviral replication making it suitable to study virus biology and develop new antiviral compounds. We consider the approach described here paradigmatic for the development of 3D tissue models for studies including viral vectors and infectious viruses.

Local to global: Working together to meet the needs of vulnerable communities.

Since 2012, the University of Wisconsin-Milwaukee (UWM) faculty from nursing and physical therapy (PT) have been working together towards a common goal: to meet the healthcare needs of vulnerable populations in Malawi and Milwaukee. Sharing valuable knowledge and understanding one another's professions have allowed us to develop interprofessional education (IPE) learning experiences for students to help identify how quality of life could be improved or enhanced for children and their families across two different geographic spaces, one in rural Malawi and the other in urban Milwaukee. IPE learning modules were implemented in UWM's community health-focused short-term study abroad programmes to Malawi. IPE learning modules were also piloted at one of UWM's nurse-managed community health centres, located in a low-income, African American community in the inner city of Milwaukee, Wisconsin. Based on survey data collected from 10 participating IPE students in Milwaukee, from nursing, occupational therapy, PT, and speech and language pathology, a pilot study yielded a statistically significant change in a positive direction for increased understanding of three interprofessional collaborative practice core competencies: values and ethics, roles and responsibilities, and teams and teamwork. In this article, we discuss the processes used to develop, implement, and evaluate IPE experiences for UWM students, which may enable other professionals to envision the various projects they can embark upon from an interprofessional perspective.

Improving Quality and Efficiency for Intussusception Management After Successful Enema Reduction.

OBJECTIVES: The purpose of this project was to implement a protocol facilitating discharge from the emergency department (ED) after successful radiologic ileocolic intussusception reduction in a pediatric referral center. METHODS: A multidisciplinary team identified drivers for successful quality improvement including educational brochures, a standardized radiologic report, an observation period in the ER with oral hydration challenges, and follow-up phone calls the day after discharge. Patient outcomes were tracked, and quarterly feedback was provided. RESULTS: Of 80 patients identified over a 24-month period, 34 (42.5%) did not qualify for discharge home due to need for surgical intervention (n = 9), specific radiologic findings (n = 11), need for additional intravenous hydration (n = 4), or other reasons (n = 7). Of 46 patients who qualified for discharge, 30 (65.2%) were successfully sent home from the ED. One patient returned with recurrent symptoms that required repeat enema reduction. Sixteen patients were observed and discharged within 23 hours. Adherence with discharge from the ED improved over time. Discharge from the ED was associated with cost savings and improved net margins at the hospital level for each encounter. CONCLUSIONS: A sustainable multidisciplinary quality improvement project to discharge intussusception patients from the ED after air-contrast enema reduction was successfully integrated in a high-volume referral center through education, standardized radiologic reporting, and protocoled follow-up.

Regulation of ß1 integrin-Klf2-mediated angiogenesis by CCM proteins.

Mechanotransduction pathways are activated in response to biophysical stimuli during the development or homeostasis of organs and tissues. In zebrafish, the blood-flow-sensitive transcription factor Klf2a promotes VEGF-dependent angiogenesis. However, the means by which the Klf2a mechanotransduction pathway is regulated to prevent continuous angiogenesis remain unknown. Here we report that the upregulation of klf2 mRNA causes enhanced egfl7 expression and angiogenesis signaling, which underlies cardiovascular defects associated with the loss of cerebral cavernous malformation (CCM) proteins in the zebrafish embryo. Using CCM-protein-depleted human umbilical vein endothelial cells, we show that the misexpression of KLF2 mRNA requires the extracellular matrix-binding receptor ß1 integrin and occurs in the absence of blood flow. Downregulation of ß1 integrin rescues ccm mutant cardiovascular malformations in zebrafish. Our work reveals a ß1 integrin-Klf2-Egfl7-signaling pathway that is tightly regulated by CCM proteins. This regulation prevents angiogenic overgrowth and ensures the quiescence of endothelial cells.

Symptoms of Persistent Behavior Problems in Children With Mild Traumatic Brain Injury.

OBJECTIVE: To investigate the effects of mild traumatic brain injury (mTBI) in children on symptom ratings of behavior problems across the first-year postinjury. SETTING: Emergency departments of 2 regional children's hospitals. PARTICIPANTS: Parents of 176 children with mTBI and 90 children with orthopedic injury aged 8 to 15 years. DESIGN: Group comparisons of postinjury parent and teacher ratings of child behavior problems controlling for background factors. MAIN MEASURES: Child Behavior Checklist and Teacher's Report Form. RESULTS: For younger but not older children in the sample, children with mTBI compared with children with orthopedic injury had higher postinjury ratings on the Child Behavior Checklist Total Behavior Problem scale (t264 = 3.34, P < .001) and higher rates of T-scores of 60 or more on this scale (odds ratio = 3.00; 95% confidence interval, 1.33-6.77; P = .008). For children with mTBI, hospitalization, motor vehicle accidents, loss of consciousness, and magnetic resonance imaging abnormality were associated with higher parent or teacher ratings. CONCLUSIONS: School-aged children with mTBI are at risk for persistent symptoms of behavior problems, especially if mTBI is more severe or occurs at a younger age. The findings justify monitoring of behavior long after injury and further research to identify risk factors for these symptoms and their association with clinical disorders.

Blood flow and Bmp signaling control endocardial chamber morphogenesis.

During heart development, the onset of heartbeat and blood flow coincides with a ballooning of the cardiac chambers. Here, we have used the zebrafish as a vertebrate model to characterize chamber ballooning morphogenesis of the endocardium, a specialized population of endothelial cells that line the interior of the heart. By combining functional manipulations, fate mapping studies, and high-resolution imaging, we show that endocardial growth occurs without an influx of external cells. Instead, endocardial cell proliferation is regulated, both by blood flow and by Bmp signaling, in a manner independent of vascular endothelial growth factor (VEGF) signaling. Similar to myocardial cells, endocardial cells obtain distinct chamber-specific and inner- versus outer-curvature-specific surface area sizes. We find that the hemodynamic-sensitive transcription factor Klf2a is involved in regulating endocardial cell morphology. These findings establish the endocardium as the flow-sensitive tissue in the heart with a key role in adapting chamber growth in response to the mechanical stimulus of blood flow.