Current progress in international pediatric emergency medicine.

PURPOSE OF REVIEW: Over the past four decades, pediatric emergency Medicine (PEM) has witnessed significant global development, with a notable increase in training programs and official recognition by regulatory bodies. However, disparities persist in the recognition of PEM as an independent subspecialty, availability of training programs on a global scale, academic recognition, and the ability to provide high-quality care to children worldwide. There is paucity of published literature regarding development of PEM globally. This review explores the current trends and challenges in international pediatric emergency medicine. RECENT FINDINGS: Current trends in international pediatric emergency medicine encompass the provision of training in pediatric-focused emergency and acute care, increased propagation of evidence-based guidelines specific to the care of children, the growth of collaborative research networks and interest groups within national and international societies. Simultaneously, the field continues to face challenges such as the lack of recognition, inequities in access, and a lack of dissemination of global PEM initiatives. SUMMARY: While recent advancements have significantly enhanced the state of international pediatric emergency medicine, including pediatric specific research networks and training programs, barriers still hinder its overall quality. Many of these obstacles are not unique to pediatric emergency medicine but are directly affected by financial disparities and lack of governmental and public recognition of the essential role of pediatric emergency care.

Inequities in Therapy for Infantile Spasms: A Call to Action.

OBJECTIVE: The aim of this study was to determine whether selection of treatment for children with infantile spasms (IS) varies by race/ethnicity. METHODS: The prospective US National Infantile Spasms Consortium database includes children with IS treated from 2012 to 2018. We examined the relationship between race/ethnicity and receipt of standard IS therapy (prednisolone, adrenocorticotropic hormone, vigabatrin), adjusting for demographic and clinical variables using logistic regression. Our primary outcome was treatment course, which considered therapy prescribed for the first and, when needed, the second IS treatment together. RESULTS: Of 555 children, 324 (58%) were non-Hispanic white, 55 (10%) non-Hispanic Black, 24 (4%) non-Hispanic Asian, 80 (14%) Hispanic, and 72 (13%) other/unknown. Most (398, 72%) received a standard treatment course. Insurance type, geographic location, history of prematurity, prior seizures, developmental delay or regression, abnormal head circumference, hypsarrhythmia, and IS etiologies were associated with standard therapy. In adjusted models, non-Hispanic Black children had lower odds of receiving a standard treatment course compared with non-Hispanic white children (odds ratio [OR], 0.42; 95% confidence interval [CI], 0.20-0.89; p = 0.02). Adjusted models also showed that children with public (vs. private) insurance had lower odds of receiving standard therapy for treatment 1 (OR, 0.42; CI, 0.21-0.84; p = 0.01). INTERPRETATION: Non-Hispanic Black children were more often treated with non-standard IS therapies than non-Hispanic white children. Likewise, children with public (vs. private) insurance were less likely to receive standard therapies. Investigating drivers of inequities, and understanding the impact of racism on treatment decisions, are critical next steps to improve care for patients with IS. ANN NEUROL 2022;92:32-44.

Identifying pediatric patients with multisystem inflammatory syndrome in children presenting to a pediatric emergency department.

OBJECTIVE: To compare clinical and laboratory features of children with Multisystem Inflammatory Syndrome in Children (MIS-C) to those evaluated for MIS-C in the Emergency Department (ED). METHODS: We conducted a retrospective review of the medical record of encounters with testing for inflammatory markers in an urban, tertiary care Pediatric ED from March 1, 2020 to July 31, 2020. We abstracted demographic information, laboratory values, selected medications and diagnoses. We reviewed the record for clinical presentation for the subset of patients admitted to the hospital for suspected MIS-C. We then used receiver operating curves and logistic regression to evaluate the utility of candidate laboratory values to predict MIS-C status. RESULTS: We identified 32 patients with confirmed MIS-C and 15 admitted and evaluated for MIS-C but without confirmation of SARS CoV-2 infection. We compared these patients to 267 encounters with screening laboratories for MIS-C. Confirmed MIS-C patients had an older median age, higher median fever on presentation and were predominantly of Hispanic and non-Hispanic Black race/ethnicity. All children with MIS-C had a C-reactive protein (CRP) >4.5 mg/dL, were more likely to have Brain Natriuretic Peptide >400 pg/mL (OR 10.50, 95%CI 4.40-25.04), D-Dimer >3 µg/mL (7.51, [3.18-17.73]), and absolute lymphocyte count (ALC) <1.5 K/mcL (21.42, [7.19-63.76]). We found CRP >4.5 mg/dL and ALC <1.5 K/mcL to be 86% sensitive and 91% specific to identify MIS-C among patients screened in our population. CONCLUSIONS: We identified that elevated CRP and lymphopenia was 86% sensitive and 91% specific for identification of children with MIS-C.

Development of Neurological Emergency Simulations for Assessment: Content Evidence and Response Process.

OBJECTIVE: To document two sources of validity evidence for simulation-based assessment in neurological emergencies. BACKGROUND: A critical aspect of education is development of evaluation techniques that assess learner's performance in settings that reflect actual clinical practice. Simulation-based evaluation affords the opportunity to standardize evaluations but requires validation. METHODS: We identified topics from the Neurocritical Care Society's Emergency Neurological Life Support (ENLS) training, cross-referenced with the American Academy of Neurology's core clerkship curriculum. We used a modified Delphi method to develop simulations for assessment in neurocritical care. We constructed checklists of action items and communication skills, merging ENLS checklists with relevant clinical guidelines. We also utilized global rating scales, rated one (novice) through five (expert) for each case. Participants included neurology sub-interns, neurology residents, neurosurgery interns, non-neurology critical care fellows, neurocritical care fellows, and neurology attending physicians. RESULTS: Ten evaluative simulation cases were developed. To date, 64 participants have taken part in 274 evaluative simulation scenarios. The participants were very satisfied with the cases (Likert scale 1-7, not at all satisfied-very satisfied, median 7, interquartile range (IQR) 7-7), found them to be very realistic (Likert scale 1-7, not at all realistic-very realistic, median 6, IQR 6-7), and appropriately difficult (Likert scale 1-7, much too easy-much too difficult, median 4, IQR 4-5). Interrater reliability was acceptable for both checklist action items (kappa = 0.64) and global rating scales (Pearson correlation r = .70). CONCLUSIONS: We demonstrated two sources of validity in ten simulation cases for assessment in neurological emergencies.

How Are Clinicians Treating Children With Sepsis in Emergency Departments in Latin America?: An International Multicenter Survey.

OBJECTIVE: Guidelines adherence in emergency departments (EDs) relies partly on the availability of resources to improve sepsis care and outcomes. Our objective was to assess the management of pediatric septic shock (PSS) in Latin America's EDs and to determine the impact of treatment coordinated by a pediatric emergency specialist (PEMS) versus nonpediatric emergency specialists (NPEMS) on guidelines adherence. METHODS: Prospective, descriptive, and multicenter study using an electronic survey administered to PEMS and NPEMS who treat PSS in EDs in 14 Latin American countries. RESULTS: We distributed 2164 surveys with a response rate of 41.5%, of which 22.5% were PEMS. Overall American College of Critical Care Medicine reported guidelines adherence was as follows: vascular access obtained in 5 minutes, 76%; fluid infusion technique, 60%; administering 40 to 60 mL/kg within 30 minutes, 32%; inotropic infusion by peripheral route, 61%; dopamine or epinephrine in cold shock, 80%; norepinephrine in warm shock, 57%; and antibiotics within 60 minutes, 82%. Between PEMS and NPEMS, the following differences were found: vascular access in 5 minutes, 87.1% versus 72.7% (P < 0.01); fluid infusion technique, 72.3% versus 55.9% (P < 0.01); administering 40 to 60 mL/kg within 30 minutes, 42% versus 29% (P < 0.01); inotropic infusion by peripheral route, 75.7% versus 56.3% (P < 0.01); dopamine or epinephrine in cold shock, 87.1% versus 77.3% (P < 0.05); norepinephrine in warm shock, 67.8% versus 54% (P < 0.01); and antibiotic administration within first 60 minutes, 90.1% versus 79.3% (P < 0.01), respectively. Good adherence criteria were followed by 24%. The main referred barrier for sepsis care was a failure in its recognition, including the lack of triage tools. CONCLUSIONS: In some Latin American countries, there is variability in self-reported adherence to the evidence-based recommendations for the treatment of PSS during the first hour. The coordination by PEMS support greater adherence to these recommendations.

Pre- and postnatal alcohol exposure delays, in female but not in male rats, the extinction of an auditory fear conditioned memory and increases alcohol consumption.

Repeated exposure to alcohol increases retrieval of fear-conditioned memories, which facilitates, among other factors, the emergence of post-traumatic stress disorder (PTSD). Individuals with PTSD are more likely to develop alcohol and substance abuse related disorders. We assessed if prenatal and early postnatal alcohol exposure (PAE) increased the susceptibility to retain aversive memories and if this was associated with subsequent heightened alcohol consumption. Pregnant Sprague-Dawley rats were exposed for 22 hr/day, throughout pregnancy and until postnatal Day 7 to a single bottle of sucralose - sweetened 10% alcohol solution (PAE Group), or to a single bottle of tap water and sucralose (Control Group). Auditory fear conditioning (AFC) was performed in the adolescent offspring at postnatal Day 40. Freezing was measured during acquisition, retention and extinction phases, followed by 3 weeks of free choice alcohol intake. Female, but not male, PAE rats exhibited impaired extinction of the aversive memory, a finding associated with higher levels of 3-4 Dihidroxyphenylacetic acid (DOPAC) in the nucleus accumbens and heightened alcohol intake, respect to controls. These findings suggest that PAE makes females more vulnerable to long-term retention of aversive memories, which coexist with heightened alcohol intake. These findings are reminiscent of those of PTSD.

Structures of the Multidrug Transporter P-glycoprotein Reveal Asymmetric ATP Binding and the Mechanism of Polyspecificity.

P-glycoprotein (P-gp) is a polyspecific ATP-dependent transporter linked to multidrug resistance in cancer; it plays important roles in determining the pharmacokinetics of many drugs. Understanding the structural basis of P-gp, substrate polyspecificity has been hampered by its intrinsic flexibility, which is facilitated by a 75-residue linker that connects the two halves of P-gp. Here we constructed a mutant murine P-gp with a shortened linker to facilitate structural determination. Despite dramatic reduction in rhodamine 123 and calcein-AM transport, the linker-shortened mutant P-gp possesses basal ATPase activity and binds ATP only in its N-terminal nucleotide-binding domain. Nine independently determined structures of wild type, the linker mutant, and a methylated P-gp at up to 3.3 Å resolution display significant movements of individual transmembrane domain helices, which correlated with the opening and closing motion of the two halves of P-gp. The open-and-close motion alters the surface topology of P-gp within the drug-binding pocket, providing a mechanistic explanation for the polyspecificity of P-gp in substrate interactions.

Clinical features and postoperative seizure outcome in patients with drug-resistant gelastic seizures without hypothalamic hamartoma.

OBJECTIVES: The objective of this study was to describe the clinical characteristics and surgical outcome in patients with gelastic seizures without hypothalamic hamartoma. METHODS: We retrospectively reviewed all the video-EEG reports over a 5-year period (2007-2011) for the occurrence of the terms "laugh" or "giggle" in the text body. All the patients with at least one documented gelastic seizure at the epilepsy monitoring unit were studied. In patients who underwent epilepsy surgery, seizure outcomes were analyzed. RESULTS: Sixteen patients (10 females and 6 males) with a mean age of 46.3years were studied. Seven patients had invasive intracranial EEG recordings. Seizure onset zone was in a temporal lobe in four patients and the frontal lobe in one patient. Two patients did not have gelastic seizures during their intracranial EEG monitoring. Nine patients underwent resective epilepsy surgery for their seizures. Six patients (67%) were seizure-free after surgery. CONCLUSION: In adult patients, gelastic seizures can be seen in patients with focal epilepsy without hypothalamic hamartoma. Nonhypothalamic hamartoma gelastic seizures originating from the temporal lobe can be amenable to surgery.

Understanding Diversity, Equity, and Inclusion Roles in Academic Neurology Departments.

Academic neurology departments across the country have been rapidly adding diversity, equity, and inclusion (DEI) programs over the past 5-10 years. These programs frequently come with leadership roles that carry a variety of names and responsibilities, such as vice chair of DEI or diversity officer. Furthermore, there are roles for members of the department to be involved with DEI work without being designated the departmental DEI leader. This article provides a framework for understanding the different responsibilities that are typically associated with each of these roles, along with reasonable expectations to associate with the respective job titles. Our goal is to prevent departments from asking too much or expecting too little based on the job title and support provided to the people in these positions. Likewise, we hope to empower DEI leaders who are currently asked to perform duties beyond their scope to obtain the title and support they have earned. For each departmental DEI role, we review prerequisites to success and potential impediments.

Simulation-based assessment of trainee's performance in post-cardiac arrest resuscitation.

Objectives: To assess trainees' performance in managing a patient with post-cardiac arrest complicated by status epilepticus. Methods: In this prospective, observational, single-center simulation-based study, trainees ranging from sub interns to critical care fellows evaluated and managed a post cardiac arrest patient, complicated by status epilepticus. Critical action items were developed by a modified Delphi approach based on American Heart Association guidelines and the Neurocritical Care Society's Emergency Neurological Life Support protocols. The primary outcome measure was the critical action item sum score. We sought validity evidence to support our findings by including attending neurocritical care physicians and comparing performance across four levels of training. Results: Forty-nine participants completed the simulation. The mean sum of critical actions completed by trainees was 10/21 (49%). Eleven (22%) trainees verbalized a differential diagnosis for the arrest. Thirty-two (65%) reviewed the electrocardiogram, recognized it as abnormal, and consulted cardiology. Forty trainees (81%) independently decided to start temperature management, but only 20 (41%) insisted on it when asked to reconsider. There was an effect of level of training on critical action checklist sum scores (novice mean score [standard deviation (SD)] = 4.8(1.8) vs. intermediate mean score (SD) = 10.4(2.1) vs. advanced mean score (D) = 11.6(3.0) vs. expert mean score (SD) = 14.7(2.2)). Conclusions: High-fidelity manikin-based simulation holds promise as an assessment tool in the performance of post-cardiac arrest care.

Paroxysmal sympathetic hyperactivity following status epilepticus in a 22-year-old with Juvenile Neuronal Ceroid Lipofuscinosis: A case report.

The Neuronal Ceroid Lipofuscinosis (NCL) refers to a group of rare neurolipidosis disorders characterized by progressive blindness, deterioration of speech and motor function, cognitive decline, behavior problems, seizures, and premature death. We report a case of a 22-year-old man with CLN3 variant, homozygous NCL (aka Juvenile Neuronal Ceroid Lipofuscinosis) complicated by epilepsy who presented with episodes of recurrent seizure-like activity following status epilepticus, but now without electrographic correlate. Episodes were accompanied by tachycardia, diaphoresis, hypertension, and a fearful facial expression likely representing paroxysmal sympathetic hyperactivity (PSH), and improved with administration of propranolol. It is possible that status epilepticus provoked these episodes of PSH.

Developing the Neurology Diversity Officer: A Roadmap for Academic Neurology Departments.

Academic Neurology Departments must confront the challenges of developing a diverse workforce, reducing inequity and discrimination within academia, and providing neurologic care for an increasingly diverse society. A neurology diversity officer should have a specific role and associated title within a neurology department as well as a mandate to focus their efforts on issues of equity, diversity and inclusion that affect staff, trainees and faculty. This role is expansive and works across departmental missions but it has many challenges related to structural intolerance and cultural gaps. In this review, we describe the many challenges that diversity officers face and how they might confront them. We delineate the role and duties of the neurology diversity officer and provide a guide to departmental leaders on how to assess qualifications and evaluate progress. Finally, we describe the elements necessary for success. A neurology diversity officer should have the financial, administrative and emotional support of leadership in order for them to carry out their mission and to truly have a positive influence.

A Global Survey of Emergency Department Responses to the COVID-19 Pandemic.

INTRODUCTION: Emergency departments (ED) globally are addressing the coronavirus disease 2019 (COVID-19) pandemic with varying degrees of success. We leveraged the 17-country, Emergency Medicine Education & Research by Global Experts (EMERGE) network and non-EMERGE ED contacts to understand ED emergency preparedness and practices globally when combating the COVID-19 pandemic. METHODS: We electronically surveyed EMERGE and non-EMERGE EDs from April 3-June 1, 2020 on ED capacity, pandemic preparedness plans, triage methods, staffing, supplies, and communication practices. The survey was available in English, Mandarin Chinese, and Spanish to optimize participation. We analyzed survey responses using descriptive statistics. RESULTS: 74/129 (57%) EDs from 28 countries in all six World Health Organization global regions responded. Most EDs were in Asia (49%), followed by North America (28%), and Europe (14%). Nearly all EDs (97%) developed and implemented protocols for screening, testing, and treating patients with suspected COVID-19 infections. Sixty percent responded that provider staffing/back-up plans were ineffective. Many sites (47/74, 64%) reported staff missing work due to possible illness with the highest provider proportion of COVID-19 exposures and infections among nurses. CONCLUSION: Despite having disaster plans in place, ED pandemic preparedness and response continue to be a challenge. Global emergency research networks are vital for generating and disseminating large-scale event data, which is particularly important during a pandemic.

SARS-CoV-2 Infection among School Population of One Developing Country. Do School Closures Protect Students and Teachers against SARS-CoV-2 Infection?

Evidence about the effectiveness of school closures as a measure to control the spread of COVID-19 is controversial. We posit that schools are not an important source of transmission; thus, we analyzed two surveillance methods: a web-based questionnaire and a telephone survey that monitored the impact of the pandemic due to COVID-19 cases in Bogotá, Colombia. We estimated the cumulative incidences for Acute Respiratory Infection (ARI) and COVID-19 for each population group. Then, we assessed the differences using the cumulative incidence ratio (CIR) and 95% confidence intervals (CI95%). The ARI incidence among students was 20.1 times higher when estimated from the telephone survey than from the online questionnaire (CIR: 20.1; CI95% 17.11-23.53). Likewise, the ARI incidence among schoolteachers was 10 times higher in the telephone survey (CIR: 9.8; CI95% 8.3-11.5). the incidence of COVID-19 among schoolteachers was 4.3 times higher than among students in the online questionnarie (CIR: 4.3, CI95%: 3.8-5.0) and 2.1 times higher in the telephone survey (CIR = 2.1, CI95%: 1.8-2.6), and this behavior was also observed in the general population data. Both methods showed a capacity to detect COVID-19 transmission among students and schoolteachers, but the telephone survey estimates were probably closer to the real incidence rate.

Collaboration with non-emergency care specialists and other emergency care providers: A research primer for low- and middle-income countries.

As emergency and acute care systems develop, the ability to broadly engage key stakeholders becomes paramount for success. Collaborating with emergency medicine clinicians as well as other providers who have already developed their specialties, administrative leadership, as well as networking locally and regionally would maximise the success of developing a sustainable emergency care system.

N-Methyl-d-Aspartate Receptor Modulation by Nicotinamide Adenine Dinucleotide Phosphate Oxidase Type 2 Drives Synaptic Plasticity and Spatial Memory Impairments in Rats Exposed Pre- and Postnatally to Ethanol.

Aims: Pre- and/or early postnatal ethanol exposure (prenatal alcohol exposure [PAE]) impairs synaptic plasticity as well as memory formation, but the mechanisms underlying these effects remain unclear. Both long-term potentiation (LTP) and spatial memory formation in the hippocampus involve the nicotinamide adenine dinucleotide phosphate oxidase type 2 (NOX2) enzyme. Previous studies have reported that N-methyl-d-aspartate receptor (NMDAR) activation increases NOX2-mediated superoxide generation, resulting in inhibition of NMDAR function, but whether NOX2 impacts NMDAR function in PAE animals leading to impaired LTP and memory formation remains unknown. We aim to evaluate whether the NOX2-NMDAR complex is involved in the long-lasting deleterious effects of PAE on hippocampal LTP and memory formation. Results: Here we provide novel evidence that PAE animals display impaired NMDAR-dependent LTP in the cornus ammonis field 1 (CA1) and NMDAR-mediated LTP in the dentate gyrus (DG). Moreover, PAE rats displayed increased NMDAR-mediated transmission in both hippocampal areas. Interestingly, NOX2 pharmacological inhibition restored NMDAR-mediated transmission and LTP in the CA1, but not in the DG. PAE also induced overexpression of NOX2 and CaMKII isoforms, but did not modify the content or the redox state of the N-methyl-d-aspartate receptor subunit-1 (NR1) subunit of NMDAR in both areas of the hippocampus. In addition, adolescent PAE rats orally fed the antioxidant and free radical scavenger apocynin exhibited significantly improved spatial memory acquisition. Innovation and Conclusion: By showing in PAE animals NOX2 overexpression and increased NMDAR-mediated transmission, which might lead to impaired synaptic plasticity and memory formation in a region-specific manner, we provide an important advance to our current understanding of the cellular mechanisms underlying PAE-dependent defective hippocampal function.

Continuous Electroencephalogram as a Biomarker of Disease Progression and Severity in Herpes Simplex Virus-1 Encephalitis.

Objective. Herpes simplex virus encephalitis (HSE) is the most common cause of sporadic fatal encephalitis worldwide and remains a devastating disease despite antiviral therapy. EEG can be an important tool in the diagnosis of HSE, and we propose that it can be used to monitor the progression of the disease in patients with treatment refractory HSE. Methods. This is a case report of a patient with HSE who was monitored on continuous EEG (CEEG) throughout course of her disease. Results. A 62-year-old woman with no history of neurologic disease, who presented with generalized weakness and lethargy for 2 weeks, and rapidly deteriorated with encephalopathy, fever, and seizures. Lumbar puncture demonstrated elevated protein and white blood cells with positive herpes simplex virus (HSV) DNA. CEEG initially showed right-sided lateralized periodic discharges and focal seizures/status epilepticus with shifting predominance, and then later progressed to be more focal on the left, and then progressed to demonstrating more generalized findings. Magnetic resonance imaging obtained 3 times confirmed what CEEG heralded with evolution from prior studies which were concordant with CEEG, suggesting disease spread. Significance. We report the case of a patient with HSE who was monitored on CEEG and propose that CEEG can be used as a marker for progression of disease and thus may prompt escalation in therapy. While imaging studies may confirm spread of disease, using CEEG may prevent the delay of treatment and lead to more rapid therapy in cases of refractory HSE.

FACETS of health disparities in epilepsy surgery and gaps that need to be addressed.

PURPOSE OF REVIEW: Disparities in treatment and outcomes of patients with epilepsy have been identified in several distinct patient populations. The purpose of this review is to organize the literature and establish clear pathways as to why certain patient populations are not receiving epilepsy surgery. By establishing the acronym FACETS (fear of treatment, access to care, communication barriers, education, trust between patient and physician, and social support), we set up a pathway to further study this area in an organized fashion, hopefully leading to objective solutions. RECENT FINDINGS: Studies revealed that African American, Hispanic, and non-English-speaking patients underwent surgical treatment for epilepsy at rates significantly lower compared to white patients. SUMMARY: This article explains possible reasons outlined by FACETS for the health disparities in epilepsy surgery that exist in patients of a certain race, socioeconomic status, and language proficiency.