Evaluation of the Use of Ketamine in Prehospital Seizure Management: A Retrospective Review of the ESO Database.

OBJECTIVES: Benzodiazepines are the primary antiseizure medication used by Emergency Medical Services (EMS) for seizures. Available literature in the United States and internationally shows 30% to 40% of seizures do not terminate with benzodiazepines called benzodiazepine refractory status epilepticus (BRSE). Ketamine is a potential treatment for BRSE due to its unique pharmacology. However, its application in the prehospital setting is mostly documented in case reports. Little is known about its use by EMS professionals for seizure management, whether as initial treatment or for BRSE, creating an opportunity to describe its current use and inform future research. METHODS: We performed a retrospective review of 9-1-1 EMS encounters with a primary or secondary impression of seizure using the ESO Data Collaborative from 2018 to 2021. We isolated encounters during which ketamine was administered. We excluded medication administrations prior to EMS arrival and encounters without medication administration. Subgroup analysis was performed to control for airway procedure as an indication for ketamine administration. We also evaluated for co-administration with other antiseizure medications, dose and route of administration, and response to treatment. RESULTS: We identified 99,576 encounters that met inclusion. There were 2,531/99,576 (2.54%) encounters with ketamine administration and 50.7% (1,283/2,531) received ketamine without an airway procedure. There were 616 cases (48%, 616/1,283) where ketamine was given without another antiseizure medication (ASM) and without any airway procedure. The remaining 667 (52%) cases received ketamine with at least one other ASM, most commonly midazolam (89%, 593/667). Adjusted for the growth in the ESO dataset, ketamine use by EMS professionals during encounters for seizures without an airway procedure increased from 0.90% (139/15,375) to 1.45% (416/28,651) an increase of 62% over the study period. CONCLUSIONS: In this retrospective review of the ESO Data Collaborative, ketamine administration for seizure encounters without an airway procedure increased over the study period, both as a single agent and with another ASM. Most ketamine administrations were for adult patients in the south and in urban areas. The frequency of BRSE, the need for effective treatment, and the growth in ketamine use warrant prospective prehospital research to evaluate the value of ketamine in prehospital seizure management.

The Success of Resident-Associated Lumbar Punctures at a Large, Single-Center Children's Hospital.

OBJECTIVES: The frequency of lumbar punctures (LPs) has declined across US children's hospitals over the past decade, potentially decreasing procedural learning opportunities for pediatric resident trainees. Our study sought to determine whether the proportion of successful LPs performed by our pediatric residents has significantly changed over time. METHODS: This study is a single-center retrospective study to evaluate our pediatric resident LP success. We evaluated our primary outcome, proportion of overall LP success over time, using linear regression. We similarly used linear regression for proportion of successful resident-associated LPs over time. We calculated the median number of LPs of all pediatric residents during the study period. RESULTS: We analyzed 3143 LPs from April 2012 to December 2019. Both the overall number of LPs performed and the proportion of LPs that were successful have not significantly changed over an 8-year period ( P > 0.05, P > 0.05). Similarly, the number of our resident-associated LPs and the proportion of successful resident-associated LPs have not changed over the study period ( P > 0.05, P > 0.05). Our pediatric residents performed a median of 3 LPs (interquartile range: 2-4) in the pediatric emergency department (PED) over residency. CONCLUSIONS: Despite national trends showing decreased LP rates at pediatric hospitals, we demonstrated stable proportions of LPs and success by our pediatric residents. Pediatric residents perform a relatively low number of LPs in the PED setting alone. Future research is needed to demonstrate whether these overall low numbers in the PED translate to procedural competency after residency graduation.

Adults Followed by Pediatric Subspecialists: A Growing Population in the Pediatric Emergency Department.

BACKGROUND: Adults are being seen with increasing frequency in pediatric emergency departments (PEDs), but the drivers behind this increase are unknown. Our primary aim was to compare adults seen in the PED followed by pediatric subspecialists to those who are not. METHODS: A retrospective study of patients 21 years or older presenting to the PED of a tertiary care children's hospital was performed from January 2011 through December 2018. Data included patient demographics, PED length of stay, disposition, and any subspecialty clinic encounters at the children's hospital in the prior year. RESULTS: A total of 10,034 adult encounters were seen in the PED over the study period; 5852 (58.3%) adult PED encounters had preceding pediatric subspecialty clinic visit(s) within a year prior. Pediatric subspecialty adult PED encounters increased by 38.9%, compared with 10.6% for other adults (P = 0.01). Encounters for pediatric subspecialty adults were significantly longer and more likely to result in admission to the children's hospital. The most common pediatric subspecialists caring for adult patients seen in the PED were hematology/oncology (1655 encounters), neurology (1572 encounters), cardiology (1217 encounters), and gastroenterology (1173 encounters). CONCLUSIONS: Pediatric subspecialty adults are presenting to the PED at a greater rate, and they require more time and resources compared with other presenting adults. As frontline providers, PEDs, physicians, and staff must be prepared to address this growing subset of patients driving the increase in adults presenting to the PED.

Psychiatric Education for Pediatric Emergency Medicine Fellows: Should We be Doing More?

The number of psychiatric encounters is steadily increasing across all pediatric emergency departments. Based on this growing national crisis, we hypothesized there is a lack of robust education in behavioral/mental health emergencies during pediatric emergency medicine (PEM) fellowship. METHODS: This was a cross-sectional survey of PEM fellowship directors. The survey was submitted to the Pediatric Emergency Medicine Program Director Survey Committee via REDCap to all 83 fellowship directors. RESULTS: Fifty-five (66%) PEM fellowship directors completed the survey from September 2019 to December 2019. Forty-three (78%) programs provide some type of didactic teaching, although only 7 (13%) programs offer more than 5 hours of didactics over 3 years of fellowship. Six (11%) programs offer electronic resources, 13 (24%) offer simulations in psychiatry, and only 4 (7%) programs require any type of psychiatry rotation. Forty-six (84%) programs do not currently use psychiatric emergencies as a competency for evaluating PEM fellows. Program directors felt significantly more confident in faculty than graduating fellows in the management of numerous diagnoses including agitation (P < 0.001), homicidal ideation (P = 0.044), neuroleptic malignant syndrome (P = 0.006), acute dystonia (P < 0.001), and heroin overdose (P = 0.022). Ninety-six percent felt online curricula would be helpful to address this knowledge gap. CONCLUSIONS: Despite growing behavioral/mental health needs in the pediatric emergency department, there continues to be opportunity to improve psychiatric education during PEM fellowship. Program directors felt more confident in faculty than graduating fellows with several psychiatric diagnoses. Pediatric emergency medicine fellowship directors expressed a strong interest in online tools to assist in the education of PEM fellows.

Aligning Provider Prescribing With Guidelines for Soft Tissue Infections.

OBJECTIVE: Despite evidence-based guidelines, antibiotics prescribed for uncomplicated skin and soft tissue infections can involve inappropriate microbial coverage. Our aim was to evaluate the appropriateness of antibiotic prescribing practices for mild nonpurulent cellulitis in a pediatric tertiary academic medical center over a 1-year period. METHODS: Eligible patients treated in the emergency department or urgent care settings for mild nonpurulent cellulitis from January 2017 to December 2017 were identified by an International Classification of Diseases, Tenth Revision, code for cellulitis. The primary outcome was appropriateness of prescribed antibiotics as delineated by adherence with the Infectious Diseases Society of America guidelines. Secondary outcomes include reutilization rate as defined by revisit to the emergency department/urgent cares within 14 days of the initial encounter. RESULTS: A total of 967 encounters were evaluated with 60.0% overall having guideline-adherent care. Common reasons for nonadherence included inappropriate coverage of MRSA with clindamycin (n = 217, 56.1%) and single-agent coverage with sulfamethoxazole-trimethoprim (n = 129, 33.3%). There were 29 revisits within 14 days of initial patient encounters or a reutilization rate of 3.0%, which was not significantly associated with the Infectious Diseases Society of America adherence. CONCLUSIONS: Our data show antibiotic prescription for nonpurulent cellulitis as a potential area of standardization and optimization of care at our center.

Siglec-9 and SHP-1 are differentially expressed in neonatal and adult neutrophils.

Neonatal PMN (polymorphonuclear neutrophils) exhibit altered inflammatory responsiveness and greater longevity compared with adult PMN; however, the involved mechanisms are incompletely defined. Receptors containing immunoreceptor tyrosine-based inhibitory motif (ITIM) domains promote apoptosis by activating inhibitory phosphatases, such as Src homology domain 2-containing tyrosine phosphatase-1 (SHP-1), that block survival signals. Sialic acid-binding immunoglobulin-like lectin (Siglec)-9, an immune inhibitory receptor with an ITIM domain, has been shown to induce cell death in adult PMN in association with SHP-1. To test our hypothesis that neonatal PMN inflammatory function may be modulated by unique Siglec-9 and SHP-1 interactions, we compared expression of these proteins in adult and neonatal PMN. Neonatal PMN exhibited diminished cellular expression of Siglec-9, which was phosphorylated in the basal state. Granulocyte-macrophage colony-stimulating factor (GM-CSF) treatment decreased Siglec-9 phosphorylation levels in neonatal PMN but promoted its phosphorylation in adult PMN, observations associated with altered survival signaling. Although SHP-1 expression was also diminished in neonatal PMN, GM-CSF treatment had minimal effect on phosphorylation status. Further analysis revealed that Siglec-9 and SHP-1 physically interact, as has been observed in other immune cells. Our data suggest that age-specific interactions between Siglec-9 and SHP-1 may influence the altered inflammatory responsiveness and longevity of neonatal PMN.

N-O chemistry for antibiotics: discovery of N-alkyl-N-(pyridin-2-yl)hydroxylamine scaffolds as selective antibacterial agents using nitroso Diels-Alder and ene chemistry.

The discovery, syntheses, and structure-activity relationships (SAR) of a new family of heterocyclic antibacterial compounds based on N-alkyl-N-(pyridin-2-yl)hydroxylamine scaffolds are described. A structurally diverse library of ∼100 heterocyclic molecules generated from Lewis acid-mediated nucleophilic ring-opening reactions with nitroso Diels-Alder cycloadducts and nitroso ene reactions with substituted alkenes was evaluated in whole cell antibacterial assays. Compounds containing the N-alkyl-N-(pyridin-2-yl)hydroxylamine structure demonstrated selective and potent antibacterial activity against the Gram-positive bacterium Micrococcus luteus ATCC 10240 (MIC(90) = 2.0 µM or 0.41 µg/mL) and moderate activity against other Gram-positive strains including antibiotic resistant strains of Staphylococcus aureus (MRSA) and Enterococcus faecalis (VRE). A new synthetic route to the active core was developed using palladium-catalyzed Buchwald-Hartwig amination reactions of N-alkyl-O-(4-methoxybenzyl)hydroxylamines with 2-halo-pyridines that facilitated SAR studies and revealed the simplest active structural fragment. This work shows the value of using a combination of diversity-oriented synthesis (DOS) and parallel synthesis for identifying new antibacterial scaffolds.