Pediatric psychogenic non-epileptic seizures: A retrospective observational cohort study at a quaternary center.

BACKGROUND: Psychogenic non-epileptic seizures (PNES) represent a common functional disorder in the pediatric population. We aimed to characterize pediatric PNES by describing their clinical characteristics, PNES semiologies, and healthcare pathway towards and after diagnosis. MATERIAL AND METHODS: This was a retrospective, observational chart review of pediatric patients aged 6 to 18 years admitted between December 2020 and December 2021 for spell classification or suspected PNES. Psychogenic non-epileptic seizure diagnosis was made by the capture of a typical event on video electroencephalogram (vEEG). We used descriptive statistics to summarize demographic and clinical characteristics. RESULTS: We included 26 patients (18 females, 69.2%) with a mean age (SD) of 13.9 (2.5) years. Pre-morbid neurologic and psychiatric conditions included: epilepsy (23.1%), migraine (46.2%), mild traumatic brain injury (26.9%), anxiety (57.7%), ADHD (34.6%), and depression (30.8%). Six patients (23.1%) had a prior diagnosis of PNES. 14 patients (53.8%) presented with convulsive, and 6 (23.1%) each with non-convulsive and mixed PNES. Patients were seen by a range of providers prior to diagnosis including ED providers (50%), neurologists (53.8%), pediatricians (34.6%), and psychology/psychiatry (11.5%). Emergency department evaluation occurred for 13 patients (50%) on 15 occasions, and six (23.1%) were admitted to the hospital. The median (p25-p75) time from PNES onset to presentation and diagnosis at our institution was 3.5 (1.5-6.2) and 4.1 (3-7) months, respectively. A total of 33 events from the 26 patients were captured on vEEG. The most frequent semiologies in our cohort were rhythmic motor (27.3%) followed by equal frequency (18.2%) of complex motor and dialeptic. Eighteen patients (69.2%) were followed after the PNES diagnosis, for a median (p25-p75) of 17.3 months (6.3-21) with variable outcome. CONCLUSION: Pediatric PNES has female predominance and often presents with comorbid psychosocial stressors and psychiatric conditions. High clinical suspicion and early recognition are crucial to decrease healthcare utilization and establish timely diagnosis and treatment.

Pediatric status epilepticus management by Emergency Medical Services (the pSERG cohort).

PURPOSE: Delayed treatment in status epilepticus (SE) is independently associated with increased treatment resistance, morbidity, and mortality. We describe the prehospital management pathway and Emergency Medical Services (EMS) timeliness in children who developed refractory convulsive status epilepticus (RCSE). METHODS: Retrospective multicenter study in the United States using prospectively collected observational data from June 2011 to March 2020. We selected pediatric patients (one month-21 years) with RCSE initiated outside the hospital and transported to the hospital by EMS. RESULTS: We included 91 patients with a median (percentile25-percentile75) age of 3.0 (1.5-7.3) years. The median time from seizure onset to hospital arrival was 45 (30-67) minutes, with a median time cared for by EMS of 24 (15-36) minutes. Considering treatment by caregivers and EMS before hospital arrival, 20 (22%) patients did not receive any anti-seizure medications (ASM) and 71 (78%) received one to five doses of benzodiazepines (BZD), without non-BZD ASM. We provided the prehospital treatment flow path of these patients through caregivers and EMS including relevant time points. Patients with a history of SE were more likely to receive the first BZD in the prehospital setting compared to patients without a history of SE (adjusted HR 3.25, 95% CI 1.72-6.12, p<0.001). CONCLUSION: In this multicenter study of pediatric RCSE, prehospital treatment may be streamlined further. Patients with a history of SE were more likely to receive prehospital rescue medication.

Early Clinical Variables Associated With Refractory Convulsive Status Epilepticus in Children.

BACKGROUND AND OBJECTIVES: The objective of this study was to determine patient-specific factors known proximate to the presentation to emergency care associated with the development of refractory convulsive status epilepticus (RSE) in children. METHODS: An observational case-control study was conducted comparing pediatric patients (1 month-21 years) with convulsive SE whose seizures stopped after benzodiazepine (BZD) and a single second-line antiseizure medication (ASM) (responsive established status epilepticus [rESE]) with patients requiring more than a BZD and a single second-line ASM to stop their seizures (RSE). These subpopulations were obtained from the pediatric Status Epilepticus Research Group study cohort. We explored clinical variables that could be acquired early after presentation to emergency medical services with univariate analysis of the raw data. Variables with p < 0.1 were retained for univariable and multivariable regression analyses. Multivariable logistic regression models were fit to age-matched and sex-matched data to obtain variables associated with RSE. RESULTS: We compared data from a total of 595 episodes of pediatric SE. Univariate analysis demonstrated no differences in time to the first BZD (RSE 16 minutes [IQR 5-45]; rESE 18 minutes [IQR 6-44], p = 0.068). Time to second-line ASM was shorter in patients with RSE (RSE 65 minutes; rESE 70 minutes; p = 0.021). Both univariable and multivariable regression analyses revealed a family history of seizures (OR 0.37; 95% CI 0.20-0.70, p = 0.0022) or a prescription for rectal diazepam (OR 0.21; 95% CI 0.078-0.53, p = 0.0012) was associated with decreased odds of RSE. DISCUSSION: Time to initial BZD or second-line ASM was not associated with progression to RSE in our cohort of patients with rESE. A family history of seizures and a prescription for rectal diazepam were associated with a decreased likelihood of progression to RSE. Early attainment of these variables may help care for pediatric rESE in a more patient-tailored manner. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that patient and clinical factors may predict RSE in children with convulsive seizures.

Bifidobacterium mellis sp. nov., isolated from the honey stomach of the honey bee Apis mellifera.

A novel Bifidobacterium strain, Bin7NT, was isolated from the honey stomach of the honey bee Apis mellifera. Cells are Gram-positive, non-motile, non-sporulating, facultative anaerobic and fructose 6-phosphate phosphoketolase-positive. Their optimal growth is at 37 °C in anaerobiosis in MRS (De Man, Rogosa and Sharpe) added with cysteine. The honey bee microbiota was composed of several phylotypes of Bifidobacterium and Lactobacillus. Comparative analysis of 16S rRNA gene sequence similarity revealed that strain Bin7NT grouped with Bifidobacterium species originating from honey bees and was closely related to Bifidobacterium asteroides DSM 20089T (99.67 % similarity). However, the highest average nucleotide identity and digital DNA-DNA hybridization values of 94.88 and 60.6 %, respectively, were obtained with Bifidobacterium choladohabitans JCM 34586T. The DNA G+C content of the type strain is 60.8 mol%. The cell-wall peptidoglycan is of the A4ß l-Orn-d-Asp type. The main cellular fatty acids of strain Bin7NT are C18 : 1 ω9c, C16 : 0, C18 : 1 ω7c and C18 : 0. Phenotypic characterization and genotyping based on the genome sequences clearly show that this strain is distinct from the type strains of the so far recognized Bifidobacterium species. Thus, Bifidobacterium mellis sp. nov. (Bin7NT=DSM 29108T=CCUG 66113T) is proposed as novel Bifidobacterium species.

Stiripentol for the treatment of seizures associated with Dravet syndrome in patients 6 months and older and taking clobazam.

INTRODUCTION: Stiripentol (STP) is a structurally unique molecule with anticonvulsant and neuroprotective properties in animal and human studies. STP enhances gamma-aminobutyric acid (GABA)ergic neurotransmission and inhibits multiple hepatic isoenzymes (i.e. cytochrome P450 system) involved in the metabolism of other antiseizure medications (ASMs) potentiating their anticonvulsant effects and has proven to be a promising therapy in Dravet Syndrome (DS). AREAS COVERED: The authors review randomized clinical trials and observational studies showing STP efficacy, safety, and tolerability when used as adjunctive therapy with VPA and clobazam in patients with DS. Moreover, they include recent evidence of its use in patients<2 years of age. EXPERT OPINION: Evidence on STP demonstrates clinically meaningful efficacy in both short and long term in patients with DS. In addition to reducing convulsive seizure frequency, STP also markedly reduces the number of status epilepticus episodes and associated medical complications which are more common in younger children. STP adverse effects are generally not severe and often resolve following STP dose reduction or adjustments of concomitant ASMs. STP is approved by the FDA for children aged 6 months and older with DS who are also taking clobazam, making it the only DS-specific ASM for children under age 1 year.

Genome Evolution of a Symbiont Population for Pathogen Defense in Honeybees.

The honeybee gut microbiome is thought to be important for bee health, but the role of the individual members is poorly understood. Here, we present closed genomes and associated mobilomes of 102 Apilactobacillus kunkeei isolates obtained from the honey crop (foregut) of honeybees sampled from beehives in Helsingborg in the south of Sweden and from the islands Gotland and Åland in the Baltic Sea. Each beehive contained a unique composition of isolates and repeated sampling of similar isolates from two beehives in Helsingborg suggests that the bacterial community is stably maintained across bee generations during the summer months. The sampled bacterial population contained an open pan-genome structure with a high genomic density of transposons. A subset of strains affiliated with phylogroup A inhibited growth of the bee pathogen Melissococcus plutonius, all of which contained a 19.5 kb plasmid for the synthesis of the antimicrobial compound kunkecin A, while a subset of phylogroups B and C strains contained a 32.9 kb plasmid for the synthesis of a putative polyketide antibiotic. This study suggests that the mobile gene pool of A. kunkeei plays a key role in pathogen defense in honeybees, providing new insights into the evolutionary dynamics of defensive symbiont populations.

Identifying Barriers to Care in the Pediatric Acute Seizure Care Pathway.

Objective: We aimed to describe the acute seizure care pathway for pediatric patients and identify barriers encountered by those involved in seizure care management. We also proposed interventions to bridge these care gaps within this pathway. Methods: We constructed a process map that illustrates the acute seizure care pathway for pediatric patients at Boston Children's Hospital (BCH). The map was designed from knowledge gathered from unstructured interviews with experts at BCH, direct observation of patient care management at BCH through a quality improvement implemented seizure diary and from findings through three studies conducted at BCH, including a prospective observational study by the pediatric Status Epilepticus Research Group, a multi-site international consortium. We also reviewed the literature highlighting gaps and strategies in seizure care management. Results: Within the process map, we identified twenty-nine care gaps encountered by caregivers, care teams, residential and educational institutions, and proposed interventions to address these challenges. The process map outlines clinical care of a patient through the following settings: 1) pre-hospitalization setting, defined as residential and educational settings before hospital admission, 2) BCH emergency department and inpatient settings, 3) post-hospitalization setting, defined as residential and educational settings following hospital discharge or clinic visit and 4) follow-up BCH outpatient settings, including neurology, epilepsy, and primary care provider clinics. The acute seizure care pathway for a pediatric patient who presents with seizures exhibits at least twenty-nine challenges in acute seizure care management. Significance: Identification of care barriers in the acute seizure care pathway provides a necessary first step for implementing interventions and strategies in acute seizure care management that could potentially impact patient outcomes.

New and emerging pharmacologic treatments for developmental and epileptic encephalopathies.

PURPOSE OF REVIEW: Summarize evidence on Developmental and Epileptic Encephalopathies (DEEs) treatments focusing on new and emerging pharmacologic therapies (see Video, http://links.lww.com/CONR/A61, Supplementary Digital Content 1, which provides an overview of the review). RECENT FINDINGS: Advances in the fields of molecular genetics and neurobiology have led to the recognition of underlying pathophysiologic mechanisms involved in an increasing number of DEEs that could be targeted with precision therapies or repurposed drugs, some of which are currently being evaluated in clinical trials. Prompt, optimal therapy is critical, and promising therapies approved or in clinical trials for tuberous sclerosis complex, Dravet and Lennox-Gastaut Syndromes including mammalian target of rapamycin inhibitors, selective membrane channel and antisense oligonucleotide modulation, and repurposed drugs such as fenfluramine, stiripentol and cannabidiol, among others, may improve seizure burden and neurological outcomes. There is an urgent need for collaborative efforts to evaluate the efficacy and safety of emerging DEEs therapies. SUMMARY: Development of new therapies promise to address unmet needs for patients with DEEs, including improvement of neurocognitive function and quality of life.

Benzodiazepine administration patterns before escalation to second-line medications in pediatric refractory convulsive status epilepticus.

OBJECTIVE: This study was undertaken to evaluate benzodiazepine (BZD) administration patterns before transitioning to non-BZD antiseizure medication (ASM) in pediatric patients with refractory convulsive status epilepticus (rSE). METHODS: This retrospective multicenter study in the United States and Canada used prospectively collected observational data from children admitted with rSE between 2011 and 2020. Outcome variables were the number of BZDs given before the first non-BZD ASM, and the number of BZDs administered after 30 and 45 min from seizure onset and before escalating to non-BZD ASM. RESULTS: We included 293 patients with a median (interquartile range) age of 3.8 (1.3-9.3) years. Thirty-six percent received more than two BZDs before escalating, and the later the treatment initiation was after seizure onset, the less likely patients were to receive multiple BZD doses before transitioning (incidence rate ratio [IRR] = .998, 95% confidence interval [CI] = .997-.999 per minute, p = .01). Patients received BZDs beyond 30 and 45 min in 57.3% and 44.0% of cases, respectively. Patients with out-of-hospital seizure onset were more likely to receive more doses of BZDs beyond 30 min (IRR = 2.43, 95% CI = 1.73-3.46, p < .0001) and beyond 45 min (IRR = 3.75, 95% CI = 2.40-6.03, p < .0001) compared to patients with in-hospital seizure onset. Intermittent SE was a risk factor for more BZDs administered beyond 45 min compared to continuous SE (IRR = 1.44, 95% CI = 1.01-2.06, p = .04). Forty-seven percent of patients (n = 94) with out-of-hospital onset did not receive treatment before hospital arrival. Among patients with out-of-hospital onset who received at least two BZDs before hospital arrival (n = 54), 48.1% received additional BZDs at hospital arrival. SIGNIFICANCE: Failure to escalate from BZDs to non-BZD ASMs occurs mainly in out-of-hospital rSE onset. Delays in the implementation of medical guidelines may be reduced by initiating treatment before hospital arrival and facilitating a transition to non-BZD ASMs after two BZD doses during handoffs between prehospital and in-hospital settings.

Factors associated with long-term outcomes in pediatric refractory status epilepticus.

OBJECTIVE: This study was undertaken to describe long-term clinical and developmental outcomes in pediatric refractory status epilepticus (RSE) and identify factors associated with new neurological deficits after RSE. METHODS: We performed retrospective analyses of prospectively collected observational data from June 2011 to March 2020 on pediatric patients with RSE. We analyzed clinical outcomes from at least 30 days after RSE and, in a subanalysis, we assessed developmental outcomes and evaluated risk factors in previously normally developed patients. RESULTS: Follow-up data on outcomes were available in 276 patients (56.5% males). The median (interquartile range [IQR]) follow-up duration was 1.6 (.9-2.7) years. The in-hospital mortality rate was 4% (16/403 patients), and 15 (5.4%) patients had died after hospital discharge. One hundred sixty-six (62.9%) patients had subsequent unprovoked seizures, and 44 (16.9%) patients had a repeated RSE episode. Among 116 patients with normal development before RSE, 42 of 107 (39.3%) patients with available data had new neurological deficits (cognitive, behavioral, or motor). Patients with new deficits had longer median (IQR) electroclinical RSE duration than patients without new deficits (10.3 [2.1-134.5] h vs. 4 [1.6-16] h, p = .011, adjusted odds ratio = 1.003, 95% confidence interval = 1.0008-1.0069, p = .027). The proportion of patients with an unfavorable functional outcome (Glasgow Outcome Scale-Extended score ≥ 4) was 22 of 90 (24.4%), and they were more likely to have received a continuous infusion. SIGNIFICANCE: About one third of patients without prior epilepsy developed recurrent unprovoked seizures after the RSE episode. In previously normally developing patients, 39% presented with new deficits during follow-up, with longer electroclinical RSE duration as a predictor.

Super-Refractory Status Epilepticus in Children: A Retrospective Cohort Study.

OBJECTIVES: To characterize the pediatric super-refractory status epilepticus population by describing treatment variability in super-refractory status epilepticus patients and comparing relevant clinical characteristics, including outcomes, between super-refractory status epilepticus, and nonsuper-refractory status epilepticus patients. DESIGN: Retrospective cohort study with prospectively collected data between June 2011 and January 2019. SETTING: Seventeen academic hospitals in the United States. PATIENTS: We included patients 1 month to 21 years old presenting with convulsive refractory status epilepticus. We defined super-refractory status epilepticus as continuous or intermittent seizures lasting greater than or equal to 24 hours following initiation of continuous infusion and divided the cohort into super-refractory status epilepticus and nonsuper-refractory status epilepticus groups. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We identified 281 patients (157 males) with a median age of 4.1 years (1.3-9.5 yr), including 31 super-refractory status epilepticus patients. Compared with nonsuper-refractory status epilepticus group, super-refractory status epilepticus patients had delayed initiation of first nonbenzodiazepine-antiseizure medication (149 min [55-491.5 min] vs 62 min [33.3-120.8 min]; p = 0.030) and of continuous infusion (495 min [177.5-1,255 min] vs 150 min [90-318.5 min]; p = 0.003); prolonged seizure duration (120 hr [58-368 hr] vs 3 hr [1.4-5.9 hr]; p < 0.001) and length of ICU stay (17 d [9.5-40 d] vs [1.8-8.8 d]; p < 0.001); more medical complications (18/31 [58.1%] vs 55/250 [22.2%] patients; p < 0.001); lower return to baseline function (7/31 [22.6%] vs 182/250 [73.4%] patients; p < 0.001); and higher mortality (4/31 [12.9%] vs 5/250 [2%]; p = 0.010). Within the super-refractory status epilepticus group, status epilepticus resolution was attained with a single continuous infusion in 15 of 31 patients (48.4%), two in 10 of 31 (32.3%), and three or more in six of 31 (19.4%). Most super-refractory status epilepticus patients (30/31, 96.8%) received midazolam as first choice. About 17 of 31 patients (54.8%) received additional treatments. CONCLUSIONS: Super-refractory status epilepticus patients had delayed initiation of nonbenzodiazepine antiseizure medication treatment, higher number of medical complications and mortality, and lower return to neurologic baseline than nonsuper-refractory status epilepticus patients, although these associations were not adjusted for potential confounders. Treatment approaches following the first continuous infusion were heterogeneous, reflecting limited information to guide clinical decision-making in super-refractory status epilepticus.

Clinical presentation of new onset refractory status epilepticus in children (the pSERG cohort).

OBJECTIVE: We aimed to characterize the clinical profile and outcomes of new onset refractory status epilepticus (NORSE) in children, and investigated the relationship between fever onset and status epilepticus (SE). METHODS: Patients with refractory SE (RSE) between June 1, 2011 and October 1, 2016 were prospectively enrolled in the pSERG (Pediatric Status Epilepticus Research Group) cohort. Cases meeting the definition of NORSE were classified as "NORSE of known etiology" or "NORSE of unknown etiology." Subgroup analysis of NORSE of unknown etiology was completed based on the presence and time of fever occurrence relative to RSE onset: fever at onset (≤24 h), previous fever (2 weeks-24 h), and without fever. RESULTS: Of 279 patients with RSE, 46 patients met the criteria for NORSE. The median age was 2.4 years, and 25 (54%) were female. Forty (87%) patients had NORSE of unknown etiology. Nineteen (48%) presented with fever at SE onset, 16 (40%) had a previous fever, and five (12%) had no fever. The patients with preceding fever had more prolonged SE and worse outcomes, and 25% recovered baseline neurological function. The patients with fever at onset were younger and had shorter SE episodes, and 89% recovered baseline function. SIGNIFICANCE: Among pediatric patients with RSE, 16% met diagnostic criteria for NORSE, including the subcategory of febrile infection-related epilepsy syndrome (FIRES). Pediatric NORSE cases may also overlap with refractory febrile SE (FSE). FIRES occurs more frequently in older children, the course is usually prolonged, and outcomes are worse, as compared to refractory FSE. Fever occurring more than 24 h before the onset of seizures differentiates a subgroup of NORSE patients with distinctive clinical characteristics and worse outcomes.

CSNK2B: A broad spectrum of neurodevelopmental disability and epilepsy severity.

CSNK2B has recently been implicated as a disease gene for neurodevelopmental disability (NDD) and epilepsy. Information about developmental outcomes has been limited by the young age and short follow-up for many of the previously reported cases, and further delineation of the spectrum of associated phenotypes is needed. We present 25 new patients with variants in CSNK2B and refine the associated NDD and epilepsy phenotypes. CSNK2B variants were identified by research or clinical exome sequencing, and investigators from different centers were connected via GeneMatcher. Most individuals had developmental delay and generalized epilepsy with onset in the first 2 years. However, we found a broad spectrum of phenotypic severity, ranging from early normal development with pharmacoresponsive seizures to profound intellectual disability with intractable epilepsy and recurrent refractory status epilepticus. These findings suggest that CSNK2B should be considered in the diagnostic evaluation of patients with a broad range of NDD with treatable or intractable seizures.

Time to Treatment in Pediatric Convulsive Refractory Status Epilepticus: The Weekend Effect.

BACKGROUND: Time to treatment in pediatric refractory status epilepticus is delayed. We aimed to evaluate the influence of weekends and holidays on time to treatment of this pediatric emergency. METHODS: We performed a retrospective analysis of prospectively collected observational data of pediatric patients with refractory status epilepticus. RESULTS: We included 329 patients (56% males) with a median (p25 to p75) age of 3.8 (1.3 to 9) years. The median (p25 to p75) time to first BZD on weekdays and weekends/holidays was 20 (6.8 to 48.3) minutes versus 11 (5 to 35) minutes, P = 0.01; adjusted hazard ratio (HR) = 1.20 (95% confidence interval [CI]: 0.95 to 1.55), P = 0.12. The time to first non-BZD ASM was longer on weekdays than on weekends/holidays (68 [42.8 to 153.5] minutes versus 59 [27 to 120] minutes, P = 0.006; adjusted HR = 1.38 [95% CI: 1.08 to 1.76], P = 0.009). However, this difference was mainly driven by status epilepticus with in-hospital onset: among 108 patients, the time to first non-BZD ASM was longer during weekdays than during weekends/holidays (55.5 [28.8 to 103.5] minutes versus 28 [15.8 to 66.3] minutes, P = 0.003; adjusted HR = 1.65 [95% CI: 1.08 to 2.51], P = 0.01). CONCLUSIONS: The time to first non-BZD ASM in pediatric refractory status epilepticus is shorter on weekends/holidays than on weekdays, mainly driven by in-hospital onset status epilepticus. Data on what might be causing this difference may help tailor policies to improve medication application timing.

SIRS y qSOFA como Predictores de Mortalidad en Sepsis Pediátrica

Resumen Introducción: La sepsis pediátrica continúa siendo una causa importante de mortalidad en países de bajos y medianos ingresos, su reconocimiento temprano en emergencias requiere del uso de criterios que nos permitan predecir anticipadamente la gravedad del paciente. Objetivo: nuestro estudio pretende comparar los criterios de SIRS y qSOFA en cuanto a su capacidad discriminatoria en mortalidad en sepsis pediátrica. Métodos: realizamos un estudio multicéntrico, prospectivo en servicios de emergencias incluyendo niños con sospecha de sepsis subsecuentemente ingresados a UTIP, en los cuales se evaluaron los puntajes en SIRS y qSOFA comparándolos con los resultados al egreso. Resultados: se enrolaron 64 pacientes, admitidos en estadios de Sepsis (19%), Shock Séptico (20,6%) y con Disfunción Multiorgánica (60,4%), con una mortalidad respectivamente de 9,5%, 14,3% y 76,2%; en 33,9% de los casos se pudo rescatar algún germen. Evaluando los criterios SIRS vemos que la ausencia de ellos se asocia con mayor sobrevivencia (p=0,044; OR 0,618: IC95% 0,5020,761), Por otro lado, 2 o más criterios qSOFA se asocia con mayor mortalidad (p=0,047; OR 3,52: IC95% 1,090-11,371). Conclusión: ambos criterios utilizados para definir sepsis en pediatría demostraron su utilidad, el uso del score qSOFA dada a su estrecha relación con la mortalidad puede emplearse para anticipar alteraciones orgánicas potencialmente mortales.

Abstract Introduction: Pediatric sepsis continues to be one of the main causes of mortality in low and middle-income countries, its early recognition in emergencies requires the use of criteria that allow us to predict the severity of the patient. Objective: our study aims to compare the SIRS criteria and qSOFA regarding its discriminatory capacity in mortality in children with sepsis. Methods: a prospective multicenter study was carried out in emergency services enrolling children with suspected sepsis subsequently admitted to the PICU, in which the scores in qSOFA and SIRS were evaluated comparing them with the results at hospital discharge. Results: 64 patients were enrolled, admitted in emergency in Sepsis (19%), Septic Shock (20.6%) and with Multiple Organ Dysfunction (60.4%) stage, with a mortality respectively of 9.5% and 14.3% and 76.2%; germ could be rescued in 33.9% of the cases; Evaluating the SIRS criteria, we see that the absence of them is associated with lower mortality (p = 0.044; OR 0.618: 95% CI 0.502-0.761); otherwise, 2 or more qSOFA criteria are associated with higher mortality (p = 0.047 ; OR 3.52: 95% CI 1.090-11.371). Conclusion: both criteria used to define sepsis in pediatrics demonstrated their usefulness, the use of the qSOFA score given its close relationship with mortality can be used to anticipate life-threatening organ alterations.

First-line medication dosing in pediatric refractory status epilepticus.

OBJECTIVE: To identify factors associated with low benzodiazepine (BZD) dosing in patients with refractory status epilepticus (RSE) and to assess the impact of BZD treatment variability on seizure cessation. METHODS: This was a retrospective study with prospectively collected data of children with convulsive RSE admitted between June 2011 and January 2019. We analyzed the initial and total BZD dose within 10 minutes of treatment initiation. We used logistic regression modeling to evaluate predictors of low BZD dosing and multivariate Cox regression analysis to assess the impact of low BZD dosing on time to seizure cessation. RESULTS: We included 289 patients (55.7% male) with a median age of 4.3 (1.3-9.5) years. BZDs were the initial medication in 278 (96.2%). Of those, 161 patients (57.9%) received a low initial dose. Low initial BZD doses occurred in both out-of-hospital (57 of 106; 53.8%) and in-hospital (104 of 172; 60.5%) settings. One hundred three patients (37.1%) received low total BZD dose. Male sex (odds ratio [OR] 2, 95% confidence interval [CI] 1.18-3.49; p = 0.012), older age (OR 1.1, 95% CI 1.05-1.17; p < 0.001), no prior diagnosis of epilepsy (OR 2.1, 95% CI 1.23-3.69; p = 0.008), and delayed BZD treatment (OR 2.2, 95% CI 1.24-3.94; p = 0.007) were associated with low total BZD dose. Patients who received low total BZD dosing were less likely to achieve seizure cessation (hazard ratio 0.7, 95% CI 0.57-0.95). CONCLUSION: BZD doses were lower than recommended in both out-of-hospital and in-hospital settings. Factors associated with low total BZD dose included male sex, older age, no prior epilepsy diagnosis, and delayed BZD treatment. Low total BZD dosing was associated with decreased likelihood of Seizure cessation. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that patients with RSE who present with male sex, older age, no prior diagnosis of epilepsy, and delayed BZD treatment are more likely to receive low total BZD doses. This study provides Class III evidence that in pediatric RSE low total BZD dose decreases the likelihood of seizure cessation.