RESUMO
OBJECTIVES: To determine the incidence of seizure-like events in a cohort of infants born preterm as well as the prevalence of associated vital sign changes (heart rate [HR], respiratory rate, and pulse oximetry [SpO2]). STUDY DESIGN: We performed prospective conventional video electroencephalogram monitoring on infants born at 23-30 weeks of gestational age during the first 4 postnatal days. For detected seizure-like events, simultaneously captured vital sign data were analyzed during the pre-event baseline and during the event. Significant vital sign changes were defined as HR or respiratory rate >±2 SD from the infant's own baseline physiologic mean, derived from a 10-minute interval before the seizure-like event. Significant change in SpO2 was defined as oxygen desaturation during the event with a mean SpO2 <88%. RESULTS: Our sample included 48 infants with median gestational age of 28 weeks (IQR 26-29) and birth weight of 1125 g (IQR 963-1265). Twelve (25%) infants had seizure-like discharges with a total of 201 events; 83% (10/12) of infants had vital sign changes during these events, and 50% (6/12) had significant vital sign changes during the majority of the seizure-like events. Concurrent HR changes occurred the most frequently. CONCLUSIONS: Individual infant variability was observed in the prevalence of concurrent vital sign changes with electroencephalographic seizure-like events. Physiologic changes associated with preterm electrographic seizure-like events should be investigated further as a potential biomarker to assess the clinical significance of such events in the preterm population.
Assuntos
Oximetria , Convulsões , Recém-Nascido , Humanos , Lactente , Estudos Prospectivos , Idade Gestacional , Convulsões/diagnóstico , Convulsões/epidemiologia , Peso ao Nascer , OxigênioRESUMO
BACKGROUND: This study aimed to assess the differences between the United States and the United Kingdom in the characteristics and posttransplant survival of patients who received donation after circulatory death (DCD) liver allografts from donors aged >60 y. METHODS: Data were collected from the UK Transplant Registry and the United Network for Organ Sharing databases. Cohorts were dichotomized into donor age subgroups (donor >60 y [D >60]; donor ≤60 y [D ≤60]). Study period: January 1, 2001, to December 31, 2015. RESULTS: 1157 DCD LTs were performed in the United Kingdom versus 3394 in the United States. Only 13.8% of US DCD donors were aged >50 y, contrary to 44.3% in the United Kingdom. D >60 were 22.6% in the United Kingdom versus 2.4% in the United States. In the United Kingdom, 64.2% of D >60 clustered in 2 metropolitan centers. In the United States, there was marked inter-regional variation. A total of 78.3% of the US DCD allografts were used locally. One- and 5-y unadjusted DCD graft survival was higher in the United Kingdom versus the United States (87.3% versus 81.4%, and 78.0% versus 71.3%, respectively; P < 0.001). One- and 5-y D >60 graft survival was higher in the United Kingdom (87.3% versus 68.1%, and 77.9% versus 51.4%, United Kingdom versus United States, respectively; P < 0.001). In both groups, grafts from donors ≤30 y had the best survival. Survival was similar for donors aged 41 to 50 versus 51 to 60 in both cohorts. CONCLUSIONS: Compared with the United Kingdom, older DCD LT utilization remained low in the United States, with worse D >60 survival. Nonetheless, present data indicate similar survivals for older donors aged ≤60, supporting an extension to the current US DCD age cutoff.
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Transplante de Fígado , Obtenção de Tecidos e Órgãos , Aloenxertos , Morte , Sobrevivência de Enxerto , Humanos , Fígado , Transplante de Fígado/efeitos adversos , Estudos Retrospectivos , Doadores de Tecidos , Resultado do Tratamento , Reino Unido , Estados UnidosRESUMO
OBJECTIVE: To describe the parental experience of recruitment and assess differences between parents who participated and those who declined to enroll in a neonatal clinical trial. STUDY DESIGN: This was a survey conducted at 12 US neonatal intensive care units of parents of infants who enrolled in the High-dose Erythropoietin for Asphyxia and encephaLopathy (HEAL) trial or who were eligible but declined enrollment. Questions assessed 6 factors of the parental experience of recruitment: (1) interactions with research staff; (2) the consent experience; (3) perceptions of the study; (4) decisional conflict; (5) reasons for/against participation; and (6) timing of making the enrollment decision. RESULTS: In total, 269 of 387 eligible parents, including 183 of 242 (75.6%) of those who enrolled their children in HEAL and 86 of 145 (59.3%) parents who declined to enroll their children in HEAL, were included in analysis. Parents who declined to enroll more preferred to be approached by clinical team members rather than by research team members (72.9% vs 49.2%, P = .005). Enrolled parents more frequently reported positive initial impressions (54.9% vs 10.5%, P < .001). Many parents in both groups made their decision early in the recruitment process. Considerations of reasons for/against participation differed by enrollment status. CONCLUSIONS: Understanding how parents experience recruitment, and how this differs by enrollment status, may help researchers improve recruitment processes for families and increase enrollment. The parental experience of recruitment varied by enrollment status. These findings can guide future work aiming to inform optimal recruitment strategies for neonatal clinical trials.
Assuntos
Tomada de Decisões , Pais/psicologia , Seleção de Pacientes , Estudos Transversais , Humanos , Lactente , Recém-Nascido , Unidades de Terapia Intensiva Neonatal/estatística & dados numéricos , Ensaios Clínicos Controlados Aleatórios como Assunto , Inquéritos e QuestionáriosRESUMO
OBJECTIVE: To examine the frequency of placental abnormalities in a multicenter cohort of newborn infants with hypoxic-ischemic encephalopathy (HIE) and to determine the association between acuity of placental abnormalities and clinical characteristics of HIE. STUDY DESIGN: Infants born at ≥36 weeks of gestation (n = 500) with moderate or severe HIE were enrolled in the High-dose Erythropoietin for Asphyxia and Encephalopathy Trial. A placental pathologist blinded to clinical information reviewed clinical pathology reports to determine the presence of acute and chronic placental abnormalities using a standard classification system. RESULTS: Complete placental pathologic examination was available for 321 of 500 (64%) trial participants. Placental abnormalities were identified in 273 of 321 (85%) and were more common in infants ≥40 weeks of gestation (93% vs 81%, P = .01). A combination of acute and chronic placental abnormalities (43%) was more common than either acute (20%) or chronic (21%) abnormalities alone. Acute abnormalities included meconium staining of the placenta (41%) and histologic chorioamnionitis (39%). Chronic abnormalities included maternal vascular malperfusion (25%), villitis of unknown etiology (8%), and fetal vascular malperfusion (6%). Infants with chronic placental abnormalities exhibited a greater mean base deficit at birth (-15.9 vs -14.3, P = .049) than those without such abnormalities. Patients with HIE and acute placental lesions had older mean gestational ages (39.1 vs 38.0, P < .001) and greater rates of clinically diagnosed chorioamnionitis (25% vs 2%, P < .001) than those without acute abnormalities. CONCLUSIONS: Combined acute and chronic placental abnormalities were common in this cohort of infants with HIE, underscoring the complex causal pathways of HIE. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02811263.
Assuntos
Hipóxia-Isquemia Encefálica/patologia , Doenças Placentárias/diagnóstico , Doenças Placentárias/epidemiologia , Doença Aguda , Doença Crônica , Estudos de Coortes , Método Duplo-Cego , Eritropoetina/uso terapêutico , Feminino , Idade Gestacional , Humanos , Hipotermia Induzida , Hipóxia-Isquemia Encefálica/terapia , Recém-Nascido , Masculino , Gravidez , Fatores de RiscoRESUMO
OBJECTIVES: To describe neonatologist continuity of care and estimate the association between these transitions and selected patient outcomes. STUDY DESIGN: We linked Children's Hospitals Neonatal Database records with masked neonatologist daily schedules at 4 centers, which use 2- and 3-week and 1-month "on service" blocks to provide care. After describing the neonatologist transitions, we estimated associations between these transitions and selected short-term patient outcomes using multivariable Poisson, logistic, and linear regression analyses, independent of length of stay (LOS) and case-mix. We also completed analyses after stratifying the cohort by LOS, birthweight, age at admission categories, and selected diagnoses. RESULTS: Stratified by LOS, patient transitions varied between centers in both unadjusted (P < .001) and multivariable analyses (adjusted incidence rate ratio; 95% CI for center B = 3.98 (3.81-4.15), center C = 4.92 (4.71-5.13), center D = 4.2 (4.0-4.4), P < .001), independent of LOS, gestational age, birthweight, surgical intervention, ventilator duration, and mortality. Only central venous line duration (adjusted incidence rate ratio 1.015, 95% CI 1.01-1.02) was minimally and independently associated with the number of transitions. No differences were observed in ventilator duration, oxygen use at neonatal intensive care unit discharge, bloodstream infections, or urinary tract infections. Surviving infants with meconium aspiration, hypoxic ischemic encephalopathy, cerebral infarction, bronchopulmonary dysplasia, and diaphragmatic hernia demonstrated similar findings. CONCLUSIONS: Transitions in neonatologists are frequent in regional neonatal intensive care units but appear unrelated to short-term patient outcomes. Future work to define continuity of care and develop effective strategies that promote longitudinal inpatient management is needed.
Assuntos
Continuidade da Assistência ao Paciente , Neonatologia , Transferência de Pacientes , Feminino , Humanos , Recém-Nascido , Masculino , Estudos Retrospectivos , Fatores de Tempo , Resultado do TratamentoRESUMO
OBJECTIVES: To evaluate plasma brain specific proteins and cytokines as biomarkers of brain injury in newborns with hypoxic-ischemic encephalopathy (HIE) and, secondarily, to assess the effect of erythropoietin (Epo) treatment on the relationship between biomarkers and outcomes. STUDY DESIGN: A study of candidate brain injury biomarkers was conducted in the context of a phase II multicenter randomized trial evaluating Epo for neuroprotection in HIE. Plasma was collected at baseline (<24 hours) and on day 5. Brain injury was assessed by magnetic resonance imaging (MRI) and neurodevelopmental assessments at 1 year. The relationships between Epo, brain-specific proteins (S100B, ubiquitin carboxy-terminal hydrolase-L1 [UCH-L1], total Tau, neuron specific enolase), cytokines (interleukin [IL]-1ß, IL-6, IL-8, IL-10, IL-12P70, IL-13, interferon-gamma [IFN-γ], tumor necrosis factor alpha [TNF-α], brain-derived neurotrophic factor [BDNF], monocyte chemoattractant protein-1), and brain injury were assessed. RESULTS: In 50 newborns with encephalopathy, elevated baseline S100B, Tau, UCH-L1, IL-1ß, IL-6, IL-8, IL-10, IL-13, TNF-α, and IFN-γ levels were associated with increasing brain injury severity by MRI. Higher baseline Tau and lower day 5 BDNF were associated with worse 1 year outcomes. No statistically significant evidence of Epo treatment modification on biomarkers was detected in this small cohort. CONCLUSIONS: Elevated plasma brain-specific proteins and cytokine levels in the first 24 hours of life are associated with worse brain injury by MRI in newborns with HIE. Only Tau and BDNF levels were found to be related to neurodevelopmental outcomes. The effect of Epo treatment on the relationships between biomarkers and brain injury in HIE requires further study. TRIAL REGISTRATION: ClinicalTrials.gov: 01913340.
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Lesões Encefálicas/sangue , Hipóxia-Isquemia Encefálica/sangue , Biomarcadores/sangue , Lesões Encefálicas/diagnóstico por imagem , Lesões Encefálicas/etiologia , Fator Neurotrófico Derivado do Encéfalo/sangue , Citocinas/sangue , Eritropoetina/uso terapêutico , Humanos , Hipóxia-Isquemia Encefálica/complicações , Hipóxia-Isquemia Encefálica/tratamento farmacológico , Recém-Nascido , Imageamento por Ressonância Magnética , Proteínas tau/sangueRESUMO
In the Neonatal Erythropoietin and Therapeutic Hypothermia Outcomes study, 9/20 erythropoietin-treated vs 12/24 placebo-treated infants with hypoxic-ischemic encephalopathy had acute brain injury. Among infants with acute brain injury, the injury volume was lower in the erythropoietin than the placebo group (P = .004). Higher injury volume correlated with lower 12-month neurodevelopmental scores. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01913340.
Assuntos
Lesões Encefálicas/diagnóstico por imagem , Eritropoetina/uso terapêutico , Hipóxia-Isquemia Encefálica/diagnóstico por imagem , Hipóxia-Isquemia Encefálica/tratamento farmacológico , Imageamento por Ressonância Magnética , Fármacos Neuroprotetores/uso terapêutico , Lesões Encefálicas/etiologia , Lesões Encefálicas/patologia , Método Duplo-Cego , Feminino , Humanos , Hipóxia-Isquemia Encefálica/patologia , Lactente , Recém-Nascido , Masculino , Estudos Prospectivos , Fatores de Tempo , Resultado do Tratamento , Estados UnidosRESUMO
OBJECTIVE: To quantify early auditory exposures in the neonatal intensive care unit (NICU) and evaluate how these are related to medical and environmental factors. We hypothesized that there would be less auditory exposure in the NICU private room, compared with the open ward. STUDY DESIGN: Preterm infants born at ≤ 28 weeks gestation (33 in the open ward, 25 in private rooms) had auditory exposure quantified at birth, 30 and 34 weeks postmenstrual age (PMA), and term equivalent age using the Language Environmental Acquisition device. RESULTS: Meaningful language (P < .0001), the number of adult words (P < .0001), and electronic noise (P < .0001) increased across PMA. Silence increased (P = .0007) and noise decreased (P < .0001) across PMA. There was more silence in the private room (P = .02) than the open ward, with an average of 1.9 hours more silence in a 16-hour period. There was an interaction between PMA and room type for distant words (P = .01) and average decibels (P = .04), indicating that changes in auditory exposure across PMA were different for infants in private rooms compared with infants in the open ward. Medical interventions were related to more noise in the environment, although parent presence (P = .009) and engagement (P = .002) were related to greater language exposure. Average sound levels in the NICU were 58.9 ± 3.6 decibels, with an average peak level of 86.9 ± 1.4 decibels. CONCLUSIONS: Understanding the NICU auditory environment paves the way for interventions that reduce high levels of adverse sound and enhance positive forms of auditory exposure, such as language.
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Exposição Ambiental/efeitos adversos , Recém-Nascido Prematuro , Desenvolvimento da Linguagem , Ruído/efeitos adversos , Estudos de Coortes , Feminino , Seguimentos , Idade Gestacional , Unidades Hospitalares , Humanos , Recém-Nascido , Unidades de Terapia Intensiva Neonatal , Tempo de Internação , Masculino , Medição de RiscoRESUMO
OBJECTIVE: To evaluate the safety and short-term outcomes of preterm neonates born at 34-35 weeks gestation with hypoxic-ischemic encephalopathy (HIE) treated with therapeutic hypothermia. STUDY DESIGN: Medical records of preterm neonates born at 34-35 weeks gestational age with HIE treated with therapeutic hypothermia were retrospectively reviewed. Short-term safety outcomes and the presence, severity (mild, moderate, severe), and patterns of brain injury on magnetic resonance imaging were reviewed using a standard scoring system, and compared with a cohort of term neonates with HIE treated with therapeutic hypothermia. RESULTS: Thirty-one preterm and 32 term neonates were identified. Therapeutic hypothermia-associated complications were seen in 90% of preterm infants and 81.3% of term infants (P = .30). In the preterm infants, hyperglycemia (58.1% vs31.3%, P = .03) and rewarming before completion of therapeutic hypothermia (19.4% vs 0.0%, P = .009) were more likely compared with term infants. All deaths occurred in the preterm group (12.9% vs 0%, P = .04). Neuroimaging showed the presence of injury in 80.6% of preterm infants and 59.4% of term infants (P = .07), with no differences in injury severity. Injury to the white matter was more prevalent in preterm infants compared with term infants (66.7% vs 25.0%, P = .001). CONCLUSIONS: Therapeutic hypothermia in infants born at 34-35 weeks gestational age appears feasible. Risks of mortality and side effects warrant caution with use of therapeutic hypothermia in preterm infants.
Assuntos
Hipotermia Induzida/efeitos adversos , Hipotermia Induzida/métodos , Hipóxia-Isquemia Encefálica/terapia , Recém-Nascido Prematuro , Índice de Apgar , Estudos de Coortes , Bases de Dados Factuais , Eletroencefalografia/métodos , Feminino , Seguimentos , Idade Gestacional , Humanos , Hipotermia Induzida/mortalidade , Hipóxia-Isquemia Encefálica/diagnóstico por imagem , Hipóxia-Isquemia Encefálica/mortalidade , Recém-Nascido , Doenças do Prematuro/diagnóstico por imagem , Doenças do Prematuro/mortalidade , Doenças do Prematuro/terapia , Imageamento por Ressonância Magnética/métodos , Masculino , Segurança do Paciente , Valores de Referência , Estudos Retrospectivos , Medição de Risco , Índice de Gravidade de Doença , Taxa de Sobrevida , Fatores de Tempo , Resultado do TratamentoRESUMO
OBJECTIVE: To quantify intercenter cost variation for perinatal hypoxic ischemic encephalopathy (HIE) treated with therapeutic hypothermia across children's hospitals. STUDY DESIGN: Prospectively collected data from the Children's Hospitals Neonatal Database and Pediatric Health Information Systems were linked to evaluate intercenter cost variation in total hospitalization costs after adjusting for HIE severity, mortality, length of stay, use of extracorporeal support or nitric oxide, and ventilator days. Secondarily, costs for intensive care unit bed, electroencephalography (EEG), and laboratory and neuroimaging testing were also evaluated. Costs were contextualized by frequency of favorable (survival with normal magnetic resonance imaging) and adverse (death or need for gastric tube feedings at discharge) outcomes to identify centers with relative low costs and favorable outcomes. RESULTS: Of the 822 infants with HIE treated with therapeutic hypothermia at 19 regional neonatal intensive care units, 704 (86%) survived to discharge. The median cost/case for survivors was $58â552 (IQR $32â476-$130â203) and nonsurvivors $29â760 (IQR $16â897-$61â399). Adjusting for illness severity and select interventions, intercenter differences explained 29% of the variation in total hospitalization costs. The widest cost variability across centers was EEG use, although low cost and favorable outcome centers ranked higher with regards to EEG costs. CONCLUSIONS: There is marked intercenter cost variation associated with treating HIE across regional children's hospitals. Our investigation may help establish references for cost and enhance quality improvement and resource utilization projects related to HIE.
Assuntos
Custos Hospitalares/estatística & dados numéricos , Hospitalização/economia , Hipotermia Induzida/economia , Hipóxia-Isquemia Encefálica/economia , Bases de Dados Factuais , Eletroencefalografia/economia , Feminino , Hospitais Pediátricos , Humanos , Hipóxia-Isquemia Encefálica/epidemiologia , Hipóxia-Isquemia Encefálica/terapia , Recém-Nascido , Unidades de Terapia Intensiva Neonatal/economia , Masculino , Neuroimagem/economia , Admissão do Paciente/estatística & dados numéricos , Estados Unidos/epidemiologiaRESUMO
OBJECTIVE: To evaluate associations between neonatal intensive care unit (NICU) room type (open ward and private room) and medical outcomes; neurobehavior, electrophysiology, and brain structure at hospital discharge; and developmental outcomes at 2 years of age. STUDY DESIGN: In this prospective longitudinal cohort study, we enrolled 136 preterm infants born <30 weeks gestation from an urban, 75-bed level III NICU from 2007-2010. Upon admission, each participant was assigned to a bedspace in an open ward or private room within the same hospital, based on space and staffing availability, where they remained for the duration of hospitalization. The primary outcome was developmental performance at 2 years of age (n = 86 infants returned for testing, which was 83% of survivors) measured using the Bayley Scales of Infant and Toddler Development, 3rd Edition. Secondary outcomes were: (1) medical factors throughout the hospitalization; (2) neurobehavior; and (3) cerebral injury and maturation (determined by magnetic resonance imaging and electroencephalography). RESULTS: At term equivalent age, infants in private rooms were characterized by a diminution of normal hemispheric asymmetry and a trend toward having lower amplitude integrated electroencephalography cerebral maturation scores (P = .02; ß = -0.52 [CI -0.95, -0.10]). At age 2 years, infants from private rooms had lower language scores (P = .006; ß = -8.3 [CI -14.2, -2.4]) and a trend toward lower motor scores (P = .02; ß = -6.3 [CI -11.7, -0.99]), which persisted after adjustment for potential confounders. CONCLUSION: These findings raise concerns that highlight the need for further research into the potential adverse effects of different amounts of sensory exposure in the NICU environment.
Assuntos
Encéfalo/patologia , Desenvolvimento Infantil , Deficiências do Desenvolvimento/diagnóstico , Comportamento do Lactente , Doenças do Prematuro/diagnóstico , Recém-Nascido Prematuro , Unidades de Terapia Intensiva Neonatal , Encéfalo/fisiopatologia , Deficiências do Desenvolvimento/fisiopatologia , Deficiências do Desenvolvimento/psicologia , Eletroencefalografia , Exposição Ambiental , Seguimentos , Humanos , Lactente , Recém-Nascido , Doenças do Prematuro/fisiopatologia , Doenças do Prematuro/psicologia , Recém-Nascido de muito Baixo Peso , Imageamento por Ressonância Magnética , Prognóstico , Estudos ProspectivosRESUMO
OBJECTIVE: To evaluate the electrographic seizure burden in neonates with hypoxic ischemic encephalopathy (HIE) treated with or without therapeutic hypothermia and stratified results by severity of HIE and severity of injury as assessed by magnetic resonance imaging (MRI). STUDY DESIGN: Between 2007 and 2011, video-electroencephalography (EEG) monitoring was initiated in neonates with moderate to severe HIE. Seizure burden (in seconds) was calculated, and brain MRI scans were quantitatively scored. Data were analyzed by ANOVA, the Student t test, and the χ(2) test. RESULTS: Sixty-nine neonates with moderate or severe HIE were prospectively enrolled, including 51 who received therapeutic hypothermia and 18 who did not. The mean duration of video-EEG monitoring was longer in the therapeutic hypothermia group (72 ± 34 hours vs 48 ± 34 hours; P = .01). The therapeutic hypothermia group had a lower electrographic seizure burden (log units) after controlling for injury, as assessed by MRI (2.9 ± 0.6 vs 6.2 ± 0.9; P = .003). A reduction in seizure burden was seen in neonates with moderate HIE (P = .0001), but not in those with severe HIE (P = .80). Among neonates with injury assessed by MRI, seizure burden was lower in those with mild (P = .0004) and moderate (P = .02) injury, but not in those with severe injury (P = .90). CONCLUSION: Therapeutic hypothermia was associated with reduced electrographic seizure burden in neonatal HIE. This effect was detected on video-EEG in infants with moderate HIE, but not in those with severe HIE. When stratified by injury as assessed by MRI, therapeutic hypothermia was associated with a reduced seizure burden in infants with mild and moderate injury, but not in those with severe injury.
Assuntos
Encefalopatias/diagnóstico , Encefalopatias/etiologia , Eletroencefalografia , Hipotermia Induzida , Hipóxia-Isquemia Encefálica/diagnóstico , Hipóxia-Isquemia Encefálica/terapia , Imageamento por Ressonância Magnética , Encefalopatias/fisiopatologia , Feminino , Humanos , Hipóxia-Isquemia Encefálica/complicações , Hipóxia-Isquemia Encefálica/fisiopatologia , Recém-Nascido , Masculino , Estudos Prospectivos , Convulsões/etiologia , Convulsões/fisiopatologia , Índice de Gravidade de Doença , Gravação em VídeoRESUMO
OBJECTIVE: To evaluate the accuracy, feasibility, and impact of limited-channel amplitude integrated electroencephalogram (aEEG) monitoring in encephalopathic infants. STUDY DESIGN: Encephalopathic infants were placed on limited-channel aEEG with a software-based seizure event detector for 72 hours. A 12-hour epoch of conventional EEG-video (cEEG) was simultaneously collected. Infants were randomly assigned to monitoring that was blinded or visible to the clinical team. If a seizure detection event occurred in the visible group, the clinical team interpreted whether the event was a seizure, based on review of the limited-channel aEEG. EEG data were reviewed independently offline. RESULTS: In more than 68 hours per infant of limited-channel aEEG monitoring, 1116 seizures occurred (>90% clinically silent), with 615 detected by the seizure event detector (55%). Detection improved with increasing duration of seizures (73% >30 seconds, 87% >60 seconds). Bedside physicians were able to accurately use this algorithm to differentiate true seizures from false-positives. The visible group had a 52% reduction in seizure burden (P = .114) compared with the blinded group. CONCLUSIONS: Monitoring for seizures with limited-channel aEEG can be accurately interpreted, compares favorably with cEEG, and is associated with a trend toward reduced seizure burden.