Publications by authors named "James M Chamberlain"

132 Publications

Differential activation of neuroinflammatory pathways in children with seizures: A cross-sectional study.

Seizure 2021 May 31;91:150-158. Epub 2021 May 31.

Division of Neuroimmunology and Neurovirology, NINDS, NIH, Bethesda, MD, United States.

Purpose: Inflammation plays a crucial role in epileptogenesis. We analyzed inflammatory cytokines in plasma and saliva from children with seizures and healthy controls and measured their associations with HHV6 and EBV infection.

Methods: We analyzed plasma from 36 children within 24 h of seizures (cases) and 43 healthy controls and saliva from 44 cases and 44 controls with a multiplex immunoassay. Saliva from all controls and 65 cases and blood from 26 controls and 35 cases were also analyzed by PCR for viral DNA. Primary outcome was cytokine levels in cases vs. controls. Secondary outcomes included detection of HHV-6 and EBV viral DNA in cases vs. controls and viral loads in cases vs. controls. Statistical analysis included the Wilcoxon Rank Sum test, Fisher's exact test, ANOVA, and Spearman correlation.

Results: Compared to controls, patients had higher levels of CCL11 (p = 0.0018), CCL26 (p<0.001), IL10 (p = 0.044), IL6 (p<0.001), IL8 (p = 0.018), and MIP1β (p = 0.0012). CCL11 was higher with 3 or more seizures (p = 0.01), seizures longer than 10 min (p = 0.001), and when EEG showed focal slowing (p = 0.02). In saliva, febrile seizures had higher levels of IL-1β (n = 7, p = 0.04) and new onset seizures had higher IL-6 (n = 15, p = 0.02). Plasma and saliva cytokine levels did not show a correlation. The frequency of HHV-6 and EBV detection was similar across groups and not different than controls. We found no correlation between viral load and cytokine levels.

Conclusions: We showed differential activation of neuroinflammatory pathways in plasma from different seizure etiologies compared to controls, unrelated to viral infection.
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http://dx.doi.org/10.1016/j.seizure.2021.05.022DOI Listing
May 2021

Racial/Ethnic Differences in Pediatric Emergency Department Wait Times.

Pediatr Emerg Care 2021 Jun 15. Epub 2021 Jun 15.

From the University of California, Davis Medical Center, Sacramento, CA Children's National Health System, The George Washington University, Washington, DC Children's Hospital of Philadelphia, University of Pennsylvania, Philadelphia, PA University of Colorado, Children's Hospital, Aurora, CO Cincinnati Children's Hospital Medical Center, UC Health, Cincinnati, OH University of Utah Myriad Genetics, Inc, Salt Lake City, UT Ann & Robert H. Lurie Children's Hospital of Chicago, Northwestern University, Chicago, IL.

Objectives: Wait time for emergency care is a quality measure that affects clinical outcomes and patient satisfaction. It is unknown if there is racial/ethnic variability in this quality measure in pediatric emergency departments (PEDs). We aim to determine whether racial/ethnic differences exist in wait times for children presenting to PEDs and examine between-site and within-site differences.

Methods: We conducted a retrospective cohort study for PED encounters in 2016 using the Pediatric Emergency Care Applied Research Network Registry, an aggregated deidentified electronic health registry comprising 7 PEDs. Patient encounters were included among all patients 18 years or younger at the time of the ED visit. We evaluated differences in emergency department wait time (time from arrival to first medical evaluation) considering patient race/ethnicity as the exposure.

Results: Of 448,563 visits, median wait time was 35 minutes (interquartile range, 17-71 minutes). Compared with non-Hispanic White (NHW) children, non-Hispanic Black (NHB), Hispanic, and other race children waited 27%, 33%, and 12% longer, respectively. These differences were attenuated after adjusting for triage acuity level, mode of arrival, sex, age, insurance, time of day, and month [adjusted median wait time ratios (95% confidence intervals): 1.11 (1.10-1.12) for NHB, 1.12 (1.11-1.13) for Hispanic, and 1.05 (1.03-1.06) for other race children compared with NHW children]. Differences in wait time for NHB and other race children were no longer significant after adjusting for clinical site. Fully adjusted median wait times among Hispanic children were longer compared with NHW children [1.04 (1.03-1.05)].

Conclusions: In unadjusted analyses, non-White children experienced longer PED wait times than NHW children. After adjusting for illness severity, patient demographics, and overcrowding measures, wait times for NHB and other race children were largely determined by site of care. Hispanic children experienced longer within-site and between-site wait times compared with NHW children. Additional research is needed to understand structures and processes of care contributing to wait time differences between sites that disproportionately impact non-White patients.
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http://dx.doi.org/10.1097/PEC.0000000000002483DOI Listing
June 2021

Research environment and resources to support pediatric emergency medicine fellow research.

AEM Educ Train 2021 Jul 9;5(3):e10585. Epub 2021 Mar 9.

Section of Emergency Medicine Children's Hospital Colorado Aurora Colorado USA.

Background: There is a need for pediatric emergency medicine (PEM) researchers, but the current state of PEM fellow research training is not well described. We sought to (1) describe resources and gaps in PEM fellowship research training and (2) assess agreement between fellow and program director (PD) perceptions of these in fellow research experience.

Methods: Surveys were distributed electronically to U.S. PEM fellows and PDs from March to April 2020. Fellows and PDs were queried on program research infrastructure and current gaps in fellow research experience. For programs that had at least one fellow and PD response, each fellow response was compared to their PD's corresponding response (reference standard). For each binary survey item, we determined the percent of responses with agreement between the fellow and PD.

Results: Of 79 fellowship programs, 70 (89%) were represented with at least one response, including responses from 59 PDs (75%) and 218 fellows (39% of all fellows, representing 80% of programs). Fellows and PDs identified mentorship and faculty engagement as the most important needs for successful fellowship research; for every one fellow there was a median of 0.8 potential faculty mentors in the division. Twenty percent of fellows were not satisfied with mentorship opportunities. There was no association between fellow career research intent (high, defined as ≥20% dedicated time, or low) with current year of training (p = 0.88), program size (p = 0.67), and area of research focus (p = 0.40). Fellows were often unaware of research being performed by division faculty.

Conclusion: PEM fellows were not consistently aware of resources available to support research training. To better support PEM fellows' research training, many programs may need to expand mentorship and increase fellows' awareness of local and external resources and opportunities.
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http://dx.doi.org/10.1002/aet2.10585DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8171771PMC
July 2021

Early Neurologic Recovery, Practice Pattern Variation, and the Risk of Endotracheal Intubation Following Established Status Epilepticus.

Neurology 2021 05 23;96(19):e2372-e2386. Epub 2021 Mar 23.

From the Division of Clinical Neurophysiology and Division of Neurocritical Care (E.S.R.), Department of Neurology, and Department of Pharmacy (M.E.B.), Massachusetts General Hospital, Boston; Department of Public Health Sciences (J.J.E., J.I.), Medical University of South Carolina, Charleston; Departments of Emergency Medicine (A.J.R., R.S.) and Pediatrics (A.J.R.), University of Michigan, Ann Arbor; Department of Emergency Medicine (T.E.T.), The Ohio State University Wexner Medical Center, Columbus; Division of Pediatric Emergency Medicine (M.H.), Department of Pediatrics, University of Utah, Salt Lake City; Department of Pediatrics (D.G.T.), Medical College of Wisconsin, Milwaukee; Division of Emergency Medicine (L.B.), Department of Pediatrics, University of Cincinnati, OH; Division of Pediatric Emergency Medicine (P.J.O.), Department of Pediatrics, UT Southwestern Medical Center, Dallas, TX; Department of Neurosciences (R.H.L.), Inova Health System, Falls Church, VA; Department of Emergency Medicine (J.B.M.), Henry Ford Hospital, Detroit, MI; Division of Pediatric Emergency Medicine (R.W.H.), Department of Pediatrics, UPMC Children's Hospital of Pittsburgh, University of Pittsburgh School of Medicine, PA; Feinberg School of Medicine (T.P.B.), Northwestern University and Rush Medical College, Chicago, IL; Department of Experimental and Clinical Pharmacology (J.C.C., L.D.C.), College of Pharmacy and Center for Orphan Drug Research, University of Minnesota, Minneapolis; Department of Neurology (D.H.L.), University of California, San Francisco; Department of Neurology (J.K.), University of Virginia, Charlottesville; Montefiore Medical Center (S.S.), Albert Einstein College of Medicine, Bronx, NY; and Division of Emergency Medicine (J.M.C.), Children's National Medical Center, Washington, DC.

Objective: To quantify the association between early neurologic recovery, practice pattern variation, and endotracheal intubation during established status epilepticus, we performed a secondary analysis within the cohort of patients enrolled in the Established Status Epilepticus Treatment Trial (ESETT).

Methods: We evaluated factors associated with the endpoint of endotracheal intubation occurring within 120 minutes of ESETT study drug initiation. We defined a blocked, stepwise multivariate regression, examining 4 phases during status epilepticus management: (1) baseline characteristics, (2) acute treatment, (3) 20-minute neurologic recovery, and (4) 60-minute recovery, including seizure cessation and improving responsiveness.

Results: Of 478 patients, 117 (24.5%) were intubated within 120 minutes. Among high-enrolling sites, intubation rates ranged from 4% to 32% at pediatric sites and 19% to 39% at adult sites. Baseline characteristics, including seizure precipitant, benzodiazepine dosing, and admission vital signs, provided limited discrimination for predicting intubation (area under the curve [AUC] 0.63). However, treatment at sites with an intubation rate in the highest (vs lowest) quartile strongly predicted endotracheal intubation independently of other treatment variables (adjusted odds ratio [aOR] 8.12, 95% confidence interval [CI] 3.08-21.4, model AUC 0.70). Site-specific variation was the factor most strongly associated with endotracheal intubation after adjustment for 20-minute (aOR 23.4, 95% CI 6.99-78.3, model AUC 0.88) and 60-minute (aOR 14.7, 95% CI 3.20-67.5, model AUC 0.98) neurologic recovery.

Conclusions: Endotracheal intubation after established status epilepticus is strongly associated with site-specific practice pattern variation, independently of baseline characteristics, and early neurologic recovery and should not alone serve as a clinical trial endpoint in established status epilepticus.

Trial Registration Information: ClinicalTrials.gov Identifier: NCT01960075.
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http://dx.doi.org/10.1212/WNL.0000000000011879DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8166444PMC
May 2021

Evaluation of Communication and Safety Behaviors During Hospital-Wide Code Response Simulation.

Simul Healthc 2021 Mar 29. Epub 2021 Mar 29.

From the Division of Emergency Medicine (D.M.R., R.B., J.M.C, P.Z.), Children's National Hospital, Washington, DC; Division of Emergency Medicine (A.A.), Children's Hospital Colorado, Aurora, CO; Department of Anesthesiology and Critical Care Medicine (M.B.), Children's Hospital of Philadelphia, Philadelphia, PA; Department of Pediatrics (R.B., J.M.C., A.G., R.I., P.Z.), George Washington University School of Medicine and Health Sciences; Simulation Program (L.N., H.A.W.), Children's National Hospital; School of Nursing & Allied Health (A.G.), Liverpool John Moores University in Liverpool, England; Division of Biostatistics and Study Methodology (R.I.), Children's Research Institute, Children's National Hospital, Washington, DC; Department of Pediatrics (M.O.), Maine Medical Center, Portland, ME; Department of Emergency Medicine (M.P.), University of Florida College of Medicine; University of Florida Center for Experiential Learning and Simulation (M.P.), University of Florida College of Medicine, Gainesville, FL; and Global Health Initiative Children's National Hospital (R.S.), Washington, DC.

Introduction: To understand the baseline quality of team communication behaviors at our organization, we implemented institution-wide simulation training and measured the performance of safety behaviors of ad hoc teams in emergent situations.

Methods: Clinicians participated in 2 interprofessional video-recorded simulation scenarios, each followed by debriefing. Using a standardized evaluation instrument, 2 reviewers independently evaluated the presence or absence of desired team safety behaviors, including escalating care, sharing a mental model, establishing leadership, thinking out loud, and identifying roles and responsibilities. We also scored the quality of sharing the mental model, closed-loop communication, and overall team performance on a 7-point scale. Discordant reviews were resolved with scoring by an additional reviewer.

Results: A total of 1404 clinicians participated in 398 simulation scenarios, resulting in 257 usable videos. Overall, teams exhibited desired behaviors at the following frequencies: escalating care, 85%; sharing mental models, 66%; verbally establishing leadership, 6%; thinking out loud, 87%; and identifying roles and responsibilities, 27%. Across all reviews, the quality of the graded behaviors (of 7 points) was 2.8 for shared mental models, 3.3 for closed-loop communication, and 3.2 for overall team performance.

Conclusions: In a simulation setting with ad hoc teams, there was variable performance on completing safety behaviors and only a fair quality of graded communication behaviors. These results establish a baseline assessment of communication and teamwork behaviors and will guide future quality improvement interventions.
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http://dx.doi.org/10.1097/SIH.0000000000000575DOI Listing
March 2021

A pharmacokinetic simulation study to assess the performance of a sparse blood sampling approach to quantify early drug exposure.

Clin Transl Sci 2021 Jul 1;14(4):1444-1451. Epub 2021 May 1.

Department of Experimental and Clinical Pharmacology, College of Pharmacy, Minneapolis, Minnesota, USA.

Estimating early exposure of drugs used for the treatment of emergent conditions is challenging because blood sampling to measure concentrations is difficult. The objective of this work was to evaluate predictive performance of two early concentrations and prior pharmacokinetic (PK) information for estimating early exposure. The performance of a modeling approach was compared with a noncompartmental analysis (NCA). A simulation study was performed using literature-based models for phenytoin (PHT), levetiracetam (LEV), and valproic acid (VPA). These models were used to simulate rich concentration-time profiles from 0 to 2 h. Profiles without residual unexplained variability (RUV) were used to obtain the true partial area under the curve (pAUC) until 2 h after the start of drug infusion. From the profiles with the RUV, two concentrations per patient were randomly selected. These concentrations were analyzed under a population model to obtain individual population PK (PopPK) pAUCs. The NCA pAUCs were calculated using a linear trapezoidal rule. Percent prediction errors (PPEs) for the PopPK pAUCs and NCA pAUCs were calculated. A PPE within ±20% of the true value was considered a success and the number of successes was obtained for 100 simulated datasets. For PHT, LEV, and VPA, respectively, the median value of the success statistics obtained using the PopPK approach of 81%, 92%, and 88% were significantly higher than the 72%, 80%, and 67% using the NCA approach (p < 0.05; Mann-Whitney U test). This study provides a means by which early exposure can be estimated with good precision from two concentrations and a PopPK approach. It can be applied to other settings in which early exposures are of interest.
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http://dx.doi.org/10.1111/cts.13004DOI Listing
July 2021

Reducing Pediatric ED Length of Stay by Reducing Diagnostic Testing: A Discrete Event Simulation Model.

Pediatr Qual Saf 2021 Mar-Apr;6(2):e396. Epub 2021 Mar 10.

Emergency Medicine Section of Data Analytics, Children's National, Washington, D.C.

Quality improvement efforts can require significant investment before the system impact of those efforts can be evaluated. We used discrete event simulation (DES) modeling to test the theoretical impact of a proposed initiative to reduce diagnostic testing for low-acuity pediatric emergency department (ED) patients.

Methods: We modified an existing DES model, built at another large, urban, academic pediatric ED, to forecast the impact of reducing diagnostic testing rates on mean ED length of stay (LOS). The modified model included local testing rates for Emergency Severity Index (ESI) 4 and 5 patients and additional processes defined by local experts. Validation was performed by comparing model output predictions of mean LOS and wait times to actual site-specific data. We determined the goal reduction in diagnostic testing rates using the Achievable Benchmark of Care methodology. Model output mean LOS and wait times, with testing set at benchmark rates, were compared to outputs with testing set at current levels.

Results: During validation testing, model output metrics approximated actual clinical data with no statistically significant differences. Compared to model outputs with current testing rates, the mean LOS with testing set at an achievable benchmark was significantly shorter for ESI 4 (difference 19.1 mins [95% confidence interval 12.2, 26.0]) patients.

Conclusion: A DES model predicted a statistically significant decrease in mean LOS for ESI 4 pediatric ED patients if diagnostic testing is performed at an achievable benchmark rate compared to current rates. DES shows promise as a tool to evaluate the impact of a QI initiative before implementation.
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http://dx.doi.org/10.1097/pq9.0000000000000396DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7952107PMC
March 2021

So much nuance: A qualitative analysis of parental perspectives on child passenger safety.

Traffic Inj Prev 2021 4;22(3):224-229. Epub 2021 Mar 4.

Children's National Hospital, Washington, DC.

Objective: To explore barriers and facilitators to optimal child restraint system (CRS) use for diverse parents of newborn infants and to obtain input from parents on the use of technology-assisted remote car seat checks as tools for promoting optimal CRS use.

Methods: Parents were recruited using purposive sampling. Interviews were conducted with English- or Spanish-speaking parents with a full term newborn and regular access to a car. Interviews were conducted by phone, and recorded and transcribed verbatim. Interviews were conducted until thematic saturation was reached. Data were organized for analysis using Atlas.ti, and codes grouped by theme using constant comparison.

Results: 30 parents were enrolled. Barriers and facilitators to optimal CRS use were classified into three themes, as were thoughts on the pros and cons regarding remote car seat checks. Themes on barriers and facilitators included motor vehicle and CRS features (such as age and size of the motor vehicle and presence of the Lower Anchors and Tethers for Children LATCH system), resources (availability, accessibility, and accuracy of resources), and parental factors (parental emotions and characteristics). Themes related to pros and cons of remote car seat checks included the ability (and challenge) of remote car seat checks to identify and correct errors, the potential use of remote car seat checks in certain situations (such as CRS transitions and periods of growth), and convenience of remote car seat checks (including increased availability and ease of access). Subthemes with further detail were arranged within each theme identified.

Conclusion: From a parent perspective, there are several identified barriers and facilitators of optimal CRS use. Although car seat checks were identified as a resource, in-person accessibility was an issue, and there were mixed opinions on technology-assisted remote car seat checks. These results provide a foundation for additional study on targeted interventions, including remote interventions for which there is an increased need due to the COVID-19 pandemic.
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http://dx.doi.org/10.1080/15389588.2021.1877276DOI Listing
April 2021

An Adapted Child Safety Seat Hassles Score Is Associated With Suboptimal Child Passenger Safety Behaviors Among Parents.

Acad Pediatr 2021 Jul 10;21(5):892-899. Epub 2021 Feb 10.

Department of Emergency Medicine, Michigan Medicine (ML Macy), Ann Arbor, Mich; Division of General Pediatrics, The Susan B. Meister Child Health Evaluation and Research (CHEAR) Unit, Michigan Medicine (ML Macy), Ann Arbor, Mich; University of Michigan Injury Prevention Center (ML Macy), Ann Arbor, Mich; Ann & Robert H. Lurie Children's Hospital of Chicago (ML Macy), Chicago, Ill; Northwestern University Feinberg School of Medicine (ML Macy), Chicago, Ill. Dr Kendi is now with Department of Pediatrics, Boston Medical Center, Boston University School of Medicine, Boston, Mass.

Objective: We modified the Child Safety Seat (CSS) Hassles Scale to characterize CSS hassles in a diverse population and test for associations between hassles and caregiver-reported child passenger safety behaviors.

Methods: Secondary analysis of a 2-site survey of caregivers seeking emergency care for their ≤10-year-old child in 2015. Caregivers answered questions regarding CSS hassles, child passenger safety behaviors, and demographics. Size-appropriate restraint use was defined by the American Academy of Pediatrics (AAP) 2011 Guidelines for Child Passenger Safety. We tested for associations between the number of hassles and adherence to AAP guidelines (including the consistent use of a size-appropriate CSS, travel in a back seat, and never traveling unrestrained).

Results: There were 238 caregivers included in analyses. Overall, caregivers endorsed a median of 5 hassles (interquartile range 2, 8). Half (50.8%) of caregivers endorsed child passenger safety behaviors that were nonadherent to AAP guidelines. Compared with caregivers reporting no hassles, there was an increased odds of not adhering to AAP child passenger safety guidelines for each additional hassle reported (adjusted odds ratio [aOR] 1.11; 95% confidence interval [CI] 1.03, 1.19). In addition, a higher number of hassles was associated with the inconsistent use of a size-appropriate CSS (aOR 1.15; 95% CI 1.06, 1.25) and as sometimes traveling unrestrained (aOR 1.13; 95% CI 1.03, 1.23).

Conclusions: Caregivers who reported more CSS hassles were more likely to report behaviors that were not adherent to AAP guidelines. Addressing CSS hassles may provide solutions for nonadherence of AAP child passenger safety guidelines.
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http://dx.doi.org/10.1016/j.acap.2021.02.003DOI Listing
July 2021

Patterns of benzodiazepine underdosing in the Established Status Epilepticus Treatment Trial.

Epilepsia 2021 Mar 10;62(3):795-806. Epub 2021 Feb 10.

Department of Experimental and Clinical Pharmacology, College of Pharmacy and Center for Orphan Drug Research, University of Minnesota, Minneapolis, Minnesota, USA.

Objective: This study was undertaken to describe patterns of benzodiazepine use as first-line treatment of status epilepticus (SE) and test the association of benzodiazepine doses with response to second-line agents in patients enrolled in the Established Status Epilepticus Treatment Trial (ESETT).

Methods: Patients refractory to an adequate dose of benzodiazepines for the treatment of SE were enrolled in ESETT. Choice of benzodiazepine, doses given prior to administration of second-line agent, route of administration, setting, and patient weight were characterized. These were compared with guideline-recommended dosing. Logistic regression was used to determine the association of the first dose of benzodiazepine and the cumulative benzodiazepine dose with the response to second-line agent.

Results: Four hundred sixty patients were administered 1170 doses of benzodiazepines (669 lorazepam, 398 midazolam, 103 diazepam). Lorazepam was most frequently administered intravenously in the emergency department, midazolam intramuscularly or intravenously by the emergency medical services personnel, and diazepam rectally prior to ambulance arrival. The first dose of the first benzodiazepine (N = 460) was lower than guideline recommendations in 76% of midazolam administrations and 81% of lorazepam administrations. Among all administrations, >85% of midazolam and >76% of lorazepam administrations were lower than recommended. Higher first or cumulative benzodiazepine doses were not associated with better outcomes or clinical seizure cessation in response to second-line medications in these benzodiazepine-refractory seizures.

Significance: Benzodiazepines as first-line treatment of SE, particularly midazolam and lorazepam, are frequently underdosed throughout the United States. This broad and generalizable cohort confirms prior single site reports that underdosing is both pervasive and difficult to remediate. (ESETT ClinicalTrials.gov identifier: NCT01960075.).
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http://dx.doi.org/10.1111/epi.16825DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8075113PMC
March 2021

Electroencephalographic Seizures in Emergency Department Patients After Treatment for Convulsive Status Epilepticus.

J Clin Neurophysiol 2020 Dec 11;Publish Ahead of Print. Epub 2020 Dec 11.

Department of Emergency Medicine, State University of New York, Downstate Health Sciences University, Brooklyn, New York, U.S.A.; Department of Emergency Medicine, The University of Michigan, Ann Arbor, Michigan, U.S.A.; The Division of Emergency Medicine, Children's National Medical Center, Washington, DC, U.S.A.; Departments of Neurology, Pediatrics and Epidemiology and Population Health, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, New York, U.S.A.; Department of Public Health Sciences, Medical University of South Carolina, Charleston, South Carolina, U.S.A.; Department of Neurology, Massachusetts General Hospital, Boston, Massachusetts, U.S.A.; Davee Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, U.S.A.; and Department of Neurology, University of Virginia, Charlottesville, Virginia, U.S.A.

Purpose: It is unknown how often and how early EEG is obtained in patients presenting with status epilepticus. The Established Status Epilepticus Treatment Trial enrolled patients with benzodiazepine-refractory seizures and randomized participants to fosphenytoin, levetiracetam, or valproate. The use of early EEG, including frequency of electrographic seizures, was determined in Established Status Epilepticus Treatment Trial participants.

Methods: Secondary analysis of 475 enrollments at 58 hospitals to determine the frequency of EEG performed within 24 hours of presentation. The EEG type, the prevalence of electrographic seizures, and characteristics associated with obtaining early EEG were recorded. Chi-square and Wilcoxon rank-sum tests were calculated as appropriate for univariate and bivariate comparisons. Odds ratios are reported with 95% confidence intervals.

Results: A total of 278 of 475 patients (58%) in the Established Status Epilepticus Treatment Trial cohort underwent EEG within 24 hours (median time to EEG: 5 hours [interquartile range: 3-10]). Electrographic seizure prevalence was 14% (95% confidence interval, 10%-19%; 39/278) in the entire cohort and 13% (95% confidence interval, 7%-21%) in the subgroup of patients meeting the primary outcome of the Established Status Epilepticus Treatment Trial (clinical treatment success within 60 minutes of randomization). Among subjects diagnosed with electrographic seizures (39), 15 (38%; 95% confidence interval, 25%-54%) had no clinical correlate on the video EEG recording.

Conclusions: Electrographic seizures may occur in patients who stop seizing clinically after treatment of convulsive status epilepticus. Clinical correlates might not be present during electrographic seizures. These findings support early initiation of EEG recordings in patients suffering from convulsive status epilepticus, including those with clinical evidence of treatment success.
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http://dx.doi.org/10.1097/WNP.0000000000000800DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8192587PMC
December 2020

Early Exposure of Fosphenytoin, Levetiracetam, and Valproic Acid After High-Dose Intravenous Administration in Young Children With Benzodiazepine-Refractory Status Epilepticus.

J Clin Pharmacol 2021 Jun 12;61(6):763-768. Epub 2021 Jan 12.

Center for Orphan Drug Research, College of Pharmacy, University of Minnesota, Minneapolis, Minnesota, USA.

Fosphenytoin (FOS) and its active form, phenytoin (PHT), levetiracetam (LEV), and valproic acid (VPA) are commonly used second-line treatments of status epilepticus. However, limited information is available regarding LEV and VPA concentrations following high intravenous doses, particularly in young children. The Established Status Epilepticus Treatment Trial, a blinded, comparative effectiveness study of FOS, LEV, and VPA for benzodiazepine-refractory status epilepticus provided an opportunity to investigate early drug concentrations. Patients aged ≥2 years who continued to seizure despite receiving adequate doses of benzodiazepines were randomly assigned to FOS, LEV, or VPA infused over 10 minutes. A sparse blood-sampling approach was used, with up to 2 samples collected per patient within 2 hours following drug administration. The objective of this work was to report early drug exposure of PHT, LEV, and VPA and plasma protein binding of PHT and VPA. Twenty-seven children with median (interquartile range) age of 4 (2.5-6.5) years were enrolled. The total plasma concentrations ranged from 69 to 151.3 μg/mL for LEV, 11.3 to 26.7 μg/mL for PHT and 126 to 223 μg/mL for VPA. Free fraction ranged from 4% to 19% for PHT and 17% to 51% for VPA. This is the first report in young children of LEV concentrations with convulsive status epilepticus as well as VPA concentrations after a 40 mg/kg dose. Several challenges limited patient enrollment and blood sampling. Additional studies with a larger sample size are required to evaluate the exposure-response relationships in this emergent condition.
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http://dx.doi.org/10.1002/jcph.1801DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8089035PMC
June 2021

The Association of Laboratory Test Abnormalities With Mortality Risk in Pediatric Intensive Care.

Pediatr Crit Care Med 2021 02;22(2):147-160

Children's National Hospital and George Washington University School of Medicine and Health Sciences, Washington, DC.

Objectives: To determine the bivariable associations between abnormalities of 28 common laboratory tests and hospital mortality and determine how mortality risks changes when the ranges are evaluated in the context of commonly used laboratory test panels.

Design: A 2009-2016 cohort from the Health Facts (Cerner Corporation, Kansas City, MO) database.

Setting: Hospitals caring for children in ICUs.

Patients: Children cared for in ICUs with laboratory data.

Interventions: None.

Measurements And Main Results: There were 2,987,515 laboratory measurements in 71,563 children. The distribution of laboratory test values in 10 groups defined by population percentiles demonstrated the midrange of tests was within the normal range except for those measured predominantly when significant abnormalities are suspected. Logistic regression analysis at the patient level combined the population-based groups into ranges with nonoverlapping mortality odds ratios. The most deviant test ranges associated with increased mortality risk (mortality odds ratios > 5.0) included variables associated with acidosis, coagulation abnormalities and blood loss, immune function, liver function, nutritional status, and the basic metabolic profile. The test ranges most associated with survival included normal values for chloride, pH, and bicarbonate/total Co2. When the significant test ranges from bivariable analyses were combined in commonly used test panels, they generally remained significant but were reduced as risk was distributed among the tests.

Conclusions: The relative importance of laboratory test ranges vary widely, with some ranges strongly associated with mortality and others strongly associated with survival. When evaluated in the context of test panels rather than isolated tests, the mortality odds ratios for the test ranges decreased but generally remained significant as risk was distributed among the components of the test panels. These data are useful to develop critical values for children in ICUs, to identify risk factors previously underappreciated, for education and training, and for future risk score development.
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http://dx.doi.org/10.1097/PCC.0000000000002610DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7855885PMC
February 2021

Identifying trigger concepts to screen emergency department visits for diagnostic errors.

Diagnosis (Berl) 2020 Nov 11. Epub 2020 Nov 11.

Center for Innovations in Quality, Effectiveness and Safety, Michael E. DeBakey Veterans Affairs Medical Center and Baylor College of Medicine, Houston, TX, USA.

Objectives: The diagnostic process is a vital component of safe and effective emergency department (ED) care. There are no standardized methods for identifying or reliably monitoring diagnostic errors in the ED, impeding efforts to enhance diagnostic safety. We sought to identify trigger concepts to screen ED records for diagnostic errors and describe how they can be used as a measurement strategy to identify and reduce preventable diagnostic harm.

Methods: We conducted a literature review and surveyed ED directors to compile a list of potential electronic health record (EHR) trigger (e-triggers) and non-EHR based concepts. We convened a multidisciplinary expert panel to build consensus on trigger concepts to identify and reduce preventable diagnostic harm in the ED.

Results: Six e-trigger and five non-EHR based concepts were selected by the expert panel. E-trigger concepts included: unscheduled ED return to ED resulting in hospital admission, death following ED visit, care escalation, high-risk conditions based on symptom-disease dyads, return visits with new diagnostic/therapeutic interventions, and change of treating service after admission. Non-EHR based signals included: cases from mortality/morbidity conferences, risk management/safety office referrals, ED medical director case referrals, patient complaints, and radiology/laboratory misreads and callbacks. The panel suggested further refinements to aid future research in defining diagnostic error epidemiology in ED settings.

Conclusions: We identified a set of e-trigger concepts and non-EHR based signals that could be developed further to screen ED visits for diagnostic safety events. With additional evaluation, trigger-based methods can be used as tools to monitor and improve ED diagnostic performance.
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http://dx.doi.org/10.1515/dx-2020-0122DOI Listing
November 2020

Racial and Ethnic Disparities in the Delayed Diagnosis of Appendicitis Among Children.

Acad Emerg Med 2020 Sep 29. Epub 2020 Sep 29.

and the, Department of Pediatrics, Ann & Robert H. Lurie Children's Hospital, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.

Background: Appendicitis is the most common surgical condition in pediatric emergency department (ED) patients. Prompt diagnosis can reduce morbidity, including appendiceal perforation. The goal of this study was to measure racial/ethnic differences in rates of 1) appendiceal perforation, 2) delayed diagnosis of appendicitis, and 3) diagnostic imaging during prior visit(s).

Methods: This was a 3-year multicenter (seven EDs) retrospective cohort study of children diagnosed with appendicitis using the Pediatric Emergency Care Applied Research Network Registry. Delayed diagnosis was defined as having at least one prior ED visit within 7 days preceding appendicitis diagnosis. We performed multivariable logistic regression to measure associations of race/ethnicity (non-Hispanic [NH]-white, NH-Black, Hispanic, other) with 1) appendiceal perforation, 2) delayed diagnosis of appendicitis, and 3) diagnostic imaging during prior visit(s).

Results: Of 7,298 patients with appendicitis and documented race/ethnicity, 2,567 (35.2%) had appendiceal perforation. In comparison to NH-whites, NH-Black children had higher likelihood of perforation (36.5% vs. 34.9%; adjusted odds ratio [aOR] = 1.21 [95% confidence interval {CI} = 1.01 to 1.45]). A total of 206 (2.8%) had a delayed diagnosis of appendicitis. NH-Black children were more likely to have delayed diagnoses (4.7% vs. 2.0%; aOR = 1.81 [95% CI = 1.09 to 2.98]). Eighty-nine (43.2%) patients with delayed diagnosis had abdominal imaging during their prior visits. In comparison to NH-whites, NH-Black children were less likely to undergo any imaging (28.2% vs. 46.2%; aOR = 0.41 [95% CI = 0.18 to 0.96]) or definitive imaging (e.g., ultrasound/computed tomography/magnetic resonance imaging; 10.3% vs. 35.9%; aOR = 0.15 [95% CI = 0.05 to 0.50]) during prior visits.

Conclusions: In this multicenter cohort, there were racial disparities in appendiceal perforation. There were also racial disparities in rates of delayed diagnosis of appendicitis and diagnostic imaging during prior ED visits. These disparities in diagnostic imaging may lead to delays in appendicitis diagnosis and, thus, may contribute to higher perforation rates demonstrated among minority children.
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http://dx.doi.org/10.1111/acem.14142DOI Listing
September 2020

Criticality: A New Concept of Severity of Illness for Hospitalized Children.

Pediatr Crit Care Med 2021 01;22(1):e33-e43

Department of Pediatrics, Division of Critical Care Medicine, Children's National Hospital and George Washington University School of Medicine and Health Sciences, Washington, DC.

Objectives: To validate the conceptual framework of "criticality," a new pediatric inpatient severity measure based on physiology, therapy, and therapeutic intensity calibrated to care intensity, operationalized as ICU care.

Design: Deep neural network analysis of a pediatric cohort from the Health Facts (Cerner Corporation, Kansas City, MO) national database.

Setting: Hospitals with pediatric routine inpatient and ICU care.

Patients: Children cared for in the ICU (n = 20,014) and in routine care units without an ICU admission (n = 20,130) from 2009 to 2016. All patients had laboratory, vital sign, and medication data.

Interventions: None.

Measurements And Main Results: A calibrated, deep neural network used physiology (laboratory tests and vital signs), therapy (medications), and therapeutic intensity (number of physiology tests and medications) to model care intensity, operationalized as ICU (versus routine) care every 6 hours of a patient's hospital course. The probability of ICU care is termed the Criticality Index. First, the model demonstrated excellent separation of criticality distributions from a severity hierarchy of five patient groups: routine care, routine care for those who also received ICU care, transition from routine to ICU care, ICU care, and high-intensity ICU care. Second, model performance assessed with statistical metrics was excellent with an area under the curve for the receiver operating characteristic of 0.95 for 327,189 6-hour time periods, excellent calibration, sensitivity of 0.817, specificity of 0.892, accuracy of 0.866, and precision of 0.799. Third, the performance in individual patients with greater than one care designation indicated as 88.03% (95% CI, 87.72-88.34) of the Criticality Indices in the more intensive locations was higher than the less intense locations.

Conclusions: The Criticality Index is a quantification of severity of illness for hospitalized children using physiology, therapy, and care intensity. This new conceptual model is applicable to clinical investigations and predicting future care needs.
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http://dx.doi.org/10.1097/PCC.0000000000002560DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7790867PMC
January 2021

Severity Trajectories of Pediatric Inpatients Using the Criticality Index.

Pediatr Crit Care Med 2021 01;22(1):e19-e32

Department of Pediatrics, Division of Critical Care Medicine, Children's National Hospital, George Washington University School of Medicine and Health Sciences, Washington, DC.

Objectives: To assess severity of illness trajectories described by the Criticality Index for survivors and deaths in five patient groups defined by the sequence of patient care in ICU and routine patient care locations.

Design: The Criticality Index developed using a calibrated, deep neural network, measures severity of illness using physiology, therapies, and therapeutic intensity. Criticality Index values in sequential 6-hour time periods described severity trajectories.

Setting: Hospitals with pediatric inpatient and ICU care.

Patients: Pediatric patients never cared for in an ICU (n = 20,091), patients only cared for in the ICU (n = 2,096) and patients cared for in both ICU and non-ICU care locations (n = 17,023) from 2009 to 2016 Health Facts database (Cerner Corporation, Kansas City, MO).

Interventions: None.

Measurements And Main Results: Criticality Index values were consistent with clinical experience. The median (25-75th percentile) ICU Criticality Index values (0.878 [0.696-0.966]) were more than 80-fold higher than the non-ICU values (0.010 [0.002-0.099]). Non-ICU Criticality Index values for patients transferred to the ICU were 40-fold higher than those never transferred to the ICU (0.164 vs 0.004). The median for ICU deaths was higher than ICU survivors (0.983 vs 0.875) (p < 0.001). The severity trajectories for the five groups met expectations based on clinical experience. Survivors had increasing Criticality Index values in non-ICU locations prior to ICU admission, decreasing Criticality Index values in the ICU, and decreasing Criticality Index values until hospital discharge. Deaths had higher Criticality Index values than survivors, steeper increases prior to the ICU, and worsening values in the ICU. Deaths had a variable course, especially those who died in non-ICU care locations, consistent with deaths associated with both active therapies and withdrawals/limitations of care.

Conclusions: Severity trajectories measured by the Criticality Index showed strong validity, reflecting the expected clinical course for five diverse patient groups.
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http://dx.doi.org/10.1097/PCC.0000000000002561DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7790848PMC
January 2021

A Multiyear Cross-sectional Study of Guideline Adherence for the Timeliness of Opioid Administration in Children With Sickle Cell Pain Crisis.

Ann Emerg Med 2020 09;76(3S):S6-S11

Department of Pediatrics, Medical College of Wisconsin, Milwaukee, WI.

Study Objective: The National Heart, Lung, and Blood Institute evidence-based guidelines for timeliness of opioid administration for sickle cell disease (SCD) pain crises recommend an initial opioid within 1 hour of arrival, with subsequent dosing every 30 minutes until pain is controlled. No multisite studies have evaluated guideline adherence, to our knowledge. Our objective was to determine guideline adherence across a multicenter network.

Methods: We conducted a multiyear cross-sectional analysis of children with SCD who presented between January 1, 2016, and December 31, 2018, to 7 emergency departments (EDs) within the Pediatric Emergency Care Applied Research Network. Visits for uncomplicated pain crisis were included, defined with an International Classification of Diseases, Ninth Revision (ICD-9) and ICD-10 code for SCD crisis and receipt of an opioid, excluding visits with other SCD complications or temperature exceeding 38.5°C (101.3°F). Times were extracted from the electronic record. Guideline adherence was assessed across sites and calendar years.

Results: A total of 4,578 visits were included. The median time to first opioid receipt was 62 minutes (interquartile range 42 to 93 minutes); between the first and second opioid receipt, 60 minutes (interquartile range 39 to 93 minutes). Overall, 48% of visits (95% confidence interval 47% to 50%) were guideline adherent for first opioid. Of 3,538 visits with a second opioid, 15% (95% confidence interval 14% to 16%) were guideline adherent. Site variation in adherence existed for time to first opioid (range 22% to 70%) and time between first and second opioid (range 2% to 36%; both P<.001). There was no change in timeliness to first dose or time between doses across years (P>.05 for both).

Conclusion: Guideline adherence for timeliness of SCD treatment is poor, with half of visits adherent for time to first opioid and one seventh adherent for second dose. Dissemination and implementation research/quality improvement efforts are critical to improve care across EDs.
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http://dx.doi.org/10.1016/j.annemergmed.2020.08.006DOI Listing
September 2020

Association of Antibiotic Choice With Hospital Length of Stay and Risk Factors for Readmission in Patients With Sickle Cell Disease and Acute Chest Syndrome: An Observational Cohort Study.

Ann Emerg Med 2020 09;76(3S):S37-S45

Department of Emergency Medicine and Trauma Services, Children's National Health System, Washington, DC.

Study Objective: We determine the association between use of specific cephalosporins and macrolides and hospital length of stay in patients with sickle cell disease (SCD) who are admitted with acute chest syndrome, and determine treatment risk factors for acute chest syndrome-related 30-day readmission.

Methods: Patients admitted to 48 US hospitals within the Pediatric Health Information System between January 2008 and December 2016 with associated International Classification of Diseases, Ninth Revision (ICD-9) or ICD-10 diagnoses of SCD and acute chest syndrome were included. Primary outcomes were hospital length of stay and acute chest syndrome-related and all-cause 30-day readmission. Data were analyzed with t tests, ANOVA, and bivariable and multivariable linear and logistic regressions.

Results: In 21,126 visits (representing 8,856 patients), median age was 11.2 years (interquartile range 6.1 to 16.5 years), 53.5% were male patients, and 77.2% had hemoglobin SS genotype. Median length of stay was 4 days (interquartile range 2 to 6 days; mean 4.76 days [SD 4.62 days]). Ceftriaxone alone (length of stay 4.75 days [SD 4.66 days]; P<.001) or the combination of ceftriaxone and azithromycin (length of stay 4.84 days [SD 4.74 days]; P<.001) was associated with the shortest length of stay and a reduced risk of acute chest syndrome-related readmission (ceftriaxone odds ratio [OR] 0.31; 95% confidence interval [CI] 0.27 to 0.35; ceftriaxone+azithromycin OR 0.20; 95% CI 0.17 to 0.24). Albuterol (OR 0.97; 95% CI 0.96 to 0.98) and RBC transfusion (OR 0.60; 95% CI 0.43 to 0.83) were also associated with decreased rates of acute chest syndrome-related 30-day readmission. All-cause 30-day readmission rate was 16.7% (95% CI 16.2% to 17.3%).

Conclusion: Guideline-compliant therapy for acute chest syndrome could preferentially include ceftriaxone and azithromycin. All-cause 30-day readmission for acute chest syndrome is lower than that reported for all-cause readmissions for SCD and more consistent with rates of readmission for pneumonia in the general population.
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http://dx.doi.org/10.1016/j.annemergmed.2020.08.011DOI Listing
September 2020

Machine Learning and Clinical Prediction Rules: A Perfect Match?

Pediatrics 2020 09;146(3)

Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.

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http://dx.doi.org/10.1542/peds.2020-012203DOI Listing
September 2020

Improving Throughput for Mid-acuity Patients in the Pediatric Emergency Department.

Pediatr Qual Saf 2020 May-Jun;5(3):e302. Epub 2020 May 26.

Emergency Medicine and Trauma Center, Children's National Hospital.

Purpose: Visits to pediatric emergency departments (EDs) are increasing, leading to overcrowding, prolonged patient wait times, and negative patient experiences. In our system, these prolonged wait times and negative experiences notably impact mid-acuity patients. As such, we sought to decrease their time-to-first-provider from 92 to 60 minutes.

Methods: After identifying inefficiencies in patient arrival, triage, and assessment, we redesigned our physical space and implemented a new triage process. Further, we deployed a new multidisciplinary front-end team consisting of a physician, nurses, and ED tech specialists to create and implement an initial management plan. Time-to-first-provider for mid-acuity patients was the main outcome measure. We examined ED length of stay (LOS) as a balancing measure. Post hoc, we measured time-to-first-nursing assessment and the proportion of high-acuity patients seen within 20 minutes as additional measures of the impact of these interventions on our system. All analyses were measured using statistical process control charts.

Results: During high patient volumes, we decreased the time-to-first-provider to 70 minutes, but exceeded our goal during low patient volumes (41 minutes). We observed a 5% decrease in LOS during both high and low patient volumes (5% and 8%, respectively). There was a 60% increase in the time-to-first-nursing assessment.

Conclusions: A new front-end process resulted in improved time-to-first-provider and LOS. The new process was associated with longer times for nursing assessments but did not negatively impact the rapid physician assessment of higher acuity patients.
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http://dx.doi.org/10.1097/pq9.0000000000000302DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7297400PMC
May 2020

Diagnostic Accuracy of Non-Invasive Thermal Evaluation of Ventriculoperitoneal Shunt Flow in Shunt Malfunction: A Prospective, Multi-Site, Operator-Blinded Study.

Neurosurgery 2020 10;87(5):939-948

Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts.

Background: Thermal flow evaluation (TFE) is a non-invasive method to assess ventriculoperitoneal shunt function. Flow detected by TFE is a negative predictor of the need for revision surgery. Further optimization of testing protocols, evaluation in multiple centers, and integration with clinical and imaging impressions prompted the current study.

Objective: To compare the diagnostic accuracy of 2 TFE protocols, with micropumper (TFE+MP) or without (TFE-only), to neuro-imaging in patients emergently presenting with symptoms concerning for shunt malfunction.

Methods: We performed a prospective multicenter operator-blinded trial of a consecutive series of patients who underwent evaluation for shunt malfunction. TFE was performed, and preimaging clinician impressions and imaging results were recorded. The primary outcome was shunt obstruction requiring neurosurgical revision within 7 d. Non-inferiority of the sensitivity of TFE vs neuro-imaging for detecting shunt obstruction was tested using a prospectively determined a priori margin of -2.5%.

Results: We enrolled 406 patients at 10 centers. Of these, 68/348 (20%) evaluated with TFE+MP and 30/215 (14%) with TFE-only had shunt obstruction. The sensitivity for detecting obstruction was 100% (95% CI: 88%-100%) for TFE-only, 90% (95% CI: 80%-96%) for TFE+MP, 76% (95% CI: 65%-86%) for imaging in TFE+MP cohort, and 77% (95% CI: 58%-90%) for imaging in the TFE-only cohort. Difference in sensitivities between TFE methods and imaging did not exceed the non-inferiority margin.

Conclusion: TFE is non-inferior to imaging in ruling out shunt malfunction and may help avoid imaging and other steps. For this purpose, TFE only is favored over TFE+MP.
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http://dx.doi.org/10.1093/neuros/nyaa128DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7566379PMC
October 2020

The association of patient weight and dose of fosphenytoin, levetiracetam, and valproic acid with treatment success in status epilepticus.

Epilepsia 2020 06 18;61(6):e66-e70. Epub 2020 May 18.

Department of Experimental and Clinical Pharmacology and Center for Orphan Drug Research, College of Pharmacy, University of Minnesota, Minneapolis, Minnesota.

The Established Status Epilepticus Treatment Trial was a blinded, comparative-effectiveness study of fosphenytoin, levetiracetam, and valproic acid in benzodiazepine-refractory status epilepticus. The primary outcome was clinical seizure cessation and increased responsiveness without additional anticonvulsant medications. Weight-based dosing was capped at 75 kg. Hence, patients weighing >75 kg received a lower mg/kg dose. Logistic regression models were developed in 235 adults to determine the association of weight (≤ or >75 kg, ≤ or >90 kg), sex, treatment, and weight-normalized dose with the primary outcome and solely seizure cessation. The primary outcome was achieved in 45.1% and 42.5% of those ≤75 kg and >75 kg, respectively. Using univariate analyses, the likelihood of success for those >75 kg (odds ratio [OR] = 0.9, 95% confidence interval [CI] = 0.54-1.51) or >90 kg (OR = 0.85, 95% CI = 0.42-1.66) was not statistically different compared with those ≤75 kg or ≤90 kg, respectively. Similarly, other predictors were not significantly associated with primary outcome or clinical seizure cessation. Our findings suggest that doses, capped at 75 kg, likely resulted in concentrations greater than those needed for outcome. Studies that include drug concentrations and heavier individuals are needed to confirm these findings.
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http://dx.doi.org/10.1111/epi.16534DOI Listing
June 2020

Racial and Ethnic Differences in Emergency Department Pain Management of Children With Fractures.

Pediatrics 2020 05 20;145(5). Epub 2020 Apr 20.

Department of Pediatrics, Ann & Robert H. Lurie Children's Hospital and Feinberg School of Medicine, Northwestern University, Chicago, Illinois.

Objectives: To test the hypotheses that minority children with long-bone fractures are less likely to (1) receive analgesics, (2) receive opioid analgesics, and (3) achieve pain reduction.

Methods: We performed a 3-year retrospective cross-sectional study of children <18 years old with long-bone fractures using the Pediatric Emergency Care Applied Research Network Registry (7 emergency departments). We performed bivariable and multivariable logistic regression to measure the association between patient race and ethnicity and (1) any analgesic, (2) opioid analgesic, (3) ≥2-point pain score reduction, and (4) optimal pain reduction (ie, to mild or no pain).

Results: In 21 069 visits with moderate-to-severe pain, 86.1% received an analgesic and 45.4% received opioids. Of 8533 patients with reassessment of pain, 89.2% experienced ≥2-point reduction in pain score and 62.2% experienced optimal pain reduction. In multivariable analyses, minority children, compared with non-Hispanic (NH) white children, were more likely to receive any analgesics (NH African American: adjusted odds ratio [aOR] 1.72 [95% confidence interval 1.51-1.95]; Hispanic: 1.32 [1.16-1.51]) and achieve ≥2-point reduction in pain (NH African American: 1.42 [1.14-1.76]; Hispanic: 1.38 [1.04-1.83]) but were less likely to receive opioids (NH African American: aOR 0.86 [0.77-0.95]; Hispanic: aOR 0.86 [0.76-0.96]) or achieve optimal pain reduction (NH African American: aOR 0.78 [0.67-0.90]; Hispanic: aOR 0.80 [0.67-0.95]).

Conclusions: There are differences in process and outcome measures by race and ethnicity in the emergency department management of pain among children with long-bone fractures. Although minority children are more likely to receive analgesics and achieve ≥2-point reduction in pain, they are less likely to receive opioids and achieve optimal pain reduction.
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http://dx.doi.org/10.1542/peds.2019-3370DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7193974PMC
May 2020

Efficacy of levetiracetam, fosphenytoin, and valproate for established status epilepticus by age group (ESETT): a double-blind, responsive-adaptive, randomised controlled trial.

Lancet 2020 04 20;395(10231):1217-1224. Epub 2020 Mar 20.

Department of Emergency Medicine, Neuro Emergencies Research, University of Michigan, Ann Arbor, MI, USA. Electronic address:

Background: Benzodiazepine-refractory, or established, status epilepticus is thought to be of similar pathophysiology in children and adults, but differences in underlying aetiology and pharmacodynamics might differentially affect response to therapy. In the Established Status Epilepticus Treatment Trial (ESETT) we compared the efficacy and safety of levetiracetam, fosphenytoin, and valproate in established status epilepticus, and here we describe our results after extending enrolment in children to compare outcomes in three age groups.

Methods: In this multicentre, double-blind, response-adaptive, randomised controlled trial, we recruited patients from 58 hospital emergency departments across the USA. Patients were eligible for inclusion if they were aged 2 years or older, had been treated for a generalised convulsive seizure of longer than 5 min duration with adequate doses of benzodiazepines, and continued to have persistent or recurrent convulsions in the emergency department for at least 5 min and no more than 30 min after the last dose of benzodiazepine. Patients were randomly assigned in a response-adaptive manner, using Bayesian methods and stratified by age group (<18 years, 18-65 years, and >65 years), to levetiracetam, fosphenytoin, or valproate. All patients, investigators, study staff, and pharmacists were masked to treatment allocation. The primary outcome was absence of clinically apparent seizures with improved consciousness and without additional antiseizure medication at 1 h from start of drug infusion. The primary safety outcome was life-threatening hypotension or cardiac arrhythmia. The efficacy and safety outcomes were analysed by intention to treat. This study is registered in ClinicalTrials.gov, NCT01960075.

Findings: Between Nov 3, 2015, and Dec 29, 2018, we enrolled 478 patients and 462 unique patients were included: 225 children (aged <18 years), 186 adults (18-65 years), and 51 older adults (>65 years). 175 (38%) patients were randomly assigned to levetiracetam, 142 (31%) to fosphenyltoin, and 145 (31%) were to valproate. Baseline characteristics were balanced across treatments within age groups. The primary efficacy outcome was met in those treated with levetiracetam for 52% (95% credible interval 41-62) of children, 44% (33-55) of adults, and 37% (19-59) of older adults; with fosphenytoin in 49% (38-61) of children, 46% (34-59) of adults, and 35% (17-59) of older adults; and with valproate in 52% (41-63) of children, 46% (34-58) of adults, and 47% (25-70) of older adults. No differences were detected in efficacy or primary safety outcome by drug within each age group. With the exception of endotracheal intubation in children, secondary safety outcomes did not significantly differ by drug within each age group.

Interpretation: Children, adults, and older adults with established status epilepticus respond similarly to levetiracetam, fosphenytoin, and valproate, with treatment success in approximately half of patients. Any of the three drugs can be considered as a potential first-choice, second-line drug for benzodiazepine-refractory status epilepticus.

Funding: National Institute of Neurological Disorders and Stroke, National Institutes of Health.
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http://dx.doi.org/10.1016/S0140-6736(20)30611-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7241415PMC
April 2020

Intravenous Magnesium in Asthma Pharmacotherapy: Variability in Use in the PECARN Registry.

J Pediatr 2020 05 5;220:165-174.e2. Epub 2020 Mar 5.

Department of Pediatrics, Ann & Robert H. Lurie Children's Hospital of Chicago, Northwestern University Feinberg School of Medicine, Chicago, IL.

Objective: To examine the use, efficacy, and safety of intravenous magnesium sulfate (IVMg) in children with asthma whose emergency department (ED) management is recorded in the Pediatric Emergency Care Applied Research Network (PECARN) Registry.

Study Design: This multicenter retrospective cohort study analyzed clinical data from 7 EDs from 2012 to 2017. We described use of IVMg in children aged 2-17 years treated for acute asthma and its effect on blood pressure. We also used multivariable analysis to examine factors associated with use of IVMg and its association with return visits within 72 hours.

Results: Across 61 854 asthma visits for children, clinicians administered IVMg in 6497 (10.5%). Median time from triage to IVMg administration was 154 minutes (IQR 84, 244). During 22 495 ED visits resulting in hospitalization after ED treatment, IVMg was administered in 5774 (25.7%) (range by site 15.9%, 50.6%). Patients were discharged home from the ED after 11.1% of IVMg administrations, and hypotension occurred after 6.8%. Variation in IVMg use was not explained by patient characteristics. Revisits did not differ between patients discharged after IVMg and those not receiving IVMg.

Conclusions: In PECARN Registry EDs, administration of IVMg occurs late in ED treatment, for a minority of the children likely to benefit, with variation between sites, which suggests the current clinical role for IVMg in preventing hospitalization is limited. Discharge after IVMg administration is likely safe. Further research should prospectively assess the efficacy and safety of early IVMg administration.
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http://dx.doi.org/10.1016/j.jpeds.2020.01.062DOI Listing
May 2020

Opioid Prescription Patterns at Emergency Department Discharge for Children with Fractures.

Pain Med 2020 09;21(9):1947-1954

Department of Pediatrics, Northwestern University Feinberg School of Medicine, Ann & Robert H. Lurie Children's Hospital of Chicago for The Pediatric Emergency Care Applied Research Network (PECARN), Chicago, Illinois, USA.

Objective: To measure the variability in discharge opioid prescription practices for children discharged from the emergency department (ED) with a long-bone fracture.

Design: A retrospective cohort study of pediatric ED visits in 2015.

Setting: Four pediatric EDs.

Subjects: Children aged four to 18 years with a long-bone fracture discharged from the ED.

Methods: A multisite registry of electronic health record data (PECARN Registry) was analyzed to determine the proportion of children receiving an opioid prescription on ED discharge. Multivariable logistic regression was performed to determine characteristics associated with receipt of an opioid prescription.

Results: There were 5,916 visits with long-bone fractures; 79% involved the upper extremity, and 27% required reduction. Overall, 15% of children were prescribed an opioid at discharge, with variation between the four EDs: A = 8.2% (95% confidence interval [CI] = 6.9-9.7%), B = 12.1% (95% CI = 10.5-14.0%), C = 16.9% (95% CI = 15.2-18.8%), D = 23.8% (95% CI = 21.7-26.1%). Oxycodone was the most frequently prescribed opioid. In the regression analysis, in addition to variation by ED site of care, age 12-18 years, white non-Hispanic, private insurance status, reduced fracture, and severe pain documented during the ED visit were associated with increased opioid prescribing.

Conclusions: For children with a long-bone fracture, discharge opioid prescription varied widely by ED site of care. In addition, black patients, Hispanic patients, and patients with government insurance were less likely to be prescribed opioids. This variability in opioid prescribing was not accounted for by patient- or injury-related factors that are associated with increased pain. Therefore, opioid prescribing may be modifiable, but evidence to support improved outcomes with specific treatment regimens is lacking.
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http://dx.doi.org/10.1093/pm/pnz348DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7553018PMC
September 2020

An Operational Framework to Study Diagnostic Errors in Emergency Departments: Findings From A Consensus Panel.

J Patient Saf 2019 Nov 25. Epub 2019 Nov 25.

Center for Innovations in Quality, Effectiveness and Safety, Michael E. DeBakey Veterans Affairs Medical Center and Baylor College of Medicine, Houston, Texas.

Objective: To create an operational definition and framework to study diagnostic error in the emergency department setting.

Methods: We convened a 17-member multidisciplinary panel with expertise in general and pediatric emergency medicine, nursing, patient safety, informatics, cognitive psychology, social sciences, human factors, and risk management and a patient/caregiver advocate. We used a modified nominal group technique to develop a shared understanding to operationally define diagnostic errors in emergency care and modify the National Academies of Sciences, Engineering, and Medicine's conceptual process framework to this setting.

Results: The expert panel defined diagnostic errors as "a divergence from evidence-based processes that increases the risk of poor outcomes despite the availability of sufficient information to provide a timely and accurate explanation of the patient's health problem(s)." Diagnostic processes include tasks related to (a) acuity recognition, information and synthesis, evaluation coordination, and (b) communication with patients/caregivers and other diagnostic team members. The expert panel also modified the National Academies of Sciences, Engineering, and Medicine's diagnostic process framework to incorporate influence of mode of arrival, triage level, and interventions during emergency care and underscored the importance of outcome feedback to emergency department providers to promote learning and improvement related to diagnosis.

Conclusions: The proposed operational definition and modified diagnostic process framework can potentially inform the development of measurement tools and strategies to study the epidemiology and interventions to improve emergency care diagnosis.
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http://dx.doi.org/10.1097/PTS.0000000000000624DOI Listing
November 2019

Randomized Trial of Three Anticonvulsant Medications for Status Epilepticus.

N Engl J Med 2019 11;381(22):2103-2113

From the Department of Neurology, University of Virginia, Charlottesville (J.K., N.F.); the Data Coordination Unit, Department of Public Health Sciences, Medical University of South Carolina, Charleston (J.E., C.M.); the Division of Emergency Medicine, Children's National Medical Center, Washington, DC (J.M.C.); the Department of Emergency Medicine, University of Michigan, Ann Arbor (W.B., R.S.); the College of Pharmacy, Department of Experimental and Clinical Pharmacology, University of Minnesota, Minneapolis (J.C.); the Department of Neurology, University of California, San Francisco, San Francisco (D.L.); the Departments of Neurology and Pediatrics, Albert Einstein College of Medicine, Montefiore Medical Center, New York (S.S.); the National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD (R.C.); St. George's University of London and St. George's University Hospitals NHS Foundation Trust, London (H.C.); and ConfluenceStat (J.T.C.) and the University of Central Florida College of Medicine (J.T.C.) - both in Orlando.

Background: The choice of drugs for patients with status epilepticus that is refractory to treatment with benzodiazepines has not been thoroughly studied.

Methods: In a randomized, blinded, adaptive trial, we compared the efficacy and safety of three intravenous anticonvulsive agents - levetiracetam, fosphenytoin, and valproate - in children and adults with convulsive status epilepticus that was unresponsive to treatment with benzodiazepines. The primary outcome was absence of clinically evident seizures and improvement in the level of consciousness by 60 minutes after the start of drug infusion, without additional anticonvulsant medication. The posterior probabilities that each drug was the most or least effective were calculated. Safety outcomes included life-threatening hypotension or cardiac arrhythmia, endotracheal intubation, seizure recurrence, and death.

Results: A total of 384 patients were enrolled and randomly assigned to receive levetiracetam (145 patients), fosphenytoin (118), or valproate (121). Reenrollment of patients with a second episode of status epilepticus accounted for 16 additional instances of randomization. In accordance with a prespecified stopping rule for futility of finding one drug to be superior or inferior, a planned interim analysis led to the trial being stopped. Of the enrolled patients, 10% were determined to have had psychogenic seizures. The primary outcome of cessation of status epilepticus and improvement in the level of consciousness at 60 minutes occurred in 68 patients assigned to levetiracetam (47%; 95% credible interval, 39 to 55), 53 patients assigned to fosphenytoin (45%; 95% credible interval, 36 to 54), and 56 patients assigned to valproate (46%; 95% credible interval, 38 to 55). The posterior probability that each drug was the most effective was 0.41, 0.24, and 0.35, respectively. Numerically more episodes of hypotension and intubation occurred in the fosphenytoin group and more deaths occurred in the levetiracetam group than in the other groups, but these differences were not significant.

Conclusions: In the context of benzodiazepine-refractory convulsive status epilepticus, the anticonvulsant drugs levetiracetam, fosphenytoin, and valproate each led to seizure cessation and improved alertness by 60 minutes in approximately half the patients, and the three drugs were associated with similar incidences of adverse events. (Funded by the National Institute of Neurological Disorders and Stroke; ESETT ClinicalTrials.gov number, NCT01960075.).
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http://dx.doi.org/10.1056/NEJMoa1905795DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7098487PMC
November 2019

Provider-Level and Hospital-Level Factors and Process Measures of Quality Care Delivered in Pediatric Emergency Departments.

Acad Pediatr 2020 May - Jun;20(4):524-531. Epub 2019 Nov 21.

Department of Pediatrics, University of California, Davis School of Medicine (JP Marcin, PS Romano, P Dayal, M Dharmar, and N Kuppermann), Sacramento, Calif; Department of Emergency Medicine, University of California, Davis School of Medicine (L Tzimenatos), Sacramento, Calif.

Objective: Differences in the quality of emergency department (ED) care are often attributed to nonclinical factors such as variations in the structure, systems, and processes of care. Few studies have examined these associations among children. We aimed to determine whether process measures of quality of care delivered to patients receiving care in children's hospital EDs were associated with physician-level or hospital-level factors.

Methods: We included children (<18 years old) who presented to any of the 12 EDs participating in the Pediatric Emergency Care Applied Research Network (PECARN) between January 2011 and December 2011. We measured quality of care from medical record reviews using a previously validated implicit review instrument with a summary score ranging from 5 to 35, and examined associations between process measures of quality and physician- and hospital-level factors using a mixed-effects linear regression model adjusted for patient case-mix, with hospital site as a random effect.

Results: Among the 620 ED encounters reviewed, we did not find process measures of quality to be associated with any physician-level factors such as physician sex, years since medical school graduation, or physician training. We found, however, that process measures of quality were positively associated with delivery at freestanding children's hospitals (1.96 points higher in quality compared to nonfreestanding status, 95% confidence interval: 0.49, 3.43) and negatively associated with higher annual ED patient volume (-0.03 points per thousand patients, 95% confidence interval: -0.05, -0.01).

Conclusion: Process measures of quality of care delivered to children were higher among patients treated at freestanding children's hospitals but lower among patients treated at higher volume EDs.
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http://dx.doi.org/10.1016/j.acap.2019.11.007DOI Listing
November 2019