Publications by authors named "Cristina Barcia Aguilar"

11 Publications

  • Page 1 of 1

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

Epilepsia 2021 Jul 12. Epub 2021 Jul 12.

Division of Epilepsy and Clinical Neurophysiology, Department of Neurology, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, USA.

Objective: This study was undertaken to describe long-term clinical and developmental outcomes in pediatric refractory status epilepticus (RSE) and identify factors associated with new neurological deficits after RSE.

Methods: We performed retrospective analyses of prospectively collected observational data from June 2011 to March 2020 on pediatric patients with RSE. We analyzed clinical outcomes from at least 30 days after RSE and, in a subanalysis, we assessed developmental outcomes and evaluated risk factors in previously normally developed patients.

Results: Follow-up data on outcomes were available in 276 patients (56.5% males). The median (interquartile range [IQR]) follow-up duration was 1.6 (.9-2.7) years. The in-hospital mortality rate was 4% (16/403 patients), and 15 (5.4%) patients had died after hospital discharge. One hundred sixty-six (62.9%) patients had subsequent unprovoked seizures, and 44 (16.9%) patients had a repeated RSE episode. Among 116 patients with normal development before RSE, 42 of 107 (39.3%) patients with available data had new neurological deficits (cognitive, behavioral, or motor). Patients with new deficits had longer median (IQR) electroclinical RSE duration than patients without new deficits (10.3 [2.1-134.5] h vs. 4 [1.6-16] h, p = .011, adjusted odds ratio = 1.003, 95% confidence interval = 1.0008-1.0069, p = .027). The proportion of patients with an unfavorable functional outcome (Glasgow Outcome Scale-Extended score ≥ 4) was 22 of 90 (24.4%), and they were more likely to have received a continuous infusion.

Significance: About one third of patients without prior epilepsy developed recurrent unprovoked seizures after the RSE episode. In previously normally developing patients, 39% presented with new deficits during follow-up, with longer electroclinical RSE duration as a predictor.
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http://dx.doi.org/10.1111/epi.16984DOI Listing
July 2021

Convolutional neural networks to identify malformations of cortical development: A feasibility study.

Seizure 2021 May 31;91:81-90. Epub 2021 May 31.

Division of Epilepsy and Clinical Neurophysiology, Department of Neurology, Boston Children's Hospital and Harvard Medical School, Boston, MA USA.

Objective: To develop and test a deep learning model to automatically detect malformations of cortical development (MCD).

Methods: We trained a deep learning model to distinguish between diffuse cortical malformation (CM), periventricular nodular heterotopia (PVNH), and normal magnetic resonance imaging (MRI). We trained 4 different convolutional neural network (CNN) architectures. We used batch normalization, global average pooling, dropout layers, transfer learning, and data augmentation to minimize overfitting.

Results: There were 45 subjects (866 images) with a normal MRI, 52 subjects (790 images) with CM, and 32 subjects (750 images) with PVNH. There was no subject overlap between the training, validation, and test sets. The InceptionResNetV2 architecture performed best in the validation set in all models and was evaluated in the test set with the following results: 1) the model distinguishing between CM and normal MRI yielded an area under the curve (AUC) of 0.89 and accuracy of 0.81; 2) the model distinguishing between PVNH and normal MRI yielded an AUC of 0.90 and accuracy of 0.84; 3) the model distinguishing between the three classes (CM, PVNH, and normal MRI) yielded an AUC of 0.88 and accuracy of 0.74. Visualization with gradient-weighted class activation maps and saliency maps showed that the deep learning models classified images based on relevant areas within each image.

Significance: This study showed that CNNs can detect MCD at a clinically useful performance level with a fully automated workflow without image feature selection.
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http://dx.doi.org/10.1016/j.seizure.2021.05.023DOI Listing
May 2021

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

Epilepsia 2021 Jul 6;62(7):1629-1642. Epub 2021 Jun 6.

Division of Epilepsy and Clinical Neurophysiology, Department of Neurology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.

Objective: We aimed to characterize the clinical profile and outcomes of new onset refractory status epilepticus (NORSE) in children, and investigated the relationship between fever onset and status epilepticus (SE).

Methods: Patients with refractory SE (RSE) between June 1, 2011 and October 1, 2016 were prospectively enrolled in the pSERG (Pediatric Status Epilepticus Research Group) cohort. Cases meeting the definition of NORSE were classified as "NORSE of known etiology" or "NORSE of unknown etiology." Subgroup analysis of NORSE of unknown etiology was completed based on the presence and time of fever occurrence relative to RSE onset: fever at onset (≤24 h), previous fever (2 weeks-24 h), and without fever.

Results: Of 279 patients with RSE, 46 patients met the criteria for NORSE. The median age was 2.4 years, and 25 (54%) were female. Forty (87%) patients had NORSE of unknown etiology. Nineteen (48%) presented with fever at SE onset, 16 (40%) had a previous fever, and five (12%) had no fever. The patients with preceding fever had more prolonged SE and worse outcomes, and 25% recovered baseline neurological function. The patients with fever at onset were younger and had shorter SE episodes, and 89% recovered baseline function.

Significance: Among pediatric patients with RSE, 16% met diagnostic criteria for NORSE, including the subcategory of febrile infection-related epilepsy syndrome (FIRES). Pediatric NORSE cases may also overlap with refractory febrile SE (FSE). FIRES occurs more frequently in older children, the course is usually prolonged, and outcomes are worse, as compared to refractory FSE. Fever occurring more than 24 h before the onset of seizures differentiates a subgroup of NORSE patients with distinctive clinical characteristics and worse outcomes.
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http://dx.doi.org/10.1111/epi.16950DOI Listing
July 2021

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

Pediatr Neurol 2021 Jul 26;120:71-79. Epub 2021 Mar 26.

Department of Pediatric Neurology, Children's Hospital of Wisconsin, Medical College of Wisconsin, Milwaukee, Wisconsin.

Background: Time to treatment in pediatric refractory status epilepticus is delayed. We aimed to evaluate the influence of weekends and holidays on time to treatment of this pediatric emergency.

Methods: We performed a retrospective analysis of prospectively collected observational data of pediatric patients with refractory status epilepticus.

Results: We included 329 patients (56% males) with a median (p25 to p75) age of 3.8 (1.3 to 9) years. The median (p25 to p75) time to first BZD on weekdays and weekends/holidays was 20 (6.8 to 48.3) minutes versus 11 (5 to 35) minutes, P = 0.01; adjusted hazard ratio (HR) = 1.20 (95% confidence interval [CI]: 0.95 to 1.55), P = 0.12. The time to first non-BZD ASM was longer on weekdays than on weekends/holidays (68 [42.8 to 153.5] minutes versus 59 [27 to 120] minutes, P = 0.006; adjusted HR = 1.38 [95% CI: 1.08 to 1.76], P = 0.009). However, this difference was mainly driven by status epilepticus with in-hospital onset: among 108 patients, the time to first non-BZD ASM was longer during weekdays than during weekends/holidays (55.5 [28.8 to 103.5] minutes versus 28 [15.8 to 66.3] minutes, P = 0.003; adjusted HR = 1.65 [95% CI: 1.08 to 2.51], P = 0.01).

Conclusions: The time to first non-BZD ASM in pediatric refractory status epilepticus is shorter on weekends/holidays than on weekdays, mainly driven by in-hospital onset status epilepticus. Data on what might be causing this difference may help tailor policies to improve medication application timing.
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http://dx.doi.org/10.1016/j.pediatrneurol.2021.03.009DOI Listing
July 2021

Descriptive epidemiology and health resource utilization for status epilepticus in the emergency department in the United States of America.

Seizure 2021 Apr 16;87:7-16. Epub 2021 Feb 16.

Division of Epilepsy and Clinical Neurophysiology, Department of Neurology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA; Instituto de Pediatría, Facultad de Medicina, Universidad Austral de Chile, Valdivia, Chile; Servicio de Neuropsiquiatría Infantil. Hospital Clínico San Borja Arriarán, Universidad de Chile, Santiago, Chile.

Objective: To describe the epidemiology and health resource utilization for convulsive status epilepticus (SE) in the emergency department (ED).

Methods: Retrospective descriptive study in the Nationwide Emergency Department Sample (NEDS). Primary SE and secondary SE (SE in a case who visited the ED for other primary reason) were compared with non-SE seizures. Secondary SE is expected to have worse outcomes and higher costs because of another primary cause for ED visit.

Results: In the period 2010-2014, there were 149,750 ED visits with primary SE; 83,459 ED with secondary SE; and 5,359,103 ED visits with non-SE seizures. On multivariable analysis adjusting for potential confounders, the odds of hospital admission were 7 times higher for primary SE than for non-SE seizures, and 5 times higher for secondary SE than for non-SE seizures; the odds of transfer to another hospital were 9 times higher for primary SE than for non-SE seizures, and 3 times higher for secondary SE than for non-SE seizures; the odds of death were 2.5 times higher for primary SE than for non-SE seizures, and 12 times higher for secondary SE than for non-SE seizures; and the charges (in January 2020 USA dollars) were $9000 higher in primary SE than in non-SE seizures, and $35,000 higher in secondary SE than in non-SE seizures.

Conclusion: Among all reasons for ED visits, SE, and in particular, secondary SE, are among the most resource-consuming conditions, being much more expensive than non-SE seizures in the ED.
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http://dx.doi.org/10.1016/j.seizure.2021.02.020DOI Listing
April 2021

Cost-effectiveness of adrenocorticotropic hormone versus oral steroids for infantile spasms.

Epilepsia 2021 02 8;62(2):347-357. Epub 2021 Jan 8.

Division of Epilepsy and Clinical Neurophysiology, Department of Neurology, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, USA.

Objective: To compare the effectiveness and cost-effectiveness of adrenocorticotropic hormone (ACTH) and oral steroids as first-line treatment for infantile spasm resolution, we performed a systematic review, meta-analysis, and cost-effectiveness study.

Methods: A decision analysis model was populated with effectiveness data from a systematic review and meta-analysis of existing literature and cost data from publicly available prices. Effectiveness was defined as the probability of clinical spasm resolution 14 days after treatment initiation.

Results: We included 21 studies with a total of 968 patients. The effectiveness of ACTH was not statistically significantly different from that of oral steroids (.70, 95% confidence interval [CI] = .60-.79 vs. .63, 95% CI = .56-.70; p = .28). Considering only the three available randomized trials with a total of 185 patients, the odds ratio of spasm resolution at 14 days with ACTH compared to high-dose prednisolone (4-8 mg/kg/day) was .92 (95% CI = .34-2.52, p = .87). Adjusting for potential publication bias, estimates became even more favorable to high-dose prednisolone. Using US prices, the more cost-effective treatment was high-dose prednisolone, with an incremental cost-effectiveness ratio (ICER) of $333 per case of spasms resolved, followed by ACTH, with an ICER of $1 432 200 per case of spasms resolved. These results were robust to multiple sensitivity analyses and different assumptions. Prednisolone at 4-8 mg/kg/day was more cost-effective than ACTH under a wide range of assumptions.

Significance: For infantile spasm resolution 2 weeks after treatment initiation, current evidence does not support the preeminence of ACTH in terms of effectiveness and, especially, cost-effectiveness.
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http://dx.doi.org/10.1111/epi.16799DOI Listing
February 2021

Status Epilepticus-Work-Up and Management in Children.

Semin Neurol 2020 12 5;40(6):661-674. Epub 2020 Nov 5.

Division of Epilepsy and Clinical Neurophysiology, Department of Neurology, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts.

Status epilepticus (SE) is one of the most common neurological emergencies in children and has a mortality of 2 to 4%. Admissions for SE are very resource-consuming, especially in refractory and super-refractory SE. An increasing understanding of the pathophysiology of SE leaves room for improving SE treatment protocols, including medication choice and timing. Selecting the most efficacious medications and giving them in a timely manner may improve outcomes. Benzodiazepines are commonly used as first line and they can be used in the prehospital setting, where most SE episodes begin. The diagnostic work-up should start simultaneously to initial treatment, or as soon as possible, to detect potentially treatable causes of SE. Although most etiologies are recognized after the first evaluation, the detection of more unusual causes may become challenging in selected cases. SE is a life-threatening medical emergency in which prompt and efficacious treatment may improve outcomes. We provide a summary of existing evidence to guide clinical decisions regarding the work-up and treatment of SE in pediatric patients.
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http://dx.doi.org/10.1055/s-0040-1719076DOI Listing
December 2020

The burden of decisional uncertainty in the treatment of status epilepticus.

Epilepsia 2020 10 22;61(10):2150-2162. Epub 2020 Sep 22.

Division of Epilepsy and Clinical Neurophysiology, Department of Neurology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.

Objective: Treatments for convulsive status epilepticus (SE) have a wide range of effectiveness. The estimated effectiveness of non-intravenous benzodiazepines (non-IV BZDs) ranges from approximately 70% to 90% and the estimated effectiveness of non-benzodiazepine antiseizure medications (non-BZD ASMs) ranges from approximately 50% to 80%. This study aimed to quantify the clinical and economic burden of decisional uncertainty in the treatment of SE.

Methods: We performed a decision analysis that evaluates how decisional uncertainty on treatment choices for SE impacts hospital admissions, intensive care unit (ICU) admissions, and costs in the United States. We evaluated treatment effectiveness based on the available literature.

Results: Use of a non-IV BZD with high estimated effectiveness, like intranasal midazolam, rather than one with low estimated effectiveness, like rectal diazepam, would result in a median (p -p ) reduction in hospital admissions from 6 (3.9-8.8) to 1.1 (0.7-1.8) per 100 cases and associated cost reductions of $638 ($289-$1064) per pediatric patient and $1107 ($972-$1281) per adult patient. For BZD-resistant SE, use of a non-BZD ASM with high estimated effectiveness, like phenobarbital, rather than one with low estimated effectiveness, like phenytoin/fosphenytoin, would result in a reduction in ICU admissions from 9.1 (7.3-11.2) to 3.9 (2.6-5.5) per 100 cases and associated cost reduction of $1261 ($445-$2223) per pediatric patient and $319 ($-93-$806) per adult patient. Sensitivity analyses showed that relatively minor improvements in effectiveness may lead to substantial reductions in downstream hospital admissions, ICU admissions, and costs.

Significance: Decreasing decisional uncertainty and using the most effective treatments for SE may substantially decrease hospital admissions, ICU admissions, and costs.
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http://dx.doi.org/10.1111/epi.16646DOI Listing
October 2020

Association of guideline publication and delays to treatment in pediatric status epilepticus.

Neurology 2020 09 1;95(9):e1222-e1235. Epub 2020 Jul 1.

From the Division of Epilepsy and Clinical Neurophysiology (I.S.F., M.A.-G., C.B.A., J.C., M.G.-L., A.V., T.L.), Department of Neurology, and Department of Neurology (R.C.T.), Department of Anesthesiology, Critical Care and Pain Medicine, Boston Children's Hospital, Harvard Medical School, MA; Department of Child Neurology (I.S.F.), Hospital Sant Joan de Déu, Universitat de Barcelona, Spain; Division of Neurology (N.S.A.), Departments of Neurology and Pediatrics, Children's Hospital of Philadelphia and University of Pennsylvania; Pediatric Neurology Unit (M.A.-G.), Department of Pediatrics, Hospital Universitari Son Espases, Universitat de les Illes Balears, Palma, Spain; Section of Pediatric Critical Care Medicine (A.A., Y.-C.L.), Department of Pediatrics, Baylor College of Medicine, Houston, TX; Division of Neurology (R.A., T.G., K.P.), Cincinnati Children's Hospital Medical Center, University of Cincinnati, OH; University of Virginia Health (J.N.B., H.P.G.), Charlottesville; Center for Neuroscience (J.L.C., W.D.G.), Children's National Medical Center, George Washington University School of Medicine and Health Sciences, Washington, DC; Departments of Pediatrics and Neurology (K.E.C.), Children's Hospital Colorado, University of Colorado School of Medicine, Aurora; Department of Pediatric Neurology (R.F.-M., K.S.), Children's Hospital of Wisconsin, Medical College of Wisconsin, Milwaukee; Instituto de Pediatría (M.G.-L.), Facultad de Medicina, Universidad Austral de Chile, Valdivia, Chile; Servicio de Neuropsiquiatría Infantil (M.G.-L.), Hospital Clínico San Borja Arriarán, Universidad de Chile, Santiago; Ruth D. & Ken M. Davee Pediatric Neurocritical Care Program (J.G., T.M.), Northwestern University Feinberg School of Medicine, Chicago, IL; Division of Pediatric and Developmental Neurology (R.M.G.), Department of Neurology, Washington University School of Medicine, St. Louis, MO; Division of Pediatric Neurology (M.A.M., D.T.), Duke University Medical Center, Duke University, Durham, NC; Department of Pediatrics and Neurology (L.A.M., E.N., M.S.W.), Seattle Children's Hospital, University of Washington; Center for Integrative Brain Research (L.A.M., E.N., M.S.W.), Seattle Children's Research Institute, WA; Department of Neurology (E.P.), Mayo Clinic, Mayo Clinic School of Medicine, Rochester, MN; Department of Neurology (J.P.), Doernbercher Children's Hospital, Oregon Health & Science University, Portland; Department of Neurology (A.O.), Nationwide Children's Hospital, Ohio State University, Columbus; Division of Child Neurology and Institute for Genomic Medicine (T.T.S.), Columbia University Irving Medical Center, New York Presbyterian Hospital, New York; Division of Critical Care Medicine (A.A.T.), The Children's Hospital of Philadelphia, Perelman School of Medicine at the University of Pennsylvania; Division of Child and Adolescent Neurology (A.V.), Department of Neurology, Mayo Clinic, Rochester, MN; Barrow Neurological Institute (A.W., K.W.), Phoenix Children's Hospital; and Department of Pediatrics (A.W., K.W.), University of Arizona School of Medicine, Phoenix.

Objective: To determine whether publication of evidence on delays in time to treatment shortens time to treatment in pediatric refractory convulsive status epilepticus (rSE), we compared time to treatment before (2011-2014) and after (2015-2019) publication of evidence of delays in treatment of rSE in the Pediatric Status Epilepticus Research Group (pSERG) as assessed by patient interviews and record review.

Methods: We performed a retrospective analysis of a prospectively collected dataset from June 2011 to September 2019 on pediatric patients (1 month-21 years of age) with rSE.

Results: We studied 328 patients (56% male) with median (25th-75th percentile [p-p]) age of 3.8 (1.3-9.4) years. There were no differences in the median (p-p) time to first benzodiazepine (BZD) (20 [5-52.5] vs 15 [5-38] minutes, = 0.3919), time to first non-BZD antiseizure medication (68 [34.5-163.5] vs 65 [33-142] minutes, = 0.7328), and time to first continuous infusion (186 [124.2-571] vs 160 [89.5-495] minutes, = 0.2236). Among 157 patients with out-of-hospital onset whose time to hospital arrival was available, the proportion who received at least 1 BZD before hospital arrival increased after publication of evidence of delays (41 of 81 [50.6%] vs 57 of 76 [75%], = 0.0018), and the odds ratio (OR) was also increased in multivariable logistic regression (OR 4.35 [95% confidence interval 1.96-10.3], = 0.0005).

Conclusion: Publication of evidence on delays in time to treatment was not associated with improvements in time to treatment of rSE, although it was associated with an increase in the proportion of patients who received at least 1 BZD before hospital arrival.
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http://dx.doi.org/10.1212/WNL.0000000000010174DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7538224PMC
September 2020

Estimating the cost of status epilepticus admissions in the United States of America using ICD-10 codes.

Seizure 2019 Oct 4;71:295-303. Epub 2019 Sep 4.

Division of Epilepsy and Clinical Neurophysiology, Department of Neurology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.

Purpose: Estimate the cost of status epilepticus (SE) admissions in the USA using claim databases based on ICD-10 codes.

Method: Descriptive retrospective study using national estimates for the year 2016 from the KID's Inpatient Database (KID) for pediatric patients and from the National Inpatient Sample (NIS) for adults. These databases are comprehensive collections of all-payer, encounter-level hospital care data in the United States of America.

Results: From a population of 6,106,405 pediatric admissions there were 580 admissions related to SE. From a population of 29,274,158 adult admissions there were 1,405 admissions related to SE. The median (p25-p75) cost of pediatric admissions related to SE was $8,749 ($4,875-$19,067) in 2016 USA dollars [$9,295 ($5,180-$20,258) in inflation-adjusted 2019 USA dollars], and for adult admissions related to SE it was $14,678 ($7,203-$28,388) in 2016 USA dollars [$15,595 ($7,653-$30,161) in inflation-adjusted 2019 USA dollars]. Transforming to 2019 USA dollars, the values from the current study are consistent with prior estimates in the literature from the KID and NIS databases with a progressive increase, except for the cost of super-refractory SE in children that has increased disproportionately.

Conclusions: This study estimates that the cost of admissions related to SE in the USA is approximately $9,000 in children and $15,000 in adults and shows that the cost estimates have not markedly changed with the advent of ICD-10.
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http://dx.doi.org/10.1016/j.seizure.2019.09.001DOI Listing
October 2019
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