Interaction of interictal epileptiform activity with sleep spindles is associated with cognitive deficits and adverse surgical outcome in pediatric focal epilepsy.

OBJECTIVE: Temporal coordination between oscillations enables intercortical communication and is implicated in cognition. Focal epileptic activity can affect distributed neural networks and interfere with these interactions. Refractory pediatric epilepsies are often accompanied by substantial cognitive comorbidity, but mechanisms and predictors remain mostly unknown. Here, we investigate oscillatory coupling across large-scale networks in the developing brain. METHODS: We analyzed large-scale intracranial electroencephalographic recordings in children with medically refractory epilepsy undergoing presurgical workup (n = 25, aged 3-21 years). Interictal epileptiform discharges (IEDs), pathologic high-frequency oscillations (HFOs), and sleep spindles were detected. Spatiotemporal metrics of oscillatory coupling were determined and correlated with age, cognitive function, and postsurgical outcome. RESULTS: Children with epilepsy demonstrated significant temporal coupling of both IEDs and HFOs to sleep spindles in discrete brain regions. HFOs were associated with stronger coupling patterns than IEDs. These interactions involved tissue beyond the clinically identified epileptogenic zone and were ubiquitous across cortical regions. Increased spatial extent of coupling was most prominent in older children. Poor neurocognitive function was significantly correlated with high IED-spindle coupling strength and spatial extent; children with strong pathologic interactions additionally had decreased likelihood of postoperative seizure freedom. SIGNIFICANCE: Our findings identify pathologic large-scale oscillatory coupling patterns in the immature brain. These results suggest that such intercortical interactions could predict risk for adverse neurocognitive and surgical outcomes, with the potential to serve as novel therapeutic targets to restore physiologic development.

Convolutional neural network-aided tuber segmentation in tuberous sclerosis complex patients correlates with electroencephalogram.

OBJECTIVE: One of the clinical hallmarks of tuberous sclerosis complex (TSC) is radiologically identified cortical tubers, which are present in most patients. Intractable epilepsy may require surgery, often involving invasive diagnostic procedures such as intracranial electroencephalography (EEG). Identifying the location of the dominant tuber responsible for generating epileptic activities is a critical issue. However, the link between cortical tubers and epileptogenesis is poorly understood. Given this, we hypothesized that tuber voxel intensity may be an indicator of the dominant epileptogenic tuber. Also, via tuber segmentation based on deep learning, we explored whether an automatic quantification of the tuber burden is feasible. METHODS: We annotated tubers from structural magnetic resonance images across 29 TSC subjects, summarized tuber statistics in eight brain lobes, and determined suspected epileptogenic lobes from the same group using EEG monitoring data. Then, logistic regression analyses were performed to demonstrate the linkage between the statistics of cortical tuber and the epileptogenic zones. Furthermore, we tested the ability of a neural network to identify and quantify tuber burden. RESULTS: Logistic regression analyses showed that the volume and count of tubers per lobe, not the mean or variance of tuber voxel intensity, were positively correlated with electrophysiological data. In 47.6% of subjects, the lobe with the largest tuber volume concurred with the epileptic brain activity. A neural network model on the test dataset showed a sensitivity of .83 for localizing individual tubers. The predicted masks from the model correlated highly with the neurologist labels, and thus may be a useful tool for determining tuber burden and searching for the epileptogenic zone. SIGNIFICANCE: We have proven the feasibility of an automatic segmentation of tubers and a derivation of tuber burden across brain lobes. Our method may provide crucial insights regarding the treatment and outcome of TSC patients.

Assessing appropriateness of pediatric emergency department visits: is it even possible?

OBJECTIVES: Numerous studies reported on the frequency of, and factors associated with inappropriate or unnecessary emergency department (ED) visits using clinician judgment as the gold standard of appropriateness. This study evaluated the reliability of clinician judgment for assessing appropriateness of pediatric ED visit. METHODS: We conducted a retrospective cohort study comparing 3 clinicians' determination of ED visit appropriateness with and without guidance from a three-question structured algorithm. We used a cohort of scheduled ED return visits deemed appropriate by the index treating clinician between May 1, 2012, and April 30, 2013. We measured the level of agreement among three clinician investigators with and without use of the structured algorithm. RESULTS: A total of 207 scheduled ED return visits were reviewed by the primary clinician reviewer who agreed with the index treating clinician for 79/207 visits (38.2%). Among a random subset of 90 return visits reviewed by all three clinicians, agreement was 67% with a Fleiss' Kappa of 0.30 (0.17-0.44). Using a three-question algorithm based on objective criteria, agreement with the index treating provider increased to 115/207 (55.6%). CONCLUSIONS: Although an important contributor to pediatric ED overcrowding, unnecessary or inappropriate visits are difficult to identify. We demonstrated poor reliability of clinician judgment to determine appropriateness of ED return visits, likely due to variability in clinical decision-making and risk-tolerance, social and systems factors impacting access and use of health care. We recommend that future studies evaluating the appropriateness of ED use standardized, objective criteria rather than clinician judgment alone.

System outcomes associated with a pediatric emergency department clinical decision unit.

OBJECTIVES: Our objectives were to describe disposition decisions and emergency department return (EDR) rates following a clinical decision unit (CDU) stay; and to determine changes to short stay (<48 hour) hospitalization rates after CDU implementation. METHODS: We conducted a retrospective cohort study of pediatric emergency department (PED) visits with a CDU stay from January 1 to December 31, 2015. Health records data were extracted onto standardized online forms, then used to determine disposition and 7-day EDR rates. Two trained investigators blindly reviewed EDR visits to determine if they were related to the index CDU stay. We compared short stay inpatient admission rates (i.e., hospital length of stay <48 hours) in 2013 and 2015, before and after CDU implementation. RESULTS: Of 1696 index CDU stays, 1503 (89%) were discharged, and 139 discharged patients (9.2%) had ≥1 clinically-related EDR. Median (IQR) CDU length of stay (LOS) was 4.4 hours (2.7-7.8) and total PED LOS (including CDU) was 7.8 hours (5.4-12.0). Asthma represented 31% of cases. Short stay hospitalization rate decreased from 3.62% in 2013 to 3.23% in 2015 (difference=0.39%; 95% CI=0.15-0.63; p=0.001). CONCLUSIONS: Most CDU patients were discharged, but 9% had a clinically-related ED revisit. CDU implementation was associated with a small but significant reduction in short stay hospitalization.

Implementation of Computerized Physician Order Entry Is Associated With Increased Thrombolytic Administration for Emergency Department Patients With Acute Ischemic Stroke.

STUDY OBJECTIVE: Electronic health record systems with computerized physician order entry and condition-specific order sets are intended to standardize patient management and minimize errors of omission. However, the effect of these systems on disease-specific process measures and patient outcomes is not well established. We seek to evaluate the effect of computerized physician order entry electronic health record implementation on process measures and short-term health outcomes for patients hospitalized with acute ischemic stroke. METHODS: We conducted a quasi-experimental cohort study of patients hospitalized for acute ischemic stroke with concurrent controls that took advantage of the staggered implementation of a comprehensive computerized physician order entry electronic health record across 16 medical centers within an integrated health care delivery system from 2007 to 2012. The study population included all patients admitted to the hospital from the emergency department (ED) for acute ischemic stroke, with an initial neuroimaging study within 2.5 hours of ED arrival. We evaluated the association between the availability of a computerized physician order entry electronic health record and the rates of ED intravenous tissue plasminogen activator administration, hospital-acquired pneumonia, and inhospital and 90-day mortality, using doubly robust estimation models to adjust for demographics, comorbidities, secular trends, and concurrent primary stroke center certification status at each center. RESULTS: Of 10,081 eligible patients, 6,686 (66.3%) were treated in centers after the computerized physician order entry electronic health record had been implemented. Computerized physician order entry was associated with significantly higher rates of intravenous tissue plasminogen activator administration (rate difference 3.4%; 95% confidence interval 0.8% to 6.0%) but not with significant rate differences in pneumonia or mortality. CONCLUSION: For patients hospitalized for acute ischemic stroke, computerized physician order entry use was associated with increased use of intravenous tissue plasminogen activator.

An electronic order set for acute myocardial infarction is associated with improved patient outcomes through better adherence to clinical practice guidelines.

BACKGROUND: Adherence to evidence-based recommendations for acute myocardial infarction (AMI) remains unsatisfactory. OBJECTIVE: Quantifying association between using an electronic AMI order set (AMI-OS) and hospital processes and outcomes. DESIGN: Retrospective cohort study. SETTING: Twenty-one community hospitals. PATIENTS: A total of 5879 AMI patients were hospitalized between September 28, 2008 and December 31, 2010. MEASUREMENTS: We ascertained whether patients were treated using the AMI-OS or individual orders (a la carte). Dependent process variables were use of evidence-based care; outcome variables were mortality and rehospitalization. RESULTS: Use of individual and combined therapies improved outcomes (eg, 50% lower odds of 30-day mortality for patients with ≥3 therapies). The 3531 patients treated using the AMI-OS were more likely to receive evidence-based therapies (eg, 50% received 5 different therapies vs 36% a la carte). These patients had lower 30-day mortality (5.7% vs 8.5%) than the 2348 treated using a la carte orders. Although AMI-OS patients' predicted mortality risk was lower (3.2%) than that of a la carte patients (4.8%), the association of improved processes and outcomes with the use of the AMI-OS persisted after risk adjustment. For example, after inverse probability weighting, the relative risk for inpatient mortality in the AMI-OS group was 0.67 (95% confidence interval: 0.52-0.86). Inclusion of use of recommended therapies in risk adjustment eliminated the benefit of the AMI-OS, highlighting its mediating effect on adherence to evidence-based treatment. CONCLUSIONS: Use of an electronic order set is associated with increased adherence to evidence-based care and better AMI outcomes.

Echocardiographic analysis of ventricular geometry and function during repair of congenital septal defects.

BACKGROUND: This study investigated changes in left ventricular (LV) geometry and systolic function after corrective surgery for atrial (ASD) and ventricular septal defects (VSD). METHODS: Transesophageal LV short-axis echocardiograms were recorded before and after operative repair of ASD (n = 11) and VSD (n = 7). Preload was measured using LV end-diastolic area indexed for body surface area. Measurements of septal-freewall (D1) and anterior-posterior (D2) endocardial diameters were used to assess LV symmetry from D1/D2. Systolic indices included stroke area, area ejection fraction, and fractional shortening. RESULTS: Preload, stroke area, area ejection fraction, and fractional shortening of D1 increased after ASD repair but decreased after VSD repair (p < 0.05). End-diastolic symmetry increased after ASD closure and decreased after VSD closure (p < 0.05). Increases in stroke area and ejection fraction after ASD correction primarily reflected increased shortening of D1. A positive correlation was found overall between percent change in end-diastolic area (EDA) and percent change in area ejection fraction (r(2) = 0.80, p < 0.0001, n = 18). CONCLUSIONS: Preload was the primary determinant of changes in LV function in this series of ASD and VSD repairs. Intraoperative changes in position of the interventricular septum affected systolic and diastolic LV symmetry and septal free wall shortening. Additional studies are needed to define changes in afterload and contractility as well as diastolic compliance and systolic mechanics.