Cross-platform validation of neurotransmitter release impairments in schizophrenia patient-derived NRXN1-mutant neurons.

Heterozygous NRXN1 deletions constitute the most prevalent currently known single-gene mutation associated with schizophrenia, and additionally predispose to multiple other neurodevelopmental disorders. Engineered heterozygous NRXN1 deletions impaired neurotransmitter release in human neurons, suggesting a synaptic pathophysiological mechanism. Utilizing this observation for drug discovery, however, requires confidence in its robustness and validity. Here, we describe a multicenter effort to test the generality of this pivotal observation, using independent analyses at two laboratories of patient-derived and newly engineered human neurons with heterozygous NRXN1 deletions. Using neurons transdifferentiated from induced pluripotent stem cells that were derived from schizophrenia patients carrying heterozygous NRXN1 deletions, we observed the same synaptic impairment as in engineered NRXN1-deficient neurons. This impairment manifested as a large decrease in spontaneous synaptic events, in evoked synaptic responses, and in synaptic paired-pulse depression. Nrxn1-deficient mouse neurons generated from embryonic stem cells by the same method as human neurons did not exhibit impaired neurotransmitter release, suggesting a human-specific phenotype. Human NRXN1 deletions produced a reproducible increase in the levels of CASK, an intracellular NRXN1-binding protein, and were associated with characteristic gene-expression changes. Thus, heterozygous NRXN1 deletions robustly impair synaptic function in human neurons regardless of genetic background, enabling future drug discovery efforts.

Gross motor function prediction using natural language processing in cerebral palsy.

AIM: To predict ambulatory status and Gross Motor Function Classification System (GMFCS) levels in patients with cerebral palsy (CP) by applying natural language processing (NLP) to electronic health record (EHR) clinical notes. METHOD: Individuals aged 8 to 26 years with a diagnosis of CP in the EHR between January 2009 and November 2020 (~12 years of data) were included in a cross-sectional retrospective cohort of 2483 patients. The cohort was divided into train-test and validation groups. Positive predictive value, sensitivity, specificity, and area under the receiver operating curve (AUC) were calculated for prediction of ambulatory status and GMFCS levels. RESULTS: The median age was 15 years (interquartile range 10-20 years) for the total cohort, with 56% being male and 75% White. The validation group resulted in 70% sensitivity, 88% specificity, 81% positive predictive value, and 0.89 AUC for predicting ambulatory status. NLP applied to the EHR differentiated between GMFCS levels I-II and III (15% sensitivity, 96% specificity, 46% positive predictive value, and 0.71 AUC); and IV and V (81% sensitivity, 51% specificity, 70% positive predictive value, and 0.75 AUC). INTERPRETATION: NLP applied to the EHR demonstrated excellent differentiation between ambulatory and non-ambulatory status, and good differentiation between GMFCS levels I-II and III, and IV and V. Clinical use of NLP may help to individualize functional characterization and management. WHAT THIS PAPER ADDS: Natural language processing (NLP) applied to the electronic health record (EHR) can predict ambulatory status in children with cerebral palsy (CP). NLP provides good prediction of Gross Motor Function Classification System level in children with CP using the EHR. NLP methods described could be integrated in an EHR system to provide real-time information.

Predictors of disease course and long-term outcomes of idiopathic intracranial hypertension in children and adolescents.

This study aimed to identify predictors for unfavorable disease course and clinical and visual outcomes in pediatric patients with idiopathic intracranial hypertension (IIH). Employing a multi-tiered approach, we retrospectively analyzed clinical, ophthalmic, and neuroimaging data from patients diagnosed with IIH between 2003 and 2021. Of the 97 patients included, 56 (58%) were females. The median age was 12 years [Interquartile range (IQR) 9, 14], and the median follow-up time was 39.0 months (IQR 14.8, 90.9). Forty-two (43%) patients had an unfavorable disease course, 28 (29%) had persistence of headache at last follow-up, and 16 (18%) had a poor visual outcome, most of them with mild visual disturbances. Poor visual outcome was more common in females compared to males [16/47 (34%) vs. 0/39, p < 0.001)]. On multivariate regression analysis, female sex and disease recurrence were significantly associated with poor visual outcomes (OR: 18.5, CI:1.3-270, P = 0.03, and OR: 5.1, CI: 1.2-22.5, P = 0.03, respectively). Patients with persistent headaches exhibited lower incidence of papilledema, lower opening pressure, and fewer neuroimaging markers indicating elevated intracranial pressure. CONCLUSIONS: This study provides insights into predictive factors for an unfavorable disease course, persistent headaches, and poor visual outcomes in patients with childhood IIH. Patients with persistent headaches may have a variant of a chronic pain syndrome warranting a different therapeutic approach. WHAT IS KNOWN: • Childhood-onset Idiopathic Intracranial hypertension (IIH) is a heterogenous disease. The knowledge on disease trajectory and long-term outcomes and its predictors is limited. WHAT IS NEW: • A higher opening pressure and factors suggestive of the metabolic syndrome predict an unfavorable disease course whereas female sex and disease recurrence are significantly associated with poor visual outcomes • A third of the patients diagnosed with IIH experience ongoing headaches despite achieving favorable visual outcomes. This subset, characterized by lower disease-severity indicators at onset may represent a distinct subgroup warranting a different therapeutic approach.

Electronic health record and patterns of care for children with cerebral palsy.

AIM: To characterize the patterns of care of children with cerebral palsy (CP) in a tertiary healthcare system. METHOD: Electronic health record data from 2009 to 2019 were extracted for children with CP. Machine learning hierarchical clustering was used to identify clusters of care. The ratio of in-person to care coordination visits was calculated for each specialty. RESULTS: The sample included 6369 children with CP (55.7% males, 44.3% females, 76.2% white, 94.7% non-Hispanic; with a mean age of 8y 2mo [SD 5y 10mo; range 0-21y; median 7y 1mo]) at the time of diagnosis. A total of 3.7 million in-person visits and care coordination notes were identified across 34 specialties. The duration of care averaged 5 years 5 months with five specialty interactions and 21.8 in-person visits per year per child. Seven clusters of care were identified, including: musculoskeletal and function; neurological; high-frequency/urgent care services; procedures; comorbid diagnoses; development and behavioral; and primary care. Network analysis showed shared membership among several clusters. INTERPRETATION: Coordination of care is a central element for children with CP. Medical informatics, machine learning, and big data approaches provide unique insights into care delivery to inform approaches to improve outcomes for children with CP. What this paper adds Seven primary clusters of care were identified: musculoskeletal and function; neurological; high-frequency/urgent care services; procedures; comorbid diagnoses; development and behavioral; and primary care. The in-person to care coordination visit ratio was 1:5 overall for healthcare encounters. Most interactions with care teams occur outside of in-person visits. The ratio of in-person to care coordination activities differ by specialty.

Describing the Delivery of Evidence-Based Physical Therapy Intervention to Individuals With Cerebral Palsy.

PURPOSE: To characterize by evidence grades and examine variation in type of physical therapy intervention delivered in routine clinical care in individuals with cerebral palsy (CP). METHODS: Retrospective data collection from the electronic record over 1 year at a tertiary care pediatric outpatient therapy division. RESULTS: Four hundred sixty-five individuals with CP received 28 344 interventions during 4335 treatment visits. Sixty-six percent of interventions were evidence-based interventions (EBIs). Significant variation was demonstrated across Gross Motor Function Classification System levels, with children classified as level V receiving the least and level III the most. The most frequent EBIs delivered were caregiver education, motor control, functional strengthening, ankle-foot orthoses, treadmill training, and fit of adaptive equipment. CONCLUSIONS: Further work is needed to determine whether amount of EBI is related to better outcomes. Combining this information with other aspects of dose (intensity, time, and frequency) may elucidate the contribution of each with outcomes.

The safety, tolerability, and effectiveness of PTL-101, an oral cannabidiol formulation, in pediatric intractable epilepsy: A phase II, open-label, single-center study.

INTRODUCTION: Several works have reported on the antiepileptic impact of cannabis-based preparations in patients with treatment-resistant epilepsy (TRE). However, current formulations suffer from low bioavailability and side effects. PTL-101, an oral formulation containing highly purified cannabidiol (CBD) embedded in seamless gelatin matrix beadlets was designed to enhance bioavailability and maintain a constant gastrointestinal transit time. METHODS: This phase II, prospective study was open to pediatric patients with TRE on stable antiepileptic drugs' (AEDs) doses, who experienced ≥4 seizures within four weeks of enrolment and with a history of ≥4 AEDs failing to provide seizure control. Following a 4-week observation period, patients began a 2-week dose-titration phase (up to ≤25mg/kg or 450mg, the lower of the two), followed by a 10-week maintenance treatment period. Caregivers recorded seizure frequency, type, and severity and ranked their global impressions after 7 and 12weeks of treatment. Responders were those showing a ≥50% reduction from baseline monthly seizure frequency. Safety assessments monitored vital signs, adverse effects, physical and neurological exams, and laboratory tests. RESULTS: Sixteen patients (age: 9.1±3.4) enrolled in the study; 11 completed the full treatment program. The average maintenance dose was 13.6±4.2mg/kg. Patient adherence to treatment regimens was 96.3±9.9%. By the end of the treatment period, 81.9% and 73.4±24.6% (p<0.05) reductions from baseline median seizure count and monthly seizure frequency, respectively, were recorded. Responders' rate was 56%; two patients became fully seizure-free. By study end, 8 (73%) caregivers reported an improved/very much improved condition, and 9 (82%) reported reduced/very much reduced seizure severity. Most commonly reported treatment-related adverse effects were sleep disturbance/insomnia, (4 (25.0%) patients), followed by somnolence, increased seizure frequency, and restlessness (3 patients each (18.8%)). None were serious or severe, and all resolved. CONCLUSIONS: PTL-101 was safe and tolerable for use and demonstrated a potent seizure-reducing effect among pediatric patients with TRE.

Development of Ontology for Self-limited Epilepsy with Centrotemporal Spikes and Application of Data Mining Algorithms to Identify New Subtypes.

BACKGROUND: Benign rolandic epilepsy or benign childhood epilepsy with centrotemporal spikes (BCECTS) is a common childhood epileptic syndrome. The syndrome resolves in adolescence, but 1-7% of patients have an atypical presentation, some of which require aggressive medical treatment. Early treatment may prevent complications and neurocognitive deterioration. Variants include Landau-Kleffner syndrome (LKS) and electrical status epilepticus during sleep (ESES). OBJECTIVES: To determine data driven identification of risk factors and characterization of new subtypes of BCECTS based on anontology. To use data mining analysis and correlation between the identified groups and known clinical variants. METHODS: We conducted a retrospective cohort study comprised of 104 patients with a diagnosis of BCECTS and a minimum of 2 years of follow-up, between the years 2005 and 2017. The medical records were obtained from the epilepsy service unit of the pediatric neurology department at Dana-Dwek Hospital, Tel Aviv Sourasky Medical Center. We developed a BCECTS ontology and performed data preprocessing and analysis using the R Project for Statistical Computing (https://www.r-project.org/) and machine learning tools to identify risk factors and characterize subgroups. RESULTS: The ontology created a uniform and understandable infrastructure for research. With the ontology, a more precise characterization of clinical symptoms and EEG activity of BCECTS was possible. Risk factors for the development of severe atypical presentations were identified: electroencephalography (EEG) with spike wave (P < 0.05), EEG without evidence of left lateralization (P < 0.05), and EEG localization (centrotemporal, frontal, or frontotemporal) (P < 0.01). CONCLUSIONS: Future use of the ontology infrastructure for expanding characterization for multicenter studies as well as future studies of the disease are needed. Identifying subgroups and adapting them to known clinical variants will enable identification of risk factors, improve prediction of disease progression, and facilitate adaptation of more accurate therapy. Early identification and frequent follow-up may have a significant impact on the prognosis of the atypical variants.

The Effect of Antipyretic Temperature Reduction on Heart Rate in Febrile Infants: a Pilot Study.

It is generally accepted that fever is associated with tachycardia and that the relationship, of an approximate increase of 10 beats/minute per °Celsius rise in temperature, is particularly pronounced in infants. It would be useful to determine how closely pulse and fever are associated during pharmacological temperature reduction, and whether it is influenced by the infectious status of the infant. Infants with fever presenting to the pediatric emergency department were prospectively enrolled in a study to determine temperature, heart rate, and the activity at initial assessment and 1 hour after antipyretic administration. Patients were also grouped into those with and without signs of serious bacterial infection for analysis. During pharmacological antipyresis, the relationship between pulse and fever deviated from the accepted norm, established during the febrile state: there was an average pulse rate reduction of 21.1 beats/minute/°Celsius decrement in fever (P = 0.0027; 95% CI, 14.05-28.15). Pulse reduction/°Celsius may also differ in infants with suspected serious bacterial infection. Our findings suggest caution in ascribing pulse changes to fever alone, especially in sick looking infants, and that this is especially true after the administration of antipyretics, which could be related to the mechanism of action of antipyretic drugs. Further research is needed to ascertain the clinical utility and importance of our observations.

Treatment Response in Pediatric Patients With Pseudotumor Cerebri Syndrome.

BACKGROUND: Pseudotumor cerebri syndrome (PTCS) is a disorder defined by increased intracranial pressure in the absence of an intracranial space-occupying lesion. This retrospective study aimed to examine the outcomes in children with PTCS. METHODS: Data was collected retrospectively from the charts of consecutive pediatric patients treated for PTCS at our hospital between 2000 and 2007 (60 patients; 36 females, 24 males). RESULTS: Forty-six patients (76.6%) responded well to acetazolamide therapy, with full resolution of symptoms, including papilledema (average treatment duration 1 year; range: 1 month-5 years). Of the 14 patients with no response to treatment, 9 (23.4%) required surgical intervention. Nonresponders tended to be younger at presentation (8.7 vs 11.5 years, P = 0.04). Twelve patients (26%) experienced relapse after acetazolamide was discontinued. The group that experienced relapse was significantly younger than the nonrelapsers (8.9 vs 12.1 years, P < 0.05). CONCLUSIONS: Younger age at presentation with PTCS was found to be a risk factor for treatment failure or relapse.

Homogeneous clusters of Alzheimer's disease patient population.

BACKGROUND: Identification of biomarkers for the Alzheimer's disease (AD) is a challenge and a very difficult task both for medical research and data analysis. METHODS: We applied a novel clustering tool with the goal to identify subpopulations of the AD patients that are homogeneous in respect of available clinical as well as in respect of biological descriptors. RESULTS: The main result is identification of three clusters of patients with significant problems with dementia. The evaluation of properties of these clusters demonstrates that brain atrophy is the main driving force of dementia. The unexpected result is that the largest subpopulation that has very significant problems with dementia has besides mild signs of brain atrophy also large ventricular, intracerebral and whole brain volumes. Due to the fact that ventricular enlargement may be a consequence of brain injuries and that a large majority of patients in this subpopulation are males, a potential hypothesis is that such medical status is a consequence of a combination of previous traumatic events and degenerative processes. CONCLUSIONS: The results may have substantial consequences for medical research and clinical trial design. The clustering methodology used in this study may be interesting also for other medical and biological domains.

Do You See It My Way? The Clinical Evaluation of ADHD by the Different Pediatric Subspecialties.

BACKGROUND: Six medical disciplines are responsible for assessment, diagnosis and treatment of people with attention deficiency hyperactivity disorder (ADHD) in Israel: family doctors, pediatricians, adult and child neurologists, adult and child psychiatrists. OBJECTIVES: To investigate differences in ADHD diagnostic practices between three different pediatric subspecialties in the clinical setting in order to establish a common ground for a future unified approach. METHODS: An anonymous web-based questionnaire was administered to child psychiatrists, pediatric neurologists and general pediatricians who are actively involved in ADHD diagnosis (n=104). RESULTS: Neurologists and pediatricians rarely use the mental status examination, while psychiatrists rarely perform a neurological or physical examination (P < 0.0001). A general clinical impression of learning abilities and/or neurodevelopmental skills was implemented more often by pediatric neurologists (P < 0.04). CONCLUSIONS: The significant differences found between the three medical specialties with regard to the clinical evaluation of ADHD could be attributed, at least in part, to the ambiguity of available guidelines concerning the clinical examination, and to the adherence of each specialty to its own "skills." Larger surveys in other countries should be considered and an effort made to create a common, "inter-disciplinary" ground on this important part of ADHD evaluation, differential diagnosis, and research.

Ascorbic acid for the treatment of methemoglobinemia: the experience of a large tertiary care pediatric hospital.

The purpose of reporting this series of patients is to illustrate the role of ascorbic acid in the treatment of severe acquired methemoglobinemia (metHb), especially when methylene blue is not available. Medical records of affected patients were reviewed to collect history of exposures, food ingestion, physical examination, pulse oximetry, blood gas, and co-oximetry results, and outcomes. Five cases of acquired metHb are presented here, all of whom received treatment with ascorbic acid and fully recovered after 24 hours of treatment. Our series emphasizes that ascorbic acid is an effective alternative in the management of acquired metHb if methylene blue is unavailable and suggests that ascorbic acid infusion may be indicated in patients with glucose-6-phosphatase dehydrogenase deficiency.

Incidence and outcomes of pediatric patients with dual diagnosis of traumatic spinal cord injury and brain injury on an inpatient rehabilitation unit.

BACKGROUND: Traumatic brain injury (TBI) and spinal cord injury (SCI) are diagnoses commonly encountered on the pediatric rehabilitation unit. However, there is limited evidence in the literature addressing the incidence of or rehabilitation outcomes in pediatric patients with a dual diagnosis of TBI and SCI. OBJECTIVE: To determine incidence and functional outcomes of the dual diagnosis population. DESIGN: Retrospective cohort study. SETTING: Inpatient rehabilitation unit within an academic pediatric hospital. PATIENTS: Pediatric patients admitted to a single inpatient rehabilitation unit with a diagnosis of traumatic SCI between 2006 and 2019. Fifty-four patient records were identified and 26 met inclusion criteria. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURE: Presence of concomitant TBI in patients with diagnosed SCI. RESULTS: Seven of 26 patients were given a dual diagnosis of TBI and SCI during their initial rehabilitation hospitalization. After review of charts, authors identified 12 additional patients with suspected dual diagnoses based on injury characteristics and symptoms. There were no significant differences in functional outcomes across diagnosis groups. CONCLUSIONS: Incidence of dual diagnosis among pediatric patients with traumatic SCI was initially found to be 27%; the retrospective review indicated that TBI may be underdiagnosed in this patient population, and the dual diagnosis incidence may be as high as 73%. All patients had improved functional outcomes during their rehabilitation stays regardless of presence or absence of TBI.

A big data approach to evaluate receipt of optimal care in childhood cerebral palsy.

PURPOSE: Through automated electronic health record (EHR) data extraction and analysis, this project systematically quantified actual care delivery for children with cerebral palsy (CP) and evaluated alignment with current evidence-based recommendations. METHODS: Utilizing EHR data for over 8000 children with CP, we developed an approach to define and quantify receipt of optimal care, and pursued proof-of-concept with two children with unilateral CP, Gross Motor Function Classification System (GMFCS) Level II. Optimal care was codified as a cluster of four components including physical medicine and rehabilitation (PMR) care, spasticity management, physical therapy (PT), and occupational therapy (OT). A Receipt of Care Score (ROCS) quantified the degree of adherence to recommendations and was compared with the Pediatric Outcomes Data Collection Instrument (PODCI) and Pediatric Quality of Life Inventory (PEDS QL). RESULTS: The two children (12 year old female, 13 year old male) had nearly identical PMR and spasticity component scores while PT and OT scores were more divergent. Functional outcomes were higher for the child who had higher adjusted ROCS. CONCLUSIONS: ROCSs demonstrate variation in real-world care delivered over time and differentiate between components of care. ROCSs reflect overall function and quality of life. The ROCS methods developed are novel, robust, and scalable and will be tested in a larger sample.IMPLICATIONS FOR REHABILITATIONOptimal practice, with an emphasis on integrated multidisciplinary care, can be defined and quantified utilizing evidence-based recommendations.Receipt of optimal care for childhood cerebral palsy can be scored using existing electronic health record data.Big Data approaches can contribute to the understanding of current care and inform approaches for improved care.

White matter characteristics in children with cerebral palsy prior to selective dorsal rhizotomy: a multicenter diffusion tensor imaging study.

OBJECTIVE: The aims of this study were to 1) assess and quantify white matter (WM) microstructural characteristics derived from diffusion tensor imaging (DTI) in children with cerebral palsy (CP) prior to selective dorsal rhizotomy (SDR), and 2) investigate potential associations between WM diffusion properties and gross motor function and spasticity in children with spastic CP who underwent SDR. METHODS: This study is a multisite study based on DT images acquired prior to SDR as well as postoperative outcome data. DTI data collected from two sites were harmonized using the ComBat approach to minimize intersite scanner difference. The DTI abnormalities between children with spastic CP and controls were analyzed and correlated with the severity of impaired mobility based on the Gross Motor Function Classification System (GMFCS). The improvement in gross motor function and spasticity after SDR surgery was assessed utilizing the Gross Motor Function Measure-66 (GMFM-66), the Modified Tardieu Scale (MTS), and the modified Ashworth scale (MAS). Alterations in these outcome measures were quantified in association with DTI abnormalities. RESULTS: Significant DTI alterations, including lower fractional anisotropy (FA) in the genu of the corpus callosum (gCC) and higher mean diffusivity (MD) in the gCC and posterior limb of the internal capsule (PLIC), were found in children in the SDR group when compared with the age-matched control group (all p < 0.05). Greater DTI alterations (FA in gCC and MD in gCC and PLIC) were associated with lower mobility levels as determined based on GMFCS level (p < 0.05). The pre- to post-SDR improvement in motor function based on GMFM-66 was statistically significant (p = 0.006 and 0.002 at 6-month and 12-month follow-ups, respectively). The SDR efficacy was also identified as improving spasticity in lower-extremity muscle groups assessed with the MTS and MAS. Partial correlation analysis presented a significant association between pre- to post-SDR MTS alteration and DTI abnormalities. CONCLUSIONS: The findings in the present study provided initial quantitative evidence to establish the WM microstructural characteristics in children with spastic CP prior to SDR surgery. The study generated data for the association between baseline DTI characteristics and mobility in children with CP prior to SDR surgery. The study also demonstrated SDR efficacy in improving motor function and spasticity based on the GMFM-66, MTS, and MAS, respectively, in association with DTI data.

Outpatient hospital utilization after single event multi-level surgery in children with cerebral palsy.

PURPOSE: This study aimed to examine outpatient hospital utilization (number of specialties seen and number of visits to each specialty) in the year after single event multi-level surgery (SEMLS) in children with cerebral palsy (CP), and to determine if utilization differs across the medical center in the year after compared to the year before SEMLS. METHODS: This retrospective cross-sectional study used electronic medical record data of outpatient hospital utilization in children with CP who underwent SEMLS. RESULTS: Thirty children with CP (Gross Motor Function Classification System Levels I-V, mean age of 9.9 years) were included. In the year after surgery, a significant difference (p = 0.001) was found for the number of specialties seen, with non-ambulatory children seeing more specialties than ambulatory children. No statistically significant difference was found between the number of outpatient visits to each specialty in the year after SEMLS. Compared to the year before SEMLS, fewer therapy visits occurred in the year after SEMLS (p < 0.001) but significantly more visits to orthopaedics (p = 0.001) and radiology (p = 0.001). CONCLUSION: Children with CP had fewer therapy visits but more orthopaedic and radiology visits the year after SEMLS. Nearly half of the children were non-ambulatory. Examination of care needs in children with CP undergoing SEMLS is justified with consideration of ambulatory status, surgical burden, and post-operative immobilization.

Developing a length of stay prediction model for newborns, achieving better accuracy with greater usability.

BACKGROUND: One in ten newborn children is born prematurely. The elongated length of stay (LOS) of these children in the Neonatal Intensive Care Unit (NICU) has important implications on hospital occupancy figures, healthcare and management costs, as well as the psychology of parents. In order to allow accurate planning and resource allocation, this study aims to create a generalizable and robust model to predict the NICU LOS of preterm newborns. METHODS: Data were collected from a large tertiary center NICU between 2011 and 2018 and relates to 5,362 newborns. The selected model was externally validated using a data set of 8,768 newborns from another tertiary center NICU. This report compares several models, such as Random Forest (RF), quantile RF, and other feature selection methods, including LASSO and AIC step-forward selection. In addition, a novel step-forward selection based on False Discovery Rate (FDR) for quantile regression is presented and evaluated. RESULTS: A high-orderquantile regression model for predicting preterm newborns' LOS that uses only four features available at birth had more attractive properties than other richer ones. The model achieved a Mean Absolute Error (MAE) of 6.26 days on the internal validation set (average LOS 27.04) and an MAE of 6.04 days on the external validation set (average LOS 29.32). The suggested model surpassed the accuracy obtained by models in the literature. It is shown empirically that the FDR-based selection has better properties than the AIC-based step-forward selection approach. CONCLUSION: This paper demonstrates a process to create a predictive model for NICU LOS in preterm newborns, where each step is reasoned. We obtain a simple and robust model for NICU LOS prediction, which achieves far better results than the current model used for financing NICUs. Utilizing this model, we have created an easy-to-use online web application to ease parents' worries and to assist NICU management: https://tzviel.shinyapps.io/calcuLOS.

Patient monitoring as a predictor of blood culture results in a tertiary neonatal intensive care unit.

We present a mesoergonomic approach to the early detection of neonatal sepsis, analyzing clinical data for 4999 patients from a neo-natal intensive care unit to predict positive culture results. The Apgar score at birth predicted positive results. For neonates with poor and intermediate Apgar scores, culture results for monitored infants were more likely to be positive than those for unmonitored infants. Thus, the medical staff tended to monitor infants who eventually had a greater chance for positive test results. A cost-effectiveness analysis indicated that for infants with high Apgar scores, the physician should decide whether to obtain a blood culture, based on the patient's characteristics. For infants with lower Apgar scores, it may be advisable to obtain a blood culture whenever one decides to monitor a neonate. The study demonstrates that staff decisions regarding a patient can serve as input for further clinical decision-making.

Early prediction of encephalopathic transformation in children with benign epilepsy with centro-temporal spikes.

BACKGROUND: Most children with Benign epilepsy with centro-temporal spikes (BECTS) undergo remission during late adolescence and do not require treatment. In a small group of patients, the condition may evolve to encephalopathic syndromes including epileptic encephalopathy with continuous spike-and-wave during sleep (ECSWS), or Landau-Kleffner Syndrome (LKS). Development of prediction models for early identification of at-risk children is of utmost importance. AIM: To develop a predictive model of encephalopathic transformation using data-driven approaches, reveal complex interactions to identify potential risk factors. METHODS: Data were collected from a cohort of 91 patients diagnosed with BECTS treated between the years 2005-2017 at a pediatric neurology institute. Data on the initial presentation was collected based on a novel BECTS ontology and used to discover potential risk factors and to build a predictive model. Statistical and machine learning methods were compared. RESULTS: A subgroup of 18 children had encephalopathic transformation. The least absolute shrinkage and selection operator (LASSO) regression Model with Elastic Net was able to successfully detect children with ECSWS or LKS. Sensitivity and specificity were 0.83 and 0.44. The most notable risk factors were fronto-temporal and temporo-parietal localization of epileptic foci, semiology of seizure involving dysarthria or somatosensory auras. CONCLUSION: Novel prediction model for early identification of patients with BECTS at risk for ECSWS or LKS. This model can be used as a screening tool and assist physicians to consider special management for children predicted at high-risk. Clinical application of machine learning methods opens new frontiers of personalized patient care and treatment.

Disordered Eating Behaviors in Young Individuals With Idiopathic Intracranial Hypertension.

BACKGROUND: The objective of this study was to assess the prevalence of disordered eating behaviors (DEBs) in young individuals with idiopathic intracranial hypertension (IIH) and to identify predictors of DEBs in this population. METHODS: Individuals with IIH aged eight to 25 years and their matched controls responded to a self-rating survey comprised of the Eating Attitude Test-26 for assessing the presence of DEBs and the Depression, Anxiety and Stress Scale. RESULTS: Fifty-three subjects with IIH and 106 healthy controls were included. DEBs were significantly more prevalent in individuals with IIH (P < 0.001). Individuals with IIH and DEBs were more likely to have longer periods of treatment [odds ratio: 1.07, 95% CI: 1.02-1.41), P = 0.008] and to have lost a significant amount of weight during the course of treatment [odds ratio: 9.06 (95% CI: 1.30-62.9), P = 0.026]. Depression, anxiety, and stress were more prevalent in the IIH group than in the controls (P = 0.004) and were associated with DEBs in these individuals (P = 0.01). CONCLUSIONS: There is an increased prevalence of DEBs among young individuals with IIH, which persists even after disease resolution, and is associated with higher reported rates of depression, anxiety, and stress. Medical caregivers should have heightened awareness to DEBs in individuals with IIH with the aim of early identification and intervention.