Fenfluramine in the treatment of Dravet syndrome: Results of a third randomized, placebo-controlled clinical trial.

Objective: This study was undertaken to assess the safety and efficacy of fenfluramine in the treatment of convulsive seizures in patients with Dravet syndrome.

Methods: This multicenter, randomized, double-blind, placebo-controlled, parallel-group, phase 3 clinical trial enrolled patients with Dravet syndrome, aged 2-18 years with poorly controlled convulsive seizures, provided they were not also receiving stiripentol. Eligible patients who had ≥6 convulsive seizures during the 6-week baseline period were randomized to placebo, fenfluramine .

Engaging the Front Line: A Case Study on Implementing Lean Methodology to Improve Central Line-Associated Bloodstream Infections.

Employee engagement is a key driver in achieving successful quality improvement initiatives. An important aspect of engagement is enabling the nursing staff to have a role in problem solving at the front line, thus improving productivity. Finding an appropriate methodology that resonates with the frontline staff can be challenging.

COVID-19 vaccine in patients with Dravet syndrome: Observations and real-world experiences.

Objective: Vaccination against the SARS-CoV-2 virus is a primary tool to combat the COVID-19 pandemic. However, vaccination is a common seizure trigger in individuals with Dravet syndrome (DS). Information surrounding COVID-19 vaccine side effects in patients with DS would aid caregivers and providers in decisions for and management of COVID-19 vaccination.

Emergency Department Initiative to Improve Sepsis Core Measure Compliance: A Hospital Network Approach.

The topic of sepsis has been realized among the last 20 years. A majority of patients with sepsis enter the health system through the emergency department, and health professionals need to provide evidence-based care. Within the health system, interdepartmental teams were formed with the purpose to set a system-wide standard to meet the evidence-based practice standards for sepsis.

Dravet syndrome: A quick transition guide for the adult neurologist.

Introduction: Dravet syndrome (DS) is still seen as a "pediatric disease", where patients receive excellent care in pediatric centers, but care is less than optimal in adult health care systems (HCS). This creates a barrier when young adults need to leave the family-centered pediatric system and enter the adult, patient-centered HCS. Here we create a guide to help with the transition from pediatric to adult for patients with DS.

Pathogenic MAST3 Variants in the STK Domain Are Associated with Epilepsy.

Objective: The MAST family of microtubule-associated serine-threonine kinases (STKs) have distinct expression patterns in the developing and mature human and mouse brain. To date, only MAST1 has been conclusively associated with neurological disease, with de novo variants in individuals with a neurodevelopmental disorder, including a mega corpus callosum.

Methods: Using exome sequencing, we identify MAST3 missense variants in individuals with epilepsy.

Utilization of Institute for Health Care Improvement Tools to Develop a Mortality Review Process.

Mortality rates have emerged as one of the main metrics determining quality of care within a hospital. In an effort to evaluate cases, this article illustrates the use of the Institute of Healthcare Improvement Global Trigger Tool as well as the implementation of a 3-prong review process in a large, urban teaching facility. In addition, the findings of the evaluation process are shared.

Dyshomeostatic modulation of Ca-activated K channels in a human neuronal model of KCNQ2 encephalopathy.

Mutations in , which encodes a pore-forming K channel subunit responsible for neuronal M-current, cause neonatal epileptic encephalopathy, a complex disorder presenting with severe early-onset seizures and impaired neurodevelopment. The condition is exceptionally difficult to treat, partially because the effects of mutations on the development and function of human neurons are unknown. Here, we used induced pluripotent stem cells (iPSCs) and gene editing to establish a disease model and measured the functional properties of differentiated excitatory neurons.

Interactive machine learning for fast and robust cell profiling.

Automated profiling of cell morphology is a powerful tool for inferring cell function. However, this technique retains a high barrier to entry. In particular, configuring image processing parameters for optimal cell profiling is susceptible to cognitive biases and dependent on user experience.

Determining Nursing Education Needs During a Rapidly Changing COVID-19 Environment.

COVID-19 created an environment that required rapid implementation of procedures and processes to minimize transmission. This led to an urgent response from the Department of Professional Practice and Education to implement education to a large number of personnel. This article describes strategies and methods employed to meet the training demands at a time when resources and supplies were limited.

A single-center, retrospective analysis of genotype-phenotype correlations in children with Dravet syndrome.

Purpose: Dravet syndrome is an early-onset epileptic encephalopathy caused most often by loss-of-function SCN1A variants. Following recognition of its genetic basis and unique clinical features, Dravet syndrome has become one of the most well-studied genetic epilepsies. We sought to evaluate the genetic diversity and correlative seizure phenotype, comorbidities, and response to antiepileptic therapies of patients with clinically-diagnosed Dravet syndrome seen in a tertiary care center.

Fenfluramine hydrochloride for the treatment of seizures in Dravet syndrome: a randomised, double-blind, placebo-controlled trial.

Background: Dravet syndrome is a rare, treatment-resistant developmental epileptic encephalopathy characterised by multiple types of frequent, disabling seizures. Fenfluramine has been reported to have antiseizure activity in observational studies of photosensitive epilepsy and Dravet syndrome. The aim of the present study was to assess the efficacy and safety of fenfluramine in patients with Dravet syndrome.

Fenfluramine for Treatment-Resistant Seizures in Patients With Dravet Syndrome Receiving Stiripentol-Inclusive Regimens: A Randomized Clinical Trial.

Importance: Fenfluramine treatment may reduce monthly convulsive seizure frequency in patients with Dravet syndrome who have poor seizure control with their current stiripentol-containing antiepileptic drug regimens.

Objective: To determine whether fenfluramine reduced monthly convulsive seizure frequency relative to placebo in patients with Dravet syndrome who were taking stiripentol-inclusive regimens.

Design, Setting, And Participants: This double-blind, placebo-controlled, parallel-group randomized clinical trial was conducted in multiple centers.

The ketogenic diet in children 3 years of age or younger: a 10-year single-center experience.

The ketogenic diet (KD) is an effective treatment option for intractable epilepsy. Here, we reviewed the last 10 years of our experience with the KD and characterized its use in patients under 3 years of age. Medical records of all patients under the age of 3 years who were treated with the ketogenic diet from April 2004 to June 2014 were retrospectively reviewed.

Seizure burden in severe early-life epilepsy: Perspectives from parents.

Objectives: Seizure burden is typically measured by seizure frequency yet it entails more than seizure counts, especially for people with severe epilepsies and their caregivers. We aimed to characterize the multi-faceted nature of seizure burden in young people and their parents who are living with severe early-life epilepsies.

Methods: A one-day workshop and a series of teleconferences were held with parents of children with severe, refractory epilepsy of early-life origin and providers for children with epilepsy.

Long-term safety and efficacy of cannabidiol in children and adults with treatment resistant Lennox-Gastaut syndrome or Dravet syndrome: Expanded access program results.

Background: Since 2014, patients with severe treatment-resistant epilepsies (TREs) have been receiving add-on cannabidiol (CBD) in an ongoing, expanded access program (EAP), which closely reflects clinical practice. We conducted an interim analysis of long-term efficacy and tolerability in patients with Lennox-Gastaut syndrome (LGS) or Dravet syndrome (DS) who received CBD treatment through December 2016.

Methods: Children and adults with LGS/DS taking stable doses of antiepileptic drugs (AEDs) at baseline were included from 25 EAP sites across the United States.

Long-term cannabidiol treatment in patients with Dravet syndrome: An open-label extension trial.

Objective: Add-on cannabidiol (CBD) significantly reduced seizures associated with Dravet syndrome (DS) in a randomized, double-blind, placebo-controlled trial: GWPCARE1 Part B (NCT02091375). Patients who completed GWPCARE1 Part A (NCT02091206) or Part B, or a second placebo-controlled trial, GWPCARE2 (NCT02224703), were invited to enroll in a long-term open-label extension trial, GWPCARE5 (NCT02224573). We present an interim analysis of the safety, efficacy, and patient-reported outcomes from GWPCARE5.

Long-term safety and treatment effects of cannabidiol in children and adults with treatment-resistant epilepsies: Expanded access program results.

Objective: Since 2014, cannabidiol (CBD) has been administered to patients with treatment-resistant epilepsies (TREs) in an ongoing expanded-access program (EAP). We report interim results on the safety and efficacy of CBD in EAP patients treated through December 2016.

Methods: Twenty-five US-based EAP sites enrolling patients with TRE taking stable doses of antiepileptic drugs (AEDs) at baseline were included.

Severe peri-ictal respiratory dysfunction is common in Dravet syndrome.

Dravet syndrome (DS) is a severe childhood-onset epilepsy commonly due to mutations of the sodium channel gene SCN1A. Patients with DS have a high risk of sudden unexplained death in epilepsy (SUDEP), widely believed to be due to cardiac mechanisms. Here we show that patients with DS commonly have peri-ictal respiratory dysfunction.

Trial of Cannabidiol for Drug-Resistant Seizures in the Dravet Syndrome.

Background: The Dravet syndrome is a complex childhood epilepsy disorder that is associated with drug-resistant seizures and a high mortality rate. We studied cannabidiol for the treatment of drug-resistant seizures in the Dravet syndrome.

Methods: In this double-blind, placebo-controlled trial, we randomly assigned 120 children and young adults with the Dravet syndrome and drug-resistant seizures to receive either cannabidiol oral solution at a dose of 20 mg per kilogram of body weight per day or placebo, in addition to standard antiepileptic treatment.