The contribution of fenfluramine to the treatment of Dravet syndrome in Spain through Multi-Criteria Decision Analysis

Introduction: Dravet Syndrome (DS) is a severe, developmental epileptic encephalopathy (DEE) that begins in infancy and is characterized by pharmaco-resistant epilepsy and neurodevelopmental delay. Despite available antiseizure medications (ASMs), there is a need for new therapeutic options with greater efficacy in reducing seizure frequency and with adequate safety and tolerability profiles.Fenfluramine is a new ASM for the treatment of seizures associated with DS as add-on therapy to other ASMs for patients aged 2 years and older. Fenfluramine decreases seizure frequency, prolongs periods of seizure freedom potentially helping to reduce risk of Sudden Unexpected Death in Epilepsy (SUDEP) and improves patient cognitive abilities positively impacting on patients' Quality of Life (QoL).Reflective Multi-Criteria Decision Analysis (MCDA) methodology allows to determine what represents value in a given indication considering all relevant criteria for healthcare decision-making in a transparent and systematic manner from the perspective of relevant stakeholders. The aim of this study was to determine the relative value contribution of fenfluramine for the treatment of DS in Spain using MCDA.Method: A literature review was performed to populate an adapted a MCDA framework for orphan-drug evaluation in Spain. A panel of ten Spanish experts, including neurologists, hospital pharmacists, patient representatives and decision-makers, scored four comparative evidence matrices.Results were analyzed and discussed in a group meeting through reflective MCDA discussion methodology. Results: Dravet syndrome is considered a severe, rare disease with significant unmet needs. Fenfluramine is perceived to have a higher efficacy profile than all available alternatives, with a better safety profile than stiripentol and topiramate and to provide improved QoL versus studied alternatives. Fenfluramine results in lower other medical costs in comparison with stiripentol and clobazam. Participants perceived that fenfluramine could lead to indirect costs savings compared to available alternatives due to its efficacy in controlling seizures. Overall, fenfluramine's therapeutic impact on patients with DS is considered high and supported by high-quality evidence.Conclusions: Based on reflective MCDA, fenfluramine is considered to add greater benefit in terms of effi-cacy, safety and QoL when compared with available ASMs.(c) 2022 The Authors. Published by Elsevier Inc

Drinking patterns and effects of alcohol on instagram intimes of covid-19

Introducción: Compartir “eventos de la bebida” se ha convertido en una práctica habitual entre las personas jóvenes en redes como Instagram. La pandemia por el Covid-19 ha reestructurado tanto sus pautas de consumo de alcohol, como los usos que hacen de las redes sociales. Objetivos y Métodos: Describir en profundidad las pautas de consu- mo de alcohol y los efectos de este consumo que se muestran en Instagram en una muestra de 118 jóvenes y ado- lescentes en España a través de la etnografía digital. Resultados y Conclusiones: Instagram es parte de la fiesta, parte imbricada en la vida cotidiana de las personas jóvenes, en la que se comparten regularmente imágenes deseables de las pautas de consumo de alcohol y sus efectos. Adolescentes y jóvenes construyen un modelo online idealizado de pautas de consumo de alcohol en el que sólo son visibles los efectos de la fase de desinhibición tras el consumo y se obvian el resto de las fases de los efectos del alcohol en el organismo. Es fundamental incluir estas nuevas formas de transmisión de las pautas de consumo de alcohol en la normativa española que regula la venta y uso de alcoholIntroduction: Sharing “drinking events” has become a common practice among young people on Instagram. The Covid-19 pandemic has restructured both their alcohol consumption patterns and their use of social networks. Ob- jective and Methods: To describe in depth the patterns of alcohol consumption and the effects of this consumption shown on Instagram in a sample of 118 young people and adolescents in Spain through digital ethnography. Results and Conclusions: Instagram is part of the party, part embedded in the daily lives of young people, in which desirable images of drinking patterns and their effects are regularly shared. Adolescents and young people build an idealized online model of alcohol consumption patterns in which only the effects of the disinhibition phase after consumption are visible and the rest of the phases of the effects of alcohol on the body are ignored. It is essential to include these new forms of transmission of alcohol consumption patterns in the Spanish regulations that regulate the sale and use of alcoho

Pautas de consumo y efectos del alcohol en Instagram en tiempos de COVID-19

Introducción: Compartir “eventos de la bebida” se ha convertido en una práctica habitual entre las personas jóvenes en redes como Instagram. La pandemia por el Covid-19 ha reestructurado tanto sus pautas de consumo de alcohol, como los usos que hacen de las redes sociales. Objetivos y Métodos: Describir en profundidad las pautas de consu- mo de alcohol y los efectos de este consumo que se muestran en Instagram en una muestra de 118 jóvenes y ado- lescentes en España a través de la etnografía digital. Resultados y Conclusiones: Instagram es parte de la fiesta, parte imbricada en la vida cotidiana de las personas jóvenes, en la que se comparten regularmente imágenes deseables de las pautas de consumo de alcohol y sus efectos. Adolescentes y jóvenes construyen un modelo online idealizado de pautas de consumo de alcohol en el que sólo son visibles los efectos de la fase de desinhibición tras el consumo y se obvian el resto de las fases de los efectos del alcohol en el organismo. Es fundamental incluir estas nuevas formas de transmisión de las pautas de consumo de alcohol en la normativa española que regula la venta y uso de alcohol.Introduction: Sharing “drinking events” has become a common practice among young people on Instagram. The Covid-19 pandemic has restructured both their alcohol consumption patterns and their use of social networks. Ob- jective and Methods: To describe in depth the patterns of alcohol consumption and the effects of this consumption shown on Instagram in a sample of 118 young people and adolescents in Spain through digital ethnography. Results and Conclusions: Instagram is part of the party, part embedded in the daily lives of young people, in which desirable images of drinking patterns and their effects are regularly shared. Adolescents and young people build an idealized online model of alcohol consumption patterns in which only the effects of the disinhibition phase after consumption are visible and the rest of the phases of the effects of alcohol on the body are ignored. It is essential to include these new forms of transmission of alcohol consumption patterns in the Spanish regulations that regulate the sale and use of alcohol.Esta investigación está financiada por el Ministerio de Ciencia e Innovación. Programas Estatal de Generación de Conocimiento y Fortalecimiento Científico y Tecnológico del Sistema de I+D+i orientada a los Retos de la Sociedad. (PID2019-105122RB-I00/AEI/10.13039/501100011033)

Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) had an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome alterations (mCA) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (mCA and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, mCA and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, individuals with clonal mosaic events (clonal mosaicism for chromosome alterations and/or loss of chromosome Y) showed an increased risk of COVID-19 lethality

El análisis pormenorizado del Childhood Autism Spectrum Test CAST permite diferenciar subtipos clínicos con dificultades en la comunicación social

El Childhood Austism Spectrum Test-CAST (Scott et al., 2012a) es una prueba de screening del síndrome de Asperger o trastorno del espectro del autismo de grado 1 (TEA1). Se busca analizarla para precisar diferentes dimensiones en su contenido. para ello, se aplicó el CAST a 254 pacientes de nuestra Unidad de Neuropediatría, de 5 a 16 años, afectos de: TEA1 (n=17); trastorno de la comunicación social (n=43); trastorno de aprendizaje procedimental (n=60); trastorno por déficit de atención (n=44); discapacidad intelectual (n=30) y discapacidad intelectual y epilepsia (n=60). Los resultados con el uso tradicional del CAST en la muestra clínica se obtienen 47.1% y 33.75% de falsos negativos y positivos, respectivamente. Se realiza un análisis factorial de los 31 ítems del cuestionario. Con una buena adecuación de los datos (KMO=0,65 y MSA=0.47-0.88) se obtienen 7 factores, que explican el 63% de la varianza total. Se comprueba la fiabilidad y la validez. El análisis discriminante indica que esta nueva corrección e interpretación permite clasificar correctamente al 86.7% de nuestra casuística con o sin dificultades en el uso social del lenguaje. Se detallan las dimensiones alteradas con más frecuencia en cada grupo clínico. Este análisis pormenorizado del CAST aporta información relevante en el diagnóstico diferencial de trastornos del neurodesarrollo

Camelostrongylus mentulatus in domestic goats from the Iberian Peninsula

©CAB International, 2003. This document is the, Published version of a Published Work that appeared in final form in Journal of Helminthology. To access the final edited and published work see https://doi.org/10.1079/JOH2003184Two male worms of Camelostrongylus mentulatus were found in one of 84 murciano-granadina goats in Murcia, south-eastern Spain. This is the first report of C. mentulatus in goats in the Iberian peninsula and the possible origin and transmission of this nematode in Spain are discusse

Drinking patterns and effects of alcohol on Instagram in times of COVID-19

Introducción: Compartir “eventos de la bebida” se ha convertido en una práctica habitual entre las personas jóvenes en redes como Instagram. La pandemia por el Covid-19 ha reestructurado tanto sus pautas de consumo de alcohol, como los usos que hacen de las redes sociales. Objetivos y Métodos: Describir en profundidad las pautas de consumo de alcohol y los efectos de este consumo que se muestran en Instagram en unamuestra de 118 jóvenes y adolescentes en España a través de la etnografía digital. Resultados y Conclusiones: Instagram es parte de la fiesta, parte imbricada en la vida cotidiana de las personasjóvenes, en la que se comparten regularmente imágenes deseables de las pautas de consumo de alcohol y sus efectos. Adolescentes y jóvenes construyen un modelo online idealizado de pautas de consumo de alcohol en el que sólo son visibleslos efectos de la fase de desinhibición tras el consumo y se obvian el resto de lasfases de los efectos del alcohol en el organismo. Esfundamental incluir estas nuevasformas de transmisión de las pautas de consumo de alcohol en la normativa española que regula la venta y uso de alcohol.Introduction: Sharing “drinking events” has become a common practice among young people on Instagram. The Covid-19 pandemic hasrestructured both their alcohol consumption patterns and their use of social networks. Objective and Methods: To describe in depth the patterns of alcohol consumption and the effects of this consumption shown on Instagram in a sample of 118 young people and adolescentsin Spain through digital ethnography. Results and Conclusions: Instagram is part of the party, part embedded in the daily lives of young people, in which desirable images of drinking patterns and their effects are regularly shared. Adolescents and young people build an idealized online model of alcohol consumption patterns in which only the effects of the disinhibition phase after consumption are visible and the rest of the phases of the effects of alcohol on the body are ignored. Itis essential to include these new forms of transmission of alcohol consumption patternsin the Spanish regulations that regulate the sale and use of alcohol

The Charlotte Project: Recommendations for patient-reported outcomes and clinical parameters in Dravet syndrome through a qualitative and Delphi consensus study.

The appropriate management of patients with Dravet Syndrome (DS) is challenging, given the severity of symptoms and the burden of the disease for patients and caregivers. This study aimed to identify, through a qualitative methodology and a Delphi consensus-driven process, a set of recommendations for the management of DS to guide clinicians in the assessment of the clinical condition and quality of life (QoL) of DS patients, with a special focus on patient- and caregiver-reported outcomes (PROs). This study was conducted in five phases, led by a multidisciplinary scientific committee (SC) including pediatric neurologists, epileptologists, a neuropsychologist, an epilepsy nurse, and members of DS patient advocates. In phases 1 and 2, a questionnaire related to patients' QoL was prepared and answered by caregivers and the SC. In phase 3, the SC generated, based on these answers and on a focus group discussion, a 70-item Delphi questionnaire, covering six topic categories on a nine-point Likert scale. In phase 4, 32 panelists, from different Spanish institutions and with a multidisciplinary background, answered the questionnaire. Consensus was obtained and defined as strong or moderate if ≥80% and 67-79% of panelists, respectively, rated the statement with ≥7. Phase 5 consisted of the preparation of the manuscript. The panelists agreed on a total of 69 items (98.6%), 54 (77.14%), and 15 (21.43%) with strong and moderate consensus, respectively. The experts' recommendations included the need for frequent assessment of patient and caregivers QoL parameters. The experts agreed that QoL should be assessed through specific questionnaires covering different domains. Likewise, the results showed consensus regarding the regular evaluation of several clinical parameters related to neurodevelopment, attention, behavior, other comorbidities, and sudden unexpected death in epilepsy (SUDEP). A consensus was also reached on the instruments, specific parameters, and caregivers' education in the routine clinical management of patients with DS. This consensus resulted in a set of recommendations for the assessment of clinical and QoL parameters, including PROs, related to the general evaluation of QoL, neurodevelopment, attention, behavior, other comorbidities affecting QoL, SUDEP, and QoL of caregivers/relatives and patients with DS