Four-year safety and effectiveness data from patients with multiple sclerosis treated with fingolimod: The Spanish GILENYA registry

Esclerosis múltiple; Reacciones adversas; Infecciones respiratoriasEsclerosi múltiple; Reaccions adverses; Infeccions respiratòriesMultiple sclerosis; Adverse reactions; Respiratory infectionsObjective To describe the profile of patients with multiple sclerosis (MS) treated with fingolimod in Spain and to assess the effectiveness and safety of fingolimod after 4 years of inclusion in the Spanish Gilenya Registry. Methods An observational, retrospective/prospective, multicenter case registry, including all patients with relapsing-remitting MS (RRMS) starting treatment with fingolimod in 43 centers in Spain. Analyses were performed in the overall population and in subgroups according to prior disease-modifying therapy (DMT): glatiramer acetate/interferon beta-1 (BRACE), natalizumab, other treatment, or naïve. Results Six hundred and sixty-six evaluable patients were included (91.1% previously treated with at least one DMT). The mean annualized relapse rate (ARR) prior to fingolimod was 1.12, and the mean EDSS at fingolimod initiation was 3.03. Fingolimod reduced the ARR by 71.4%, 75%, 75.5%, and 80.3%, after 1, 2, 3 and 4 years, respectively (p<0.001). This significant reduction in the ARR continued to be observed in all subgroups. After 4 years, the EDSS showed a minimal deterioration, with the EDSS scores from year 1 to year 4 remaining mostly stable. The percentage of patients without T1 Gd+ lesions progressively increased from 45.6% during the year prior to fingolimod initiation to 88.2% at year 4. The proportion of patients free from new/enlarged T2 lesions after 4 years of fingolimod treatment was 80.3%. This trend in both radiological measures was also observed in the subgroups. Adverse events (AEs) were experienced by up to 41.6% of patients (most commonly: lymphopenia [12.5%] and urinary tract infection [3.7%]). Most AEs were mild in severity, 3.6% of patients had serious AEs. Conclusions The patient profile was similar to other observational studies. The results obtained from the long-term use of fingolimod showed that it was effective, regardless of prior DMT, and it had adequate safety results, with a positive benefit-risk balance.The study was funded by the Academia Española de Esclerosis Múltiple y Otras Enfermedades Autoinmunes (ACADEM), with a restricted investigational grant form Novartis. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

COVID-19 Outcomes and Vaccination in People with Relapsing Multiple Sclerosis Treated with Ofatumumab

COVID-19; Ofatumumab; VaccinationCOVID-19; Ofatumumab; VacunaciónCOVID-19; Ofatumumab; VacunacióIntroduction The SARS-CoV-2 pandemic necessitated better understanding of the impact of disease-modifying therapies on COVID-19 outcomes and vaccination. We report characteristics of COVID-19 cases and vaccination status in ofatumumab-treated relapsing multiple sclerosis (RMS) patients. Methods COVID-19 data analyzed were from the ongoing, open-label, long-term extension phase 3b ALITHIOS study from December 2019 (pandemic start) and post-marketing cases from August 2020 (ofatumumab first approval) up to 25 September 2021. COVID-19 cases, severity, seriousness, outcomes, vaccination status, and breakthrough infection were evaluated. Results As of 25 September 2021, 245 of 1703 patients (14.4%) enrolled in ALITHIOS receiving ofatumumab (median exposure: 2.45 years) reported COVID-19 (confirmed: 210; suspected: 35). Most COVID-19 was of mild (44.1%) or moderate (46.5%) severity, but 9% had severe/life-threatening COVID-19. There were 24 serious cases (9.8%) with 23 patients hospitalized; 22 recovered and 2 died. At study cut-off, 241 patients (98.4%) had recovered or were recovering or had recovered with sequelae and 2 (0.8%) had not recovered. Ofatumumab was temporarily interrupted in 39 (15.9%) patients. Before COVID-19 onset, IgG levels were within the normal range in all COVID-19–affected patients, while IgM was < 0.4 g/l in 23 (9.4%) patients. No patient had a reinfection. Overall, 559 patients were vaccinated (full, 476; partial, 74; unspecified, 9). Breakthrough infection was reported in 1.5% (7/476) patients, and 11 reported COVID-19 after partial vaccination. As of 25 September 2021, the Novartis Safety Database (~ 4713 patient-treatment years) recorded 90 confirmed COVID-19 cases receiving ofatumumab. Most cases were non-serious (n = 80), and ten were serious (1 medically significant, 9 hospitalized, 0 deaths). Among 36 of 90 cases with outcomes reported, 30 recovered and 6 did not recover. Conclusion COVID-19 in RMS patients on ofatumumab was primarily of mild/moderate severity and non-serious in these observational data. Most recovered from COVID-19 without treatment interruption. Two people died with COVID-19. Breakthrough COVID-19 despite being fully/partially vaccinated was uncommon.The study sponsor (Novartis Pharma AG, Basel, Switzerland) participated in the design and conduct of the study, data collection, data management, data analysis and data interpretation; preparation, review, and approval of the manuscript, as well as writing of the report and decision to submit the paper for publication. All authors had full access to all study data and took final responsibility for the decision to submit the manuscript for publication. The journal rapid service fee for this publication was funded by Novartis Pharma AG, Basel, Switzerland

La sucesión look and say

En esta breve nota queremos presentar las denominadas sucesiones look and say como recurso a la hora de abordar contenidos relacionados con la búsqueda de patrones, así como para plantear pequeñas investigaciones en el aula. El contenido de este artículo viene motivado por la sesión «sucesiones look and say» desarrollada el 4 de Noviembre de 2016 dentro del taller de talento matemático para 4º de la ES

La escuela secundaria frente al desafío de la universalización: Debates y experiencias en Argentina

Argentina estableció en el año 2006 la obligatoriedad de la escolaridad secundaria, acoplándose a la tendencia de la región. Durante ese proceso se desarrolló un significativo debate acerca si la escuela es universalizable con las características que presenta actualmente, producto de un largo proceso histórico que ha consolidado una matriz de funcionamiento. ¿Presenta la escuela las características que la hagan factible de abarcar exitosamente a todas las clases sociales, a todas las culturas y trayectorias escolares? Este debate supuso revisar el discurso de la inclusión de un país que había impulsado un sistema escolar igualitario desde su origen, construyendo una equivalencia entre igualdad, inclusión y homogeneidad. La perdurabilidad de ese discurso y cómo el formato escolar consagrado – en la cotidianeidad escolar y en la imagen social – son un obstáculo en sí mismo para la universalización de la escolarización. Esa impronta fue muy productiva en ese sistema, aún cuando no estuvo exenta de las marcas de estratificación y sesgo de clase que la cultura escolar ha asumido en los distintos países. Este artículo reseña algunos ejes de este debate producido en la última década en Argentina; para ello pondrá a disposición la presentación de dos nuevas modalidades de escuela que – una como iniciativa de políticas educativas específicas y otra como resultado de procesos comunitarios autónomos – han desarrollado formatos institucionales novedosos para buscar hacer posible la escolarización de poblaciones escolares diversas. In 2006 Argentina established compulsory secondary schooling, joining the regional trend. During that process a significant debate was developed about whether the school is universalizable with the characteristics that it currently presents, the product of a long historical process that has consolidated a functioning matrix. Does the school present the characteristics that make it feasible to successfully cover all social classes, all cultures, and all school trajectories? This debate focuses on speeches about inclusion within a country that had promoted an egalitarian school system since its inception, building an equivalence between equality, inclusion and homogeneity. The durability of this discourse and how the consecrated school format- in school everyday life and in the social image - is an obstacle in itself for the universalization of schooling. This configuration was very productive in that system, even though it was not exempt from the stratification and class bias marking school culture that has assumed in other countries. This article summarizes some axes of that debate produced in the last decade in Argentina. We present two new school modalities - one as an initiative of specific educational policies and the another as a result of autonomous community processes - that have developed innovative institutional formats to make possible the schooling of diverse school populations

Retinal inner nuclear layer volume reflects inflammatory disease activity in multiple sclerosis: a longitudinal OCT study

Inner nuclear layer; Multiple sclerosis; Optical coherence tomographyCapa nuclear interna; Esclerosis múltiple; Tomografía de coherencia ópticaCapa nuclear interior; Esclerosi múltiple; Tomografia de coherència òpticaBackground: The association of peripapillary retinal nerve fibre layer (pRNFL) and ganglion cell-inner plexiform layer (GCIPL) thickness with neurodegeneration in multiple sclerosis (MS) is well established. The relationship of the adjoining inner nuclear layer (INL) with inflammatory disease activity is less well understood. Objective: The objective of this paper is to investigate the relationship of INL volume changes with inflammatory disease activity in MS. Methods In this longitudinal, multi-centre study, optical coherence tomography (OCT) and clinical data (disability status, relapses and MS optic neuritis (MSON)) were collected in 785 patients with MS (68.3% female) and 92 healthy controls (63.4% female) from 11 MS centres between 2010 and 2017 and pooled retrospectively. Data on pRNFL, GCIPL and INL were obtained at each centre. Results: There was a significant increase in INL volume in eyes with new MSON during the study (N=61/1562, β=0.01mm3, p<.001). Clinical relapses (other than MSON) were significantly associated with increased INL volume (β=0.005, p=.025). INL volume was independent of disease progression (β=0.002mm3, p=.474). Conclusion: Our data demonstrate that an increase in INL volume is associated with MSON and the occurrence of clinical relapses. Therefore, INL volume changes may be useful as an outcome marker for inflammatory disease activity in MSON and MS treatment trials

Reformas Educativas y Profesorado de Secundaria: El Peso de la Tradición Docente

A pesar de los cambios propuestos por diferentes reformas educativas que han tenido lugar en el ámbito español durante los últimos 40 años, cabe preguntarse en qué medida la etapa de educación secundaria guarda, todavía, más relación con sus orígenes –Plan Pidal, 1857– que con los derivados de las sucesivas reformas. Realizamos un recorrido histórico por leyes orgánicas de educación de ámbito español poniendo nuestra mirada en la etapa de educación secundaria obligatoria y centrando nuestra reflexión en aspectos tan importantes como el peso de la tradición docente. Algunos principios pedagógicos que inspiraban las reformas educativas que han tenido lugar en nuestro país, planteaban en un modelo de enseñanza más comprensiva y no tan academicista. Se pretendía que dicha etapa educativa, que actualmente es de carácter obligatorio, fuese una etapa a la que toda la población pudiese acceder, pero, además, también pudiese superar con éxito. Sin embargo, este modelo de enseñanza comprensiva promulgado por las sucesivas reformas es un modelo educativo que todavía no ha calado, con suficiente profundidad, en la cultura de un profesorado de secundaria que ha sido formado en una tradición docente muy diferente y en el que todavía, hoy en día, podemos percibir el peso de la tradición. Despite the changes proposed by different educational reforms that have taken place in the Spanish context during the last 40 years, it is worth asking to what extent the secondary education stage still has more relation with its origins -Plan Pidal, 1857- than with the derivatives of the successive reforms. We made a historical journey through organic laws of education in the Spanish area, focusing our attention on the stage of compulsory secondary education and focusing our reflection on aspects as important as the weight of the teaching tradition. Some principles of educational reforms that have taken place in our country were inspired by a more pedagogic teaching model and not so academic model. It was intended that this educational stage, which is currently mandatory catarter, was a stage to which all the population could access but also could also overcome successfully. However, this model of comprehensive education promulgated by the reforms, is an educational model that has not yet penetrated, with sufficient depth, into the culture of a secondary school teacher who has been trained in a very different teaching tradition and in which today we can see the weight of tradition

Saldos de la Reforma Educativa en México, Nuevas Regulaciones de la Gestión y el Trabajo Docente en Educación Básica

En 2013, se implementó una política gubernamental de Reforma Educativa en la educación básica mexicana con el objetivo de darle a los niños y jóvenes maestros más preparados, escuelas bien construidas y equipadas, y además la posibilidad de seguir estudiando más y mejor. Al cierre del gobierno que puso en marcha la Reforma, es pertinente hacer una revisión de los saldos que deja la implementación de esta política en la gestión y el desarrollo del trabajo docente en los maestros de educación básica pública. Las formulaciones políticas de innovación y cambio en la educación y el trabajo de los docentes en México, descritas en esta reforma, se inscriben en la lógica internacional que ha ido generando una nueva definición de las relaciones entre la escuela y la sociedad. Estas políticas no sólo implican la existencia de nuevos marcos legales y lineamientos de actuación, sino que instituyen un programa político e ideológico que ha establecido una nueva orientación, objetivos y voluntad en la sociedad. Las nuevas regulaciones de la gestión y práctica de la docencia pública vinculan la política, cultura, economía y el Estado, a través de pautas que cubren los ámbitos de la cotidianidad educativa y el accionar de los sujetos inmersos en este ámbito desde la gestión y organización administrativa, académica y de contenidos, hasta la reconfiguración del sentido de la docencia desde una visión enfocada en la eficacia y eficiencia racionalista. En el presente artículo se presentan de manera exploratoria, los saldos en materia laboral y de sentido de la docencia pública, a partir de la implementación de la Reforma Educativa. The Education Reform of 2013, was a government policy implemented in Mexican basic education with the aim of giving children and young people better prepared teachers, well-built and equipped schools, and more and better opportunities for study. Now at the end of the government that implemented the reform, it is appropriate to examine the balances left by this policy in terms of management and labor development for public education teachers. Policy formulations for innovation and change in education and teacher’s work in Mexico are part of the international logic that has generated a new definition of the relations between schools and society. These policies not only imply the existence of new legal frameworks and guidelines for action, but they also institute a political and ideological program that established a new orientation, new objectives, and new will in society. New regulations on the management and practice of public teaching link politics, culture, economy and the state through guidelines that cover the areas of everyday education. The actions of individuals immersed in management, administrative, academic and content organization tasks reconfigure the meaning of teaching based on rationalist effectiveness and efficiency

Políticas para la Gestión de la Educación Pública Obligatoria en Uruguay

El presente trabajo tiene como propósito analizar la gestión de las políticas educativas públicas de Uruguay, tomando como marco temporal de referencia, dos hitos identificados como relevantes: (i) el período 1995-2004 que denominaremos “Reforma Rama” y (ii) el período 2005-2018, que llamaremos “Administración FA”. Para abordar y analizar ambos períodos hemos utilizado el modelo de Subirats et al (2012), el cual define una serie de momentos en los ciclos de las políticas públicas - que en este caso - asociaremos a las educativas. Desde esta perspectiva, las políticas públicas son consideradas un “flujo continuo de decisiones y procedimientos a los que se trata de darle sentido” (Subirats et al., 2012, p. 33). Esta perspectiva permite establecer algunos parámetros comunes desde los cuales analizar dos momentos históricos diferentes. Identificar los temas jerarquizados como “relevantes” o “problemáticos” que requieren solución; situar el lugar que estos temas tomaron en la agenda pública nacional; analizar la formulación y gestión de programas que surgieron, e identificar las propuestas de evaluación que fueron definidas e implementadas para realizar su seguimiento y evaluar su impacto. El modelo de análisis utilizado ha permitido abordar temas sustanciales de la agenda educativa dentro de la franja obligatoria. Todos los componentes innovadores analizados requirieron para su puesta en marcha del diseño de las políticas públicas, la revisión de las normativas vigentes y el fortalecimiento de la gestión para su implementación. El estudio ha permitido identificar los procesos de articulación o disrupción que se generaron entre ambos ciclos, como forma de analizar las capacidades locales para producir sinergias entre los diferentes procesos innovadores puestos en marcha durante las últimas décadas. The purpose of this paper is to analyze the management of public education policies in Uruguay, taking as a reference time frame, two relevant milestones: (i) the period 1995-2004, which we will call “Rama Reform, ” and (ii) the period 2005-2018, which we will call “FA Administration”. To analyze both periods we have used a model developed by Joan Subirats, which defines a series of moments in the public policy cycles, which in this case, we will associate with the educational ones. From this perspective, public policies are considered a “continuous flow of decisions and procedures that are intended to make sense” (Subirats et al., 2012, p. 33). This perspective allows us to establish some common parameters from which to analyze two different historical moments: identify the hierarchical issues as “relevant” or “problematic” that require solution; place the place that these issues took on the national public agenda; analyze the formulation and management of programs that emerged, and identify the evaluation proposals that were defined and implemented to monitor and evaluate their impact. This model addressed substantial issues on the educational agenda within the mandatory range. For their implementation, all the analyzed innovative components required the revision of current regulations and the strengthening of management. This study identifies articulation and disruption processes that were generated between both cycles, as a way of analyzing local capacities to produce synergies between the different innovative processes implemented during the last decades

MS disease activity in RESTORE: a randomized 24-week natalizumab treatment interruption study

Objective: RESTORE was a randomized, partially placebo-controlled exploratory study evaluating multiple sclerosis (MS) disease activity during a 24-week interruption of natalizumab. Methods: eligible patients were relapse-free through the prior year on natalizumab and had no gadolinium-enhancing lesions on screening brain MRI. Patients were randomized 1:1:2 to continue natalizumab, to switch to placebo, or to receive alternative immunomodulatory therapy (other therapies: IM interferon β-1a [IM IFN-β-1a], glatiramer acetate [GA], or methylprednisolone [MP]). During the 24-week randomized treatment period, patients underwent clinical and MRI assessments every 4 weeks. Results: patients (n = 175) were randomized to natalizumab (n = 45), placebo (n = 42), or other therapies (n = 88: IM IFN-β-1a, n = 17; GA, n = 17; MP, n = 54). Of 167 patients evaluable for efficacy, 49 (29%) had MRI disease activity recurrence: 0/45 (0%) natalizumab, 19/41 (46%) placebo, 1/14 (7%) IM IFN-β-1a, 8/15 (53%) GA, and 21/52 (40%) MP. Relapse occurred in 4% of natalizumab patients and in 15%-29% of patients in the other treatment arms. MRI disease activity recurred starting at 12 weeks (n = 3 at week 12) while relapses were reported as early as 4-8 weeks (n = 2 in weeks 4-8) after the last natalizumab dose. Overall, 50/167 patients (30%), all in placebo or other-therapies groups, restarted natalizumab early because of disease activity. Conclusions: MRI and clinical disease activity recurred in some patients during natalizumab interruption, despite use of other therapies. Classification of evidence: this study provides Class II evidence that for patients with MS taking natalizumab who are relapse-free for 1 year, stopping natalizumab increases the risk of MS relapse or MRI disease activity as compared with continuing natalizumab

Academic success in schools in the Algarve: when leadership is part of the solution and not of the problem

This paper presents the results of a case study conducted among school principals in the southern region of Portugal, located in urban, suburban and rural settings. The five cases that comprise this study were subjected to a final rating of “Very Good” in the external evaluation process of schools, whose data were collected through semi-structured interviews and documentary analysis (regulations and educational project, reports of the external evaluation of responsibility of Inspeção Geral de Educação e Ciência de Portugal). The data collected in this exploratory study were systematized and analyzed according to the following indicators: the students’ academic success, the teachers’ professional development, the organizational development and the identifying features of schools principals. Overall, we cannot affirm the existence of differences according to geographical area, although some particularities which proved to be interesting and indicative of good leadership practices could be highlighted.info:eu-repo/semantics/publishedVersio