[XVI Post-ECTRIMS Meeting: review of the new developments presented at the 2023 ECTRIMS Congress (I)]. / XVI Reunión Post-ECTRIMS: revisión de las novedades presentadas en el Congreso ECTRIMS 2023 (I).

The XVI Post-ECTRIMS meeting took place in Seville on 20 and 21 October 2023. This meeting was attended by neurologists specialising in multiple sclerosis (MS) from Spain, who shared a summary of the most interesting innovations at the ECTRIMS congress, which had taken place in Milan the previous week. The aim of this article is to summarise new developments related to the pathogenesis, diagnosis and prognosis of MS. The contributions of innate immunity and central nervous system resident cells, including macrophages and microglia in MS pathophysiology and as therapeutic targets were discussed. Compartmentalised intrathecal inflammation was recognised as central to understanding the progression of MS, and the relationship between inflammatory infiltrates and disease progression was highlighted. Perspectives in demyelinating pathologies were reviewed, focusing on neuromyelitis optica and myelin oligodendrocyte glycoprotein antibody-associated disease, highlighting their pathophysiological and diagnostic differences compared to MS. Advances in neuroimaging were also discussed, and especially the analysis of active chronic lesions, such as paramagnetic rim lesions. In the absence of clinical improvements in trials of remyelinating treatments, methodological strategies to optimise the design of future studies were proposed. Breakthroughs in detecting the prodromal phase of MS, the use of biomarkers in body fluids to assess activity, progression and treatment response, and research on progression independent of flares were addressed. The need to define criteria for radiologically isolated syndrome and to clarify the concept was also discussed.

TITLE: XVI Reunión Post-ECTRIMS: revisión de las novedades presentadas en el Congreso ECTRIMS 2023 (I).La XVI edición de la reunión Post-ECTRIMS se celebró los días 20 y 21 de octubre de 2023 en Sevilla. Este encuentro reunió a neurólogos especialistas en esclerosis múltiple (EM) de España, quienes compartieron un resumen de las innovaciones más destacables del congreso ECTRIMS, acontecido en Milán la semana anterior. El objetivo de este artículo es sintetizar las novedades relativas a la patogenia, el diagnóstico y el pronóstico de la EM. Se destacaron las contribuciones de la inmunidad innata y las células residentes del sistema nervioso central, incluyendo macrófagos y microglía, en la patofisiología de la EM y como objetivos terapéuticos. La inflamación intratecal compartimentada se reconoció como fundamental para entender la progresión de la EM, y destaca la relación entre infiltrados inflamatorios y la evolución de la enfermedad. Se revisaron perspectivas en patologías desmielinizantes, enfocadas en la neuromielitis óptica y la enfermedad asociada a anticuerpos contra la glucoproteína de mielina de oligodendrocitos, subrayando sus distinciones patofisiológicas y diagnósticas con la EM. También se abordaron los avances en neuroimagen, especialmente en el análisis de las lesiones crónicas activas, como las lesiones con borde paramagnético. Ante la ausencia de mejoras clínicas en ensayos de tratamientos remielinizantes, se propusieron estrategias metodológicas para optimizar el diseño de futuros estudios. Se abordaron los avances en la detección de la fase prodrómica de la EM, el uso de biomarcadores en fluidos corporales para evaluar la actividad, la progresión y la respuesta al tratamiento, y la investigación sobre la progresión independiente de la actividad de brote. Además, se debatió sobre la necesidad de definir criterios para el síndrome radiológico aislado o precisar su concepto.

Chitosan for the treatment of inflammation of the oral mucosa: A systematic review.

BACKGROUND: Chitosan is a cheap, accessible, nontoxic, biocompatible, and biodegradable compound. Also, this polysaccharide possesses antibacterial and anti-inflammatory properties. Consequently, a wide range of chitosan applications in the dentistry field has been explored. This work aimed to conduct a systematic review to address the clinical efficacy of chitosan for the treatment of oral mucositis. MATERIAL AND METHODS: The design of the included studies were observational studies, randomized clinical trials (RCT), and non-randomized clinical trials (non-RCT), whereas, a series of cases, in vivo, and in vitro studies were excluded. The search was performed in PubMed, Web of Science, Scopus, Dentistry and Oral Sciences Source, and ClinicalTrials. Gray literature was searched at Google Scholar. Relevant data from all included studies were recorded. The risk of bias (using RoB 2) and the quality (using Grading of Recommendations Assessment, Development, and Evaluation, GRADE) assessments were carried out. RESULTS: From the 8413 records screened, 5 clinical trials fully met the eligibility criteria, which comprised a total of 192 participants suffering oral lesions and pain related to oral mucositis. 100% of the included studies exhibited a high risk of bias. The quality of the studies was between low and very low. CONCLUSIONS: The results of the included studies suggest that chitosan can diminish pain and improve the healing of ulcers in oral mucositis. However, there is no conclusive evidence of chitosan as a superior treatment for oral mucositis compared with other current therapies.

[15th Post-ECTRIMS Meeting: a review of the latest developments presented at the 2022 ECTRIMS Congress (Part II)]. / XV Reunión Post-ECTRIMS: revisión de las novedades presentadas en el Congreso ECTRIMS 2022 (II).

INTRODUCTION: On 4 and 5 November 2022, Madrid hosted the 15th edition of the Post-ECTRIMS Meeting, where neurologists specialised in multiple sclerosis outlined the latest developments presented at the 2022 ECTRIMS Congress, held in Amsterdam from 26 to 28 October. AIM: To synthesise the content presented at the 15th edition of the Post-ECTRIMS Meeting, in an article broken down into two parts. DEVELOPMENT: This second part describes the new developments in terms of therapeutic strategies for escalation and de-escalation of disease-modifying therapies (DMT), when and in whom to initiate or switch to highly effective DMT, the definition of therapeutic failure, the possibility of treating radiologically isolated syndrome and the future of personalised treatment and precision medicine. It also considers the efficacy and safety of autologous haematopoietic stem cell transplantation, different approaches in clinical trial design and outcome measures to assess DMT in progressive stages, challenges in the diagnosis and treatment of cognitive impairment, and treatment in special situations (pregnancy, comorbidity and the elderly). In addition, results from some of the latest studies with oral cladribine and evobrutinib presented at ECTRIMS 2022 are shown.

TITLE: XV Reunión Post-ECTRIMS: revisión de las novedades presentadas en el Congreso ECTRIMS 2022 (II).Introducción. El 4 y el 5 de noviembre se celebró en Madrid la Reunión Post-ECTRIMS, en la que neurólogos expertos en esclerosis múltiple resumieron las principales novedades presentadas en el congreso de ECTRIMS 2022, celebrado entre el 26 y el 28 de octubre en Ámsterdam. Objetivo. Sintetizar las ponencias que tuvieron lugar en la Reunión Post-ECTRIMS, en un artículo desglosado en dos partes. Desarrollo. En esta segunda parte, se presentan las novedades sobre las estrategias terapéuticas de escalado y desescalado de los tratamientos modificadores de la enfermedad (TME), cuándo y a quién iniciar o cambiar a TME de alta eficacia, la definición de fracaso terapéutico, la posibilidad de tratar el síndrome radiológico asilado, el futuro del tratamiento personalizado y la medicina de precisión, la eficacia y seguridad del autotrasplante de células madre hematopoyéticas, diferentes aproximaciones en el diseño de ensayos clínicos y en las medidas de resultados para evaluar TME en fases progresivas, retos en el diagnóstico y tratamiento del deterioro cognitivo, y tratamiento en situaciones especiales (embarazo, comorbilidad y personas mayores). Además, se muestran los resultados de algunos de los últimos estudios realizados con cladribina oral y evobrutinib presentados en el ECTRIMS 2022.

[15th Post-ECTRIMS Meeting: a review of the latest developments presented at the 2022 ECTRIMS Congress (Part I)]. / XV Reunión Post-ECTRIMS: revisión de las novedades presentadas en el Congreso ECTRIMS 2022 (I).

INTRODUCTION: On 4 and 5 November 2022, Madrid hosted the 15th edition of the Post-ECTRIMS Meeting, where neurologists specialised in multiple sclerosis (MS) outlined the most relevant novelties presented at the 2022 ECTRIMS Congress, held in Amsterdam from 26 to 28 October. AIM: To synthesise the content presented at the 15th edition of the Post-ECTRIMS Meeting, in an article broken down into two parts. DEVELOPMENT: In this first part, the initial events involved in the onset of MS, the role played by lymphocytes and the migration of immune system cells into the central nervous system are presented. It describes emerging biomarkers in body fluids and imaging findings that are predictive of disease progression and useful in the differential diagnosis of MS. It also discusses advances in imaging techniques which, together with a better understanding of the agents involved in demyelination and remyelination processes, provide a basis for dealing with remyelination in the clinical setting. Finally, the mechanisms triggering the inflammatory reaction and neurodegeneration involved in MS pathology are reviewed.

TITLE: XV Reunión Post-ECTRIMS: revisión de las novedades presentadas en el Congreso ECTRIMS 2022 (I).Introducción. El 4 y el 5 de noviembre se celebró en Madrid la XV edición de la Reunión Post-ECTRIMS, donde neurólogos expertos en esclerosis múltiple (EM) resumieron las principales novedades presentadas en el congreso de ECTRIMS 2022, celebrado en Ámsterdam entre el 26 y el 28 de octubre. Objetivo. Sintetizar las ponencias que tuvieron lugar en la Reunión Post-ECTRIMS, en un artículo desglosado en dos partes. Desarrollo. En esta primera parte se presentan los primeros eventos involucrados en el inicio de la EM, la implicación de los linfocitos y la migración de células del sistema inmunitario hacia el sistema nervioso central. Se describen los biomarcadores emergentes en fluidos corporales y los hallazgos de imagen que permiten predecir la evolución de la enfermedad, y que resultan útiles en el diagnóstico diferencial de la EM. También se exponen los avances en las técnicas de imagen que, junto con un mayor conocimiento de los agentes involucrados en los procesos de desmielinización y remielinización, proporcionan una base para abordar la remielinización en el entorno clínico. Por último, se repasan los mecanismos desencadenantes de la reacción inflamatoria y la neurodegeneración implicados en la patología de la EM.

A symmetric version of the Euler equations by using Generalized Bernoulli Method.

The aim of this article is to show a way to extend the usefulness of the Generalized Bernoulli Method (GBM) with the purpose to apply it for the case of variational problems with functionals that depend explicitly of all the variables. Moreover, after expressing the Euler equations in terms of this extension of GBM, we will see that the resulting equations acquire a symmetric form, which is not shared by the known Euler equations. We will see that this symmetry is useful because it allows us to recall these equations with ease. The presentation of three examples shows that by applying GBM, the Euler equations are obtained just as well as it does the known Euler formalism but with much less effort, which makes GBM ideal for practical applications. In fact, given a variational problem, GBM establishes the corresponding Euler equations by means of a systematic procedure, which is easy to recall, based in both elementary calculus and algebra without having to memorize the known formulas. Finally, in order to extend the practical applications of the proposed method, this work will employ GBM with the purpose to apply it for the case of solving isoperimetric problems.

Edad retiniana como biomarcador predictivo del grado de retinopatía diabética / Retinal age as a predictive biomarker of the diabetic retinopathy grade

Objetivo Aplicar técnicas de inteligencia artificial, mediante algoritmos de aprendizaje profundo, para el desarrollo y optimización de un sistema de predicción de la edad de una persona con base en una retinografía color, y estudiar una posible relación entre la evolución de la retinopatía diabética (RD) y un envejecimiento prematuro de la retina. Métodos Se entrenó una red convolucional para calcular la edad de una persona con base en una retinografía. Dicho entrenamiento fue realizado sobre un conjunto de retinografías de pacientes con diabetes previamente dividido en 3 subconjuntos (entrenamiento, validación y test). La diferencia entre la edad cronológica del paciente y la edad biológica de la retina se definió como gap de edad retiniano. Resultados Se utilizó un conjunto de 98.400 imágenes para la fase de entrenamiento, 1.000 imágenes para la fase de validación y 13.544 para la fase de test. El gap retiniano de los pacientes sin RD fue de 0,609 años y el de los pacientes con RD de 1,905 años (p<0,001), siendo la distribución por grado de RD de: RD leve 1,541 años; RD moderada 3,017 años; RD severa 3,117 años, y RD proliferativa 8,583 años. Conclusiones El gap de edad retiniano muestra una diferencia en positivo de media entre las personas diabéticas con RD frente a las que no tienen RD, y además aumenta progresivamente, de acuerdo con el grado de RD. Estos resultados podrían indicar la existencia de una relación entre la evolución de la enfermedad y un envejecimiento prematuro de la retina (AU)

Objective To apply artificial intelligence techniques, through deep learning algorithms, for the development and optimization of a system for predicting the age of a person based on a color retinography, and to study a possible relationship between the evolution of retinopathy diabetes (RD) and premature aging of the retina. Methods A convolutional network was trained to calculate the age of a person based on a retinography. Said training was carried out on a set of retinographies of patients with diabetes previously divided into 3 subsets (training, validation and test). The difference between the chronological age of the patient and the biological age of the retina was defined as the retinal age gap. Results A set of 98,400 images was used for the training phase, 1000 images for the validation phase and 13,544 for the test phase. The retinal gap of the patients without RD was 0.609 years and that of the patients with RD was 1905 years (p<0.001), with the distribution by degree of RD being: mild RD 1541 years; moderate RD 3017 years; RD severe 3117 years, and proliferative RD 8583 years. Conclusions The retinal age gap shows a positive mean difference between diabetics with RD versus those without RD, and it increases progressively, according to the degree of RD. These results could indicate the existence of a relationship between the evolution of the disease and premature aging of the retina (AU)

Retinal age as a predictive biomarker of the diabetic retinopathy grade.

OBJECTIVE: To apply artificial intelligence (AI) techniques, through deep learning algorithms, for the development and optimization of a system for predicting the age of a person based on a color retinography and to study a possible relationship between the evolution of retinopathy diabetes and premature ageing of the retina. METHODS: A convolutional network was trained to calculate the age of a person based on a retinography. Said training was carried out on a set of retinographies of patients with diabetes previously divided into three subsets (training, validation and test). The difference between the chronological age of the patient and the biological age of the retina was defined as the retinal age gap. RESULTS: A set of 98,400 images was used for the training phase, 1000 images for the validation phase and 13,544 for the test phase. The retinal gap of the patients without DR was 0.609 years and that of the patients with DR was 1905 years (p < 0.001), with the distribution by degree of DR being: mild DR: 1541 years, moderate DR: 3017 years, DR severe: 3117 years and proliferative DR: 8583 years. CONCLUSIONS: The retinal age gap shows a positive mean difference between diabetics with DR versus those without DR, and it increases progressively, according to the degree of DR. These results could indicate the existence of a relationship between the evolution of the disease and premature ageing of the retina.

A multidisciplinary consensus statement on the optimal pharmacological treatment for metastatic hormone-sensitive prostate cancer.

Androgen deprivation therapy (ADT) is the mainstay treatment for metastatic hormone-sensitive prostate cancer (mHSPC). The addition of docetaxel or new hormone therapies (abiraterone, apalutamide, or enzalutamide) improves overall survival and is currently the standard of care. However, the decision on the specific regimen to accompany ADT should be discussed with the patient, considering factors such as possible associated toxicities, duration of treatment, comorbidities, patient preferences, as there is no sufficient evidence to recommend one regimen over the other in most cases. This paper summarizes the evidence on the management of mHSPC and provides consensus recommendations on the optimal treatment in combination with ADT in mHSPC patients, with special attention to the patient's clinical profile.

Análisis e implementación de un modelo asistencial basado en la integración de un farmacéutico de hospital en un Servicio de Hematología y Hemoterapia / Analysis and implementation of a healthcare model based on the integration of a hospital pharmacist in a Hematology and Hemotherapy Service

Objetivo: Analizar el impacto sanitario y económico, así como evaluar la actividad clínica y asistencial, que supone la integración de un farmacéutico de hospital en un Servicio de Hematología y Hemoterapia. Material y métodos: Se trata de un estudio observacional prospectivo, unicéntrico, realizado en un hospital de tercer nivel desde enero de 2014 hasta febrero de 2019, diseñado para definir las funciones y las actividades clínicas a realizar por un farmacéutico de hospital integrado en un Servicio de Hematología de un hospital de tercer nivel y medir los resultados que se obtienen mediante la adopción de este nuevo modelo asistencial integrado Hematología-Farmacia, basado en la multidisciplinariedad. Resultados: El farmacéutico se integró totalmente en la actividad clínica diaria del equipo multidisciplinar perteneciente al Servicio de Hematología y Hemoterapia, siendo un facilitador del trabajo diario de los profesionales del Servicio de Hematología y un mediador de las necesidades de ambos servicios implicados (Hematología y Farmacia). Esta integración permitió garantizar la seguridad en la administración de tratamientos hematológicos en 9.125 pacientes hematológicos, reducir los errores de medicación en un 95%, detectar y notificar 45 reacciones adversas a medicamentos, diseñar medidas de eficiencia y seguimiento de las mismas en patologías de elevado impacto económico como mieloma múltiple, leucemia linfática crónica, leucemia mieloide crónica y hemofilia, consiguiendo un ahorro de 1.500.000 euros, entre otros resultados. Conclusiones: La integración de un farmacéutico de hospital en un Servicio de Hematología constituye una medida de innovación y eficiencia, mejora la calidad asistencial, garantiza la seguridad, favorece la sostenibilidad del sistema sanitario y facilita la incorporación de innovación. (AU)

Objective: To analyze the health and economic impact and to evaluate the clinical and care activity of the integration of a hospital pharmacist in a Hematology and Hemotherapy Service. Material and methods: This is a prospective, single-centre, observational study conducted in a tertiary hospital from January 2014 to February 2019, designed to define the functions and clinical activities to be performed by a hospital pharmacist integrated into a Hematology and Hemotherapy Service of a tertiary hospital and to measure the results obtained by adopting this new integrated Hematology-Pharmacy care model, based on multidisciplinarity. Results: The pharmacist was fully integrated into the daily clinical activity of the multidisciplinary team belonging to the Hematology and Hemotherapy Service, being a facilitator of the daily work of the professionals of the Hematology Service and a mediator of the needs of both services involved (Hematology and Pharmacy). This integration made it possible to guarantee safety in the administration of hematological treatments in 9,125 hematological patients, to reduce medication errors by 95%, to detect and notify 45 adverse drug reactions, to design efficiency measures and follow-up of these in pathologies with a high economic impact such as multiple myeloma, chronic lymphatic leukemia, chronic myeloid leukemia and hemophilia, achieving savings of 1,500,000 euros, among other results. Conclusions: The integration of a hospital pharmacist in a Hematology and Hemotherapy Service constitutes a measure of innovation and efficiency, improves the quality of care, guarantees safety, favours the sustainability of the health system and facilitates the incorporation of innovation. (AU)

Valores de normalidad de sensibilidad retiniana y fijación foveal mediante microperimetría fotópica y escotópica en población sana / Fotopic and scotopic retinal sensitivity and foveal fixation normal values using microperimetry in healthy population

Objetivo Analizar los valores de sensibilidad retiniana y fijación foveal, en población sana, en condiciones fotópicas y escotópicas usando el microperímetro MP3-S (Nidek, Gamagori, Japón). Métodos Estudio observacional, transversal, unicéntrico. Se realizó una microperimetría (MP) fotópica y escotópica con una rejilla de estímulos personalizada de 13 puntos centrada en fóvea de 4,5×4,5mm en voluntarios sanos, sin enfermedad ocular. Se utilizó el ICC para evaluar la fiabilidad de la MP fotópica y escotópica. Resultados Se evaluaron 102 ojos de 54 voluntarios sanos (edad media: 49,8±15 años). La sensibilidad retiniana media (SRM) en la prueba fotópica y escotópica fue de 28,87±3,3 y 15,72±1,9dB, respectivamente. No se hallaron diferencias al comparar la SRM por grupo de sexos. Sin embargo, al analizar la SRM por grupos de edad se encontraron diferencias estadísticamente significativas en ambas modalidades de la prueba, siendo mayor la SRM en el grupo de sujetos menores de 35 años, con 30,3±1,7dB en la fotópica y 16,3±1,3dB en la escotópica, y menor en el grupo de mayores de 65 años, con 26,7±2,2dB en la fotópica y 13,8±1,8dB en la escotópica, con p=0,0001. En el análisis de fiabilidad, el coeficiente alfa de Cronbach reveló una excelente fiabilidad de la MP fotópica (0,958) y una buena fiabilidad de la MP escotópica (0,841). Conclusión La MP es un test con buena fiabilidad tanto en condiciones fotópicas como escotópicas. La SRM en condiciones fotópicas y escotópicas no difiere según el sexo, pero sí disminuye con la edad. Existe una correlación positiva entre la SRM fotópica y la escotópica (AU)

Purpose To determine normal values of fotopic and scotopic retinal sensitivity and foveal fixation obtained by microperimetry, using MP3-S microperimeter (Nidek, Gamagori, Japan), in a healthy population. Methods Observational, cros-sectional, single centre study. Fotopic and scotopic microperimetry (MP) was performed using with a customized 13-point fovea-centered pattern in healthy volunteers without ocular pathology. A intraclass correlation coefficient was performed to evaluate fotopic and scotopic MP reliability. Results We analyzed 102 eyes of 54 healthy volunteers (mean age 49.8±15 years old). The fotopic and scotopic mean retinal sensitivity (MRS) was 28.87±3.3dB and 15.72±1.9dB (95% CI 15.35-16.09), respectively, showing a significant statistical difference (P<.05). No differences were found when comparing MRS by gender group. However, when analyzing the MRS by age groups, statistically significant differences were found in both modalities of the test, MRS being higher in the group of subjects under 35 years of age, with 30.3±1.7dB in the photopic and 16.3±1.3dB in the scotopic, and lower in the group of older than 65 years, with 26.7±2.2dB in the photopic and 13.8±1.8dB in the scotopic, with P=.0001. The reliability analysis of both tests revealed an excellent reliability of the fotopic MP with a Cronbach alpha of 0.958 and a good reliability of 0.841 in scotopic MP. Conclusion MP is a test with good reliability both under photopic and scotopic conditons. MRS and fixation stability under photopic and scotopic conditions do not differ according to sex, but it does decrease with age. There is a positive correlation between photopic and scotopic MRS (AU)

Mutational spectrum of the iduronate-2-sulfatase gene in Mexican patients with Hunter syndrome.

OBJECTIVE: Hunter syndrome, or mucopolysaccharidosis type II (MPS II), is caused by deficiency of the lysosomal enzyme iduronate-2-sulfatase (IDS), which is responsible for degrading heparan and dermatan sulfate. The IDS gene is located on chromosome Xq28; pathological variants in this gene mostly consist of missense mutations and small and larger deletions, which produce different phenotypes. However, there is only one record in our population concerning the molecular mechanism of this disease; a genotype-phenotype description is not available. PATIENTS AND METHODS: There were included 24 unrelated male patients; clinical features were recorded at a database, fluorometric IDS enzyme activity testing was done for each individual, followed by Sanger sequencing to identify mutations. RESULTS: The mutational spectrum was found in 16 out of 24 Mexican patients with MPS II, and its range of phenotypes was described. The most frequent variants were of the missense type. The most affected exons were exon 3 (c.275T>G, c.284_287del, c.325T>C), exon 8 (c.1035G>C, c.550G>A), exon 9 (c.1403G>C, c.1229_1229del), and exon 7 (c.979A>C; this variant has not been previously reported). Exon 5 (c.438C>T, a non-pathogenic variant) was the least frequent. It was also found that the most severely affected patients were those with large deletions (2 out of 24) [rsaIDS: IDSP1 (P164)x0, FMR1, AFF2 (P164)x2] involving genes and pseudogenes. We found 2 patients with a synonymous mutation in exon 4. CONCLUSIONS: Our results confirmed reports in the literature, since the most frequent variants were reported in exons 3 and 8. However, this result varies from one previous report in our population, which mentions large deletions and rearrangements as the most frequent alterations, since complex rearrangements were not found. According to what has been previously found, the most severely affected patients are those in which a whole gene has been deleted.

Fotopic and scotopic retinal sensitivity and foveal fixation normal values using microperimetry in healthy population.

PURPOSE: To determine normal values of fotopic and scotopic retinal sensitivity and foveal fixation obtained by microperimetry, using MP3-S microperimeter (Nidek, Gamagori, Japan), in a healthy population. METHODS: Observational, crossectional, single centre study. Fotopic and scotopic microperimetry was performed using with a customized 13-point fovea-centered pattern in healthy volunteers without ocular pathology. A intraclass correlation coefficient (ICC) was performed to evaluate fotopic and scotopic microperimetry reliability. RESULTS: We analyzed 102 eyes of 54 patients with a mean age of 49.8 +/- 15 years old. The fotopic and scotopic mean retinal sensitivity (MRS) was 28.55±3.3dB (95% CI=[27.87-29.23]) and 15.72±1.9dB (95% CI=[15.35-16.09]) respectively, showing a significant statistical difference (p<0.05). No differences were found when comparing SRM by gender group. However, when analyzing the SRM by age groups, statistically significant differences were found in both modalities of the test; SRM being higher in the group of subjects under 35 years of age with 30.3±1.7dB in the photopic and 16.3±1.3dB in the scotopic; and lower in the group of older than 65 years with 26.7±2.2dB in the photopic and 13.8±1.8dB in the scotopic with p=0.0001. The reliability analysis of both tests, revealed an excellent reliability of the fotopic microperimetry with a Crombach alpha of 0.958 and a good reliability of 0.841 in scotopic microperimetry. CONCLUSIONS: Microperimetry is a test with good reliability both under photopic and scotopic conditions. SRM and fixation stability under photopic and scotopic conditions do not differ according to sex, but it does decrease with age. There is a positive correlation between photopic and scotopic SRM.

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

OBJECTIVE: 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.