Incidence and prevalence of multiple sclerosis in Spain: a systematic review.

INTRODUCTION: Greater understanding of the prevalence and incidence of multiple sclerosis in Spain and their temporal trends is necessary to improve the allocation of healthcare resources and to study aetiological factors. METHODS: We performed a systematic search of the MedLine database and reviewed the reference lists of the articles gathered. We collected studies reporting prevalence or incidence rates of multiple sclerosis in any geographical location in Spain, with no time limits. In 70% of cases, data were extracted by 2 researchers (FGL and EAC); any discrepancies were resolved by consensus. RESULTS: We identified 51 prevalence and 33 incidence studies published between 1968 and 2018. In the adjusted analysis, the number of prevalent cases per 100 000 population increased by 26.6 (95% confidence interval [CI], 21.5-31.8) every 10 years. After adjusting for year and latitude, the number of incident cases per 100 000 population increased by 1.34 (95% CI, 0.98-1.69) every 10 years. We observed a trend toward higher prevalence and incidence rates at higher latitudes. CONCLUSIONS: The prevalence of multiple sclerosis in Spain has increased in recent decades, although case ascertainment appears to be incomplete in many studies. Incidence rates have also increased, but this may be due to recent improvements in the detection of new cases.

Consensus statement on the use of alemtuzumab in daily clinical practice in Spain.

INTRODUCTION: Alemtuzumab is a highly effective drug approved by the European Medicines Agency as a disease-modifying drug for the treatment of relapsing-remitting multiple sclerosis. OBJECTIVE: A consensus document was drafted on the management of alemtuzumab in routine clinical practice in Spain. DEVELOPMENT: A group of multiple sclerosis specialists reviewed articles addressing treatment with alemtuzumab in patients with multiple sclerosis and published before December 2017. The included studies assessed the drug's efficacy, effectiveness, and safety; screening for infections and vaccination; and administration and monitoring aspects. The initial proposed recommendations were developed by a coordinating group and based on the available evidence and their clinical experience. The consensus process was carried out in 2 stages, with the initial threshold percentage for group agreement established at 80%. The final document with all the recommendations agreed by the working group was submitted for external review and the comments received were considered by the coordinating group. CONCLUSION: The present document is intended to be used as a tool for optimising the management of alemtuzumab in routine clinical practice.

Planes de atención a niños y adolescentes con asma en España, un análisis por comunidades autónomas / Care plans for children and adolescents with asthma in Spain, an analysis by autonomous communities

Introducción y objetivo: describir cómo realizan los pediatras de Atención Primaria (PAP) el manejo de los niños y adolescentes con asma en España. Material y métodos: estudio transversal, observacional y descriptivo para conocer los planes/guías de atención al asma en edad pediátrica por comunidades autónomas (CC. AA.), y ciudades autónomas de Ceuta y Melilla, la inclusión de esta actividad en sus carteras de servicios (CS) y cómo se registra en la historia clínica informatizada del paciente, mediante encuesta telemática a las asociaciones autonómicas de PAP, y telefónica para Ceuta y Melilla. En los planes encontrados, se evaluó la presencia de criterios diagnósticos, tratamiento y seguimiento del asma, recursos disponibles e indicadores de calidad asistencial, de acuerdo con un protocolo definido y adaptado a las recomendaciones de las guías de práctica clínica, y el grado de variabilidad de los mismos. Resultados: el 50% de las CC. AA. españolas tienen planes para el manejo de niños y adolescentes con asma, en diez se incluye esta actividad en su CS y 11 disponen de módulo de registro informático específico. De los nueve documentos encontrados, tres son planes y seis guías. Los primeros obtienen mayor puntuación global al aplicar el protocolo. De los parámetros estudiados, solo tener documento escrito y clasificar la gravedad del asma al diagnóstico figuran en todos los planes. Conclusiones: en España hay una gran variabilidad en la atención al asma en Pediatría y no todas las CC. AA. tienen implementados planes de trabajo, ni registro informatizado de esta actividad. Para garantizar la equidad en el manejo de estos pacientes convendría que todas las regiones implantasen un plan integral de atención actualizado (AU)

Introduction and objective: to describe the management of children and adolescents with asthma by primary care paediatricians (PCPs) in Spain.Materials and methods: we conducted a cross-sectional descriptive study to assess the paediatric asthma care plans/guidelines of the autonomous communities (ACs) of Spain and Ceuta and Melilla, the inclusion of an asthma care pathway in the list of services covered by regional health systems and the documentation of asthma care in health records. The study was performed through an online survey of regional primary care paediatrics associations and by telephone for the autonomous cities of Ceuta and Melilla. We evaluated the identified documents using a reference protocol that we developed based on current clinical practice guidelines and included items pertaining to asthma diagnosis, treatment, and monitoring, available resources and care quality indicators, and assessed the differences in these documents.Results: We found that 50% of ACs in Spain have care plans/guidelines for the management of asthma in children and adolescents. In 10 ACs, asthma care is included in the official list of health care services, and in 11, the electronic health records included a specific module devoted to asthma. Of the 9 asthma care documents identified in the survey, 3 were care plans and 6 were guidelines. The former achieved higher global scores in the comparison with the reference. Of all parameters under study, the only 2 fulfilled by all the plans/guidelines were the existence of a print asthma management document and the classification of the severity of asthma at diagnosis... (AU)

Consensus statement on the use of alemtuzumab in daily clinical practice in Spain. / Consenso de expertos sobre el uso de alemtuzumab en la práctica clínica diaria en España.

INTRODUCTION: Alemtuzumab is a highly effective drug approved by the European Medicines Agency as a disease-modifying drug for the treatment of relapsing-remitting multiple sclerosis. OBJECTIVE: A consensus document was drafted on the management of alemtuzumab in routine clinical practice in Spain. DEVELOPMENT: A group of multiple sclerosis specialists reviewed articles addressing treatment with alemtuzumab in patients with multiple sclerosis and published before December 2017. The included studies assessed the drug's efficacy, effectiveness, and safety; screening for infections and vaccination; and administration and monitoring aspects. The initial proposed recommendations were developed by a coordinating group and based on the available evidence and their clinical experience. The consensus process was carried out in 2 stages, with the initial threshold percentage for group agreement established at 80%. The final document with all the recommendations agreed by the working group was submitted for external review and the comments received were considered by the coordinating group. CONCLUSION: The present document is intended to be used as a tool for optimising the management of alemtuzumab in routine clinical practice.

Manejo de los efectos adversos de apremilast desde un abordaje multidisciplinar / Multidisciplinary Management of the Adverse Effects of Apremilast

En el presente artículo, en base a una revisión de la literatura y su experiencia personal, un equipo multidisciplinar de 14 profesionales sanitarios (incluyendo dermatólogos, reumatólogos, neurólogos, gastroenterólogos, farmacéuticos y enfermeras) ha elaborado una serie de recomendaciones generales y específicas (basadas en la fisiopatología) para el manejo de los efectos adversos secundarios a apremilast que con mayor frecuencia conducen a la suspensión del tratamiento (diarrea, náuseas y cefalea). Se aportan algoritmos sencillos de manejo que incluyen aspectos clínicos de evaluación y sugerencias de tratamiento farmacológico. Los efectos adversos de apremilast pueden ser abordados desde un punto de vista multidisciplinar y la optimización en su manejo pretende proporcionar un beneficio clínico a los pacientes que los sufren

We present a series of general and specific recommendations based on pathophysiologic considerations for managing the most common adverse effects of apremilast that lead to treatment discontinuation: diarrhea, nausea, and headache. The recommendations are based on a review of the literature and the experience of a multidisciplinary team of 14 experts including dermatologists, rheumatologists, neurologists, gastroenterologists, pharmacists, and nurses. We propose a series of simple algorithms that include clinical actions and suggestions for pharmacologic treatment. The adverse effects of apremilast can be managed from a multidisciplinary approach. The purpose of optimizing management is to bring clinical benefits to patients

Multidisciplinary Management of the Adverse Effects of Apremilast. / Manejo de los efectos adversos de apremilast desde un abordaje multidisciplinar.

We present a series of general and specific recommendations based on pathophysiologic considerations for managing the most common adverse effects of apremilast that lead to treatment discontinuation: diarrhea, nausea, and headache. The recommendations are based on a review of the literature and the experience of a multidisciplinary team of 14 experts including dermatologists, rheumatologists, neurologists, gastroenterologists, pharmacists, and nurses. We propose a series of simple algorithms that include clinical actions and suggestions for pharmacologic treatment. The adverse effects of apremilast can be managed from a multidisciplinary approach. The purpose of optimizing management is to bring clinical benefits to patients.

Consenso para el tratamiento de la esclerosis múltiple 2016. Sociedad Española de Neurología / Consensus statement on the treatment of multiple sclerosis by the Spanish Society of Neurology in 2016

La incorporación de nuevos medicamentos para modificar el curso de la esclerosis múltiple y la complejidad de su uso plantea la conveniencia de utilizar consensos terapéuticos. El consenso actual ha sido elaborado por el grupo de enfermedades desmielinizantes de la Sociedad Española de Neurología y actualiza consensos previamente publicados. Se enumeran los medicamentos aprobados para la esclerosis múltiple con sus indicaciones oficiales. Se analizan aspectos relacionados con el tratamiento, como la presencia de actividad, la precocidad, el mantenimiento terapéutico, el seguimiento, el fallo terapéutico, los cambios de medicación y el tratamiento en situaciones especiales. Se elaboran indicaciones de tratamiento desde el síndrome desmielinizante aislado a las distintas formas de esclerosis múltiple detallando recomendaciones de tratamiento inicial, cambios de medicación, con consideraciones sobre terapia combinada e inducción y aspectos prácticos del uso de medicamentos

With the advent of new disease-modifying drugs, the treatment of multiple sclerosis is becoming increasingly complex. Using consensus statements is therefore advisable. The present consensus statement, which was drawn up by the Spanish Society of Neurology's study group for demyelinating diseases, updates previous consensus statements on the disease. The present study lists the medications currently approved for multiple sclerosis and their official indications, and analyses such treatment-related aspects as activity, early treatment, maintenance, follow-up, treatment failure, changes in medication, and special therapeutic situations. This consensus statement includes treatment recommendations for a wide range of demyelinating diseases, from isolated demyelinating syndromes to the different forms of multiple sclerosis, as well as recommendations for initial therapy and changes in drug medication, and additional comments on induction and combined therapy and practical aspects of the use of these drugs

Consensus statement on the treatment of multiple sclerosis by the Spanish Society of Neurology in 2016. / Consenso para el tratamiento de la esclerosis múltiple 2016. Sociedad Española de Neurología.

With the advent of new disease-modifying drugs, the treatment of multiple sclerosis is becoming increasingly complex. Using consensus statements is therefore advisable. The present consensus statement, which was drawn up by the Spanish Society of Neurology's study group for demyelinating diseases, updates previous consensus statements on the disease. The present study lists the medications currently approved for multiple sclerosis and their official indications, and analyses such treatment-related aspects as activity, early treatment, maintenance, follow-up, treatment failure, changes in medication, and special therapeutic situations. This consensus statement includes treatment recommendations for a wide range of demyelinating diseases, from isolated demyelinating syndromes to the different forms of multiple sclerosis, as well as recommendations for initial therapy and changes in drug medication, and additional comments on induction and combined therapy and practical aspects of the use of these drugs.

Educación en el niño y adolescente con asma (1.ª parte). Terapia inhalada en el asma: ¿cómo elegir el dispositivo y la técnica de inhalación más adecuados para cada niño? / Education in children and adolescents with asthma (part 1). Inhaled therapy in asthma: how to choose the most appropiate device and inhalation technique for each child?

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Quality of life in caregivers of children with asthma: Validity and reliability of the IFABI-R questionnaire

BACKGROUND: Parents'/caregivers' quality of life is an important aspect to consider when handling paediatric asthma, but there is a paucity of valid and reliable instruments to measure it. The Family Impact of Childhood Bronchial Asthma (IFABI-R) is a recently developed questionnaire to facilitate the assessment of asthma-related parents'/caregivers' quality of life. This study researches the psychometric properties of IFABI-R. METHODS: Parents/main caregivers of 462 children between 4 and 14 years of age with active asthma were included in the sample. IFABI-R was administered on two different occasions and a number of other variables related to the parents'/caregivers' quality of life were measured: child's asthma control, family functioning, and parents'/caregivers' perception of asthma symptoms in the child. IFABI-R evaluative and discriminative properties were analysed, and the minimal important change in the IFABI-R score was identified. RESULTS: IFABI-R showed high internal consistency (Cronbach's alpha = 0.941), cross-sectional construct validity (correlation with the degree of child's asthma control, family functioning and parent/caregiver perception of the child's asthma symptoms), longitudinal construct validity (correlation of changes in the IFABI-R with changes in asthma control and changes in the perception of symptoms), sensitivity to change and test-retest reliability. An absolute change of 0.3 units in IFABI-R related to a minimal significant change in the parents'/caregivers' quality of life. CONCLUSIONS: IFABI-R is a reliable and valid instrument to study the quality of life of parents/caregivers of children with asthma

No disponible

Quality of life in caregivers of children with asthma: Validity and reliability of the IFABI-R questionnaire.

BACKGROUND: Parents'/caregivers' quality of life is an important aspect to consider when handling paediatric asthma, but there is a paucity of valid and reliable instruments to measure it. The Family Impact of Childhood Bronchial Asthma (IFABI-R) is a recently developed questionnaire to facilitate the assessment of asthma-related parents'/caregivers' quality of life. This study researches the psychometric properties of IFABI-R. METHODS: Parents/main caregivers of 462 children between 4 and 14 years of age with active asthma were included in the sample. IFABI-R was administered on two different occasions and a number of other variables related to the parents'/caregivers' quality of life were measured: child's asthma control, family functioning, and parents'/caregivers' perception of asthma symptoms in the child. IFABI-R evaluative and discriminative properties were analysed, and the minimal important change in the IFABI-R score was identified. RESULTS: IFABI-R showed high internal consistency (Cronbach's alpha=0.941), cross-sectional construct validity (correlation with the degree of child's asthma control, family functioning and parent/caregiver perception of the child's asthma symptoms), longitudinal construct validity (correlation of changes in the IFABI-R with changes in asthma control and changes in the perception of symptoms), sensitivity to change and test-retest reliability. An absolute change of 0.3 units in IFABI-R related to a minimal significant change in the parents'/caregivers' quality of life. CONCLUSIONS: IFABI-R is a reliable and valid instrument to study the quality of life of parents/caregivers of children with asthma.

Assessment of the reproducibility of oligoclonal IgM band detection for its application in daily clinical practice.

BACKGROUND: The presence of oligoclonal IgM bands (OCMB) in cerebrospinal fluid (CSF) is an unfavourable prognostic marker in multiple sclerosis. There is no commercial test to investigate OCMB status. However, a sensitive and specific isoelectrofocusing (IEF) and western blot method was described. We aimed to study the inter-centre reproducibility of this technique, a necessary condition for a reliable test to be incorporated into clinical practice. METHODS: The presence of OCMB was analysed by IEF and western blot with prior reduction of pentameric IgM. We assayed the reproducibility of this test in a blinded multicentre study performed in 13 university hospitals. Paired-CSF and serum samples from 52 neurological patients were assayed at every centre. RESULTS: Global analysis rendered a concordance of 89.8% with a kappa value of 0.71. CONCLUSION: These data indicate that OCMB detection by means of IEF and western blot with IgM reduction shows a good interlaboratory reproducibility and thus can be used in daily clinical setting.

Regulation of cannabinoid receptor gene expression and endocannabinoid levels in lymphocyte subsets by interferon-ß: a longitudinal study in multiple sclerosis patients.

Evidence suggests the involvement of the cannabinoid system in the pathogenesis of multiple sclerosis (MS). We studied cannabinoid receptor (CB)1 and CB2 receptor gene expression in B, natural killer (NK) and T cells from MS patients before and after 1 year of interferon beta therapy, and compared these levels to those of healthy controls. We also measured the production of the endocannabinoids anandamide (AEA) and 2-arachidonoylglycerol (2-AG) and the gene expression of the endocannabinoid-degrading enzyme fatty acid amide hydrolase (FAAH) in these cells. Prior to interferon therapy, MS patients showed significantly elevated CB2 expression in B cells, but not in T or NK cells. These levels decreased gradually within 6 months to 1 year of interferon treatment. CB1 expression was elevated in all cell subsets, but only reached statistical significance in T cells; all levels decreased progressively over time. Before treatment, AEA but not 2-AG levels were significantly elevated in the three cell populations; after 1 year of treatment, all values decreased to control levels. The expression of FAAH was unchanged. The different expression of cannabinoid receptor genes and the increased level of AEA in lymphocytes point to a possible role of the cannabinoid system in MS immune response and its modulation by interferon.

Documento del Grupo de Consenso de la Sociedad Española de Neurología sobre el uso de medicamentos en esclerosis múltiple / Consensus Statement on medication use in multiple sclerosis by the Spanish Society of Neurology's study group for demyelinating diseases

La terapia de la esclerosis múltiple está en rápida evolución. En un plazo próximo, se prevé la incorporación de nuevos fármacos que pueden modificar las pautas actuales de tratamiento. Mientras tanto, el Grupo de Enfermedades Desmielinizantes de la Sociedad Española de Neurología encargado del consenso sobre la utilización de medicamentos para la EM, ha considerado necesaria una puesta al día de las indicaciones actuales y de los principios de tratamiento de esta enfermedad (AU)

Treatments for multiple sclerosis therapy are rapidly evolving. It is believed that new drugs will be approved in the near future, thereby changing current indications for treatment. In this context, the Spanish Society of Neurology's study group on demyelinating diseases, which evaluates medication use in MS, has decided to draw up a consensus statement on the current indications and guidelines for multiple sclerosis treatment (AU)

Consensus Statement on medication use in multiple sclerosis by the Spanish Society of Neurology's study group for demyelinating diseases.

Treatments for multiple sclerosis therapy are rapidly evolving. It is believed that new drugs will be approved in the near future, thereby changing current indications for treatment. In this context, the Spanish Society of Neurology's study group on demyelinating diseases, which evaluates medication use in MS, has decided to draw up a consensus statement on the current indications and guidelines for multiple sclerosis treatment.

Neuroprotective agents: cannabinoids.

Chronic inflammation and neurodegeneration are the main pathological traits of multiple sclerosis that coexist in all stages of the disease course, with complex and still nonclarified relationships. Currently licensed medications have efficacy to control aspects related to inflammation, but have been unable to modify pure progression. Experimental work has provided robust evidence of the immunomodulatory and neuroprotective properties that cannabinoids exert in animal models of multiple sclerosis. Through activation of the CB2 receptor, cannabinoids modulate peripheral blood lymphocytes, interfere with migration across the blood-brain barrier and control microglial/macrophage activation. CB1 receptors present in neural cells have a fundamental role in direct neuroprotection against several insults, mainly excitotoxicity. In multiple sclerosis, several reports have documented the disturbance of the endocannabinoid system. Considering the actions demonstrated experimentally, cannabinoids might be promising agents to target the main aspects of the human disease.

IL28B polymorphisms are not associated with the response to interferon-ß in multiple sclerosis.

Recent studies have revealed an association between interleukin 28B (IL28B) and response to IFN-alpha treatment in hepatitis C patients. Here we investigated the influence of IL28B polymorphisms in the response to interferon-beta (IFNß) in multiple sclerosis (MS) patients. We genotyped two SNPs of the IL28B gene (rs8099917 and rs12979860) in 588 MS patients classified into responders (n=281) and non-responders (n=307) to IFNß. Combined analysis of the study cohorts showed no significant associations between SNPs rs8099917 and rs12979860 and the response to treatment. These findings do not support a role of IL28B polymorphisms in the response to IFNß in MS patients.

Utility of oligoclonal IgG band detection for MS diagnosis in daily clinical practice.

An early and accurate diagnosis of multiple sclerosis (MS) is very important, since it allows early treatment initiation, which reduces the activity of the disease. Oligoclonal IgG band (OCGB) detection is a good ancillary tool for MS diagnosis. However, it was argued that its usefulness was limited by the high interlaboratory variability. In the last years, different techniques for OCGB detection have appeared. We performed a blinded aleatorized multicenter study in 19 Spanish hospitals to assess the accuracy and reproducibility of OCGB detection in this new scenario. We studied cerebrospinal fluid (CSF) and serum samples from 114 neurological patients. Every hospital contributed to the study with triplicated pairs of CSF and serum samples of six patients and analyzed 18 different samples. Global analysis rendered a sensitivity of 92.1%, a specificity of 95.1% and a Kappa value of 0.81. This shows that current techniques for OCGB detection have good accuracy and a high interlaboratory reproducibility and thus, represent a good tool for MS diagnosis. When we analyzed separately the different techniques used for OCGB detection, the highest concordance was observed in western blot with alkaline phosphatase detection (kappa=0.91). This indicates that high sensitivity techniques improve the reproducibility of this assay.

Anticuerpos monoclonales. Aspectos básicos / Monoclonal antibodies. Basic features

Introducción: Los anticuerpos monoclonales son una poderosa herramienta para el diagnóstico de laboratorio y un instrumento cada vez más utilizado en el tratamiento de diversas enfermedades. Desarrollo: El descubrimiento y caracterización de los anticuerpos tiene una larga historia, que es la de la propia inmunología. En este artículo se hace una introducción histórica sobre la inmunidad humoral hasta el hallazgo de los anticuerpos monoclonales y se revisan conceptos relativos a la estructura y funciones de los anticuerpos, así como a la generación de diversidad, activación y maduración de los linfocitos B. Se mencionan las principales técnicas de producción de anticuerpos monoclonales y se enumeran algunas de sus aplicaciones en patología humana. Conclusiones: Los anticuerpos monoclonales han producido desde su descubrimiento una revolución de gran calado en el diagnóstico y el tratamiento de numerosas enfermedades. La utilización de anticuerpos monoclonales humanizados y humanos ha mejorado notablemente su tolerancia. La tecnología actual de fabricación de estos anticuerpos permite nuevos dise˜nos que pueden ampliar sus posibles aplicaciones en medicina (AU)

Introduction: Monoclonal antibodies are a powerful tool in laboratory diagnosis and are increasingly used in the treatment of several diseases. Development: Antibody development and characterization has a long history and goes back to immunology itself. The present article provides a historical introduction to humoral immunity until the discovery of monoclonal antibodies and reviews concepts relating to the structure and function of antibodies, as well as to the generation of diversity, activation and maturation of B lymphocytes. The main techniques for producing monoclonal antibodies are outlined and some of their applications in human disease are described Conclusions: Since their discovery, monoclonal antibodies have revolutionized the diagnosis and treatment of numerous diseases. The use of human and humanized monoclonal antibodies has markedly improved their tolerability. Current technology for manufacturing these antibodies allows new designs that may broaden their possible applications in medicine(AU)