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This paper seeks to discover whether the performance of university students has improved in the wake of the changes in higher education introduced by the Bologna Declaration of 1999 and the construction of the European Higher Education Area. A principal component analysis is used to construct a multi-dimensional performance variable called the LEArning Society-adapted Outcome Index. A quantile regression is then applied to ensure that the analysis does not focus solely on average figures, and the performance of students of various types is analyzed. Significant improvements are found in the acquisition of systemic and interpersonal skills and in student satisfaction but not in cognitive aspects. There are improvements in students of all types, but they are smaller among the best students.

Este trabajo pretende analizar la relación entre la percepción de las empresas del País Vasco sobre la importancia de la valoración de los intangibles y los resultados que obtienen. Para el logro de este objetivo se ha realizado una encuesta a 440 directores financieros. Del análisis de sus espuestas y de los resultados económico-financieros de sus empresas, se concluye que las empresas que consideran importante la valoración financiera de sus intangibles, especialmente por motivos internos, obtienen mejores resultados aunque las mejoras no son estadísticamente significativas. Asimismo, las empresas más interesadas en la valoración de sus intangibles por motivos externos presentan una mayor necesidad de presentar garantías frente a terceros sobre su capacidad de generar rendimientos.

This paper seeks to discover whether the performance of university students has improved in the wake of the changes in higher education introduced by the Bologna Declaration of 1999 and the construction of the European Higher Education Area. A principal component analysis is used to construct a multi-dimensional performance variable called the LEArning Society-adapted Outcome Index. A quantile regression is then applied to ensure that the analysis does not focus solely on average figures, and the performance of students of various types is analyzed. Significant improvements are found in the acquisition of systemic and interpersonal skills and in student satisfaction but not in cognitive aspects. There are improvements in students of all types, but they are smaller among the best students. [ABSTRACT FROM AUTHOR]

Introduction: Multiple sclerosis (MS) is a chronic disease affecting the central nervous system and is characterised by inflammation, demyelination, gliosis, and axonal damage. The introduction of dimethyl fumarate and teriflunomide has led to an increase in the number of alternative first-line therapies for MS. The objective of this study was to evaluate the economic impact of the incorporation of new oral therapies at the reference unit (CSUR) at Hospital Universitario Puerta de Hierro Majadahonda., Materials and Methods: We performed a retrospective observational study including patients diagnosed with MS, who underwent treatment with disease-modifying drugs in 2015 and were followed up for a minimum mean time of one year. Data were collected from patients' electronic clinical histories and the pharmacy service's programme for dispensing drugs to outpatients., Results: Evaluating the cost of changing 125 patients' treatment from other drugs to dimethyl fumarate and teriflunomide, and comparing this with the cost that would have resulted from maintaining their previous treatment, demonstrated a total saving of €169,107.31 over the study period., Conclusions: In addition to contributing new therapeutic alternatives, dimethyl fumarate and teriflunomide produced an economic saving in MS treatment at our hospital., (Copyright © 2017 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.)

Introduction: Angelman syndrome is a neurodevelopmental disorder of genetic origin, with important clinical motor, behavioural, communicative and electroencephalographic manifestations, with particular relevance as regards the presence of epileptic seizures., Aims: To describe the electroencephalographic characteristics (qualitatively and quantitatively) of patients diagnosed with Angelman syndrome and to determine the electroencephalographic profile according to age and genetic alteration., Patients and Methods: A retrospective observational study in which the demographic, clinical and electroencephalographic characteristics of 51 patients with Angelman syndrome were analysed., Results: A higher delta power was evident in all brain regions, with a maximum peak in the frontopolar and temporal regions, and a lower power in the alpha and beta frequency range in all regions, with a greater preponderance in younger patients, and a trend that decreases with age. The coherence showed a predominance of delta and theta in the frontopolar region, which was higher for all frequencies in the deletion group, where delta was predominant, especially in the frontopolar region., Conclusion: The electroencephalogram could be a useful biomarker as a qualitative and quantitative tool in the investigation of Angelman syndrome and in measuring the response to possible therapies under investigation.

Background: The recent development of highly effective treatments for multiple sclerosis (MS) and the potential risk of infectious complications require the development of prevention and risk minimisation strategies. Vaccination is an essential element of the management of these patients. This consensus statement includes a series of recommendations and practical scenarios for the vaccination of adult patients with MS who are eligible for highly effective immunosuppressive treatments., Methodology: A formal consensus procedure was followed. Having defined the scope of the statement, we conducted a literature search on recommendations for the vaccination of patients with MS and specific vaccination guidelines for immunosuppressed patients receiving biological therapy for other conditions. The modified nominal group technique methodology was used to formulate the recommendations., Development: Vaccination in patients who are candidates for immunosuppressive therapy should be considered before starting immunosuppressive treatment providing the patient's clinical situation allows. Vaccines included in the routine adult vaccination schedule, as well as some specific ones, are recommended depending on the pre-existing immunity status. If immunosuppressive treatment is already established, live attenuated vaccines are contraindicated. For vaccines with a correlate of protection, it is recommended to monitor the serological response in an optimal interval of 1-2 months from the last dose., (Copyright © 2020 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.)

Introduction: Like every year, after the ECTRIMS Congress, renowned Spanish neurologists who are experts in multiple sclerosis presented the main novelties in research in this field at the Post-ECTRIMS Meeting., Aim: To summarise the content presented at the 12th edition of the Post-ECTRIMS Meeting, which took place in September 2019 in Sevilla and is presented in two parts., Development: In this second part, the most recent evidence on the use of disease-modifying treatments during pregnancy is presented. Details are provided concerning the results of phase 3 clinical trials conducted to evaluate the efficacy and safety of two potential disease-modifying treatments for relapsing-remitting multiple sclerosis: ponesimod and ofatumumab. For the progressive forms, both available disease modifying treatments and others still in the research phase are reviewed. In the field of stem cell therapies, the article includes the results of the only clinical trial carried out to date comparing patients with relapsing-remitting multiple sclerosis treated with autologous haematopoietic stem cell transplantation and those treated with disease-modifying therapies. There are no important developments as regards symptomatic treatments, although the European Academy of Neurology has published a guide on palliative care. The various sources of information that collect pharmacovigilance data in the post-marketing setting are reviewed., Conclusions: Patients diagnosed in recent years tend to have less severe multiple sclerosis, probably due to the fact that it is diagnosed in its milder stages together with the steady increase in the number of treatments available.

Introduction: Cladribine is a prodrug, a synthetic analogue of deoxyadenosine, approved for use as selective immune reconstitution therapy in very active recurring multiple sclerosis in adults., Aims: To review the development of the drug, its mechanism of action and the efficacy and safety data obtained to date, as well as to establish recommendations of Spanish experts for its use in clinical practice., Development: The treatment of multiple sclerosis has been simplified with cladribine tablets, and two short courses of administration for two consecutive years (maximum 20 days) are needed to maintain an efficacy of up to four years after the first dose. Results of clinical trials have demonstrated the safety, tolerability and long-term efficacy of cladribine tablets in patients with recurring multiple sclerosis. Thus, patients treated with cladribine presented a significant reduction in the rate of flare-ups, in the risk of disability progression and in the development of new lesions in magnetic resonance imaging compared to those treated with placebo. In terms of safety, the treated patients had a higher frequency of lymphopenia, in relation to its mechanism of action, and of infections by herpes zoster virus. Long-term results with eight years' follow-up have shown that treated patients are not at greater risk of developing serious events, such as malignant neoplasms or opportunistic infections., Conclusions: Cladribine is the first short-course oral therapy that has been shown to be effective and safe in patients with very active recurring multiple sclerosis, and with a sustained effect over time. The recommendations of Spanish experts on its usage are a fundamental complement to the considerations described by the regulatory agencies.

Introduction: Gait impairment, a frequent sign in multiple sclerosis (MS), places a major burden on patients since it results in progressive loss of personal and social autonomy, along with work productivity. This guide aims to provide recommendations on how to evaluate gait impairment and use prolonged-release fampridine (PR-fampridine) as treatment for MS patients with gait impairment in Spain., Development: PR-fampridine dosed at 10mg every 12hours is currently the only drug approved to treat gait impairment in adults with MS. Additionally, PR-fampridine has been shown in clinical practice to significantly improve quality of life (QoL) in patients who respond to treatment. Treatment response can be assessed with the Timed 25-Foot Walk (T25FW) or the 12-item MS Walking Scale (MSWS-12); tests should be completed before and after starting treatment. The minimum time recommended for evaluating treatment response is 2 weeks after treatment onset. Patients are considered responders and permitted to continue the treatment when they demonstrate a decrease in their T25FW time or an increase in MSWS-12 scores. A re-evaluation is recommended at least every 6 months. The SF-36 (Short Form-36) and the MSIS-29 (MS Impact Scale-29) tests are recommended for clinicians interested in performing a detailed QoL assessment. This drug is generally well-tolerated and has a good safety profile. It should be taken on an empty stomach and renal function must be monitored regularly., Conclusions: These recommendations will help ensure safer and more efficient prescription practices and easier management of PR-fampridine as treatment for gait impairment in Spanish adults with MS., (Copyright © 2015 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.)

Introduction: Natalizumab treatment has been shown to be very efficacious in clinical trials and very effective in clinical practice in patients with relapsing-remitting multiple sclerosis, by reducing relapses, slowing disease progression, and improving magnetic resonance imaging patterns. However, the drug has also been associated with a risk of progressive multifocal leukoencephalopathy (PML). The first consensus statement on natalizumab use, published in 2011, has been updated to include new data on diagnostic procedures, monitoring for patients undergoing treatment, PML management, and other topics of interest including the management of patients discontinuing natalizumab., Material and Methods: This updated version followed the method used in the first consensus. A group of Spanish experts in multiple sclerosis (the authors of the present document) reviewed all currently available literature on natalizumab and identified the relevant topics would need updating based on their clinical experience. The initial draft passed through review cycles until the final version was completed., Results and Conclusions: Studies in clinical practice have demonstrated that changing to natalizumab is more effective than switching between immunomodulators. They favour early treatment with natalizumab rather than using natalizumab in a later stage as a rescue therapy. Although the drug is very effective, its potential adverse effects need to be considered, with particular attention to the patient's likelihood of developing PML. The neurologist should carefully explain the risks and benefits of the treatment, comparing them to the risks of multiple sclerosis in terms the patient can understand. Before treatment is started, laboratory tests and magnetic resonance images should be available to permit proper follow-up. The risk of PML should be stratified as high, medium, or low according to presence or absence of anti-JC virus antibodies, history of immunosuppressive therapy, and treatment duration. Although the presence of anti-JC virus antibodies is a significant finding, it should not be considered an absolute contraindication for natalizumab. This update provides general recommendations, but neurologists must use their clinical expertise to provide personalised follow-up for each patient., (Copyright © 2013 Sociedad Española de Neurología. Published by Elsevier España, S.L.U. All rights reserved.)

Introduction: Natalizumab is very effective at reducing relapses and delaying disease progression in patients with relapsing-remitting multiple sclerosis (RRMS). However, treatment has also been associated with a risk of progressive multifocal leukoencephalopathy (PML). The aim of this article is to provide a consensus view on the assessment and stratification of these risks, and to improve the management of natalizumab-treated patients., Development: At an initial meeting of experts on multiple sclerosis (the authors of this consensus), the relevant topics of the consensus were determined and assigned for further elaboration. Topics included how to establish benefit and risk in general, stratification for risk of PML, informing patients of benefits/risks, and how to monitor patients during treatment and after discontinuing treatment. During the drafting phase, all available information published or presented at international meetings was reviewed. After a series of review sessions and meetings, the final draft was produced., Conclusions: Although natalizumab is a very effective drug, its use needs to be considered carefully in view of possible adverse effects and the risk of PML in particular. The neurologist should carefully explain the risks and benefits of treatment in terms the patient can best understand. Before starting treatment, baseline laboratory tests and magnetic resonance imaging (MRI) should be available for future comparisons in the event of suspected PML. The risk of PML should be stratified into high, medium and low risk groups according to presence or absence of anti-JC virus antibodies, prior immunosuppressive therapy, and treatment duration. The follow-up, and frequency of MRI scans in particular, should depend on the risk group to which patient belongs. As our understanding of the risk factors for PML develops, it should be possible to offer patients increasingly individualised therapy. This is a consensus that establishes general recommendations, but neurologists must use their clinical expertise to monitor patients individually., (Copyright © 2011 Sociedad Española de Neurología. Published by Elsevier España. All rights reserved.)

Introduction: The availability of new drugs has been a significant advance in the therapy of multiple sclerosis over the last years. However, the control of the disease is far from being complete, and some patients respond poorly or not at all to the new drugs., Development: The present paper reviews the approved therapies for multiple sclerosis and examines the advantages of the association of drugs, both with known and possible efficacy, as well as the theoretical basis for such associations and their possible clinical indications. Different designs for clinical trials in combination therapy are analyzed with a consideration of the current difficulties for the use of placebo in multiple sclerosis forms associated with relapses., Conclusions: The achievement of a higher efficacy than the present one is a major challenge in multiple sclerosis therapy. Combination therapy appears to be a reasonable option for that purpose.

Immunosuppressive drugs have been used for decades in the treatment of multiple sclerosis. The recent availability of immunomodulators has caused a major change in the treatment of this disease, but has not meant the disappearance of the use of immunosuppressive drugs, some of which (such as mitoxantrone) have been introduced recently. At present, it is difficult to assess the precise indications for these drugs, since most efficacy studies were made before the availability of magnetic resonance imaging, on criteria which are now considered obsolete. Independently of their value in monotherapy, immunosuppressants may probably be useful in combination with immunomodulators. We review the experience with the most widely used immunosuppressants and mention those drugs which might be used in the near future.

Objective: The ability of natural human interferon beta (n-hIFN beta) to reduce multiple sclerosis (MS) activity was investigated in 60 patients with relapsing-remitting MS (RRMS)., Patients and Methods: Patients were randomized to receive either 9 MIU (33 micrograms) of n-hIFN beta by subcutaneous route, three times per week, on alternate days, during one year, or no treatment (control group) during the first six months and then switched to the same treatment for the following six months. Disease activity was monitored monthly by both magnetic resonance imaging (MRI) and clinical parameters. An intergroup analysis (first 6 months of the study) showed fewer active lesions and lower exacerbation rate in the treatment group than in the control group. Similarly, there were more exacerbation-free patients in the treatment group during this time., Results: When switched to treatment, the control group showed a significant reduction in the number of active lesions (p = 0.00001) and the exacerbation rate decreased by half. Exacerbation-free patients more than doubled (p = 0.006) and the median time to first exacerbation was significantly prolonged (96 vs > 180 days; p = 0.019). Treatment was extended for 12 additional months at a dose of 6 MIU (22 micrograms) once a week and disease activity persisted under control in 88% of patients. Treatment with n-hIFN beta was well tolerated, adverse events being mild and self-limiting. Sera were analyzed for anti-IFN beta antibodies and neutralizing activity was found in 12% of the patients after two years., Conclusion: The results of this phase II study show, that n-hIFN beta promotes a significant reduction of disease activity in RRMS as shown by both MRI and clinical variables, and that the treatment is well tolerated, with low antigenicity.

Preliminary results of a multicenter, randomized study on the effect of natural interferon beta (n-INFN-beta) in relapsing-remitting MS are reported. Sixty patients received either no treatment or n-IFN-beta (9 MIU three times a week, subcutaneously). After 6 months, the n-IFN-beta-treated group showed a 58% median reduction in the number of active lesions detected on monthly magnetic resonance imaging scans as well as a 38% reduction in the exacerbation rate as compared with the control group. Side-effects were mild and self-limiting. The study continues according to the protocol.

A patient with ankylosing spondylitis developed a neurological disorder suggesting multiple sclerosis. An increased level of gammaglobulin was detected in the analysis of the cerebro spinal fluid. The response to steroid therapy, however, was unusual to that of multiple sclerosis since clinical manifestations disappeared shortly after, recurred some months later after discontinuance of the treatment, and subside again when the administration of corticosteroids was repeated. On the other hand, the patient developed an acute right peroneal neuritis with slowness of the conduction velocity. Although the association of a clinical picture resembling multiple sclerosis with ankylosing spondylitis has been reported, there are a few, and sometimes poorly documented, published cases. The literature is reviewed and the possibility of a relationship between the isolated peripheral neuritis and the underlying disease is suggested.