Social value of a set of proposals for the ideal approach of multiple sclerosis within the Spanish National Health System: a social return on investment study.

BACKGROUND: Multiple Sclerosis (MS) is a chronic inflammatory, demyelinating and neurodegenerative disease that in many cases produces disability, having a high impact in patients' lives, reducing significantly their quality of life. The aim of this study was to agree on a set of proposals to improve the current management of MS within the Spanish National Health System (SNHS) and apply the Social Return on Investment (SROI) method to measure the potential social impact these proposals would create. METHODS: A Multidisciplinary Working Team of nine experts, with representation from the main stakeholders regarding MS, was set up to agree on a set of proposals to improve the management of MS. A forecast SROI analysis was carried out, with a one-year timeframe. Data sources included an expert consultation, a narrative literature review and a survey to 532 MS patients. We estimated the required investment of a hypothetical implementation, as well as the potential social value that it could create. We calculated outcomes in monetary units and we measured intangible outcomes through financial proxies. RESULTS: The proposed ideal approach revealed that there are still unmet needs related to MS that can be addressed within the SNHS. Investment would amount to 148 million € and social return to 272 million €, so each euro invested could yield almost €2 of social return. CONCLUSIONS: This study could guide health interventions, resulting in money savings for the SNHS and increases in patients' quality of life.

Practical tool to identify Spasticity-Plus Syndrome amongst patients with multiple sclerosis. Algorithm development based on a conjoint analysis.

Introduction: The Spasticity-Plus Syndrome (SPS) in multiple sclerosis (MS) refers to a combination of spasticity and other signs/symptoms such as spasms, cramps, bladder dysfunction, tremor, sleep disorder, pain, and fatigue. The main purpose is to develop a user-friendly tool that could help neurologists to detect SPS in MS patients as soon as possible. Methods: A survey research based on a conjoint analysis approach was used. An orthogonal factorial design was employed to form 12 patient profiles combining, at random, the eight principal SPS signs/symptoms. Expert neurologists evaluated in a survey and a logistic regression model determined the weight of each SPS sign/symptom, classifying profiles as SPS or not. Results: 72 neurologists participated in the survey answering the conjoint exercise. Logistic regression results of the survey showed the relative contribution of each sign/symptom to the classification as SPS. Spasticity was the most influential sign, followed by spasms, tremor, cramps, and bladder dysfunction. The goodness of fit of the model was appropriate (AUC = 0.816). Concordance between the experts' evaluation vs. model estimation showed strong Pearson's (r = 0.936) and Spearman's (r = 0.893) correlation coefficients. The application of the algorithm provides with a probability of showing SPS and the following ranges are proposed to interpret the results: high (> 60%), moderate (30-60%), or low (< 30%) probability of SPS. Discussion: This study offers an algorithmic tool to help healthcare professionals to identify SPS in MS patients. The use of this tool could simplify the management of SPS, reducing side effects related with polypharmacotherapy.

The evolution of multiple sclerosis in Spain over the last decade from the patient's perspective.

BACKGROUND: Updated information about self-reported experience and satisfaction with care of MS patients (PwMS) in Spain is scarce. We aim to describe, from PwMS' perspective, the disease impact, the quality of life and the satisfaction level with the social and healthcare support in Spain, and its evolution over the last decade. METHODS: Multicentre observational study, based on a cross-sectional nationwide survey, completed by 432 PwMS in Spain throughout 2018. The results were compared with those of a similar study carried out in 2007 (370 patients), whose database was retrieved as baseline information. RESULTS: 432 patients recruited from 61 neurology units fully completed the study e-survey (mean age: 43.7 years; 71.4% women). The personal profile of patients was largely similar between the 2007 and 2018 samples. The proportion of patients who identified themselves as having relapsing-remitting MS was higher in 2018 (77.1% vs. 56.7 in 2007; p = 0.0001). Overall, 2018 patients considered themselves more labour-active, less disabled, more independent in movement, and as higher family income earners. The proportion of patients satisfied or very satisfied with healthcare services accessibility increased over time (54.9% in 2007 vs. 66.2 in 2018; p = 0.0009). Similarly, more patients considered their health condition to be good or very good in 2018 (55.8% vs. 33.7% in 2007; p = 0.0001). In contrast, there seems to be little progress in social support terms and opportunities equality. CONCLUSIONS: Health condition of PwMS seems to have improved over the last decade, which could be the result of an increasingly effective health care. However, more social protection measures are needed.

Patient experience and self-perceived biopsychosocial burden of people living with multiple sclerosis: An epidemiological survey (BPS-MuScle study) in Spain.

BACKGROUND: Updated information on the self-perceived biopsychosocial burden and the healthcare experience among people living with multiple sclerosis in Spain is scarce.We aim to describe the self-reported disease experience of patients diagnosed with MS in Spain and to estimate their biopsychosocial burden. METHODS: Multicentre epidemiological study based on a cross-sectional nationwide survey completed by a geographically stratified sample of MS patients in Spain. RESULTS: A total of 490 surveys completed at 61 neurology units across Spain were analysed. Mean age was 43.7 ± 10.0 years (range:21-72), 71.4% were women. Most patients identified themselves as having relapsing-remitting MS (77.1%), 81.9% retained independent mobility. Most patients considered their health condition to be good (39.4%) or very good (13.1%). Mean EuroQoL questionnaire score was 69.2 ± 21.5. Most patients expressed high level of satisfaction with access to and quality of health care. However, 53.7% considered that sadness or depression interfered with their daily life. Concerns about social support were also mentioned. CONCLUSION: Most people living with MS in Spain consider that their health condition is at least good but more psychological support and social protection measures are needed. Insights obtained from this study may help to better manage the condition in the future.

[Factors associated with long-term prognosis after ischemic stroke treated with fibrinolytic agents]. / Análisis de factores asociados al pronóstico a largo plazo en el ictus isquémico fibrinolisado.

OBJECTIVES: To analyze the variables associated with better functional outcome 3 months after ischemic stroke treated with fibrinolytic agents. MATERIAL AND METHODS: The cases of 63 patients with characteristics leading to activation of a stroke code were analyzed retrospectively. The patients received fibrinolytic therapy in a referral hospital for the western district of Malaga, Spain. We recorded the time until start of fibrinolytic therapy, severity according to the National Institute of Health Stroke Scale (NIHSS) at baseline and at 24 hours, and functional outcome at 3 months according to the modified Rankin Scale. RESULTS: Data for 63 patients with a mean (SD) age of 65 (11) years were included. The mean time until start of fibrinolytic therapy was 151 (42) minutes. The mean NIHSS scores were 15.5 (4.8) points at baseline and 9.1 (7.13) at 24 hours. The mean change in score at 24 hours was 6.3 (5.8) points. The findings of correlation analysis between scores on the modified Rankin scale and other variables were as follows: NIHSS score at 24 hours, ρ = 0.73; P < .01; NIHSS at baseline, ρ = 0.34; P = .01); age, ρ = 0.41; P = .001); time until start of fibrinolysis, ρ = 0.21; P = .09); change in NIHSS score at 24 hours, ρ = -0.61; P = .001). CONCLUSION: The prognosis for the functional recovery of patients given intravenous fibrinolytic therapy after stroke depends on such factors as age, time treatment is started, severity, and the patient's status at 24 hours. The last factor is the one that is most strongly related to prognosis.

OBJETIVO: Analizar las variables que influyen en un mejor pronóstico funcional a los tres meses en un grupo de pacientes con ictus isquémico agudo fibrinolisado. METODO: Se analizaron retrospectivamente 63 pacientes con características de código ictus y que recibieron fibrinolisis en un hospital de referencia de Málaga Oeste. Se determinó el tiempo de inicio de fibrinolisis (TIF), la gravedad del infarto mediante la puntuación NIHSS basal y a las 24 horas y el pronóstico funcional a los 3 meses mediante la escala Rankin modificada (mRS). RESULTADOS: Se incluyeron 63 pacientes, edad media 65 (DE 11) años. El TIF fue de 151 (DE 42) minutos. Se obtuvo una puntuación media en la escala NIHSS basal de 15,5 (DE 4,8) y a las 24 horas de 9,1 (DE 7,13), y una diferencia media de NIHSS a las 24 horas de 6,3 (DE 5,8). Se realizó análisis de correlación entre mRS y NIHSS a las 24 horas (Rho = 0,73; p < 0,01); NIHSS a la llegada (Rho = 0,34; p = 0,01); edad (Rho = 0,41; p = 0,001); TIF (Rho = 0,21; p = 0,09); y diferencia de NIHSS a las 24 h (Rho = ­0,61; p = 0,001). CONCLUSIONES: El pronóstico funcional de los pacientes con ictus agudo que reciben tratamiento fibrinolítico endovenoso depende de factores como la edad, el tiempo desde que se administra el tratamiento, la gravedad inicial del infarto y la situación del paciente a las 24 horas, siendo este último el factor el más relacionado con el pronóstico funcional.

Mesenchymal properties of SJL mice-stem cells and their efficacy as autologous therapy in a relapsing-remitting multiple sclerosis model.

INTRODUCTION: Mesenchymal stem cells (MSCs) are a multipotent population of adult stem cells, which may represent a promising therapeutic approach for neurological autoimmune diseases such as multiple sclerosis. The mouse is the most used species for obtaining and studying the characteristics of MSC and their potential as autologous transplants in pre-clinical models. However, conflicting data have been published disclosing intraspecies variations. The choice of the mouse strain and the tissue source appear, among others, as important factors in the experimental application of MSCs. METHODS: Adipose tissue-derived MSCs obtained from the SJL/JCrl mouse strain (SJL-AdMSC) have been cultured for a long time (from passage 0 up to 15) under controlled experimental conditions, and their growth rate, morphology, stromal and haematopoietic marker expression profiles and differentiation capacity towards adipocytes, osteocytes and chondrocytes have been determined. Moreover, their preclinical efficacy has been assessed by autologous transplant in relapsing-remitting experimental autoimmune encephalomielitis (RR-EAE)-induced SJL mice (a well established mice model for the study of RR-multiple sclerosis). RESULTS: We demonstrate that SJL-AdMSCs show the same fibroblastic shape, growth rate, profile of markers expression and multipotency described for MSCs in every passage evaluated (up to passage 15). Additionally, SJL-AdMSCs ameliorate the RR-EAE course, suggesting that they could modulate disease progression. Moreover, their features studied are fully comparable with the standardized Ad-MSCs obtained from the C57BL/6 mouse strain, which strengthens their use in cell therapy. CONCLUSION: SJL-AdMSCs might be a suitable source of Ad-MSCs for studies related to the properties of MSCs and their application as promising therapeutic tools in autologous transplants in experimental medicine.

[Guidelines on the appropriate use of animal models for developing therapies in multiple sclerosis]. / Guía de uso adecuado de modelos animales para el desarrollo de terapias en esclerosis múltiple.

INTRODUCTION: The advance in the achievement of effective therapies for multiple sclerosis (MS), the definition of appropriate therapeutic windows and to establish better diagnostic and prognostic biomarkers have become a challenging task for both researchers and clinicians. Some pitfalls in clinical trials might be related to lack of adequacy of the preclinical studies in MS experimental animal models. AIM: To standardize the methodological protocols of experimental models by developing a set of guidelines for preclinical studies by groups of experts from REEM (Spanish Network for MS). DEVELOPMENT: A guide with recommendations for the application of MS models including a detailed assessment of appropriate experimental models taking into account the objective of the study that has been presented. Standards and quality criteria necessary in a preclinical study have been included. CONCLUSIONS: Standardized animal models of MS are essential to increase the success of the preclinical findings in order to transfer them to the clinical practice.

The effectiveness of glatiramer acetate in clinical practice: an observational study.

AIM: To evaluate the clinical effectiveness and safety of glatiramer acetate for use in routine clinical practice. PATIENTS AND METHODS: A retrospective, observational study was conducted on patients with multiple sclerosis who were treated with glatiramer acetate in clinical practice. The primary outcome was the clinical effectiveness of glatiramer acetate treatment. RESULTS: The study included a total of 104 patients (women, 59.6%; age at onset of glatiramer acetate treatment, 39.9 ± 10.9 years; prior treatment for multiple sclerosis, 30.8%). The patients had received glatiramer acetate treatment for an average of 3.6 ± 1.9 years. During the first year of glatiramer acetate treatment, the relapse rate decreased by 60%. At this time, the number of relapses had decreased for 47 patients (45.1%), 67 patients (68.4%) had not suffered a relapse and 78 patients (75.0%) showed no signs of progression. During the second year of glatiramer acetate treatment, the relapse rate decreased by 70%. At this time, the number of relapses had decreased for 43 patients (41.3%), 63 patients (75.9%) had not suffered a relapse and 59 patients (56.7%) showed no signs of progression. There were no reported relapses or progression in 56 patients (53.8%) and 41 patients (39.4%) during the first and second years of treatment, respectively. Discontinuation of glatiramer acetate was necessary in only three patients. The most common adverse effects included fatigue (28.9%) and spasticity (7.7%). CONCLUSION: This evaluation of glatiramer acetate use in clinical practice supports the effectiveness and the safety profile observed in previously published clinical trial studies.

[Pharmacological targets in multiple sclerosis]. / Dianas farmacologicas en la esclerosis multiple.

Multiple sclerosis is the most frequent chronic inflammatory, demyelinating and neurodegenerative disease in young adults, but has no definitive pharmacological treatment. It is a heterogeneous disease from the immunological, neuropathological and clinical point of view, as well as in terms of its response to different therapies. Over the last two decades, pharmacology has focused on developing drugs that are capable of modifying the course of this disease, with the aim of reducing the frequency of the outbreaks and the speed at which the disability produced by the disease progresses. Nevertheless, today, there are no drugs that are capable of offering a curative effect that can fully stabilise the disease, and neuroprotective and neuroreparative strategies are still in their early stages. In this work we carry out a critical review of the different pathogenic paths involved in multiple sclerosis and we discuss the different pharmacological approaches that have been followed, based on the clinical trials that are currently being conducted. In the near future it is to be expected that, first, we will manage to stabilise the disease completely and, later, recover some of the functions altered by this disease. Research is being conducted at such a rate that we have to be optimistic and think that soon we will be able to improve the situation of those who suffer from the disease.

Killer cell immunoglobulin-like receptor genes in Spanish multiple sclerosis patients.

Killer cell immunoglobulin-like receptors (KIRs) are regulators of cytolytic activity of natural killer and certain T cells through interactions with human leukocyte antigen (HLA) class I ligands. KIRs have been shown to contribute to the pathogenesis of several autoimmune diseases, but their role in multiple sclerosis (MS) is still unclear. Here we determined the influence of KIR genes and their HLA class I ligands on susceptibility to MS and on the response to interferon-beta treatment in a Spanish population. KIR and HLA genotyping were performed in 200 MS patients and 200 controls. Significantly higher frequencies were found for KIR2DL5 and KIR3DS1 genes in MS patients and the carriage of the KIR2DL1 gene was associated with a higher progression index. Moreover, the frequency of the HLA-Bw4 motif was significantly reduced in MS patients. The KIR2DL1 and HLA-C2 matches were more frequent in MS patients, whereas the KIR3DL1 and HLA-Bw4 matches were more frequent in healthy controls. Nevertheless, non significant associations were found between all the KIR genes and therapeutic response to interferon-beta. Our results confirm that the carriage of HLA-Bw4 is a protective factor in MS and suggest that KIR2DL5 and KIR3DS1 may have a predisposing role in the disease.

[Review of the novelties presented at the 26th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) (I)]. / Revision de las novedades presentadas en el XXVI Congreso del Comite Europeo para el Tratamiento e Investigacion en Esclerosis Multiple (ECTRIMS) (I).

The new insights presented at European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS), held in the city of Gothenburg, Sweden, in October 2010, have been summarized at the third edition of Post-ECTRIMS meeting held in Madrid in November 2010. The age is an important factor related to the course and prognosis of multiple sclerosis (MS). The evolution to progressive disease persists more than 50 years after diagnosis of MS and a reduction in the delay of diagnosis has been detected. Several strategies have been proposed in order to improve the efficacy of magnetic resonance regarding prognosis and course of disease. The studies presented at the Congress reflect the influence of gender on course and severity of disease symptoms, showing an increase of worldwide prevalence of MS in women. Neuroprotective action of estrogen receptor beta has been reported. The genome wide association studies have allowed investigators to identify numerous susceptible alleles. In this regard, HLA class II genes, seems to contribute to genetic risk for developing neutralizing antibodies against beta-interferon. Vitamin D deficiency and Epstein-Barr virus have been highlighted as risk factors for MS in the reported findings. On the subject of the ongoing controversy regarding the role of inflammation and degeneration in MS, several arguments have been found to support the role of CNS autoimmunity to explain the presence of inflammatory phenomenon. The available data hold the potential therapeutic role of mesenchymal cells given the involvement of these stem cells in CNS repair.