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2.
Sci Rep ; 13(1): 20531, 2023 11 22.
Artigo em Inglês | MEDLINE | ID: mdl-37993589

RESUMO

The objective of this study was to analyze the perceived barriers to dual career success and athletic identity of student-athletes according to disability type and level of professionalization. The final sample consisted of 203 student-athletes with disabilities from five European countries. The questionnaires used were ESTPORT, EBBS and AIMS. Depending on disability type, it was found that student-athletes with hearing and physical impairment showed the highest difficulty in reconciling sports and studies (p = 0.001); that student-athletes with a hearing impairment showed the highest score in the barrier 'the cost of education is high' (p = 0.023); that student-athletes with a physical impairment had the highest scores in the barrier 'Exercise tires me' (p = 0.013); that student-athletes with cerebral palsy showed the highest scores in the barrier 'I do not have enough university/educational institution support' (p = 0.014) and 'Exercise facilities do not have convenient timetables for me' (p = 0.001). Depending on sports professionalization level, semi-professional student-athletes showed the highest values in the barrier 'the university/educational institution is far from my training center' (p = 0.040); while professional student-athletes had the highest score in the barrier 'exercise takes too much time from family responsibilities' (p = 0.034). In most of the variables related to identity as athletes, professional student-athletes showed the highest values, followed by semi-professional athletes (p = 0.043- < 0.001). In conclusion, the self-perception of barriers is quite relevant, with differences arising from disability type and level of professionalization, whereas the identity as an athlete is only different according to the level of professionalization.


Assuntos
Pessoas com Deficiência , Esportes , Humanos , Atletas , Estudantes , Autoimagem
3.
Mult Scler Relat Disord ; 75: 104762, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37229800

RESUMO

BACKGROUND: Alemtuzumab is a highly effective treatment for relapsing remitting multiple sclerosis (RRMS), but in recent years safety-related concerns had emerged due to description of novel serious side effects not registered in CARE-MS I and CARE-MS II phase 3 studies, nor in TOPAZ extension study. Data about alemtuzumab use in real clinical practice are limited and based mainly on retrospective studies with small sample sizes. Therefore, more information about effectiveness and safety of alemtuzumab in this context is needed. METHODS: A multicenter observational prospective study to investigate effectivity and safety of alemtuzumab in a real-world setting was performed. Primary endpoints were the change in annualized relapse rate (ARR), and in disability measured by EDSS score. Secondary endpoints were the cumulative probability of confirmed 6-month disability improvement and worsening. Disability worsening and disability improvement were considered when the EDSS score was increased or decreased, respectively, in 1 point if baseline EDSS score was <5.0, or in 0.5 point if baseline EDSS score was ≥5.5, confirmed over 6 months. Other secondary endpoint was the proportion of patients who achieved NEDA-3 status (absence of clinical relapses, disability EDSS progression, and MRI disease activity as depicted by new/enlarging T2 lesions or Gadolinium enhancing T1 lesions). Adverse events also were recorded. RESULTS: A total of 195 RRMS patients (70% female) who started alemtuzumab treatment were included. Mean of follow-up was 2.38 years. Alemtuzumab significantly reduced the annualized relapse rate from baseline with risk reductions of 86%, 83.5%, and 84%, at 12, 24, and 36 months of follow-up respectively (Friedman test, p-value < 0.05 for all comparisons). Alemtuzumab also significantly reduced EDSS score over one and two years after starting alemtuzumab treatment (Friedman test, p-value<0.001 for both comparisons). A high proportion of patients presented confirmed 6-month stability or disability improvement (92%, 82%, and 79%, over 1, 2 and 3 years of follow-up respectively). The proportion of patients who retained NEDA-3 status at 12, 24 and 36 months were 61%, 49%, and 42%, respectively. Baseline characteristics associated with a lower probability of achieving NEDA-3 were younger age, sex female, high ARR, elevated number of previous treatments, and switch from a second line therapy. Infusion related reactions were the most frequent adverse event observed. The most common infections were urinary tract infections (50%), and upper respiratory tract infections (19%) over the 3 years of follow- up. Secondary thyroid autoimmunity was developed in 18.5% of patients. CONCLUSION: Alemtuzumab has demonstrated in real clinical practice high effectiveness in controlling multiple sclerosis activity, and no unexpected adverse events were observed.


Assuntos
Esclerose Múltipla Recidivante-Remitente , Esclerose Múltipla , Humanos , Feminino , Masculino , Alemtuzumab/efeitos adversos , Estudos Retrospectivos , Esclerose Múltipla/tratamento farmacológico , Esclerose Múltipla Recidivante-Remitente/tratamento farmacológico , Esclerose Múltipla Recidivante-Remitente/induzido quimicamente , Recidiva
4.
PLoS One ; 16(10): e0258437, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34644366

RESUMO

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.


Assuntos
Cloridrato de Fingolimode/uso terapêutico , Imunossupressores/uso terapêutico , Esclerose Múltipla/tratamento farmacológico , Adulto , Feminino , Cloridrato de Fingolimode/efeitos adversos , Humanos , Imunossupressores/efeitos adversos , Linfopenia/etiologia , Masculino , Pessoa de Meia-Idade , Recidiva , Sistema de Registros , Estudos Retrospectivos , Espanha , Resultado do Tratamento
5.
Neurologia (Engl Ed) ; 36(5): 346-352, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34714232

RESUMO

INTRODUCTION: The safety and effectiveness of natalizumab in patients with relapsing-remitting multiple sclerosis (RRMS) has been demonstrated in clinical trials. However, due to the limitations of these trials, it is important to know how the condition behaves under long-term clinical practice conditions. OBJECTIVE: To determine the long-term effectiveness of natalizumab in patients with RRMS by means of annual evaluation of the "no evidence of disease activity" (NEDA) parameter, which includes number of relapses, disability (measured with the Expanded Disability Status Scale), and brain MRI parameters. PATIENTS AND METHODS: We performed a retrospective study of patients with RRMS from 3 centres who were treated with one or more doses of natalizumab. Each year, we evaluated NEDA status and safety based on the percentage of patients who discontinued treatment with natalizumab and experienced adverse reactions. RESULTS: The study included 89 patients, most of whom received treatment for 2 to 4 years, with a follow-up period of up to 7 years. Natalizumab significantly reduces the radiological and clinical progression of the disease, as well as the annual rate of relapses. The NEDA parameter demonstrates the effectiveness of the drug, with values of 75.28% for year one and 66.67% for year 7. Twenty-five patients (28.1%) dropped out after a median of 4 years. Fourteen of these patients (56%) dropped out due to the appearance of anti-JC virus antibodies, either in isolation or associated with another cause. Four dropouts (16%) were due to treatment ineffectiveness, with one patient dying due to progressive multifocal leukoencephalopathy. CONCLUSIONS: Natalizumab is highly effective as measured by the NEDA long-term remission parameter.


Assuntos
Esclerose Múltipla Recidivante-Remitente , Esclerose Múltipla , Humanos , Fatores Imunológicos/efeitos adversos , Esclerose Múltipla Recidivante-Remitente/tratamento farmacológico , Natalizumab/efeitos adversos , Estudos Retrospectivos
6.
Neurología (Barc., Ed. impr.) ; 36(5): 346-352, junio 2021. tab, graf
Artigo em Espanhol | IBECS | ID: ibc-219901

RESUMO

Introducción: La efectividad y seguridad de natalizumab en pacientes con esclerosis múltiple remitente recurrente (EMRR) se demostró en ensayos clínicos. Sin embargo, por las limitaciones de estos es importante saber cómo se comporta en condiciones de práctica clínica a largo plazo.ObjetivoConocer la eficacia a largo plazo de natalizumab en pacientes con EMRR mediante la evaluación anual del no evidence of disease activity (NEDA), que incluye número de brotes, discapacidad medida con EDSS y parámetros de RM cerebral.Pacientes y métodosEstudio retrospectivo y multicéntrico (n = 3) de pacientes con EMRR tratados con una o más dosis de natalizumab. Se evaluó el estado NEDA cada año y la seguridad a partir del porcentaje de pacientes que discontinuaron y que presentaron efectos adversos.ResultadosIncluimos 89 pacientes, la mayoría recibieron tratamiento durante 2 a 4 años, con una duración del seguimiento de hasta 7 años. Natalizumab reduce significativamente la progresión radiológica y clínica de la enfermedad, así como la tasa anual de brotes, demostrándose su eficacia con el parámetro NEDA, 75,28% al primer año y 66,67% al séptimo año. Veinticinco pacientes (28,1%) han abandonado el estudio en una mediana de tiempo de 4 años, 14 pacientes (56%) por aparición de anticuerpos contra el virus JC, como causa única o asociada a otro motivo, 4 abandonos (16%) fueron por ineficacia, un paciente falleció a causa de LMP.ConclusionesNatalizumab presenta una alta eficacia medida mediante el parámetro de remisión NEDA a largo plazo. (AU)


Introduction: The safety and effectiveness of natalizumab in patients with relapsing-remitting multiple sclerosis (RRMS) has been demonstrated in clinical trials. However, due to the limitations of these trials, it is important to know how the condition behaves under long-term clinical practice conditions.ObjectiveTo determine the long-term effectiveness of natalizumab in patients with RRMS by means of annual evaluation of the “no evidence of disease activity” (NEDA) parameter, which includes number of relapses, disability (measured with the Expanded Disability Status Scale), and brain MRI parameters.Patients and methodsWe performed a retrospective study of patients with RRMS from 3 centres who were treated with one or more doses of natalizumab. Each year, we evaluated NEDA status and safety based on the percentage of patients who discontinued treatment with natalizumab and experienced adverse reactions.ResultsThe study included 89 patients, most of whom received treatment for 2 to 4 years, with a follow-up period of up to 7 years. Natalizumab significantly reduces the radiological and clinical progression of the disease, as well as the annual rate of relapses. The NEDA parameter demonstrates the effectiveness of the drug, with values of 75.28% for year one and 66.67% for year 7. Twenty-five patients (28.1%) dropped out after a median of 4 years. Fourteen of these patients (56%) dropped out due to the appearance of anti–JC virus antibodies, either in isolation or associated with another cause. Four dropouts (16%) were due to treatment ineffectiveness, with one patient dying due to progressive multifocal leukoencephalopathy.ConclusionsNatalizumab is highly effective as measured by the NEDA long-term remission parameter. (AU)


Assuntos
Humanos , Natalizumab , Esclerose Múltipla , Pacientes , Leucoencefalopatias , Imunossupressores
7.
Epilepsy Res ; 172: 106570, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33621770

RESUMO

BACKGROUND: Perampanel (PER) is an effective adjunctive therapy for controlling focal-onset seizures (FOS), but few studies have examined its effects as an early add-on for the treatment of FOS in daily clinical practice. METHODS: Our retrospective, multicenter, observational study evaluated the effectiveness and safety of PER as an early add-on in 77 patients with FOS, with and without focal to bilateral tonic-clonic seizures (FBTCS) after 3, 6 and 12 months in a real-world setting. RESULTS: After 12 months of treatment (median dose 6 [4,8] mg/day), the retention rate was 79.2 % and 60 % of patients (39/65) experienced a ≥50 % reduction in seizure frequency relative to baseline. The seizure-free rate was 38.5 % for all seizures (25/65) and 60 % for FBTCS (12/20). The responder rate at 12 months was significantly higher when PER was given with one concomitant AED (72.2 %) compared to when PER was given with two concomitant AEDs (44.8 %). Drug-related adverse events (AEs) were reported in 40.3 % of patients, most of them being mild (64.2 %). Twelve patients (15.6 %) discontinued treatment because of AEs. CONCLUSIONS: PER is an effective and safe early add-on for patients with refractory FOS, especially for those with FBTCS.


Assuntos
Anticonvulsivantes , Piridonas , Anticonvulsivantes/efeitos adversos , Quimioterapia Combinada , Humanos , Nitrilas , Piridonas/efeitos adversos , Estudos Retrospectivos , Convulsões/tratamento farmacológico , Resultado do Tratamento
8.
Neurología (Barc., Ed. impr.) ; 32(1): 29-39, ene.-feb. 2017. tab, ilus, graf
Artigo em Espanhol | IBECS | ID: ibc-160470

RESUMO

Introducción: A pesar de la efectividad de los tratamientos inyectables para la esclerosis múltiple (EM), las reacciones adversas y el dolor pueden implicar problemas de satisfacción y adherencia. Se presenta la validación de la versión española del Multiple Sclerosis Treatment Concerns Questionnaire (MSTCQ)©, que evalúa la satisfacción con el dispositivo de autoinyección (DA), 4 dimensiones: sistema de inyección (A), efectos secundarios (B) (síntomas pseudogripales, reacciones, satisfacción), experiencia con el tratamiento (C) y beneficios (D). Métodos: Dos fases de estudio: 1) Adaptación cultural con expertos (n = 6) y pacientes (n = 27). 2) Estudio observacional, transversal y multicéntrico de validación. Se evaluaron 143 pacientes adultos con EM que utilizaban el DA Extavijec(TM) 30G. Cuestionarios: MSTCQ©; Patient-Reported Indices for Multiple Sclerosis (PRIMUS©), y Treatment Satisfaction Questionnaire for Medication (TSQM©). Propiedades psicométricas: factibilidad (% casos válidos y distribución de puntuaciones); fiabilidad (α-Cronbach) y test-retest (n = 41, coeficiente correlación intraclase [CCI]), y validez de constructo (análisis factorial A y B, [AF]) y convergente (Spearman-rho MSTCQ© versus TSQM©). Resultados. Edad media (DT) 41,94 (10,47) años, 63% mujeres, 88,11% con EM remitente-recurrente, media (DT) EDSS 2,68 (1,82) puntos. Alta cumplimentación del MSTCQ© (perdidos 0-2,80%). Alta consistencia interna: puntuación total (A + B) α = 0,89, por dimensiones (A, B y C) α = 0,76, 0,89 y 0,92, respectivamente. Excelente concordancia test-retest en las puntuación total (CC I= 0,98), por dimensiones (A, B y C) CCI = 0,82, 0,97 y 0,89, respectivamente. El AF corroboró la estructura interna del cuestionario original. Correlación moderada (Rho = 0,42-0,74) y significativa (p < 0,05 y p < 0,01) entre las puntuación total y por dimensiones del MSTCQ© y el TSQM©. Conclusiones. Se constatan adecuadas propiedades psicométricas de la versión española del MSTCQ


Introduction: Although subcutaneous treatments for multiple sclerosis (MS) have been shown to be effective, adverse reactions and pain may adversely affect treatment satisfaction and adherence. This study presents an adapted and validated Spanish version of the Multiple Sclerosis Treatment Concerns Questionnaire© (MSTCQ), which evaluates satisfaction with the injection device (ID) across 4 domains: injection system (A), side effects (B) (flu-like symptoms, reactions, and satisfaction), experience with treatment (C) and benefits (D). Methods: Two study phases: 1) Cultural adaptation process with input from experts (n = 6) and patients (n = 30). 2) Validation obtained by means of an observational, cross-sectional, multi-centre study evaluating 143 adult MS patients using an ID. Tools employed: MSTCQ©, Patient-Reported Indices for Multiple Sclerosis (PRIMUS©), and Treatment Satisfaction Questionnaire for Medication (TSQM©). Psychometric properties: Feasibility (percentage of valid cases and floor/ceiling effects); Reliability (Cronbach α) and test-retest correlation (n = 41, intraclass correlation coefficient, ICC); and construct validity (factor analysis of domains A and B) and convergent validity (Spearman rank-order correlation for MSTCQ© vs TSQM©). Results: Mean age (SD) was 41.94 (10.47) years, 63% of the group were women, and 88.11% presented relapsing-remitting MS. Mean (SD) EDSS score was 2.68 (1.82) points. MSTCQ© completion was high (0%-2.80% missing data). Internal consistency was high at α=0.89 for the total score (A+B) and α = 0.76, 0.89, and 0.92 for domains A, B, and C, respectively. The version demonstrated excellent test-retest reliability for the total (ICC = 0.98) and for domains A, B, and C: ICC = 0.82, 0.97, and 0.89, respectively. Factor analysis corroborated the internal structure of the original questionnaire. The association between total and domain scores on both the MSTCQ© and the TSQM© was moderately strong (Rho = 0.42-0.74) and significant (P < .05 and P < .01). Conclusion: The Spanish version of MSTCQ© demonstrates appropriate psychometric properties


Assuntos
Humanos , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Esclerose Múltipla/epidemiologia , Esclerose Múltipla/prevenção & controle , Esclerose Múltipla/terapia , Satisfação do Paciente/estatística & dados numéricos , Psicometria/métodos , Tradução , Inquéritos e Questionários , Recusa do Paciente ao Tratamento/estatística & dados numéricos , 28599 , Adaptação a Desastres
9.
Neurologia ; 32(1): 29-39, 2017.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-25697827

RESUMO

INTRODUCTION: Although subcutaneous treatments for multiple sclerosis (MS) have been shown to be effective, adverse reactions and pain may adversely affect treatment satisfaction and adherence. This study presents an adapted and validated Spanish version of the Multiple Sclerosis Treatment Concerns Questionnaire© (MSTCQ), which evaluates satisfaction with the injection device (ID) across 4 domains: injection system (A), side effects (B) (flu-like symptoms, reactions, and satisfaction), experience with treatment (C) and benefits (D). METHODS: Two study phases: 1) Cultural adaptation process with input from experts (n=6) and patients (n=30). 2) Validation obtained by means of an observational, cross-sectional, multi-centre study evaluating 143 adult MS patients using an ID. Tools employed: MSTCQ©, Patient-Reported Indices for Multiple Sclerosis (PRIMUS©), and Treatment Satisfaction Questionnaire for Medication (TSQM©). Psychometric properties: Feasibility (percentage of valid cases and floor/ceiling effects); Reliability (Cronbach α) and test-retest correlation (n=41, intraclass correlation coefficient, ICC); and construct validity (factor analysis of domains A and B) and convergent validity (Spearman rank-order correlation for MSTCQ© vs TSQM©). RESULTS: Mean age (SD) was 41.94 (10.47) years, 63% of the group were women, and 88.11% presented relapsing-remitting MS. Mean (SD) EDSS score was 2.68 (1.82) points. MSTCQ© completion was high (0%-2.80% missing data). Internal consistency was high at α=0.89 for the total score (A+B) and α=0.76, 0.89, and 0.92 for domains A, B, and C, respectively. The version demonstrated excellent test-retest reliability for the total (ICC=0.98) and for domains A, B, and C: ICC=0.82, 0.97, and 0.89, respectively. Factor analysis corroborated the internal structure of the original questionnaire. The association between total and domain scores on both the MSTCQ© and the TSQM© was moderately strong (Rho=0.42-0.74) and significant (P<.05 and P<.01). CONCLUSION: The Spanish version of MSTCQ© demonstrates appropriate psychometric properties.


Assuntos
Características Culturais , Esclerose Múltipla/tratamento farmacológico , Psicometria , Inquéritos e Questionários/normas , Adulto , Estudos Transversais , Feminino , Humanos , Injeções Subcutâneas/métodos , Masculino , Esclerose Múltipla/psicologia , Dor/etiologia , Medição da Dor , Satisfação do Paciente , Reprodutibilidade dos Testes
10.
Rev Neurol ; 63(s01): S13-S18, 2016 Sep 05.
Artigo em Espanhol | MEDLINE | ID: mdl-27658431

RESUMO

INTRODUCTION: The effectiveness and safety of fingolimod in patients with relapsing-remitting multiple sclerosis (RRMS) have been proven in clinical trials. Yet, due to their limitations, it is important to know how it behaves under everyday clinical practice conditions. Hence, the aim of this study is to evaluate the effectiveness and safety of fingolimod after 12 months' usage in clinical practice in Galicia. PATIENTS AND METHODS: We conducted a retrospective, multi-centre study (n = 8) of patients with RRMS who were treated with one or more doses of fingolimod, 0.5 mg/day. Effectiveness was assessed -annualised relapse rate (ARR), changes in the score on the Expanded Disability Status Scale (EDSS), percentage of patients free from relapses, free from progression of disability and free from activity in resonance- for the total number of patients and according to previous treatment. Safety was assessed based on the percentage of patients who withdrew and presented adverse side effects. RESULTS: After 12 months' use, fingolimod reduced the ARR by 87% (1.7 to 0.23; p < 0.0001) and, consequently, 81% of patients were free from relapses. The score was reduced by 9%. In all, 91% of patients were free from progression of disability and 72% were free from resonance activity. No signs of disease activity were found in 43% of the patients. Most of the benefits of fingolimod differed depending on previous treatment. About a third of the patients reported adverse side effects, but only 2% of them withdrew for this reason. CONCLUSIONS: In clinical practice, most of the results on the effectiveness of the clinical trials conducted with fingolimod were observed during the first 12 months of treatment. A better safety profile was observed than that reported in the clinical trials.


TITLE: Fingolimod: efectividad y seguridad en la practica clinica habitual. Estudio observacional, retrospectivo y multicentrico en Galicia.Introduccion. La efectividad y seguridad del fingolimod en pacientes con esclerosis multiple remitente recurrente (EMRR) se demostro en ensayos clinicos. Sin embargo, por las limitaciones de estos, es importante saber como se comporta en condiciones de practica clinica habitual. Asi, el objetivo de este estudio es evaluar la efectividad y seguridad del fingolimod despues de 12 meses de uso en la practica clinica en Galicia. Pacientes y metodos. Estudio retrospectivo y multicentrico (n = 8) de pacientes con EMRR y tratados con una o mas dosis de fingolimod, 0,5 mg/dia. Se evaluo la efectividad ­tasa anualizada de brotes (TAB), cambio en la puntuacion de la escala expandida del estado de discapacidad (EDSS), porcentaje de pacientes libres de brotes, libres de progresion de discapacidad y libres de actividad en resonancia­ para el total de pacientes y segun tratamiento previo. Se evaluo la seguridad a partir del porcentaje de pacientes que discontinuaron y que presentaron efectos adversos. Resultados. Despues de 12 meses de uso, el fingolimod redujo un 87% la TAB (de 1,7 a 0,23; p < 0,0001) y, en consecuencia, un 81% de pacientes estuvo libre de brotes. La puntuacion de la EDSS disminuyo un 9%. Un 91% de pacientes estuvo libre de progresion de discapacidad y un 72%, libre de actividad en resonancia. En el 43% de los pacientes no se evidenciaron signos de la actividad de la enfermedad. La mayoria de los beneficios del fingolimod difirieron segun el tratamiento previo. Alrededor de un tercio de los pacientes comunicaron efectos adversos, pero solo el 2% discontinuo debido a ellos. Conclusiones. La mayoria de los resultados de efectividad de los ensayos clinicos del fingolimod se observa durante los 12 primeros meses de tratamiento en la practica clinica. Se observo un mejor perfil de seguridad al comunicado en los ensayos clinicos.

11.
Clin Exp Immunol ; 182(2): 220-9, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26212048

RESUMO

Adoptive T cell therapy of cancer employs a large number of ex-vivo-propagated T cells which recognize their targets either by virtue of their endogenous T cell receptor (TCR) or via genetic reprogramming. However, both cell-extrinsic and intrinsic mechanisms often diminish the in-vivo potency of these therapeutic T cells, limiting their clinical efficacy and broader use. Direct activation of human T cells by Toll-like receptor (TLR) ligands induces T cell survival and proliferation, boosts the production of proinflammatory cytokines and augments resistance to regulatory T cell (Treg) suppression. Removal of the TLR ligand-binding region results in constitutive signalling triggered by the remaining cytosolic Toll/interleukin-1 receptor (TIR) domain. The use of such TIR domains therefore offers an ideal means for equipping anti-tumour T cells with the arsenal of functional attributes required for improving current clinical protocols. Here we show that constitutively active (ca)TLR-4 can be expressed efficiently in human T cells using mRNA electroporation. The mere expression of caTLR-4 mRNA in polyclonal CD8 and CD4 T cells induced the production of interferon (IFN)-γ, triggered the surface expression of CD25, CD69 and 4-1BB and up-regulated a panel of cytokines and chemokines. In tumour-infiltrating lymphocytes prepared from melanoma patients, caTLR-4 induced robust IFN-γ secretion in all samples tested. Furthermore, caTLR-4 enhanced the anti-melanoma cytolytic activity of tumour-infiltrating lymphocytes and augmented the secretion of IFN-γ, tumour necrosis factor (TNF)-α and granulocyte-macrophage colony-stimulating factor (GM-CSF) for at least 4 days post-transfection. Our results demonstrate that caTLR-4 is capable of exerting multiple T cell-enhancing effects and can potentially be used as a genetic adjuvant in adoptive cell therapy.


Assuntos
Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , RNA Mensageiro/imunologia , Receptor 4 Toll-Like/imunologia , Antígenos CD/imunologia , Antígenos CD/metabolismo , Antígenos de Diferenciação de Linfócitos T/imunologia , Antígenos de Diferenciação de Linfócitos T/metabolismo , Linfócitos T CD4-Positivos/metabolismo , Linfócitos T CD8-Positivos/metabolismo , Linhagem Celular Tumoral , Células Cultivadas , Quimiocinas/imunologia , Quimiocinas/metabolismo , Citocinas/imunologia , Citocinas/metabolismo , Eletroporação , Citometria de Fluxo , Expressão Gênica/imunologia , Fator Estimulador de Colônias de Granulócitos e Macrófagos/imunologia , Fator Estimulador de Colônias de Granulócitos e Macrófagos/metabolismo , Humanos , Interferon gama/imunologia , Interferon gama/metabolismo , Subunidade alfa de Receptor de Interleucina-2/imunologia , Subunidade alfa de Receptor de Interleucina-2/metabolismo , Células K562 , Lectinas Tipo C/imunologia , Lectinas Tipo C/metabolismo , Linfócitos do Interstício Tumoral/imunologia , Linfócitos do Interstício Tumoral/metabolismo , RNA Mensageiro/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Receptor 4 Toll-Like/genética , Receptor 4 Toll-Like/metabolismo , Transfecção/métodos , Membro 9 da Superfamília de Receptores de Fatores de Necrose Tumoral/imunologia , Membro 9 da Superfamília de Receptores de Fatores de Necrose Tumoral/metabolismo , Fator de Necrose Tumoral alfa/imunologia , Fator de Necrose Tumoral alfa/metabolismo
16.
Seizure ; 22(1): 77-9, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23127776

RESUMO

OBJECTIVE: Treatment of status epilepticus (SE) has not changed in the last few decades, benzodiazepines plus phenytoin or valproate being the most common treatment. Once this first and second line treatment has failed SE is considered refractory (RSE). This study aimed to assess the efficacy and tolerability of intravenous (iv) lacosamide (LCM) in RSE. METHOD: Patients with RSE who were treated with ivLCM in six Spanish centers were prospectively included. Efficacy was defined as cessation of seizures after starting ivLCM, with no need for any further antiepileptic drug. All patients had been unsuccessfully treated following the standard protocol (benzodiazepines plus phenytoin or valproate) before ivLCM was added. RESULTS: Thirty-four patients were included, 52.9% men, with mean age of 60.15 years. In 58.9% of patients the etiology was symptomatic, and the most common type of SE was focal convulsive (82.4%). Mean initial bolus dose of LCM was 323.53mg. ivLCM was effective in more than half of patients (64.7%), with termination of SE before 12h in 50% of them. ivLCM was used as a fourth or later option in 76.5% of patients. No serious adverse events attributable to LCM were reported. CONCLUSIONS: LCM might be a fast, effective and safe add-on treatment in RSE.


Assuntos
Acetamidas/administração & dosagem , Anticonvulsivantes/administração & dosagem , Estado Epiléptico/tratamento farmacológico , Administração Intravenosa , Adulto , Idoso , Idoso de 80 Anos ou mais , Quimioterapia Combinada , Feminino , Humanos , Lacosamida , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Espanha , Resultado do Tratamento , Adulto Jovem
17.
Pediatr. aten. prim ; 13(52): 571-574, oct.-dic. 2011.
Artigo em Espanhol | IBECS | ID: ibc-97054

RESUMO

Los quistes de la glándula pineal, habitualmente asintomáticos, suelen ser un hallazgo incidental en pruebas de imagen realizadas por otro motivo. Se han relacionado ocasionalmente con diversos síntomas como cefalea, crisis epilépticas o trastornos psíquicos, siendo el factor más importante para que se conviertan en sintomáticos su tamaño o la presencia de un sangrado intraquístico. Presentamos el caso de una mujer de 14 años de edad con quiste en la glándula pineal de pequeño tamaño y sangrado en su interior que consulta por cambios en las características de su cefalea habitual y manifestaciones psicoafectivas(AU)


Pineal gland cysts usually asymptomatic are usually an incidental finding on imaging performed for another reason. They have occasionally been associated to various symptoms such as headache, seizures or mental disorders, being its size or the presence of intracystic bleeding the most important risk factors for becoming symptomatic. We report the case of a 14 years old woman with a small pineal cyst with intracystic bleeding that refers changes in the characteristics of her usual headache and psycho-affective manifestations(AU)


Assuntos
Humanos , Feminino , Adolescente , Cefaleia/diagnóstico , Cefaleia/terapia , Síncope/complicações , Síncope/diagnóstico , Medo/psicologia , Imageamento por Ressonância Magnética/instrumentação , Imageamento por Ressonância Magnética/métodos , Cefaleia/complicações , Cefaleia/fisiopatologia , Glândula Pineal/patologia , Glândula Pineal , /métodos
18.
Neurología (Barc., Ed. impr.) ; 26(1): 32-38, ene.-feb. 2010. tab, graf
Artigo em Espanhol | IBECS | ID: ibc-102229

RESUMO

Introducción: Se ha realizado una estimación económica de los costes de epilepsia en adultos.Métodos: Estudio observacional prospectivo realizado durante 6 meses, en pacientes epilépticos mayores de 14 años. Se excluyeron los pacientes con enfermedades concomitantes que pudieran influir en la evolución de la epilepsia. Los costes directos incluyeron: tratamiento administrado, número de consultas en Neurología, Atención Primaria, y Urgencias, número de días de ingreso hospitalario, número y tipo de pruebas diagnósticas, uso de los medios de transporte al hospital y desde el hospital, y los apoyos psicopedagógicos y sociales por epilepsia. Los costes indirectos se analizaron en función de la pérdida de productividad laboral de los pacientes, con consideración de los familiares cuando los pacientes necesitaban supervisión a causa de la epilepsia. Los costes totales se derivaron de la suma de los costes directos e indirectos. Los costes intangibles se evaluaron según el cuestionario QOLIE-10. Resultados:La media de los costes directos por paciente fue de 1.055,2 €. El gasto económico medio en los costes indirectos ascendió a 1.528,8 € por paciente. El total de los costes asociados a la epilepsia supuso una media de 2.584 € por cada paciente, derivados sobre todo de la pérdida de productividad laboral (p<0,05). En los costes intangibles, según la escala QOLIE-10, la media obtenida fue de 77,8. Conclusiones: El mayor porcentaje de los costes asociados a la epilepsia corresponde a la pérdida de productividad laboral de los pacientes. Los costes del sufrimiento psicológico y social en epilepsia provocan deterioro de la calidad de vida (AU)


Introduction: A financial estimate has been made of the costs of epilepsy in adults. Methods: A prospective, observational study, over a period of 6 months, on epileptic patients over 14 years-old. Patients with concomitant diseases that could influence the outcome of the epilepsy were excluded. The direct costs included: treatment received, number of visits to neurology, primary care, and emergencies, number of days admitted to hospital, number and type of diagnostic tests, use of transport to and from hospital, and psychopedagogic and social support due to the epilepsy. The indirect costs were analysed according to, loss of work productivity of the patients, taking into account families where the patient needed supervision due to epilepsy. The total costs were derived from the sum of the direct and indirect costs. The intangible costs were calculated according to QOLIE-10 questionnaire.Results: The mean direct cost per patient was 1,055.2 €. The mean indirect financial costs came to 1,528.8 € per patient. The total cost associated to epilepsy was a mean of 2,584 € for each patient, mainly arising from loss of work days (p<.05). For intangible costs according to the QOLIE-10 scale a mean of 77.8 was obtained.Conclusions: The greatest percentage of costs associated to epilepsy is due to the work productivity loss by the patients. The costs of psychological and social suffering in epilepsy lead to a deterioration in the quality of life (AU)


Assuntos
Humanos , Epilepsia/economia , /estatística & dados numéricos , Custos Diretos de Serviços/estatística & dados numéricos , Custos de Medicamentos/estatística & dados numéricos , Efeitos Psicossociais da Doença , Custos Hospitalares/estatística & dados numéricos , Anticonvulsivantes/uso terapêutico
19.
Neurologia ; 26(1): 32-8, 2011.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-21163205

RESUMO

INTRODUCTION: A financial estimate has been made of the costs of epilepsy in adults. METHODS: A prospective, observational study, over a period of 6 months, on epileptic patients over 14 years-old. Patients with concomitant diseases that could influence the outcome of the epilepsy were excluded. The direct costs included: treatment received, number of visits to neurology, primary care, and emergencies, number of days admitted to hospital, number and type of diagnostic tests, use of transport to and from hospital, and psychopedagogic and social support due to the epilepsy. The indirect costs were analysed according to, loss of work productivity of the patients, taking into account families where the patient needed supervision due to epilepsy. The total costs were derived from the sum of the direct and indirect costs. The intangible costs were calculated according to QOLIE-10 questionnaire. RESULTS: The mean direct cost per patient was 1,055.2 €. The mean indirect financial costs came to 1,528.8 € per patient. The total cost associated to epilepsy was a mean of 2,584 € for each patient, mainly arising from loss of work days (p<.05). For intangible costs according to the QOLIE-10 scale a mean of 77.8 was obtained. CONCLUSIONS: The greatest percentage of costs associated to epilepsy is due to the work productivity loss by the patients. The costs of psychological and social suffering in epilepsy lead to a deterioration in the quality of life.


Assuntos
Efeitos Psicossociais da Doença , Epilepsia/economia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Epilepsia/psicologia , Hospitalização/economia , Humanos , Pessoa de Meia-Idade , Estudos Prospectivos , Qualidade de Vida , Inquéritos e Questionários , Adulto Jovem
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