RESUMO
BACKGROUND: Natalizumab and fingolimod are used as high-efficacy treatments in relapsing-remitting multiple sclerosis. Several observational studies comparing these two drugs have shown variable results, using different methods to control treatment indication bias and manage censoring. The objective of this empirical study was to elucidate the impact of methods of causal inference on the results of comparative effectiveness studies. METHODS: Data from three observational multiple sclerosis registries (MSBase, the Danish MS Registry and French OFSEP registry) were combined. Four clinical outcomes were studied. Propensity scores were used to match or weigh the compared groups, allowing for estimating average treatment effect for treated or average treatment effect for the entire population. Analyses were conducted both in intention-to-treat and per-protocol frameworks. The impact of the positivity assumption was also assessed. RESULTS: Overall, 5,148 relapsing-remitting multiple sclerosis patients were included. In this well-powered sample, the 95% confidence intervals of the estimates overlapped widely. Propensity scores weighting and propensity scores matching procedures led to consistent results. Some differences were observed between average treatment effect for the entire population and average treatment effect for treated estimates. Intention-to-treat analyses were more conservative than per-protocol analyses. The most pronounced irregularities in outcomes and propensity scores were introduced by violation of the positivity assumption. CONCLUSIONS: This applied study elucidates the influence of methodological decisions on the results of comparative effectiveness studies of treatments for multiple sclerosis. According to our results, there are no material differences between conclusions obtained with propensity scores matching or propensity scores weighting given that a study is sufficiently powered, models are correctly specified and positivity assumption is fulfilled.
Assuntos
Esclerose Múltipla Recidivante-Remitente , Esclerose Múltipla , Cloridrato de Fingolimode/uso terapêutico , Humanos , Esclerose Múltipla/tratamento farmacológico , Esclerose Múltipla Recidivante-Remitente/tratamento farmacológico , Natalizumab/uso terapêutico , Resultado do TratamentoRESUMO
BACKGROUND: The most frequent phenotypes of dysferlin myopathy are limb-girdle muscular dystrophy 2B (LGMD2B) and Miyoshi myopathy (MM). Our objective was to find clinical or MRI markers to differentiate phenotypes of dysferlin myopathy regardless of initial symptoms. METHODS: This retrospective study included 29 patients with confirmed mutations in the DYSF gene (14 MM, 12 LGMD2B, 1 asymptomatic hyperCKemia, and 2 symptomatic carriers). All underwent an annual clinical examination (Medical Research Council scale), functional status assessment, and creatine kinase, pulmonary, and cardiac testing. For research purposes, we performed lower limb MRI studies in all 29 patients to identify the pattern of muscle impairment and to quantify involvement. Statistical correlations between MRI findings and phenotype, disease duration, and functional status were determined. RESULTS: The mean clinical follow-up was 6.4 +/- 5.7 years. No significant differences were found in the rate of progression, functional prognosis, or mutations between patients with MM and patients with LGMD2B. The MRI pattern of muscle involvement was the same for patients with MM and patients with LGMD2B. The adductor magnus and gastrocnemius medialis were the first to be impaired in both phenotypes. The progression of muscle involvement correlated with clinical status. CONCLUSIONS: Splitting dysferlin myopathy into separate phenotypes does not reveal significant differences in terms of rate of progression, prognosis, genotype, or MRI pattern. The finding that proximal and distal muscles are already impaired in the MRI at onset in both MM and LGMD2B favors grouping all phenotypes under the term dysferlin myopathy.
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Imageamento por Ressonância Magnética , Proteínas de Membrana/genética , Proteínas Musculares/genética , Distrofia Muscular do Cíngulo dos Membros/genética , Distrofia Muscular do Cíngulo dos Membros/patologia , Atividades Cotidianas , Adolescente , Adulto , Idoso , Criança , Estudos de Coortes , Progressão da Doença , Disferlina , Seguimentos , Genótipo , Humanos , Lactente , Perna (Membro)/patologia , Pessoa de Meia-Idade , Músculo Esquelético/patologia , Distrofia Muscular do Cíngulo dos Membros/fisiopatologia , Fenótipo , Prognóstico , Estudos Retrospectivos , Índice de Gravidade de Doença , Adulto JovemRESUMO
INTRODUCTION: The description of a highly sensitive and specific biomarker for neuromyelitis optica (NMO-IgG/aquaporin-4 antibody) extended the clinical spectrum of NMO to limited forms such as optic neuritis (ON) and longitudinally extensive myelitis (LEM). OBJECTIVE: To asses the sensitivity and specificity of our assay, and to describe the clinical characteristics of the patients who were tested for NMO-IgG. METHODS: NMO-IgG was analysed by immunohistochemistry and confirmed by assay on HEK cells transfected with aquaporin-4. The clinical information was obtained from forms filled in by the referring neurologists. RESULTS: A total of 580 samples from 518 patients were analysed from November 2005 to September 2008. Clinical information was available from 358 (68%) patients. All 33 (100%) positive cases were followed up. Twenty-eight of the 43 (65%) patients diagnosed with NMO by the revised criteria of 2006 were positive; the sensitivity was 62.5% when applying the same criteria, but discounting the criterion of NMO-IgG status, or 57% when applying the criteria of 1999. NMO-IgG was detected in 3 (13%) of the recurrent LEM and 2 (4%) of the recurrent ON. NMO-IgG was not detected in the remaining patients (96 with a final diagnosis of multiple sclerosis; 80 with myelitis; 28 with non-recurrent ON; and 33 other diagnosis). CONCLUSIONS: No false positive cases were found in this large and non-selected study. NMO-IgG positive cases were mostly associated with NMO, and only in a low percentage with recurrent ON or LEM.