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- Eslicarbazepine acetate as monotherapy in clinical practice: Outcomes from Euro-EsliPublication . Holtkamp, M; Delanty, N; Sales, F; Serratosa, J; McMurray, R; Villanueva, VOBJECTIVES: To assess the effectiveness and safety/tolerability of eslicarbazepine acetate (ESL) monotherapy in clinical practice in Europe. MATERIALS AND METHODS: Euro-Esli was a pooled analysis of 14 European clinical practice studies. Responder rate (≥50% seizure frequency reduction) and seizure freedom rate (seizure freedom at least since prior visit) were assessed after 3, 6 and 12 months of ESL treatment and at last visit. Adverse events (AEs) and AEs leading to ESL discontinuation were assessed throughout follow-up. A subanalysis was conducted to assess outcomes for patients treated initially with ESL monotherapy and for patients treated at the last visit with ESL monotherapy. RESULTS: ESL was used as monotherapy in 88/2045 (4.3%) patients initially and in 229/1340 (17.1%) patients at the last visit. At 12 months, responder and seizure freedom rates were 94.1% and 88.2%, respectively, in patients treated initially with ESL monotherapy, and 93.2% and 77.4%, respectively, in patients treated at the last visit with ESL monotherapy. Corresponding values for patients treated initially with ESL adjunctive therapy were 74.8% and 39.0%, respectively; and for patients treated at the last visit with ESL adjunctive therapy, corresponding values were 70.4% and 25.9%, respectively. Safety and tolerability were generally comparable in patients treated with ESL as monotherapy or adjunctive therapy. The most commonly reported AEs (≥5% of patients in any group) were dizziness, somnolence, instability/ataxia, and fatigue. CONCLUSIONS: These clinical practice data support the use of ESL as monotherapy, as well as adjunctive therapy, for focal-onset seizures, complementing evidence from clinical trials.
- Erlangen Score as a tool to predict progression from mild cognitive impairment to dementia in Alzheimer's diseasePublication . Baldeiras, I; Santana, I; Leitão, MJ; Vieira, D; Duro, D; Mroczko, B; Kornhuber, J; Lewczuk, PBACKGROUND: The previously described and validated Erlangen Score (ES) algorithm enables interpretation of the cerebrospinal fluid (CSF) biomarkers of Alzheimer's disease (AD), ordering them on an ordinal scale: from neurochemically normal (ES = 0) through improbable AD (ES = 1), possible AD (ES = 2 or 3), to probable AD (ES = 4). Here we assess the accuracy of the ES in predicting hazards of progression from the mild cognitive impairment (MCI) stage of AD to the dementia stage of the disease (Alzheimer's disease dementia (ADD)) in a novel, single-center cohort. METHODS: Baseline CSF biomarkers (amyloid beta (Aβ) 1-42, Aβ42/40, Tau, and pTau181), interpreted according to the ES, were used to estimate time to progression from the MCI stage of AD to ADD, conditional on age, gender, APOE ε4 genotype, and Mini Mental State Examination score in 144 MCI subjects, using the Extended Cox Model; the subjects were followed-up until they developed dementia or until they had been cognitively stable for at least 2 years. In addition, ES distributions were studied in 168 ADD cases and 66 neurologic controls. Further, we stratified MCI patients into those who progressed to ADD faster (within 3 years, n = 47) and those who progressed slower (n = 74). RESULTS: The distributions of the ES categories across the four diagnostic groups (Controls, MCI-Stable, MCI-AD, and ADD) were highly significantly different (Kruskal-Wallis χ2(df = 3) = 151.4, p < 0.001), with significant contrasts between each pair (p < 0.005), except between the ADD and the MCI-AD groups (p = 1.0). MCI patients with ES = 2 or 3 had 6-8 times higher hazards to progress to ADD compared to patients with ES = 0 or 1 in the first 3 follow-up years, and then their hazards decreased to those of the group with ES = 0 or 1. Patients with ES = 4 had hazards 8-12 times higher compared to the ES = 0 or 1 group. Faster progressors with ES = 2 or 3 had, in comparison to slower progressors, significantly lower Aβ1-42, Aβ1-40, and Aβ42/40, but comparable Tau and pTau181. A highly significant difference of the ES distributions between these two groups was observed (p < 0.001). CONCLUSIONS: Our current results reconfirm and extend the conclusions of the previously published report that the Erlangen Score is a useful tool facilitating interpretation of a complex pattern of the CSF AD biomarkers.
- Vascular effects of a polyphenolic fraction from Oxalis pes-caprae L.: role of α-adrenergic receptors Sub-typesPublication . Fonseca, DA; Ferreira, M; Campos, MG; Antunes, PE; Antunes, MJ; Cotrim, MDOxalis pes-caprae L. is a plant of the Oxalidaceae family, from which several compounds have been previously identified. Recently, we showed that an Oxalis pes-caprae L. extract inhibits the vasopressor effect of noradrenaline. In this work we aimed to explore the mechanisms involved in this effect. The results confirmed that the flavonoid fraction present in the extract inhibits noradrenaline-induced contractions and that this effect is concentration-dependent. Also, a parallel shift to the right in the noradrenaline concentration-response curve was observed, suggesting a decrease in efficacy and also in potency. Together these results support the assumption that the extract could exert a non-competitive antagonism on the α-adrenergic receptors. However, experiments in the presence of competitive antagonists for α-adrenergic receptor sub-types (i.e. prazosin, yohimbine and phentolamine) showed that the effect may not be directly mediated by α-adrenergic receptors. Thus, the interaction of this extract with the adrenergic system remains to be confirmed.