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- Baumgartner, T., et al.
(författare)
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A survey of the European Reference Network EpiCARE on clinical practice for selected rare epilepsies
- 2021
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Ingår i: Epilepsia Open. - : Wiley. - 2470-9239. ; 6:1, s. 160-170
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Clinical care of rare and complex epilepsies is challenging, because evidence-based treatment guidelines are scarce, the experience of many physicians is limited, and interdisciplinary treatment of comorbidities is required. The pathomechanisms of rare epilepsies are, however, increasingly understood, which potentially fosters novel targeted therapies. The objectives of our survey were to obtain an overview of the clinical practice in European tertiary epilepsy centers treating patients with 5 arbitrarily selected rare epilepsies and to get an estimate of potentially available patients for future studies. Methods: Members of the European Reference Network for rare and complex epilepsies (EpiCARE) were invited to participate in a web-based survey on clinical practice of patients with Dravet syndrome, tuberous sclerosis complex (TSC), autoimmune encephalitis, and progressive myoclonic epilepsies including Unverricht Lundborg and Unverricht-like diseases. A consensus-based questionnaire was generated for each disease. Results: Twenty-six of 30 invited epilepsy centers participated. Cohorts were present in most responding centers for TSC (87%), Dravet syndrome (85%), and autoimmune encephalitis (71%). Patients with TSC and Dravet syndrome represented the largest cohorts in these centers. The antiseizure drug treatments were rather consistent across the centers especially with regard to Dravet syndrome, infantile spasms in TSC, and Unverricht Lundborg / Unverricht-like disease. Available, widely used targeted therapies included everolimus in TSC and immunosuppressive therapies in autoimmune encephalitis. Screening for comorbidities was routinely done, but specific treatment protocols were lacking in most centers. Significance: The survey summarizes the current clinical practice for selected rare epilepsies in tertiary European epilepsy centers and demonstrates consistency as well as heterogeneity in the treatment, underscoring the need for controlled trials and recommendations. The survey also provides estimates for potential participants of clinical trials recruited via EpiCARE, emphasizing the great potential of Reference Networks for future studies to evaluate new targeted therapies and to identify novel biomarkers. © 2020 The Authors. Epilepsia Open published by Wiley Periodicals LLC on behalf of International League Against Epilepsy
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- Andermann, E., et al.
(författare)
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Psychiatric and cognitive adverse events: A pooled analysis of three phase III trials of adjunctive eslicarbazepine acetate for partial-onset seizures
- 2018
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Ingår i: Epilepsy and Behavior. - : Elsevier BV. - 1525-5050. ; 82, s. 119-127
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To evaluate the nature and incidence of psychiatric and cognitive adverse events (AEs) reported with eslicarbazepine acetate (ESL) used as adjunctive treatment for refractory partial-onset seizures (POS) in adults. Methods: This was a post-hoc analysis of data pooled from three randomized double-blind, placebo-controlled trials (BIA-2093-301, -302, -304). After an 8-week baseline period, patients received placebo or adjunctive ESL 400 mg (studies 301 and 302 only), 800 mg, or 1200 mg once daily (QD) for 14 weeks (2-week titration period, 12-week maintenance period). Psychiatric and cognitive AEs were identified from individual patient data. Suicidality was also evaluated using the Columbia-Classification Algorithm of Suicide Assessment (C-CASA), or the Columbia-Suicide Severity Rating Scale (C-SSRS). P-values were obtained using the chi-square test of independence or Fisher's exact test, without correcting for multiplicity. Results: The analysis population included 1447 patients (ESL, n = 1021; placebo, n = 426). Psychiatric treatment-emergent AEs (TEAEs) occurred in 10.8% of patients receiving ESL, and in a comparable proportion (10.3%) of patients receiving placebo (p = 0.802). The incidence of depression and suicidality-related TEAEs was higher for ESL (7.4%) vs. placebo (3.8%) (p = 0.009). The occurrence of these TEAEs differed between treatment groups (p = 0.010), but there was no notable trend between increasing ESL dose and increasing incidence of depression and suicidality-related TEAEs. Aggression/hostility-related TEAEs occurred in <0.1% of patients taking ESL vs. 0.9% taking placebo. The incidence of cognitive TEAEs was higher for ESL (7.1%) vs. placebo (4.0%) (p = 0.023); incidences of memory impairment, attention disturbance, apathy, and aphasia were higher for ESL 1200 mg than for other treatment groups. Incidences of psychiatric and cognitive serious AEs were (0.6% and 0.2% with ESL, and 0.5% and 0% with placebo, respectively. Psychiatric and cognitive TEAEs leading to discontinuation occurred in 1.9% and 1.4% of patients taking ESL. and 0.7% and 0.5% taking placebo, respectively. Conclusions: In phase III clinical trials of adjunctive ESL for treatment-refractory POS, psychiatric and cognitive TEAEs were reported infrequently with ESL and placebo. The incidences of depression and suicidality-related TEAEs and of cognitive TEAEs were higher for patients taking ESL vs. placebo. Incidences of psychiatric and cognitive SAEs, and TEAEs leading to discontinuation, were low with ESL and placebo. © 2017
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- Carreno-Quintero, Natalia, et al.
(författare)
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Non-targeted discovery of high-value bio-products in Nicotiana glauca L : a potential renewable plant feedstock
- 2024
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Ingår i: Bioresources and bioprocessing. - : Springer Nature. - 2197-4365. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- The evaluation of plant-based feedstocks is an important aspect of biorefining. Nicotiana glauca is a solanaceous, non-food crop that produces large amounts of biomass and is well adapted to grow in suboptimal conditions. In the present article, compatible sequential solvent extractions were applied to N. glauca leaves to enable the generation of enriched extracts containing higher metabolite content comparing to direct leaf extracts. Typically, between 60 to 100 metabolite components were identified within the fractions. The occurrence of plant fatty acids, fatty acid alcohols, alkanes, sterols and terpenoids was detected by gas liquid chromatography-mass spectrometry (GC-MS) and metabolite identification was confirmed by comparison of physico-chemical properties displayed by available authentic standards. Collectively, co-products such waxes, oils, fermentable sugars, and terpenoids were all identified and quantified. The enriched fractions of N. glauca revealed a high level of readily extractable hydrocarbons, oils and high value co-products. In addition, the saccharification yield and cell wall composition analyses in the stems revealed the potential of the residue material as a promising lignocellulosic substrate for the production of fermentable sugars. In conclusion a multifractional cascade for valuable compounds/commodities has been development, that uses N. glauca biomass. These data have enabled the evaluation of N. glauca material as a potential feedstock for biorefining.
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- Gidal, B. E., et al.
(författare)
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Exposure-safety and efficacy response relationships and population pharmacokinetics of eslicarbazepine acetate
- 2018
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Ingår i: Acta Neurologica Scandinavica. - : Hindawi Limited. - 0001-6314. ; 138:3, s. 203-211
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Tidskriftsartikel (refereegranskat)abstract
- ObjectivesEslicarbazepine acetate (ESL) is a once-daily (QD) oral antiepileptic drug (AED) for focal-onset seizures (FOS). Pharmacokinetic (PK) and pharmacodynamic (PD) models were developed to assess dose selection, identify significant AED drug interactions, and quantitate relationships between exposure and safety and efficacy outcomes from Phase 3 trials of adjunctive ESL. MethodsEslicarbazepine (the primary active metabolite of ESL) population PK was evaluated using data from 1351 subjects enrolled in 14 studies (11 Phase 1 and three Phase 3 studies) after multiple oral doses ranging from 400 to 1200mg. Population PK and PD models related individual eslicarbazepine exposures to safety outcomes and efficacy responses. ResultsEslicarbazepine PK was described by a one-compartment model with linear absorption and elimination. The probability of a treatment-emergent adverse event (TEAE; dizziness, headache, or somnolence) was higher with an initial dose of ESL 800mg than with an initial dose of ESL 400mg QD. Body weight, sex, region, and baseline use of carbamazepine (CBZ) or lamotrigine were also found to influence the probability of TEAEs. Eslicarbazepine exposure influenced serum sodium concentration, standardized seizure frequency, and probability of response; better efficacy outcomes were predicted in patients not from Western Europe (WE; vs WE patients) and those not taking CBZ (vs taking CBZ) at baseline. ConclusionsPharmacokinetic and PK/PD modeling were implemented during the development of ESL for adjunctive treatment of FOS in adults. This quantitative approach supported decision-making during the development of ESL, and contributed to dosing recommendations and labeling information related to drug interactions.
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- Kivekäs, Niku, et al.
(författare)
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Contribution of ship traffic to aerosol particle concentrations downwind of a major shipping lane
- 2014
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Ingår i: Atmospheric Chemistry And Physics. - : Copernicus GmbH. - 1680-7316 .- 1680-7324. ; 14:16, s. 8255-8267
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Tidskriftsartikel (refereegranskat)abstract
- Particles in the atmosphere are of concern due to their toxic properties and effects on climate. In coastal areas, ship emissions can be a significant anthropogenic source. In this study we investigated the contribution from ship emissions to the total particle number and mass concentrations at a remote location. We studied the particle number concentration (12 to 490 nm in diameter), the mass concentration (12 to 150 nm in diameter) and number and volume size distribution of aerosol particles in ship plumes for a period of 4.5 months at Hovsore, a coastal site on the western coast of Jutland in Denmark. During episodes of western winds, the site is about 50 km downwind of a major shipping lane and the plumes are approximately 1 hour old when they arrive at the site. We have used a sliding percentile-based method for separating the plumes from the measured background values and to calculate the ship plume contribution to the total particle number and PM0.15 mass concentration (mass of particles below 150 nm in diameter, converted from volume assuming sphericity) at the site. The method is not limited to particle number or volume concentration, but can also be used for different chemical species in both particle and gas phase. The total number of analyzed ship plumes was 726, covering on average 19% of the time when air masses were arriving at the site over the shipping lane. During the periods when plumes were present, the particle concentration exceeded the background values on average by 790 cm(-3) by number and 0.10 gm(-3) by mass. The corresponding daily average values were 170 cm-3 and 0.023 gm-3, respectively. This means that the ship plumes contributed between 11 and 19% to the particle number concentration and between 9 and 18% to PM0.15 during days when air was arriving over the shipping lane. The estimated annual contribution from ship plumes, where all wind directions were included, was in the range of 5-8% in particle number concentration and 4-8% in PM0.15.
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