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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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- 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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- Tobin, J. J., et al.
(författare)
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Deuterium-enriched water ties planet-forming disks to comets and protostars
- 2023
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 615:7951, s. 227-230
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Tidskriftsartikel (refereegranskat)abstract
- Water is a fundamental molecule in the star and planet formation process, essential for catalysing the growth of solid material and the formation of planetesimals within disks1,2. However, the water snowline and the HDO:H2O ratio within proto-planetary disks have not been well characterized because water only sublimates at roughly 160 K (ref. 3), meaning that most water is frozen out onto dust grains and that the water snowline radii are less than 10 AU (astronomical units)4,5. The sun-like protostar V883 Ori (M* = 1.3 M⊙)6 is undergoing an accretion burst7, increasing its luminosity to roughly 200 L⊙ (ref. 8), and previous observations suggested that its water snowline is 40-120 AU in radius6,9,10. Here we report the direct detection of gas phase water (HDO and [Formula: see text]) from the disk of V883 Ori. We measure a midplane water snowline radius of approximately 80 AU, comparable to the scale of the Kuiper Belt, and detect water out to a radius of roughly 160 AU. We then measure the HDO:H2O ratio of the disk to be (2.26 ± 0.63) × 10-3. This ratio is comparable to those of protostellar envelopes and comets, and exceeds that of Earth's oceans by 3.1σ. We conclude that disks directly inherit water from the star-forming cloud and this water becomes incorporated into large icy bodies, such as comets, without substantial chemical alteration.
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