Safety and efficacy of dronedarone from clinical trials to real-world evidence: implications for its use in atrial fibrillation.

Efficacy and safety of dronedarone was shown in the ATHENA trial for paroxysmal or persistent atrial fibrillation (AF) patients. Further trials revealed safety concerns in patients with heart failure and permanent AF. This review summarizes insights from recent real-world studies and meta-analyses, including reports on efficacy, with focus on liver safety, mortality risk in patients with paroxysmal/persistent AF, and interactions of dronedarone with direct oral anticoagulants. Reports of rapidly progressing liver failure in dronedarone-prescribed patients in 2011 led to regulatory cautions about potential liver toxicity. Recent real-world evidence suggests dronedarone liver safety profile is similar to other antiarrhythmics and liver toxicity could be equally common with many Class III antiarrhythmics. Dronedarone safety concerns (increased mortality in patients with permanent AF) were raised based on randomized controlled trials (RCT) (ANDROMEDA and PALLAS), but comedication with digoxin may have increased the mortality rates in PALLAS, considering the dronedarone-digoxin pharmacokinetic (PK) interaction. Real-world data on apixaban-dronedarone interactions and edoxaban RCT observations suggest no significant safety risks for these drug combinations. Median trough plasma concentrations of dabigatran 110 mg during concomitant use with dronedarone are at acceptable levels, while PK data on the rivaroxaban-dronedarone interaction are unavailable. In RCTs and real-world studies, dronedarone significantly reduces AF burden and cardiovascular hospitalizations, and demonstrates a low risk for proarrhythmia in patients with paroxysmal or persistent AF. The concerns on liver safety must be balanced against the significant reduction in hospitalizations in patients with non-permanent AF and low risk for proarrhythmias following dronedarone treatment

Lineability within probability theory settings

[EN] The search of lineability consists on finding large vector spaces of mathematical objects with special properties. Such examples have arisen in the last years in a wide range of settings such as in real and complex analysis, sequence spaces, linear dynamics, norm-attaining functionals, zeros of polynomials in Banach spaces, Dirichlet series, and non-convergent Fourier series, among others. In this paper we present the novelty of linking this notion of lineability to the area of Probability Theory by providing positive (and negative) results within the framework of martingales, random variables, and certain stochastic processes.This work was partially supported by Ministerio de Educacion, Cultura y Deporte, projects MTM2013-47093-P and MTM2015-65825-P, by the Basque Government through the BERC 2014-2017 program and by the Spanish Ministerio de Economia y Competitividad: BCAM Severo Ochoa excellence accreditation SEV-2013-0323.Conejero, JA.; Fenoy, M.; Murillo Arcila, M.; Seoane Sepúlveda, JB. (2017). Lineability within probability theory settings. Revista de la Real Academia de Ciencias Exactas Físicas y Naturales Serie A Matemáticas. 111(3):673-684. https://doi.org/10.1007/s13398-016-0318-yS6736841113Aizpuru, A., Pérez-Eslava, C., García-Pacheco, F.J., Seoane-Sepúlveda, J.B.: Lineability and coneability of discontinuous functions on $$\mathbb{R}$$ R . Publ. Math. Debrecen 72(1–2), 129–139 (2008)Aron, R., Gurariy, V.I., Seoane, J.B.: Lineability and spaceability of sets of functions on $$\mathbb{R}$$ R . Proc. Am. Math. Soc. 133(3), 795–803 (2005, electronic)Aron, R.M., González, L.B., Pellegrino, D.M., Sepúlveda J.B.S.: Lineability: the search for linearity in mathematics. Monographs and Research Notes in Mathematics. CRC Press, Boca Raton (2016)Ash, R.B.: Real analysis and probability. Probability and mathematical statistics, No. 11. Academic Press, New York-London (1972)Barbieri, G., García-Pacheco, F.J., Puglisi, D.: Lineability and spaceability on vector-measure spaces. Stud. Math. 219(2), 155–161 (2013)Bernal-González, L., Cabrera, M.O.: Lineability criteria, with applications. J. Funct. Anal. 266(6), 3997–4025 (2014)Bernal-González, L., Pellegrino, D., Seoane-Sepúlveda, J.B.: Linear subsets of nonlinear sets in topological vector spaces. Bull. Am. Math. Soc. (N.S.), 51(1), 71–130 (2014)Berndt, B.C.: What is a $$q$$ q -series? In: Ramanujan rediscovered, Ramanujan Math. Soc. Lect. Notes Ser., vol. 14, pp. 31–51. Ramanujan Math. Soc., Mysore (2010)Bertoloto, F.J., Botelho, G., Fávaro, V.V., Jatobá, A.M.: Hypercyclicity of convolution operators on spaces of entire functions. Ann. Inst. Fourier (Grenoble) 63(4), 1263–1283 (2013)Billingsley, P.: Probability and measure. Wiley Series in Probability and Mathematical Statistics, 3rd edn, A Wiley-Interscience Publication. Wiley, New York (1995)Botelho, G., Fávaro, V.V.: Constructing Banach spaces of vector-valued sequences with special properties. Mich. Math. J. 64(3), 539–554 (2015)Cariello, D., Seoane-Sepúlveda, J.B.: Basic sequences and spaceability in $$\ell _p$$ ℓ p spaces. J. Funct. Anal. 266(6), 3797–3814 (2014)Drewnowski, L., Lipecki, Z.: On vector measures which have everywhere infinite variation or noncompact range. Dissertationes Math. (Rozprawy Mat.) 339, 39 (1995)Dugundji, J.: Topology. Allyn and Bacon, Inc., Boston, Mass.-London-Sydney (1978, Reprinting of the 1966 original, Allyn and Bacon Series in Advanced Mathematics)Enflo, P.H., Gurariy, V.I., Seoane-Sepúlveda, J.B.: Some results and open questions on spaceability in function spaces. Trans. Am. Math. Soc. 366(2), 611–625 (2014)Fonf, V.P., Zanco, C.: Almost overcomplete and almost overtotal sequences in Banach spaces. J. Math. Anal. Appl. 420(1), 94–101 (2014)Gámez-Merino, J.L., Seoane-Sepúlveda, J.B.: An undecidable case of lineability in $$\mathbb{R}^{\mathbb{R}}$$ R R . J. Math. Anal. Appl. 401(2), 959–962 (2013)Gurariĭ, V.I.: Linear spaces composed of everywhere nondifferentiable functions. C. R. Acad. Bulgare Sci. 44(5), 13–16 (1991)Muñoz-Fernández, G.A., Palmberg, N., Puglisi, D., Seoane-Sepúlveda, J.B.: Lineability in subsets of measure and function spaces. Linear Algebra Appl. 428(11–12), 2805–2812 (2008)Walsh, J.B.: Martingales with a multidimensional parameter and stochastic integrals in the plane. In: Lectures in probability and statistics (Santiago de Chile, 1986), Lecture Notes in Math., vol. 1215, pp. 329–491. Springer, Berlin (1986)Wise, G.L., Hall, E.B.: Counterexamples in probability and real analysis. The Clarendon Press, Oxford University Press, New York (1993

Advances for Treating in-Hospital Cardiac Arrest: Safety and Effectiveness of a New Automatic External Cardioverter-Defibrillator

OBJECTIVES: The purpose of this study was to prospectively analyze the performance and safety of a new programmable, fully automatic external cardioverter-defibrillator (AECD) in a European multicenter trial. BACKGROUND Although, the response time to cardiac arrest (CA) is a major determinant of mortality and morbidity, in-hospital strategies have not significantly changed during the last 30 years. METHODS: Patients (n = 117) at risk of CA in monitored wards (n = 51) and patients undergoing electrophysiologic testing or implantable cardioverter-defibrillator (ICD) implantation (n = 66) were enrolled. The accuracy of the automatic response of the device to any change of rhythm (lasting >1 s and >4 beats) was confirmed by reviewing the simultaneously recorded Holter data and the programmed parameters. RESULTS: During 1,240 h, 1,988 episodes of rhythm changes were documented. A total of 115 episodes lasted > or =10 s or needed treatment (pacing, n = 32; ICD, n = 51; AECD, n = 35) for termination. The device detected ventricular tachyarrhythmias with a sensitivity of 100% and specificity of 97.6% (true negatives, n = 1,454; true positives, n = 499; false positives, n = 35; false negatives, n = 0). The false positives were all caused by T-wave oversensing during ventricular pacing. There were no complications or adverse events. The mean response time was 14.4 s for those episodes needing a full charge of the capacitor. CONCLUSIONS: This new AECD is safe and effective in detecting, monitoring, and treating spontaneous arrhythmias. This fully automatic device shortens the response time to treatment, and it is likely that it will significantly improve the outcome of patients with in-hospital CA

Design and validation of the 1-week memory battery for assessing episodic memory and accelerated long-term forgetting in cognitively unimpaired subjects

Subtle decline in memory is thought to arise in the preclinical phase of Alzheimer's disease (AD). However, detecting these initial cognitive difficulties cross-sectionally has been challenging, and the exact nature of the decline is still debated. Accelerated long-term forgetting (ALF) has been recently suggested as one of the earliest and most sensitive indicators of memory dysfunction in subjects at risk of developing AD. The objective of this study was to design and validate the 1-week memory battery (1WMB) for assessing episodic memory and ALF in cognitively unimpaired individuals.The 1WMB is unique in that it assesses multimodal memory and measures recall at both short delay (20 min) and at long term (1 week). Forty-five cognitively unimpaired subjects were assessed with 1WMB and standardized neuropsychological tests. Subjective cognitive decline (SCD), levels of anxiety and depression, and cognitive reserve were also measured.The tests of 1WMB showed a high internal consistency, and concurrent validity was observed with standard tests of episodic memory and executive functions. The analysis revealed a greater loss of information at 1 week compared to short-term forgetting (20 min). Performance in the 1WMB was affected by age and educational level, but was not associated with levels of anxiety and depression. Unlike standard tests, performance in the 1WMB correlated with measures of SCD.Our findings indicate that the 1WMB has good psychometric properties, and future studies are needed to explore its potential usefulness to assess cognitively unimpaired subjects at increased risk of developing AD. (PsycInfo Database Record (c) 2023 APA, all rights reserved)

Incidence and drug treatment of emotional distress after cancer diagnosis : a matched primary care case-control study

Notes This work is published under the standard license to publish agreement. After 12 months the work will become freely available and the license terms will switch to a Creative Commons Attribution-NonCommercial-Share Alike 3.0 Unported License.Peer reviewedPublisher PD

Synaptic, axonal damage and inflammatory cerebrospinal fluid biomarkers in neurodegenerative dementias

INTRODUCTION: Synaptic damage, axonal neurodegeneration, and neuroinflammation are common features in Alzheimer's disease (AD), frontotemporal dementia (FTD), and Creutzfeldt-Jakob disease (CJD). METHODS: Unicentric cohort of 353 participants included healthy control (HC) subjects, AD continuum stages, genetic AD and FTD, and FTD and CJD. We measured cerebrospinal fluid neurofilament light (NF-L), neurogranin (Ng), 14-3-3, and YKL-40 proteins. RESULTS: Biomarkers showed differences in HC subjects versus AD, FTD, and CJD. Disease groups differed between them except AD versus FTD for YKL-40. Only NF-L differed between all stages within the AD continuum. AD and FTD symptomatic mutation carriers presented differences with respect to HC subjects. Applying the AT(N) system, 96% subjects were positive for neurodegeneration if 14-3-3 was used, 94% if NF-L was used, 62% if Ng was used, and 53% if YKL-40 was used. DISCUSSION: Biomarkers of synapse and neurodegeneration differentiate HC subjects from neurodegenerative dementias and between AD, FTD, and CJD. NF-L and 14-3-3 performed similar to total tau when AT(N) system was applied

Spanish experience on the design of radon surveys based on the use of geogenic information

One of the requirements of the recently approved EU-BSS (European Basic Safety Standards Directive, EURATOM, 2013) is the design and implementation of national radon action plans in the member states (Annex XVIII). Such plans require radon surveys. The analysis of indoor radon data is supported by the existing knowledge about geogenic radiation. With this aim, we used the terrestrial gamma dose rate data from the MARNA project. In addition, we considered other criterion regarding the surface of Spain, population, permeability of rocks, uranium and radium contain in soils because currently no data are available related to soil radon gas concentration and permeability in Spain. Given that, a Spanish radon map was produced which will be part of the European Indoor Radon Map and a component of the European Atlas of Natural Radiation. The map indicates geographical areas with high probability of finding high indoor radon concentrations. This information will support legislation regarding prevention of radon entry both in dwellings and workplaces. In addition, the map will serve as a tool for the development of strategies at all levels: individual dwellings, local, regional and national administration

Revealing the last 13,500 years of environmental history from the multiproxy record of a mountain lake (Lago Enol, northern Iberian Peninsula)

This is the author's accepted manuscript. The final publication is available at Springer via http://dx.doi.org/10.1007/s10933-009-9387-7.We present the Holocene sequence from Lago Enol (43°16′N, 4°59′W, 1,070 m a.s.l.), Cantabrian Mountains, northern Spain. A multiproxy analysis provided comprehensive information about regional humidity and temperature changes. The analysis included sedimentological descriptions, physical properties, organic carbon and carbonate content, mineralogy and geochemical composition together with biological proxies including diatom and ostracod assemblages. A detailed pollen study enabled reconstruction of variations in vegetation cover, which were interpreted in the context of climate changes and human impact. Four distinct stages were recognized for the last 13,500 years: (1) a cold and dry episode that includes the Younger Dryas event (13,500–11,600 cal. year BP); (2) a humid and warmer period characterizing the onset of the Holocene (11,600–8,700 cal. year BP); (3) a tendency toward a drier climate during the middle Holocene (8,700–4,650 cal. year BP); and (4) a return to humid conditions following landscape modification by human activity (pastoral activities, deforestation) in the late Holocene (4,650–2,200 cal. year BP). Superimposed on relatively stable landscape conditions (e.g. maintenance of well established forests), the typical environmental variability of the southern European region is observed at this site.The Spanish Inter-Ministry Commission of Science and Technology (CICYT), the Spanish National Parks agency, the European Commission, the Spanish Ministry of Science, and the European Social Fund

Revealing the last 13,500 years of environmental history from the multiproxy record of a mountain lake (Lago Enol, northern Iberian Peninsula)

This is the author's accepted manuscript. The final publication is available at Springer via http://dx.doi.org/10.1007/s10933-009-9387-7.We present the Holocene sequence from Lago Enol (43°16′N, 4°59′W, 1,070 m a.s.l.), Cantabrian Mountains, northern Spain. A multiproxy analysis provided comprehensive information about regional humidity and temperature changes. The analysis included sedimentological descriptions, physical properties, organic carbon and carbonate content, mineralogy and geochemical composition together with biological proxies including diatom and ostracod assemblages. A detailed pollen study enabled reconstruction of variations in vegetation cover, which were interpreted in the context of climate changes and human impact. Four distinct stages were recognized for the last 13,500 years: (1) a cold and dry episode that includes the Younger Dryas event (13,500–11,600 cal. year BP); (2) a humid and warmer period characterizing the onset of the Holocene (11,600–8,700 cal. year BP); (3) a tendency toward a drier climate during the middle Holocene (8,700–4,650 cal. year BP); and (4) a return to humid conditions following landscape modification by human activity (pastoral activities, deforestation) in the late Holocene (4,650–2,200 cal. year BP). Superimposed on relatively stable landscape conditions (e.g. maintenance of well established forests), the typical environmental variability of the southern European region is observed at this site.The Spanish Inter-Ministry Commission of Science and Technology (CICYT), the Spanish National Parks agency, the European Commission, the Spanish Ministry of Science, and the European Social Fund