Réduire ou ralentir la fibrillation auriculaire : est-ce la bonne question en 2010 ?

RésuméPourquoi et comment traiter la fibrillation atriale ? Cette question a paru simple pendant de nombreuses années : la fibrillation atriale, trouble du rythme cardiaque, doit être traitée par des médicaments anti-arythmiques, tant qu’ils peuvent être efficaces. Les effets secondaires de ces médicaments, comme le bénéfice fréquemment apporté par un simple traitement bradycardisant a amené à discuter il y a une dizaine d’années deux stratégies thérapeutiques, réduire ou ralentir. Mais ce choix largement mis en avant dans les précédentes recommandations thérapeutiques, apparaît aujourd’hui réducteur. En 2010 on peut sans doute proposer deux objectifs thérapeutiques, traiter les symptômes et traiter le risque cardiovasculaire associée à la fibrillation. La gêne symptomatique entraînée par l’arythmie doit être toujours évaluée chez nos patients, volontiers selon la classification récente EHRA. Parallèlement la fibrillation fait partie du continuum cardiovasculaire, et constitue un marqueur de risque supplémentaire : il apparaît certain que le contrôle de ce risque supplémentaire associé à la fibrillation ne dépend pas uniquement du traitement de l’arythmie proprement dite.SummaryWhy and how to treat atrial fibrillation? This question seemed simple for many years: atrial fibrillation, a cardiac arrhythmia, should be treated with antiarrhythmic drugs, as long as they can be effective. Side effects of these drugs, as good benefit often provided by a simple bradycardic treatment led to discuss it some 10 years ago 2 therapeutic strategies: rhythm control or rate control. But this choice widely highlighted in the previous guidelines, now seems simplistic. In 2010 we can probably offer two therapeutic goals, treat symptoms and treat cardiovascular risk associated with atrial fibrillation. The discomfort caused by symptomatic arrhythmia should always be assessed in our patients, as by the recent EHRA classification. Meanwhile fibrillation is part of the cardiovascular continuum, and is a marker of an additional risk: it appears certain that the control of this additional risk does not depend solely on the treatment of the arrhythmia itself

Les effets pro-arythmiques des médicaments

RésuméLes effets pro-arythmiques des médicaments sont fréquents et graves, et sont associés à une surmortalité non négligeable. La polymédication augmente le nombre d’effets indésirables et d’interactions graves voire mortelles. Certains sont facilement évitables. Cependant, au-delà de l’allongement de l’intervalle QT, d’autres mécanismes peuvent avoir un rôle majeur comme les dysfonctions du RyR2, responsable d’arythmie calcium-dépendantes par surcharge calcique intracellulaire, avec apparition de post-dépolarisations tardives, sans modifications de l’intervalle QT. Les bloqueurs des canaux sodiques sont également un problème sérieux de part le risque de démasquer ou d’aggraver une dysfonction du canal sodique chez des patients atteints de syndrome de Brugada asymptomatique ou non. Leur dépistage à un stade précoce du développement des médicaments peut avoir un intérêt majeur.SummaryThe cardiac safety of new and marketed drugs is a major concern for public authorities, patients, physicians as well as pharmaceutical companies. Letal adverse drug reactions are indeed a leading cause of death worldwide and increase at a greater rate than the increase in total hospital admission. The increasing use of polypharmacy in current clinical practice is also associated to a growing number of side effects and interactions leading to fatal adverse events. Measurement of the QT interval is an established, albeit incomplete, approach to assess the proarrhythmic risk of a drug. Ventricular arrhythmia (VA) can be caused by a QT-prolonging drug inducing abnormal repolarization of the action potential (AP) of ventricular cardiomyocytes. Emerging evidence, derived from recent understanding of these mechanisms and of similar mechanisms reported for heart failure (HF), suggest that diastolic Ca2+ leak from the sarcoplasmic reticulum (SR) related to RyR2 dysfunction can induce Ca2+ dependent arrhythmia. In this report, we review mechanisms underlying drug-induced arrhythmogenic effects and Ca2+ dependent arrhythmia, and, for the latter, we discuss some of the issues associated to worsening of cardiac arrhythmias

Publisher’s Note: “Dispersion calibration for the National Ignition Facility electron–positron–proton spectrometers for intense laser matter interactions” [Rev. Sci. Instrum. 92, 033516 (2021)] (Rev. Sci. Instrum. 92, 059902 (2021)

Electron-positron pairs, produced in intense laser-solid interactions, are diagnosed using magnetic spectrometers with image plates, such as the National Ignition Facility (NIF) Electron Positron Proton Spectrometers (EPPS). Although modeling can help infer the quantitative value, the accuracy of the models needs to be verified to ensure measurement quality. The dispersion of low-energy electrons and positrons may be affected by fringe magnetic fields near the entrance of the EPPS. We have calibrated the EPPS with six electron beams from a Siemens Oncor linear accelerator (linac) ranging in energy from $2.7$--$15.2$ $\mathrm{MeV}$ as they enter the spectrometer. A Geant4 TOPAS Monte-Carlo simulation was set up to match depth dose curves and lateral profiles measured in water at $100$ $\mathrm{cm}$ source-surface distance. An accurate relationship was established between the bending magnet current setting and the energy of the electron beam at the exit window. The simulations and measurements were used to determine the energy distributions of the six electron beams at the EPPS slit. Analysis of the scanned image plates together with the determined energy distribution arriving in the spectrometer provide improved dispersion curves for the EPPS.Comment: Published in Review of Scientific Instruments, 5 pages, 3 figures, This article may be downloaded for personal use only. Any other use requires prior permission of the author and AIP Publishin

Safety and Efficacy of Ranibizumab in Diabetic Macular Edema (RESOLVE Study*): A 12-month, randomized, controlled, double-masked, multicenter phase II study

The expression of vascular endothelial growth factor (VEGF) is elevated in diabetic macular edema (DME). Ranibizumab binds to and inhibits multiple VEGF variants. We investigated the safety and efficacy of ranibizumab in DME involving the foveal center

Updating known distribution models for forecasting climate change impact on endangered species

To plan endangered species conservation and to design adequate management programmes, it is necessary to predict their distributional response to climate change, especially under the current situation of rapid change. However, these predictions are customarily done by relating de novo the distribution of the species with climatic conditions with no regard of previously available knowledge about the factors affecting the species distribution. We propose to take advantage of known species distribution models, but proceeding to update them with the variables yielded by climatic models before projecting them to the future. To exemplify our proposal, the availability of suitable habitat across Spain for the endangered Bonelli’s Eagle (Aquila fasciata) was modelled by updating a pre-existing model based on current climate and topography to a combination of different general circulation models and Special Report on Emissions Scenarios. Our results suggested that the main threat for this endangered species would not be climate change, since all forecasting models show that its distribution will be maintained and increased in mainland Spain for all the XXI century. We remark on the importance of linking conservation biology with distribution modelling by updating existing models, frequently available for endangered species, considering all the known factors conditioning the species’ distribution, instead of building new models that are based on climate change variables only.Ministerio de Ciencia e Innovación and FEDER (project CGL2009-11316/BOS

Graefes Arch Clin Exp Ophthalmol

Purpose To report the effectiveness of intravitreal aflibercept (IVT-AFL) treatment for diabetic macular edema (DME) in French clinical practice. Methods APOLLON (NCT02924311) was a prospective, observational cohort study of patients with DME. Effectiveness was evaluated by change from baseline in best-corrected visual acuity (BCVA) at 12 months in treatment-naïve patients (i.e., had not received any anti-vascular endothelial growth factor [anti-VEGF] agent, laser, or steroid at IVT-AFL treatment start) and previously treated patients (i.e., previously treated with anti-VEGF agents other than IVT-AFL, laser, or steroids at IVT-AFL treatment start). Secondary endpoints included change in central retinal thickness (CRT) over 12 months, frequency of injections, and proportion of patients with safety events. Results Of the 147 patients followed for at least 12 months and included in the effectiveness analysis, 52.4% (n = 77) were treatment-naïve and 47.6% (n = 70) were previously treated. Mean (standard deviation [SD]) BCVA score at baseline was 62.7 (14.3) Early Treatment Diabetic Retinopathy Study (ETDRS) letters in treatment-naïve patients and 60.0 (13.7) ETDRS letters in previously treated patients. At month 12, mean (SD) change in BCVA was + 7.8 (12.3) letters in treatment-naïve patients and + 5.0 (11.3) letters in previously treated patients. Mean CRT decreased in both patient cohorts. The mean (SD) number of IVT-AFL injections at month 12 was 7.6 (2.5) for treatment-naïve patients and 7.6 (2.3) for previously treated patients. Of 388 patients included in the safety analysis, ocular treatment-emergent adverse events occurred in 54.1% (n = 210) of patients. Conclusion IVT-AFL treatment was associated with improvements in functional and anatomic outcomes in both treatment-naïve and previously treated patients with DME in France

Back from a Predicted Climatic Extinction of an Island Endemic: A Future for the Corsican Nuthatch

The Corsican Nuthatch (Sitta whiteheadi) is red-listed as vulnerable to extinction by the IUCN because of its endemism, reduced population size, and recent decline. A further cause is the fragmentation and loss of its spatially-restricted favourite habitat, the Corsican pine (Pinus nigra laricio) forest. In this study, we aimed at estimating the potential impact of climate change on the distribution of the Corsican Nuthatch using species distribution models. Because this species has a strong trophic association with the Corsican and Maritime pines (P. nigra laricio and P. pinaster), we first modelled the current and future potential distribution of both pine species in order to use them as habitat variables when modelling the nuthatch distribution. However, the Corsican pine has suffered large distribution losses in the past centuries due to the development of anthropogenic activities, and is now restricted to mountainous woodland. As a consequence, its realized niche is likely significantly smaller than its fundamental niche, so that a projection of the current distribution under future climatic conditions would produce misleading results. To obtain a predicted pine distribution at closest to the geographic projection of the fundamental niche, we used available information on the current pine distribution associated to information on the persistence of isolated natural pine coppices. While common thresholds (maximizing the sum of sensitivity and specificity) predicted a potential large loss of the Corsican Nuthatch distribution by 2100, the use of more appropriate thresholds aiming at getting closer to the fundamental distribution of the Corsican pine predicted that 98% of the current presence points should remain potentially suitable for the nuthatch and its range could be 10% larger in the future. The habitat of the endemic Corsican Nuthatch is therefore more likely threatened by an increasing frequency and intensity of wildfires or anthropogenic activities than by climate change

Finite element analysis of the effect of cementing concepts on implant stability and cement fatigue failure

Background and purpose Two contradictory cementing techniques (using an undersized stem versus a canal-filling stem) can both lead to excellent survival rates, a phenomenon known as the “French paradox”. Furthermore, previous studies have indicated that the type of bone supporting the cement mantle may affect implant survival. To further evaluate the mechanical consequences of variations in cementing technique, we studied the effect of implant size and type of bone supporting the cement mantle on the mechanical performance of cemented total hip arthroplasty, using finite element analysis

On Component Forces in Physics: A Pragmatic View

Do component forces exist? I argue that the answer lies in the affirmative, on historical and operational grounds