Persistent transient myocardial ischemia despite beta-adrenergic blockade predicts a higher risk of adverse cardiac events in patients with coronary artery disease

AbstractObjectives. We evaluated the prevalence and prognostic significance of transient myocardial ischemia despite beta-adrenergic blockade in patients with coronary artery disease.Background. Persistence of transient ischemia despite therapy may correspond to a subset of high risk patients with coronary disease. The impact of beta-blocker withdrawal in these patients remains unknown.Methods. Patients (n = 313) with documented coronary artery disease and beta-blocker therapy, with (group I, n = 84) or without (group II, n = 229) transient ischemia on ambulatory electrocardiographic monitoring, were followed up during 21 ± 9 months for cardiac events (death, myocardial infarction, percutaneous transluminal coronary angioplasty, coronary artery bypass surgery and worsening angina). Occurrence of events was compared by log-rank test.Results. The number of coronary stenoses did not differ significantly between groups I and II. Beta-blocker therapy was discontinued more frequently during follow-up in group II (25% vs. 14% in group I, p = 0.04). Cumulative percentage of death or myocardial infarction, or both, tended to be higher in group I at 30 months (17% vs. 5% in group II, p = 0.09). Coronary angioplasty and bypass surgery were significantly more frequent in group I (p = 0.01 and 0.0008, respectively). Transient ischemia was associated with a higher cumulative probability of adverse events (p = 0.004). The number of coronary stenoses, presence of transient ischemia and beta-blocker withdrawal were the only significant prognostic factors of cardiac events in the Cox model. In group I patients, the relative hazard of cardiac events was increased threefold when beta-blocker therapy was interrupted.Conclusions. These data suggest that 1) the occurrence of transient ischemia despite beta-blocker therapy identifies a subset of high risk patients with coronary artery disease, and 2) the interruption of beta-blocker therapy increases the risk of adverse cardiac events

Multiple major disease-associated clones of Legionella pneumophila have emerged recently and independently.

Legionella pneumophila is an environmental bacterium and the leading cause of Legionnaires' disease. Just five sequence types (ST), from more than 2000 currently described, cause nearly half of disease cases in northwest Europe. Here, we report the sequence and analyses of 364 L. pneumophila genomes, including 337 from the five disease-associated STs and 27 representative of the species diversity. Phylogenetic analyses revealed that the five STs have independent origins within a highly diverse species. The number of de novo mutations is extremely low with maximum pairwise single-nucleotide polymorphisms (SNPs) ranging from 19 (ST47) to 127 (ST1), which suggests emergences within the last century. Isolates sampled geographically far apart differ by only a few SNPs, demonstrating rapid dissemination. These five STs have been recombining recently, leading to a shared pool of allelic variants potentially contributing to their increased disease propensity. The oldest clone, ST1, has spread globally; between 1940 and 2000, four new clones have emerged in Europe, which show long-distance, rapid dispersal. That a large proportion of clinical cases is caused by recently emerged and internationally dispersed clones, linked by convergent evolution, is surprising for an environmental bacterium traditionally considered to be an opportunistic pathogen. To simultaneously explain recent emergence, rapid spread and increased disease association, we hypothesize that these STs have adapted to new man-made environmental niches, which may be linked by human infection and transmission

Streptococcus agalactiae clones infecting humans were selected and fixed through the extensive use of tetracycline

Streptococcus agalactiae (Group B Streptococcus, GBS) is a commensal of the digestive and genitourinary tracts of humans that emerged as the leading cause of bacterial neonatal infections in Europe and North America during the 1960s. Due to the lack of epidemiological and genomic data, the reasons for this emergence are unknown. Here we show by comparative genome analysis and phylogenetic reconstruction of 229 isolates that the rise of human GBS infections corresponds to the selection and worldwide dissemination of only a few clones. The parallel expansion of the clones is preceded by the insertion of integrative and conjugative elements conferring tetracycline resistance (TcR). Thus, we propose that the use of tetracycline from 1948 onwards led in humans to the complete replacement of a diverse GBS population by only few TcR clones particularly well adapted to their host, causing the observed emergence of GBS diseases in neonates. \ua9 2014 Macmillan Publishers Limited. All rights reserved

Low Clinical Burden of 2009 Pandemic Influenza A (H1N1) Infection during Pregnancy on the Island of La Réunion

BACKGROUND: Pregnant women have been identified as a group at risk, both for respiratory complications than for the admissions to the Intensive Care Unit (ICU) during the 2009 H1N1 influenza pandemic (pdm). The purpose of this prospective register-based cohort-study was to characterize the clinical virulence of the pdm (H1N1/09)v during pregnancy in La Réunion. METHODS/PRINCIPAL FINDINGS: Over a twelve-week pdm wave (13 July to 3 October 2009), 294 pregnant women presented with an influenza-like illness (ILI) to one of the three maternity departments of the South Reunion area, Indian Ocean. Out of these, 278 were checked by RT-PCR for influenza viruses (157 positive and 121 negative, of whom, 141 with pdm flu and 132 with ILIs of non pdm origin, 5 untyped). The median body temperature was higher in women experiencing pdm flu than in those with non pdm ILI (38.9 degrees C versus 38.3 degrees C, P<0.0001), without evidence linked to circulating viremia. Oseltamivir was given for 86% of pdm flu cases in a median time inferior than 48 hrs (range 0-7 days). The hospitalization rate for pdm flu was of 60% and not associated with underlying conditions. Six viral pneumonia and fourteen asthma attacks were observed among 84 hospitalized pdm flu cases, of whom, only one led to the ICU for an acute lung injury. No maternal death occurred during the pdm wave. None adverse pregnancy outcome was associated with pdm flu. No congenital birth defect, nor early-onset neonatal influenza infection was attributable to pdm flu exposure. CONCLUSIONS/SIGNIFICANCE: This report mitigates substantially the presumed severity of pandemic H1N1/09 influenza infection during pregnancy. The reasons for which the clinical burden of H1N1/09 influenza virus may differ worldwide raise questions about a differential local viral-strain effect and public health preparedness, notably in timely access to special care and antiviral treatments

Essais cliniques des traitements

Classiquement contre-indiqué chez l'insuffisant cardiaque, le traitement β-bloquant administré à doses progressivement croissantes s'est avéré au contraire bénéfique chez les patients avec insuffisance cardiaque par altération de la fonction systolique, en antagonisant les effets délétères cardiaques directs et indirects des catécholamines. C'est probablement par l'amélioration de la fonction ventriculaire et la prévention des arythmies sévères que le traitement β-bloquant améliore la survie, réduit la mortalité subite ainsi que les hospitalisations pour décompensation de l'insuffisance cardiaque. Le bénéfice est a priori dose-dépendant, bien que peu de données prospectives permettent de l'affirmer. Parmi les substances étudiées, le bisoprolol, le métoprolol et le carvédilol induisent un bénéfice d'amplitude similaire avec une réduction de 34 % de la mortalité dans les grands essais cliniques. Le bucindolol, en revanche, n'a pas induit de bénéfice significatif sur la mortalité au cours de l'étude BEST. Les raisons de ce résultat restent à élucider. En termes de stratégie thérapeutique, le traitement β-bloquant est initié chez des patients stabilisés par un traitement associant diurétiques et inhibiteurs de l'enzyme de conversion (IEC). Des études sont en cours pour évaluer l'intérêt d'un démarrage plus précoce et en premier du β-bloquant afin de mieux prévenir en particulier la mort subite qui survient plus fréquemment aux stades initiaux de la maladie

De l'ischémie à l'insuffisance cardiaque : la fréquence cardiaque – acteur ou marqueur ?

La fréquence cardiaque en rythme sinusal est assurée par l'automatisme des cellules du nœud sinusal soustendu par le courant If induit par l'hyperpolarisation et modulé par l'influence du tonus sympathique et parasympathique. La valeur de la fréquence cardiaque au repos, comme sa variabilité, sont des marqueurs du pronostic vital dans des pathologies comme l'insuffisance coronaire ou l'insuffisance cardiaque. Mais la fréquence cardiaque est également directement un acteur de la régulation de la contractilité cardiaque et de la consommation myocardique en oxygène en interférant avec les mécanismes du couplage excitation-contraction. L'intérêt thérapeutique potentiel d'une action pharmacologique sur la fréquence cardiaque concerne surtout son ralentissement, comme mis à profit dans l'insuffisance coronaire avec les antagonistes calciques et les β-bloquants, et dans l'insuffisance cardiaque avec ces derniers également. La possibilité de ralentir directement l'automatisme sinusal avec des substances comme l'ivabradine, bloqueur du canal If, ouvre des perspectives thérapeutiques intéressantes, notamment en association avec les β-bloquants, ce qui devrait permettre de combiner le bénéfice des deux substances et d'atteindre des niveaux plus bas de fréquence cardiaque par rapport à la limite imposée par la tolérance et les concentrations atteintes avec les doses maximales administrables de β-bloquants

Les bases pharmacologiques de la thérapeutique. Analyse pharmacologique du résumé des caractéristiques d’un produit ( le « RCP ») pour le thérapeute

Le résumé des caractéristiques d’un produit (le RCP), principale annexe de son dossier d’autorisation de mise sur le marché, comporte 12 rubriques. Les rubriques 1 à 3 concernent la dénomination, le dosage, la forme pharmaceutique et la composition du médicament. La rubrique 4 est celle des données cliniques (indications, posologies, modes d’administration, contre-indications, précautions d’emploi, interactions, impact et risques sur la fertilité, la contraception, la grossesse et l’allaitement, les effets sur la capacité à la conduite automobile et l’utilisation des machines, les effets indésirables et les risques en relation avec un surdosage. La rubrique 5 est celle des propriétés pharmacologiques (pharmacodynamie et pharmacocinétique). La rubrique 6 fournit les informations d’ordre pharmaceutique (excipients, nature du contenant, durée et modalités de conservation, modalités d’élimination des déchets etc…). Les rubriques 7 à 10 sont administratives (dates et titulaire d’autorisationde mise sur le marché), les rubriques 11 et 12 concernent les radiopharmaceutiques (dosimétrie et modalités de préparation)