Shocks as predictors of survival in patients with implantable cardioverter-defibrillators

AbstractOBJECTIVESThe objective of the study was to determine whether the occurrence of shocks for ventricular tachyarrhythmias during therapy with implantable cardioverter-defibrillators (ICD) is predictive of shortened survival.BACKGROUNDVentricular tachyarrhythmias eliciting shocks are often associated with depressed ventricular function, making assessment of shocks as an independent risk factor difficult.METHODSConsecutive patients (n = 421) with a mean follow-up of 756 ± 523 days were classified into those who had received no shock (n = 262) or either one of two shock types, defined as single (n = 111) or multiple shocks (n = 48) per arrhythmia episode. Endpoints were all-cause and cardiac deaths. A survival analysis using a stepwise proportional hazards model evaluated the influence of two primary variables, shock type and left ventricular ejection fraction (LVEF <35% or >35%). Covariates analyzed were age, gender, NYHA Class, coronary artery disease, myocardial infarction, coronary revascularization, defibrillation threshold and tachyarrhythmia inducibility.RESULTSThe most complete model retained LVEF (p = 0.005) and age (p = 0.023) for the comparison of any shock versus no shock (p = 0.031). The occurrence of any versus no shock, or of multiple versus single shocks significantly decreased survival at four years, and these differences persisted after adjustment for LVEF. In the LVEF subgroups <35% and <25%, occurrence of multiple versus no shock more than doubled the risk of death. Compared with the most favorable group LVEF ≥35% and no shock, risk in the group multiple shocks and LVEF <35% was increased 16-fold.CONCLUSIONSIn defibrillator recipients, shocks act as potent predictors of survival independent of several other risk factors, particularly ejection fraction

Human TrkAR649W mutation impairs nociception, sweating and cognitive abilities: a mouse model of HSAN IV

A functional nerve growth factor (NGF)-TrkA system is an essential requisite for the generation and maintenance of long-lasting thermal and mechanical hyperalgesia in adult mammals. Indeed, mutations in the gene encoding for TrkA are responsible for a rare condition, named Hereditary Sensory and Autonomic Neuropathy type IV (HSAN IV), characterized by the loss of response to noxious stimuli, anhidrosis and cognitive impairment. However, to date, there is no available mouse model to properly understand how the NGF-TrkA system can lead to pathological phenotypes that are distinctive of HSAN IV. Here, we report the generation of a knock-in mouse line carrying the HSAN IV TrkAR649W mutation. First, by in vitro biochemical and biophysical analyses, we show that the pathological R649W mutation leads to kinase-inactive TrkA also affecting its membrane dynamics and trafficking. In agreement with the HSAN IV human phenotype, TrkAR649W/m mice display a lower response to thermal and chemical noxious stimuli, correlating with reduced skin innervation, in addition to decreased sweating in comparison to TrkAh/m controls. Moreover, the R649W mutation decreases anxiety-like behavior and compromises cognitive abilities, by impairing spatial-working and social memory. Our results further uncover unexplored roles of TrkA in thermoregulation and sociability. In addition to accurately recapitulating the clinical manifestations of HSAN IV patients, our findings contribute to clarify the involvement of the NGF-TrkA system in pain sensation

Low-Dose Oral Ethinylestradiol With Concomitant Low-Dose Acetylsalicylic Acid for Advanced Castrate-Resistant Prostate Cancer

BACKGROUND: The aim of the present study was to evaluate the activity and tolerability of low-dose oral ethinylestradiol (EE) and luteinizing hormone-releasing hormone analogue with concomitant low-dose acetylsalicylic acid (ASA) as a thromboprophylactic agent for advanced castrate-resistant prostate cancer (CRPC). PATIENTS AND METHODS: The patients received an EE dose of 150 \u3bcg daily (50 \u3bcg 3 times daily) and an ASA dose of 100 mg once daily. The primary endpoint was the prostate-specific antigen response. RESULTS: A total of 32 patients were enrolled. A PSA response was observed in 19 patients (59.3%; 95% confidence interval [CI], 41%-76%). The median progression-free survival was 9.4 months (95% CI, 6.5-14.1 months). The treatment was generally well tolerated and no grade 3-4 toxicity was observed. Only 1 patient interrupted EE because of a cardiac event and 1 patient experienced grade 2 nausea and vomiting. No major bleeding occurred. CONCLUSION: Low-dose EE with concomitant low-dose ASA is safe, showing potential activity in patients with advanced CRPC, and should be investigated furthe

Lice (Haematopinus tuberculatus) in water buffalo farms from central Italy

The aim of the present study was to obtain information about the presence and distribution of the suckling louse Haematopinus tuberculatus in water buffalo farms in central Italy. The survey was carried out on 127 farms (epidemiological units), selected using a grid approach within a Geographical Information System, followed by proportional allocation. In each farm 6 buffaloes were examined in order to detect the louse presence. Parasitological examinations were performed on each buffalo at predilection sites. A total of 762 water buffaloes were examined. H. tuberculatus was found in the 11.0% (14/127) of the farms and in the 4.5% (34/762) of the animals. The presence H. tuberculatus should be routinely considered because it is a cause of serious health, production and economic damages in intensive breeding buffaloes

Liver-Targeting of Interferon-Alpha with Tissue-Specific Domain Antibodies

PMCID: PMC3581439This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Identificación y descripción epidemiológica de artículos de revisión de efectos adversos en la atención sanitaria publicados en idioma español

Antecedentes: Las revisiones sistemáticas de la literatura científica constituyen una importante fuente de evidencia para la toma de decisiones en medicina particularmente al momento de contemplar posibles efectos adversos (EA) de las intervenciones. Estudios anteriores han caracterizado epidemiológicamente artículos de revisión publicados sin utilizar restricción alguna de idioma o limitándose al inglés, mientras que no sonabundantes los estudios de revisiones escritos en español.Objetivos: Identificar artículos de revisión de efectos adversos en la atención sanitaria publicados en idioma español y describirlos epidemiológicamente.Métodos: Se realizó una búsqueda en MEDLINE, BVS y DARE utilizando estrategias que incluían términos afines a “efecto adverso” y “revisión”, para el período 2010-2014 e idioma español. De los artículos recuperados se registraron características relevantes, calcularon frecuencias y se analizó homogeneidad. Resultados: Se recuperaron 62 revisiones narrativas (RN) y 29 revisiones sistemáticas/metaanálisis (RS/MA). La palabra “Revisión” en el título fue empleada en 16,1% de RN y en 89,6% de RS/MA (p&lt;0,0001).  En el 76,9% de las revisiones, estudiar los EA no fue el principal objetivo y en el 68,1% la intervención fue farmacológica. El número de autores fue mayor en las RS/MA que en las RN (p=0,0371).Discusión: Se considera insuficiente el número de revisiones de EA recuperados en español. Dado que las RS/MA, al estar elaboradas con rigor metodológico, aportan evidencia confiable para la toma de decisiones en la práctica clínica, su escaso número no favorece la actualización de los profesionales de habla hispana.</p

Pharmacokinetic Characteristics, Pharmacodynamic Effect and In Vivo Antiviral Efficacy of Liver-Targeted Interferon Alpha

Work carried out by JM was funded by the National Institutes of Health (NIH). NIH contract number is HHSN272201000039I/HHSN27200001/ A19

Juxtaposing BTE and ATE – on the role of the European insurance industry in funding civil litigation

One of the ways in which legal services are financed, and indeed shaped, is through private insurance arrangement. Two contrasting types of legal expenses insurance contracts (LEI) seem to dominate in Europe: before the event (BTE) and after the event (ATE) legal expenses insurance. Notwithstanding institutional differences between different legal systems, BTE and ATE insurance arrangements may be instrumental if government policy is geared towards strengthening a market-oriented system of financing access to justice for individuals and business. At the same time, emphasizing the role of a private industry as a keeper of the gates to justice raises issues of accountability and transparency, not readily reconcilable with demands of competition. Moreover, multiple actors (clients, lawyers, courts, insurers) are involved, causing behavioural dynamics which are not easily predicted or influenced. Against this background, this paper looks into BTE and ATE arrangements by analysing the particularities of BTE and ATE arrangements currently available in some European jurisdictions and by painting a picture of their respective markets and legal contexts. This allows for some reflection on the performance of BTE and ATE providers as both financiers and keepers. Two issues emerge from the analysis that are worthy of some further reflection. Firstly, there is the problematic long-term sustainability of some ATE products. Secondly, the challenges faced by policymakers that would like to nudge consumers into voluntarily taking out BTE LEI

Penilaian Kinerja Keuangan Koperasi di Kabupaten Pelalawan

This paper describe development and financial performance of cooperative in District Pelalawan among 2007 - 2008. Studies on primary and secondary cooperative in 12 sub-districts. Method in this stady use performance measuring of productivity, efficiency, growth, liquidity, and solvability of cooperative. Productivity of cooperative in Pelalawan was highly but efficiency still low. Profit and income were highly, even liquidity of cooperative very high, and solvability was good

Search for stop and higgsino production using diphoton Higgs boson decays

Results are presented of a search for a "natural" supersymmetry scenario with gauge mediated symmetry breaking. It is assumed that only the supersymmetric partners of the top-quark (stop) and the Higgs boson (higgsino) are accessible. Events are examined in which there are two photons forming a Higgs boson candidate, and at least two b-quark jets. In 19.7 inverse femtobarns of proton-proton collision data at sqrt(s) = 8 TeV, recorded in the CMS experiment, no evidence of a signal is found and lower limits at the 95% confidence level are set, excluding the stop mass below 360 to 410 GeV, depending on the higgsino mass