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Garrido C.,Charles III University of Madrid | De Mendoza C.,Charles III University of Madrid | Alvarez E.,Charles III University of Madrid | Garcia F.,Hospital Clinico Universitario San Cecilio | And 6 more authors.
AIDS Research and Human Retroviruses | Year: 2012

Raltegravir (RAL) resistance is associated with the selection of integrase mutations at positions 92, 143, 148, and/or 155. A substantial proportion of RAL failures, however, occurs in the absence of these changes. An examination of RAL plasma concentrations may help in interpreting this observation. All early RAL virological failures seen at 22 clinics in Spain during 2009 were identified. HIV integrase sequences and RAL plasma trough concentrations (C t) were examined. A total of 106 patients experiencing virological failure on RAL were identified. Only the earliest sample on failure was examined. Integrase sequences could be obtained for 89 (84%), of whom 30 (33.7%) depicted primary RAL resistance mutations (15 N155H, eight Q148H/R, three Y143R, one E92Q, and three more than one of them). Another nine (10.1%) patients showed only secondary changes. The remaining 50 RAL early failures (56.2%) did not select any integrase change. RAL C t could be measured in 66 patients at failure and in 21 of them before failure. In a control group of 37 patients with viral suppression on RAL, detectable plasma levels were seen in all cases, with greater median RAL C t than in failures, either at the time of viral rebound (p<0.001) or before it (p=0.055). Moreover, median C t at the time of failure was greater in patients selecting primary RAL resistance mutations than in the rest of the failures (p<0.001). Undetectable RAL C t was seen only in patients failing RAL without integrase resistance mutations (64.1% of them). RAL failures in the absence of integrase resistance mutations mainly reflect poor drug compliance. © Copyright 2012, Mary Ann Liebert, Inc.

Garrido C.,Charles III University of Madrid | Villacian J.,Virco | Zahonero N.,Charles III University of Madrid | Pattery T.,Virco | And 6 more authors.
Antimicrobial Agents and Chemotherapy | Year: 2012

The failure of raltegravir (RAL) is generally associated with the selection of mutations at integrase position Y143, Q148, or N155. However, a relatively high proportion of failures occurs in the absence of these changes. Here, we report the phenotypic susceptibilities to RAL and elvitegravir (EVG) for a large group of HIV-infected patients failing on RAL-containing regimens. Plasma from HIV-infected individuals failing on RAL-containing regimens underwent genotypic and phenotypic resistance testing (Antivirogram v2.5.01; Virco). A control group of patients failing on other regimens was similarly tested. Sixty-one samples were analyzed, 40 of which belonged to patients failing on RAL-containing regimens. Full RAL susceptibility was found in 20/21 controls, while susceptibility to EVG was diminished in 8 subjects, with a median fold change (FC) of 2.5 (interquartile range [IQR], 2.1 to 3.1). Fourteen samples from patients with RAL failures showed diminished RAL susceptibility, with a median FC of 38.5 (IQR, 10.8 to 103.2). Primary integrase resistance mutations were found in 11 of these samples, displaying a median FC of 68.5 (IQR, 23.5 to 134.3). The remaining 3 samples showed a median FC of 2.5 (IQR, 2 to 2.7). EVG susceptibility was diminished in 19/40 samples from patients with RAL failures (median FC, 7.71 [IQR, 2.48 to 99.93]). Cross-resistance between RAL and EVG was high (R2=0.8; P<0.001), with drug susceptibility being more frequently reduced for EVG than for RAL (44.3% versus 24.6%; P=0.035). Susceptibility to RAL and EVG is rarely affected in the absence of primary integrase resistance mutations. There is broad cross-resistance between RAL and EVG, which should preclude their sequential use. Resistance to EVG seems to be more frequent and might be more influenced by integrase variability. Copyright © 2012, American Society for Microbiology. All Rights Reserved.

Ruiz-Gimenez J.,Hospital Universitario Virgen Of Las Nieves | Sanchez-Alvarez J.C.,Hospital Clinico Universitario San Cecilio | Canadillas-Hidalgo F.,Hospital Universitario Reina Sofia
Seizure | Year: 2010

Background: A high number of patients with epilepsy have comorbidities. The type of comorbidity is an important factor in deciding on the most suitable treatment, including that for acute epileptic seizures and chronic antiepileptic treatment. Evidence-based criteria should guide the selection of the appropriate antiepileptic drugs given specific comorbidities. Methods: We performed a comprehensive search of the scientific literature on epilepsy treatment in patients with the following comorbidities: heart disease, lung disease, liver disease, kidney disease, porphyria, organ transplantation, thyroid disease, metabolic disorder, infection, mental disability, psychiatric disorder, cognitive impairment, stroke, and brain tumour. Results: Most of the studies were case series and retrospective analyses. No randomised controlled trials specifically designed for this type of clinical situation were identified. The level of scientific evidence to guide clinical decisions is therefore low. Conclusions: In this review we make recommendations based on the best scientific evidence available for treating epilepsy in patients with other comorbidities, including the treatment of epileptic seizures in acute situations as well as chronic antiepileptic treatment. When no scientific evidence is available, our recommendations are based on pharmacokinetic criteria and tolerability of antiepileptic drugs, using accumulated experience and the consensus of the members of the Andalusian Epilepsy Society. © 2010 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

Heijmen R.,St Antonius Ziekenhuis | Fattori R.,Ospedale SantOrsola Malpighi | Thompson M.,St Georges Vascular Institute | Dai-Do D.,Universitatsspital Bern | And 12 more authors.
European Journal of Vascular and Endovascular Surgery | Year: 2014

Objective The VIRTUE Registry describes the mid-term clinical and morphological results of thoracic endovascular repair (TEVR) in patients with type B aortic dissection. Methods This was a prospective cohort study. The VIRTUE Registry is a prospective, multicentre clinical trial that enrolled patients with complicated acute (<15 days), subacute (15-92 days), and chronic (>92 days) type B aortic dissections treated with the Valiant endograft. One hundred patients were enrolled and the clinical outcomes described at the 3-year follow-up. Analysis of the aortic area and false lumen thrombosis rates defined the morphological response to TEVR in the three clinical groups. Results Three-year all-cause mortality (18%, 4%, and 24%), dissection related mortality (12%, 4%, and 9%), aortic rupture (2%, 0%, and 4%), retrograde type A dissection (5%, 0%, and 0%), and aortic reintervention rates (20%, 22%, and 39%) were, respectively, defined for patients with acute (n = 50), subacute (n = 24), and chronic (n = 26) dissections. Analysis of aortic morphology observed that patients with subacute dissection demonstrated a similar degree of aortic remodelling to patients with acute dissection. Patients with acute and subacute dissection exhibited greater aortic plasticity than patients with chronic dissection. Conclusions The principle clinical findings suggest that TEVR is able to provide good protection from aortic-related death in the mid-term, but with a high rate of aortic reintervention. Analysis of aortic morphology suggested that aortic remodelling in subacute patients is similar to the acute group. Retention of aortic plasticity in the subacute group lengthens the therapeutic window for the treatment of uncomplicated type B dissection. © 2014 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.

Ruiz-Carrascosa J.C.,Hospital Clinico Universitario San Cecilio
Actas Dermo-Sifiliograficas | Year: 2012

Patients with psoriasis have an increased risk of cardiovascular events, and there is evidence of a correlation between the immune processes that occur in psoriasis and those seen in other chronic inflammatory disorders such as atheromatous disease. The occurrence of major cardiovascular events in patients with plaque psoriasis being treated with ustekinumab caused alarm among some researchers, but a thorough analysis of the findings to date has confirmed the cardiovascular safety of this agent. © 2012 Elsevier Espana, S.L. y AEDV.

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