Hospital de Órbigo, Spain
Hospital de Órbigo, Spain

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Manns M.,Medizinische Hochschule Hanover | Marcellin P.,University Paris Diderot | Poordad F.,University of Texas Health Science Center at San Antonio | De Araujo E.S.A.,University of Sao Paulo | And 12 more authors.
The Lancet | Year: 2014

Background Pegylated interferon (peginterferon) alfa 2a or 2b plus ribavirin regimens were the standard of care in patients with hepatitis C virus (HCV) infection, but the sustained virological response can be suboptimum in patients with HCV genotype 1 infection. The efficacy, safety, and tolerability of the combination of simeprevir, a one-pill, once-daily, oral HCV NS3/4A protease inhibitor versus placebo, plus peginterferon alfa 2a or 2b plus ribavirin was assessed in treatment-naive patients with HCV genotype 1 infection. Methods In the QUEST-2, phase 3 study, done at 76 sites in 14 countries (Europe, and North and South Americas), patients with confirmed chronic HCV genotype 1 infection and no history of HCV treatment were randomly assigned with a computer-generated allocation sequence in a ratio of 2:1 and stratified by HCV genotype 1 subtype and host IL28B genotype to receive simeprevir (150 mg once daily, orally), peginterferon alfa 2a (180 μg once weekly, subcutaneous injection) or 2b (according to bodyweight; 50 μg, 80 μg, 100 μg, 120 μg, or 150 μg once weekly, subcutaneous injection), plus ribavirin (1000-1200 mg/day or 800-1400 mg/day, orally; simeprevir group) or placebo (once daily, orally), peginterferon alfa 2a or 2b, plus ribavirin (placebo group) for 12 weeks, followed by just peginterferon alfa 2a or 2b plus ribavirin. Total treatment duration was 24 weeks or 48 weeks (simeprevir group) based on criteria for response-guided therapy (ie, HCV RNA <25 IU/mL undetectable or detectable at week 4 and undetectable week 12) or 48 weeks (placebo). Patients, study personnel, and the sponsor were masked to treatment assignment. The primary efficacy endpoint was sustained virological response at 12 weeks after the planned end of treatment (SVR12). Analyses were by intention to treat. The trial is registered with ClinicalTrials.gov, number NCT01290679. Results from the primary (SVR12, week 60) analysis are presented. Findings 209 (81%) of 257 patients in the simeprevir group and 67 (50%) of 134 in the placebo group had SVR12 (adjusted difference 32·2%, 95% CI 23·3- 41·2; p<0·0001). The incidences of adverse events were similar in the simeprevir and placebo groups at 12 weeks (246 [96%] vs 130 [97%]) and for the entire treatment (249 [97%] vs 132 [99%]), irrespective of the peginterferon alfa used. The most common adverse events were headache, fatigue, pyrexia, and influenza-like illness at 12 weeks (95 [37%) vs 45 [34%], 89 [35%] vs 52 [39%], 78 [30%] vs 48 [36%], and 66 [26%] vs 34 [25%], respectively) and for the entire treatment (100 [39%] vs 49 [37%], 94 [37%] vs 56 [42%], 79 [31%] vs 53 [40%], and 66 [26%] vs 35 [26%], respectively). Rash and photosensitivity frequencies were higher in the simeprevir group than in the placebo group (61 [24%] vs 15 [11%] and ten [4%] vs one [<1%], respectively). There was no difference in the prevalence of anaemia between the simeprevir and placebo groups (35 [14%] vs 21 [16%], respectively, at 12 weeks, and 53 [21%] vs 37 [28%], respectively, during the entire treatment). Interpretation Addition of simeprevir to either peginterferon alfa 2a or peginterferon alfa 2b plus ribavirin improved SVR in treatment-naive patients with HCV genotype 1 infection, without worsening the known adverse events associated with peginterferon alfa plus ribavirin. Funding Janssen Infectious Diseases-Diagnostics. © 2014 Elsevier Ltd.


Fattori R.,San Salvatore Hospital | Cao P.,Hospital San Camillo Forlanini | De Rango P.,Hospital Santa Maria Misericordia | Czerny M.,University of Bern | And 4 more authors.
Journal of the American College of Cardiology | Year: 2013

An expert multidisciplinary panel in the treatment of type B aortic dissection reviewed available literature to develop treatment algorithms using a consensus method. Data from 63 studies published from 2006 to 2012 were retrieved for a total of 1,548 patients treated medically, 1,706 patients who underwent open surgery, and 3,457 patients who underwent thoracic endovascular repair (TEVAR). For acute (first 2 weeks) type B aortic dissection, the pooled early mortality rate was 6.4% with medical treatment and increased to 10.2% with TEVAR and 17.5% with open surgery, mostly for complicated cases. Limited data for treatment of subacute (2 to 6 weeks after onset) type B aortic dissection showed an early mortality rate of 2.8% with TEVAR. In chronic (after 6 weeks) type B aortic dissection, 5-year survival of 60% to 80% was expected with medical therapy because complications were likely. If interventional treatment was applied, the pooled early mortality rate was 6.6% with TEVAR and 8.0% with open surgery. Medical treatment of uncomplicated acute, subacute, and chronic type B aortic dissection is managed with close image monitoring. Hemodynamic instability, organ malperfusion, increasing periaortic hematoma, and hemorrhagic pleural effusion on imaging identify patients with complicated acute type B aortic dissection requiring urgent aortic repair. Recurrence of symptoms, aortic aneurysmal dilation (>55 mm), or a yearly increase of >4 mm after the acute phase are predictors of adverse outcome and need for delayed aortic repair ("complicated chronic aortic dissections"). The expert panel is aware that this consensus document provides proposal for strategies based on nonrobust evidence for management of type B aortic dissection, and that literature results were largely heterogeneous and should be interpreted cautiously. © 2013 American College of Cardiology Foundation.


Lorente L.,Hospital Universitario Of Canarias | Blot S.,Ghent University | Rello J.,Hospital Vall DHebron
American Journal of Respiratory and Critical Care Medicine | Year: 2010

In the past 2 years, American, Canadian, and European scientific societies have published their new evidence-based guidelines for ventilator-associated pneumonia (VAP) prevention. However, these guidelines did not review some potentially useful strategies, such as the use of an endotracheal tube with an ultrathin cuff membrane, an endotracheal tube with a low-volume/low-pressure cuff, a device for continuous monitoring of the endotracheal tube cuff pressure, a device to remove biofilm from the inner site of the endotracheal tube, and saline instillation before tracheal suctioning. Only a few guidelines analyze the time of tracheostomy, and so no firm recommendations can be made regarding its importance. In addition, the guidelines diverge on the use of heat and moisture exchangers or heated humidifiers and on the use of an endotracheal tube coated with antimicrobial agents. The current review focuses on measures of VAP prevention for which there is no clear recommendation, or the use of which is controversial. A review of the literature suggests that the use of an endotracheal tube with an ultrathin and tapered-shape cuffmembrane and coated in antimicrobial agents may reduce the risk of VAP. These features offer an attractive way to optimize the VAP prevention capacity of endotracheal tubeswitha lumenfor subglottic secretion drainage. We believe that early tracheostomy should be considered, based on the length reduction of mechanical ventilation and intensive care unit stay, reduction of mortality, and on patient comfort, although early tracheostomy has not yet been shown to favorably impact the incidence of VAP. We believed that heat and moisture exchangers should be considered based on the benefits in terms of cost savings. More research is necessary to clarify the role of continuous cuff pressure monitoring, removal of biofilm formation in the endotracheal tubes, and routine saline instillation before tracheal suctioning.


Falip M.,Hospital Of Bellvitge Feixa Llarga S N | Salas-Puig X.,Hospital Vall dHebron | Cara C.,UCB Pharma
CNS Drugs | Year: 2013

Inflammation is one of the most important endogenous defence mechanisms in an organism. It has been suggested that inflammation plays an important role in the pathophysiology of a number of human epilepsies and convulsive disorders, and there is clinical and experimental evidence to suggest that inflammatory processes within the CNS may either contribute to or be a consequence of epileptogenesis. This review discusses evidence from human studies on the role of inflammation in epilepsy and highlights potential new targets in the inflammatory cascade for antiepileptic drugs. A number of mechanisms have been shown to be involved in CNS inflammatory reactions. These include an inflammatory response at the level of the blood-brain barrier (BBB), immune-mediated damage to the CNS, stress-induced release of inflammatory mediators and direct neuronal dysfunction or damage as a result of inflammatory reactions. Mediators of inflammation in the CNS include interleukin (IL)-1β, tumour necrosis factor-α, nuclear factor-κB and toll-like receptor-4 (TLR4). IL-1β, BBB and high-mobility group box-1-TLR4 signalling appear to be the most promising targets for anticonvulsant agents directed at inflammation. Such agents may provide effective therapy for drug-resistant epilepsies in the future. © 2013 Springer International Publishing Switzerland.


Evangelista A.,Hospital Vall dHebron
Current Cardiology Reports | Year: 2011

Bicuspid aortic valve (BAV) is the most common form of congenital heart disease, with frequent and premature occurrence of cardiac events, dominated by significant valvular dysfunction. BAV has a high prevalence of aortic wall abnormalities such as ascending aortic dilatation. Because more rapid aortic dilatation can occur, once the ascending aorta reaches 40 mm, annual imaging with echocardiography or other imaging techniques is indicated. The most feared complication is aortic dissection. However, the actual incidence of this complication is low (4%). Although limited data exist regarding prophylactic intervention, it is suggested that elective surgical repair of BAV-associated aortic dilatation should be more aggressively recommended. In patients with BAV, the decision to indicate surgical treatment in aortic diameters between 50 and 55 mm should be based on patient age, body size, comorbidities, type of surgery, and the presence of additional risk factors. © 2011 Springer Science+Business Media, LLC.


Catalan M.,University of Barcelona | Selva-O'Callaghan A.,Hospital Vall dHebron | Grau J.M.,University of Barcelona
Autoimmunity Reviews | Year: 2014

Sporadic inclusion body myositis (sIBM) is the most common acquired muscle disease in elderly individuals, particularly men. Its prevalence varies among ethnic groups but is estimated at 35 per one million people over 50. Genetic as well as environmental factors and autoimmune processes might both have a role in its pathogenesis. Unlike other inflammatory myopathies, sIBM causes very slowly progressive muscular weakness and atrophy, having a distinctive pattern of muscle involvement and different forms of clinical presentation. In some cases a primary autoimmune disease coexists. Diagnosis is suspected on clinical grounds and is established by typical muscle pathology. As a rule sIBM is refractory to conventional forms of immunotherapy. © 2014 Elsevier B.V.


Evangelista A.,Hospital Vall dHebron
Heart | Year: 2014

Imaging techniques play a crucial role in the diagnosis, follow-up and management of aortic aneurysms. Ultrasound, CT and MRI have strengths and limitations in the assessment of this disease depending on the aorta segment involved, reason for the study (screening, follow-up or surgical indication) and patient characteristics. Ultrasound, transthoracic or abdominal, is highly useful in the diagnosis and follow-up of proximal ascending aorta and abdominal aorta aneurysms, respectively. However, other imaging modalities may be required to confirm measurements and add information on adjacent structures or the involvement of aortic branches. Transoesophageal echocardiography is frequently limited to perioperative indications. CT plays a central role in the diagnosis, risk stratification and management of most aneurysms, particularly those located distal to the proximal ascending aorta. Advantages of CT over other imaging modalities include rapid image acquisition, its multiplanar capacity with submillimetric spatial resolution and wide availability. The main limitations of CT are the radiation exposure and need for nephotoxic contrast administration. MRI is less readily available but overcomes these limitations and adds functional and biomechanical information, and is mainly indicated in young individuals who require repetitive studies and long-term follow-up. Aortic diameters are the cornerstone of current clinical practice in aortic aneurysms, and some limitations in accuracy and reproducibility measurements may generate errors in clinical decision making. Better understanding of imaging modalities, beyond the simple clinical application of diameters, may improve the management of this disease. In addition, new biomechanical and metabolic information could potentially provide a more reliable prediction of the risk of aneurysm rupture.


Salat D.,Hospital Vall dHebron | Noyce A.J.,University College London | Schrag A.,University College London | Tolosa E.,University of Barcelona
The Lancet Neurology | Year: 2016

Neurodegeneration in Parkinson's disease starts years before a clinical diagnosis can be reliably made. The prediagnostic phase of the disease offers a window of opportunity in which disease-modifying therapies-ie, those aimed at delaying or preventing the progression to overt disease and its many complications-could be most beneficial, but no such therapies are available at present. The unravelling of the mechanisms of neurodegeneration from the earliest stages, however, could lead to the development of new interventions whose therapeutic potential will need to be assessed in adequately designed clinical trials. Advances in the understanding of this prediagnostic phase of Parkinson's disease (for which the clinical diagnostic and prognostic markers used in more advanced disease stages are not applicable) will lead to the identification of biomarkers of neurodegeneration and its progression. These biomarkers will, in turn, help to identify the optimum population to be included and the most appropriate outcomes to be assessed in trials of disease-modifying drugs. Potential risks to minimally symptomatic participants, some of whom might not progress to manifest Parkinson's disease, and individuals who do not wish to know their mutation carrier status, could pose specific ethical dilemmas in the design of these trials. © 2016 Elsevier Ltd.


Simo-Servat O.,Hospital Vall dHebron
Mediators of inflammation | Year: 2012

Diabetic retinopathy (DR) is the major cause of acquired blindness in working-age adults. Current treatments for DR (laser photocoagulation, intravitreal corticosteroids, intravitreal antivascular endothelial growth factor (VEGF) agents, and vitreo-retinal surgery) are applicable only at advanced stages of the disease and are associated with significant adverse effects. Therefore, new pharmacological treatments for the early stages of the disease are needed. Vitreous fluid obtained from diabetic patients undergoing vitreoretinal surgery is currently used to explore the events that are taking place in the retina for clinical research. However, several confounding factors such as vitreous haemorrhage and concentration of vitreous proteins should be considered in the analysis of the results. In this paper we will focus on the vitreous fluid as a tool for exploring the mediators of DR and in particular the molecules related to inflammatory pathways. In addition, their role in the pathogenesis of DR will be discussed. The usefulness of new technologies such as flow cytometry and proteomics in identifying new candidates involved in the inflammatory process that occurs in DR will be overviewed. Finally, a more personalized treatment based on vitreous fluid analysis aiming to reduce the burden associated with DR is suggested.


Cordoba J.,Hospital Vall dHebron
Journal of Hepatology | Year: 2011

Hepatic encephalopathy (HE) is a common complication of cirrhosis that requires careful appraisal of the clinical manifestations, evaluation of the underlying neurological disorders, and assessment of liver function and the portal-systemic circulation. This article reviews recent developments in the assessment of HE and discusses the controversy regarding the use of a categorical or a continuous approach in measuring the severity of this condition. New scales facilitate effective monitoring and assessment of episodic HE. Neuropsychological test batteries and neurophysiological tests are of value for evaluating cognitive function in outpatients and can establish the diagnosis of minimal HE, and the severity of low-grade HE. These tools allow better evaluation of the origin of cognitive complaints and help in estimating the risk of accidents. It is now possible to complete the evaluation with measurement of the effects of cognitive impairment on daily living. In difficult cases, imaging of the brain and portal-systemic circulation with magnetic resonance imaging is especially helpful. Based on these studies, neurological signs and symptoms can be attributed to HE in patients with mild liver disease and in those with complex neurological manifestations. The new methods presented are also valuable for investigating the neurological manifestations occurring after liver transplantation. © 2010 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

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