Hospital Universitario La Paz

Madrid, Spain

Hospital Universitario La Paz

Madrid, Spain
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ABSTRACT:: In two double-blind Phase 3 trials, 1733 antiretroviral-naïve adults were randomized to tenofovir alafenamide (TAF) or tenofovir disoproxil fumarate (TDF), each coformulated with elvitegravir/cobicistat/emtricitabine (E/C/F). At 144 weeks, TAF was superior to TDF in virologic efficacy, with 84.2% vs. 80.0% having HIV-1 RNA <50 copies/mL (difference 4.2%; 95%CI 0.6% to 7.8%). TAF had less impact than TDF on bone mineral density and renal biomarkers. No participants on TAF had renal-related discontinuations vs 12 on TDF (P<0.001), with no cases of proximal tubulopathy for TAF vs 4 for TDF. There were greater increases in lipids with TAF vs. TDF, with no difference in the total cholesterol to high density lipoprotein ratio. For initial HIV therapy, E/C/F/TAF is superior to E/C/F/TDF in efficacy and bone and renal safety. Copyright © 2017 Wolters Kluwer Health, Inc. All rights reserved.


OBJECTIVE:: We compared the baseline characteristics, effectiveness, and tolerance of DAA-based regimens taken by HCV-monoinfected and HCV-HIV-coinfected individuals in clinical practice. DESIGN:: We performed a prospective observational study in 2 tertiary centers in Madrid, Spain that included all HCV-monoinfected and HCV/HIV-coinfected patients undergoing HCV treatment with all-oral DAA regimens in a routine clinical setting from April 2015 to November 2015. We evaluated sustained virological response 12 weeks after the end of therapy (SVR12), adverse events (AEs), and baseline and treatment characteristics. RESULTS:: The study population comprised 1634 patients: 1152 HCV-monoinfected patients (70%) and 482?HCV/HIV-coinfected patients (30%). Fifty percent had cirrhosis, and 47% were peginterferon/ribavirin–experienced. HCV/HIV-coinfected patients were younger (median age [IQR] 51 [48–54] years vs. 59 [50–68] years; p?


Tamargo J.,Complutense University of Madrid | Lopez-Sendon J.,Hospital Universitario La Paz
Nature Reviews Drug Discovery | Year: 2011

Despite considerable therapeutic advances, heart failure remains a medical and socioeconomic problem. Thus, there is a compelling need for new drugs that could improve clinical outcomes. In recent years, new potential therapeutic targets that are involved in the pathogenesis of heart failure have been identified, and new drugs are currently under investigation. A repeated finding is that the positive results that have been observed in preclinical studies and Phase II trials are not always confirmed in Phase III studies. This Review analyses the new therapeutic targets (for example, ventricular remodelling, reningangiotensing aldosterone system activation, defects in Ca 2+ cycling, and so on), the mechanism of action, efficacy and future perspectives of new drugs that are currently under development for the treatment of heart failure, and the possible explanations for the discrepancy between Phase II and Phase III trials. © 2011 Macmillan Publishers Limited. All rights reserved.


Espinosa E.,Hospital Universitario La Paz
Cancer metastasis reviews | Year: 2012

Gene signatures can provide prognostic and predictive information to help in the treatment of early-stage breast cancer. Although many of these signatures have been described, only a few have been properly validated. MammaPrint and OncoType offer prognostic information and identify low-risk patients who do not benefit from adjuvant chemotherapy. With regard to prediction of response, molecular subtypes of breast cancer differ in their sensitivity to chemotherapy, although further studies are needed in this field. Cost, small sample size, and the need to use central laboratories are common limitations to the widespread use of these tools.


To investigate the accuracy of composite scores in classifying RA patients who are in remission using the absence of inflammatory activity detected by ultrasound (US) as a gold standard. Ninety-seven RA patients who were classified by their rheumatologists as being in remission were studied. Disease activity was assessed by the DAS-28 and simplified disease activity index (SDAI). US examination was performed in mode B and power Doppler (PD) in 42 joints. Synovial hypertrophy (SH) and PD were present in 92 (94.8%) and 41 (42.3%) patients. If we consider 'remission' to be the absence of joints with PD signal, no differences were found by DAS-28 between patients in remission and those not in remission, although differences were present by SDAI. We then calculated the sensitivity (S), specificity (Sp) and positive likelihood ratio (LR) of different SDAI cut-off points to predict absence of PD signal. SDAI < 5 had an S of 65% (95% CI 52, 76), Sp of 55% (95% CI 39, 69) and LR of 1.45 (95% CI 0.98, 2.15), whereas SDAI < 3.3 had an S of 57% (95% CI 44, 69), Sp of 74% (95% CI 58, 85) and LR of 2.24 (95% CI 1.25, 4.01). Our results suggest that the SDAI classification of remission is closer to the concept of an absence of inflammatory activity, as defined by the absence of positive PD signal by US.


Villanueva R.,Hospital Universitario La Paz
Psychiatry Research | Year: 2012

Relative to non-human primates, in humans the cerebellum, and prefrontal cortex are brain regions which have undergone major evolutionary changes. In recent decades, progress in molecular biology and advances in the development of functional neuroimaging analysis have shown that the evolution of the human cerebellum was accompanied by the acquisition of more functions than were previously deduced from human post-mortem studies and animal experimentation. These new cerebellar functions included the control of attention and other cognitive functions, emotions and mood, and social behavior, which were all thought to represent cortical functions. The importance of this new view of cerebellar physiology has been confirmed by the frequency of neuropsychiatric disorders in individuals with cerebellar abnormalities. The information collected in this review emphasizes the importance of cerebellar studies in establishing the physiological substrate of mental diseases. © 2012 Elsevier Ltd.


Tovar J.A.,Hospital Universitario La Paz
Orphanet Journal of Rare Diseases | Year: 2012

Congenital Diaphragmatic Hernia (CDH) is defined by the presence of an orifice in the diaphragm, more often left and posterolateral that permits the herniation of abdominal contents into the thorax. The lungs are hypoplastic and have abnormal vessels that cause respiratory insufficiency and persistent pulmonary hypertension with high mortality. About one third of cases have cardiovascular malformations and lesser proportions have skeletal, neural, genitourinary, gastrointestinal or other defects. CDH can be a component of Pallister-Killian, Fryns, Ghersoni-Baruch, WAGR, Denys-Drash, Brachman-De Lange, Donnai-Barrow or Wolf-Hirschhorn syndromes. Some chromosomal anomalies involve CDH as well. The incidence is < 5 in 10,000 live-births. The etiology is unknown although clinical, genetic and experimental evidence points to disturbances in the retinoid-signaling pathway during organogenesis. Antenatal diagnosis is often made and this allows prenatal management (open correction of the hernia in the past and reversible fetoscopic tracheal obstruction nowadays) that may be indicated in cases with severe lung hypoplasia and grim prognosis. Treatment after birth requires all the refinements of critical care including extracorporeal membrane oxygenation prior to surgical correction. The best hospital series report 80% survival but it remains around 50% in population-based studies. Chronic respiratory tract disease, neurodevelopmental problems, neurosensorial hearing loss and gastroesophageal reflux are common problems in survivors. Much more research on several aspects of this severe condition is warranted. © 2012 Tovar; licensee BioMed Central Ltd.


Rodriguez-Merchan E.C.,Hospital Universitario La Paz
Haemophilia | Year: 2012

If continuous prophylaxis is not feasible due to expense or lack of venous access, we must aggressively treat major haemarthroses (including arthrocentesis) to prevent progression to synovitis, recurrent joint bleeds, and ultimately end-stage osteoarthritis (haemophilic arthropathy). For the treatment of chronic haemophilic synovitis, radiosynovectomy should always be indicated as the first procedure. If, after three procedures with 6-month interval, radiosynovectomy fails, an arthroscopic synovectomy must be indicated. Between the second and fourth decades, many haemophilic patients develop joint destruction (arthropathy). At this stage possible treatments include alignment osteotomy, arthroscopic joint debridement, arthrodesis (joint fusion) and total joint arthroplasty. For the hip press-fit uncemented components (hemispherical acetabulum, flanged femoral stem, metal-to-polyethylene) are recommended whilst for the knee a posterior-stabilized (PS) cemented design is advised. Muscular problems must not be underestimated in haemophilia due to their risk of developing compartment syndromes (which will require surgical decompression) and pseudotumours (which will require surgical removal or percutaneous treatment). Regarding patients with inhibitors, the advent of APCCs and rFVIIa has made major orthopaedic surgery possible, leading to an improved quality of life for haemophilia patients. Concerning local fibrin seal, it is not always necessary to achieve haemostasis in all surgical procedures performed in persons with haemophilia. However, it could be a good adjunct therapy, mainly when a surgical field potentially will bleed more than expected (i.e. patients with inhibitors), and also in some orthopaedic procedures (mainly the surgical removal of pseudotumours). © 2011 Blackwell Publishing Ltd.


Villanueva R.,Hospital Universitario La Paz
Neural Plasticity | Year: 2013

We survey studies which relate abnormal neurogenesis to major depressive disorder. Clinically, descriptive gene and protein expression analysis and genetic and functional studies revised here show that individual alterations of a complex signaling network, which includes the hypothalamic-pituitary-adrenal axis; the production of neurotrophins and growth factors; the expression of miRNAs; the production of proinflammatory cytokines; and, even, the abnormal delivery of gastrointestinal signaling peptides, are able to induce major mood alterations. Furthermore, all of these factors modulate neurogenesis in brain regions involved in MDD, and are functionally interconnected in such a fashion that initial alteration in one of them results in abnormalities in the others. We highlight data of potential diagnostic significance and the relevance of this information to develop new therapeutic approaches. Controversial issues, such as whether neurogenesis is the basis of the disease or whether it is a response induced by antidepressant treatments, are also discussed. © 2013 Rosa Villanueva.


Patent
Hospital Universitario La Paz | Date: 2013-08-14

The present invention relates to a surgical device for interrupted suture. It integrates a hollow needle (2) suitable for perforating selectable tissues and allowing the passage there through of a biocompatible T-suture thread (3), with an anchor (4); and a cylindrical rod (7) sized to be introduced and linearly displaced through the inside of the channel of said needle to push the mentioned anchor (4), to expulse it through the distal end of the needle (2). The device further comprises driving means comprising a pusher arranged for pushing the mentioned rod (7) by its proximal end and energy retaining and releasing means associated to the mentioned pusher for - applying a push force thereto and causing, at will, a quick displacement of predetermined length, for pushing the suture once that the end is in a body cavity.

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