PubMed | Instituto Portugues Of Oncologia Of Lisbon, Hospital Fernando Fonseca, Centro Hospitalar Of Lisbon Norte, Hemato Oncology Unit and 2 more.
Type: Journal Article | Journal: Annals of hematology | Year: 2016
Patients with multiple myeloma (MM) and severe renal impairment (SRI) have shorter survival than MM patients without renal failure. Although lenalidomide is a highly active drug, this immunomodulatory agent is frequently neglected in this context due to its predominant renal clearance and, consequently, an increased risk of toxicity. This risk might be overcome with the proper lenalidomide dose adjustment to renal function. This study evaluates the outcomes of 23 relapsed MM patients with SRI (baseline creatinine clearance (CrCl) <30mL/min) treated with lenalidomide-dexamethasone (LenDex), including 56% (13 patients) under hemodialysis. The median CrCl at start of LenDex was 19mL/min; an overall response rate (partial response or better) of 56% was obtained, with a median follow-up from start of LenDex of 52months (8-79). The median time until maximal response was 4months, and in 58% (7/12), the response was longer than 2years. Nine percent had renal improvement, but all the 13 patients on hemodialysis remained under treatment. LenDex was interrupted in three cases because of adverse events (infections and cutaneous events); 78% of the patients were on thromboprophylaxis with aspirin. It is important to notice that, after initial dose adjustment of therapy, there should be a continuous process of dose adjustment, taking into account variations in renal function. Furthermore, lenalidomide dose adjustment should be made according to the individual tolerance, even with stable renal function. LenDex dose adjustment, according to these principles, does not negatively impact response and improves treatment tolerance. It has a clear potential to treat this group of patients and to induce long duration of responses [event-free survival (EFS) 20.5m and overall survival (OS) 42.6m].
Polido-Pereira J.,University of Lisbon |
Vieira-Sousa E.,University of Lisbon |
Fonseca J.E.,University of Lisbon |
Fonseca J.E.,Centro Hospitalar Of Lisbon Norte
Autoimmunity Reviews | Year: 2011
Despite the enthusiastic progresses in the field of rheumatoid arthritis pharmacotherapy the presence of prognostic factors associated with an unfavorable outcome and the inappropriate and/or delayed initiation of DMARDs can diminish the likelihood of achieving remission and increase the probability of refractoriness to treatment.During the last decade we have experience exciting developments regarding the approval of new treatment options but few patients are reaching sustained remission and refractory patients continue to be a problem. Thus, it is critical to understand how clinicians can decrease the risk of refractoriness by close monitoring disease activity, using well defined and accepted composite measures, and by early and optimized use of DMARDs, including biologics.The goal of this review paper is to offer an evidence based roadmap to prevent and to deal with refractory RA. © 2011.
Zeuzem S.,Goethe University Frankfurt |
Jacobson I.M.,New York Medical College |
Baykal T.,AbbVie |
Marinho R.T.,Centro Hospitalar Of Lisbon Norte |
And 16 more authors.
New England Journal of Medicine | Year: 2014
BACKGROUND: In this phase 3 trial we evaluated the efficacy and safety of the interferon-free combination of ABT-450 with ritonavir (ABT-450/r), ombitasvir (also known as ABT-267), dasabuvir (also known as ABT-333), and ribavirin for the retreatment of HCV in patients who were previously treated with peginterferon-ribavirin. METHODS: We enrolled patients with HCV genotype 1 infection and no cirrhosis who had previously been treated with peginterferon-ribavirin and had a relapse, a partial response, or a null response. Patients were randomly assigned in a 3:1 ratio to receive coformulated ABT-450/r-ombitasvir (at a once-daily dose of 150 mg of ABT-450, 100 mg of ritonavir, and 25 mg of ombitasvir) and dasabuvir (250 mg twice daily) with ribavirin (1000 or 1200 mg daily) or matching placebos during the 12-week double-blind period. The primary end point was the rate of sustained virologic response 12 weeks after the end of study treatment. The primary efficacy analysis compared this rate among patients assigned to the active regimen with a historical response rate (65%) among previously treated patients with HCV genotype 1 infection and no cirrhosis who had received retreatment with telaprevir and peginterferon-ribavirin. RESULTS: A total of 394 patients received at least one study-drug dose. In the active-regimen group, 286 of 297 patients had a sustained virologic response at post-treatment week 12, for an overall rate of 96.3% (95% confidence interval, 94.2 to 98.4). This rate was noninferior and superior to the historical control rate. Rates were 95.3% among patients with a prior relapse (82 of 86 patients), 100% among patients with a prior partial response (65 of 65 patients), and 95.2% among patients with a prior null response (139 of 146 patients). Pruritus occurred more frequently with the active regimen (in 13.8% of patients) than with placebo (5.2%, P = 0.03). Three patients in the active-regimen group (1.0%) discontinued the study drugs owing to adverse events. Hemoglobin values of grade 2 (8.0 to <10.0 g per deciliter) and grade 3 (6.5 to <8.0 g per deciliter) occurred in 4.7% and 0.3% of patients in the active-regimen group, respectively. CONCLUSIONS: Rates of response to a 12-week interferon-free combination regimen were more than 95% among previously treated patients with HCV genotype 1 infection, including patients with a prior null response. Copyright © 2014 Massachusetts Medical Society.
Aldir I.,Centro Hospitalar Of Lisbon Ocidental |
Horta A.,Centro Hospitalar do Porto |
Serrado M.,Centro Hospitalar Of Lisbon Norte
Current Medical Research and Opinion | Year: 2014
Objectives: Review of the available data on the currently available single-tablet regimens (STRs), from the analysis of efficacy and safety to the key points of value in terms of adherence, quality of life and pharmacoeconomic evaluation. Methods: For this narrative review, literature searches have been performed in PubMed, IndexRevMed and Cochrane, using the search terms HIV, single-tablet, one-pill, single dose, fixed-dose, and STR. These have been reviewed and complemented with the most recent publications of interest. Results: Fixed-dose combinations are a significant advance in antiretroviral treatment simplification, contributing to an increase in compliance with complex chronic therapies, thus improving patients' quality of life. Reducing the number of pills and daily doses is associated with higher adherence and better quality of life. As a fixed-dose combination tablet given once daily, EFV/FTC/TDF was the first available STR combining efficacy, tolerability and convenience, with the simplest dosing schedule and smallest numbers of pills of any ART combination therapy. The RPV/FTC/TDF is a next-generation NNRTI-based STR, a once daily complete ART regimen for the treatment of HIV-1 infection. Recently the combination of EVG/COBI/FTC/TDF was also approved by the European Commission, and is the first integrase inhibitor-based STR. Receiving antiretroviral therapy as once daily STR is associated with both clinical and economic benefits, which confirms previous research. Conclusions: The associated benefits of STRs provide a valid strategy for the treatment of HIV-infected patients. © 2014 Informa UK Ltd.
Da Cunha Fragoso E.G.,Centro Hospitalar Of Lisbon Norte |
Goncalves J.M.R.,Centro Hospitalar Of Lisbon Norte
Journal of Bronchology and Interventional Pulmonology | Year: 2011
Summary: Since its introduction in daily medical practice in the late 20th century, flexible bronchoscopy has had an increasing role in the everyday life of the pulmonologist. Not only for diagnosis, but also for therapeutic interventions, it has achieved widespread use and is now performed in a diversity of clinical scenarios. For several reasons, from easy performance in trained hands to versatility, diagnostic reliability, and safety, flexible bronchoscopy is now widely accepted and increasingly used in the management of critically ill patients. The knowledge of the unique features of intensive care unit patients, as well as indications and contraindications for the procedure, is paramount in achieving optimal results, while minimizing potential risks and complications. Performing bronchoscopy in an unstable patient, often on mechanical ventilation, requires awareness of the specific pathophysiological impact of the procedure. This in turn determines respiratory and cardiovascular derangements frequently observed during the procedure. This article reviews indications, pathophysiology, technical aspects, complications, and contraindications of flexible bronchoscopy in the critical care patient. Copyright © 2011 by Lippincott Williams & Wilkins.
Ruivo J.A.,Centro Hospitalar Of Lisbon Norte |
Alcantara P.,Centro Hospitalar Of Lisbon Norte
Revista Portuguesa de Cardiologia | Year: 2012
Levels of physical activity in modern urbanized society are clearly insufficient to maintain good health, and to prevent cardiovascular and other disease. Aerobic exercise is almost completely free of secondary effects, and is a useful adjunctive therapy in treating hypertension. There are several possible mechanisms to account for the beneficial effects of exercise in reducing blood pressure, the resulting physiological effects usually being classified as acute, post-exercise or chronic. Variations in genetic background, hypertension etiology, pharmacodynamics and pharmacokinetics may explain the different blood pressure responses to exercise among hypertensive patients. The present review discusses the different pathophysiological aspects of the response to exercise in hypertensives, including its modulators and diagnostic and prognostic usefulness, as well as the latest guidelines on prescribing and monitoring exercise regimes and drug therapy in the clinical follow-up of active hypertensive patients. ©2011 Sociedade Portuguesa de Cardiologia Published by Elsevier España, S.L. All rights reserved.
Santos Dias J.,Centro Hospitalar Of Lisbon Norte
Techniques in Vascular and Interventional Radiology | Year: 2012
Benign prostatic hyperplasia (BPH) is a very common condition, related to aging and causing symptoms, called lower urinary tract symptoms. On account of its huge prevalence, it is important for clinicians who are involved in the management of patients with BPH to be aware of the very strict recommendations for BPH evaluation. In this article, we describe the different steps and procedures doctors should follow to evaluate these patients; symptoms and signs of BPH are reviewed, as well as the clinical evaluation steps and examinations available. The basic evaluation of the patients with BPH should include, according to the recommendations of the most relevant international guidelines, lower urinary tract symptoms evaluation with appropriate symptom scores, digital rectal examination, voiding charts, prostate-specific antigen and creatinine measurement, urinalysis, and imaging of the urinary tract. © 2012 Elsevier Inc.
Oliveira Santos M.,University of Lisbon |
Brito D.,University of Lisbon |
Brito D.,Centro Hospitalar Of Lisbon Norte
Revista Portuguesa de Cardiologia | Year: 2013
Familial amyloid polyneuropathy type I (FAP type I) is a rare hereditary systemic amyloidosis caused by the Val30Met mutation in the transthyretin (TTR) gene. The clinical onset and spectrum are variable and depend on phenotypic heterogeneity. Cardiac complications (dysrhythmias and conduction disturbances, cardiomyopathy and dysautonomia) indicate a poor prognosis, even after liver transplantation. We report an atypical case of FAP type I, highlighting the severe cardiac involvement and its complications. Early diagnosis of amyloid heart disease is increasingly important in the context of several clinical trials of promising new and experimental drugs. © 2012 Sociedade Portuguesa de Cardiologia. Published by Elsevier Espana.
Cascao R.,University of Lisbon |
Vidal B.,University of Lisbon |
Raquel H.,University of Lisbon |
Neves-Costa A.,University of Lisbon |
And 5 more authors.
Autoimmunity Reviews | Year: 2012
We have previously reported an increase in interleukin (IL)-1β and IL-17 levels, and a continuous activation of caspase-1 in early rheumatoid arthritis (RA) patients. These results suggest that drugs targeting IL-1β regulatory pathways, in addition to tumor necrosis factor (TNF), may constitute promising therapeutic agents in early RA. We have recently used a THP-1 macrophage-like cell line to screen 2320 compounds for those that down-regulate both IL-1β and TNF secretion. Celastrol was one of the most promising therapeutic candidates identified in that study. Our main goal in the present work was to investigate whether administration of celastrol is able to attenuate inflammation in a rat model of adjuvant-induced arthritis (AIA). Moreover, since IL-1β is known to play a role in the polarization of Th17 cells, we also investigate whether administration of digoxin, a specific inhibitor of Th17 cells polarization, is able to attenuate inflammation in the same rat model. We found that celastrol administration significantly suppressed joint inflammation. The histological and immunohistochemical evaluation revealed that celastrol-treated rats had a normal joint structure with complete abrogation of the inflammatory infiltrate and cellular proliferation. In contrast, we observed that digoxin administration significantly ameliorated inflammation but only if administrated in the early phase of disease course (after 4. days of disease induction), and it was not efficient at inhibiting the infiltration of immune cells within the joint and in preventing damage. Thus, our results suggest that celastrol has significant anti-inflammatory and anti-proliferative properties and can constitute a potential anti-inflammatory drug with therapeutic efficacy in the treatment of immune-mediated inflammatory diseases such as RA. Furthermore, we find that early inhibition of Th17 cells polarization ameliorates arthritis but it is not as effective as celastrol. © 2012 Elsevier B.V.
PubMed | Centro Hospitalar Of Lisbon Norte and University of Lisbon
Type: Journal Article | Journal: The Journal of hospital infection | Year: 2016
Despite great efforts to enhance European epidemiological surveillance on carbapenemase-producing Enterobacteriaceae (CPE), information from several countries remains scarce. To address CPE epidemiology in Portugal, we have undertaken a retrospective cohort study of adults with CPE cultures identified in the microbiology laboratory of a tertiary hospital, in 2012. Sixty patients from 25 wards or intensive care units were identified. This is, to the best of our knowledge, the first report of clinical data on CPE in Portugal. It shows a hospital-wide CPE dissemination and alerts us to an evolving epidemiological situation not previously described.