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Sciarra A.,University of Rome La Sapienza | Abrahamsson P.A.,Skåne University Hospital | Brausi M.,Estenses Sant Agostino Institute | Galsky M.,Mount Sinai School of Medicine | And 3 more authors.
European Urology | Year: 2013

Context Intermittent androgen deprivation (IAD) in prostate cancer (PCa) patients has been proposed to delay development of castration resistance and to reduce the side effects and costs of androgen deprivation therapy (ADT). Objective This review analyzes (1) the oncologic and quality of life (QoL) results from randomized phase 3 trials comparing IAD and continuous ADT and (2) the prognostic parameters for IAD. Evidence acquisition We searched the Medline and Cochrane Library databases (primary fields: prostate neoplasm and intermittent androgen deprivation; secondary fields: randomized trials, survival, quality of life, predictors) without language restriction. Evidence synthesis We found seven extensively described phase 3 trials randomizing 4675 patients to IAD versus continuous ADT. Other randomized trials investigating IAD have been performed, but available data are limited and have been published only in preliminary fashion. In all seven trials, patients spent most of their time on, rather than off, ADT. The induction periods ranged from 3 mo to 8 mo; in all but one trial, the PSA level designated for ADT discontinuation was <4 ng/ml. Mean follow-up ranged from 40-108 mo. Collectively, these trials support the concept that, mainly in metastatic cases, IAD can produce oncologic results similar to continuous ADT. In terms of overall survival, the hazard ratios for IAD and continuous ADT were very similar (range: 0.98-1.08). The QoL benefit of IAD appears to be modest at best. With IAD, QoL is likely influenced by the duration of the off-treatment periods and by the rate of testosterone recovery. Conclusions The evidence indicates that IAD is not inferior to continuous ADT. Data are insufficient to determine whether IAD is able to prevent the long-term complications of ADT. More comparative analysis focused on QoL is warranted. © 2013 European Association of Urology.


Davison J.A.,Wolfe Eye Clinic | Cunha J.P.,Centro Hospitalar Of Lisbon Central | Schwiegerling J.,University of Arizona | Muftuoglu O.,Ankara University
Graefe's Archive for Clinical and Experimental Ophthalmology | Year: 2011

Background: Recent reviews of blue light-filtering intraocular lenses (IOLs) have stated their potential risks for scotopic vision and circadian photoentrainment. Some authors have challenged the rationale for retinal photoprotection that these IOLs might provide. Our objective is to address these issues by providing an updated clinical perspective based on the results of the most recent studies. Methods: This article evaluates the currently available published papers assessing the potential risks and benefits of blue light-filtering IOLs. It summarizes the results of seven clinical and two computational studies on photoreception, and several studies related to retinal photoprotection, all of which were not available in the previous reviews. These results provide a clinical risk/benefit analysis for an updated review for these IOLs. Results: Most clinical studies comparing IOLs with and without the blue light-filtering feature have found no difference in clinical performance for; visual acuity, contrast sensitivity, color vision, or glare. For blue light-filtering IOLs, three comparative clinical studies have shown improved contrast sensitivity and glare reduction; but one study, while it showed satisfactory overall color perception, demonstrated some compromise in mesopic comparative blue color discrimination. Comparative results of two recent clinical studies have also shown improved performance for simulated driving under glare conditions and reduced glare disability, better heterochromatic contrast threshold, and faster recovery from photostress for blue light-filtering IOLs. Two computational and five clinical studies found no difference in performance between IOLs with or without blue light-filtration for scotopic vision performance and photo entrainment of the circadian rhythm. The rationale for protection of the pseudophakic retina against phototoxicity is discussed with supporting results of the most recent computational, in-vitro, animal, clinical, and epidemiological investigations. Conclusions: This analysis provides an updated clinical perspective which suggests the selection of blue light-filtering IOLs for patients of any age, but especially for pediatric and presbyopic lens exchange patients with a longer pseudophakic life. Without clinically substantiated potential risks, these patients should experience the benefit of overall better quality of vision, reduced glare disability at least in some conditions, and better protection against retinal phototoxicity and its associated potential risk for AMD. © 2011 The Author(s).


Ramalho J.,University of North Carolina at Chapel Hill | Ramalho J.,Centro Hospitalar Of Lisbon Central | Castillo M.,University of North Carolina at Chapel Hill | AlObaidy M.,University of North Carolina at Chapel Hill | And 6 more authors.
Radiology | Year: 2015

Purpose: To determine if a correlation exists between the number of previous enhanced magnetic resonance (MR) imaging examinations and high signal intensity in the globus pallidus (GP) and dentate nucleus (DN) in patients who received gadodiamide (Omniscan), a linear nonionic gadolinium-based contrast agent, and in those who received gadobenate dimeglumine (MultiHance), a linear ionic contrast agent. Materials and Methods: Institutional review board approval was obtained for this single-center retrospective study, with waiver of informed consent. The study population included 69 patients divided into two groups: Group 1 included patients who underwent gadodiamide-enhanced MR imaging, and group 2 included patients who underwent gadobenate dimeglumine-enhanced MR imaging. Two radiologists conducted a quantitative analysis of unenhanced T1-weighted images by using region of interest measurements. The GP-to-thalamus (TH) signal intensity ratio, DN-to-middle cerebellar peduncle (MCP) signal intensity ratio and relative percentage change (Rchange) between the first and last examinations for each patient were calculated. Relation between the signal intensity ratios and Rchange and the number of enhanced MR imaging examinations was analyzed by using a generalized additive model. Inter- and intraobserver agreement was evaluated with the Lin concordance correlation coefficient test. Results: Group 1 included 23 patients (19 female), with a mean of 5.0 doses ± 2.4 (standard deviation) (range, 3-11 doses) administered. Group 2 included 46 patients (24 female) with a mean of 4.6 doses ± 2.2 (range, 3-11 doses) administered. The interval between the first and last examination was 1500.1 days ± 780.2 (range, 98-3097 days) for group 1 and 1086.2 days ± 582.9 (range, 94-2633) for group 2. All patients had normal liver and renal function. Gadodiamide showed a significant increase in DN:MCP and GP:TH (P < .001 for both) and in Rchange (P = .001 for GP:TH, P < .001 for DN:MCP). In group 2, there was no significant increase in DN:MCP or GP:TH over time or in Rchange for GP:TH, but there was a significant trend toward an increase in Rchange for DN:MCP (P = .013). Interobserver agreement was almost perfect (0.99; 95% confidence interval: 0.99, 0.99) for all evaluated structures. Intraobserver agreement was substantial to almost perfect for both readers. Conclusion: A significant increase in GP:TH and DN:MCP is associated with multiple gadodiamide-enhanced studies but not with gadobenate dimeglumine-enhanced studies, likely reflecting differences in stability and elimination of both contrast agents. Rate-of-change data indirectly suggest gadolinium deposition in the DN with gadobenate dimeglumine use, although it is considerably less than that with gadodiamide use. Copyright © 2015 Radiological Society of North America.


Grant
Agency: Cordis | Branch: H2020 | Program: RIA | Phase: PHC-26-2014 | Award Amount: 5.46M | Year: 2015

EmERGE will develop a mHealth platform to enable self-management of HIV in patients with stable disease. The platform will build upon and integrate the existing mHealth solutions operated by pioneering healthcare providers in the UK and Spain and apply a rigorous co-design approach to ensure patient and clinician input to the solution. The platform will provide users with web based and mobile device applications which interface securely with relevant medical data and facilitate remote access to key healthcare providers EATG, the European HIV patient organisation, will provide a direct and deep interaction with representative patients and clinicians from 5 EU countries. The platform and interfaces will be validated in a large study of 3900 patients using a tailored HTA process, MAST, specifically developed for the assessment of mHealth solutions including translatability as a key factor. Based on prior work showing a high uptake rate and use of mHealth in HIV patient populations, EmERGE aims to demonstrate the benefits to patients and simultaneous increases in cost-effectiveness for healthcare providers by reducing face-to-face consultations, estimated at 6000 saved per year within this study alone. Patient reported outcomes will be agreed and used in the assessment and development of the system which also aims to increase adherence and enable frailty to be reported using mHealth technology. Innovation will be given priority from the beginning by developing new business models of care provision, targeting key stakeholders in the EU health provider sector, including policymakers and clinicians, while eliciting demand from patients to highlight and initiate the widespread implementation and compensation of mHealth solutions within the timeframe of the project. Guidelines and policy briefs will be produced to evidence the benefits and disseminate the lessons learned to support the uptake of mHealth for self-management of other chronic diseases.


Wolff J.M.,AKH Viersen | Abrahamsson P.-A.,Skåne University Hospital | Irani J.,University of Poitiers | Calais Da Silva F.,Centro Hospitalar Of Lisbon Central
BJU International | Year: 2014

Use of intermittent androgen-deprivation therapy (IADT) in patients with prostate cancer has been evaluated in several studies, in an attempt to delay the development of castration resistance and reduce side-effects associated with ADT. However it is still not clear whether survival is adversely affected in patients treated with IADT. In this review, we explore the available data in an attempt to identify the most suitable candidate patients for IADT, and discuss factors that may inform appropriate patient stratification. ADT is first-line treatment for advanced/metastatic prostate cancer and is also recommended for use with definitive radiotherapy for high-risk localised prostate cancer. The changes in hormone levels induced by ADT can lead to short- and long-term side-effects which, although treatable in most cases, can significantly reduce the tolerability of ADT treatment. IADT has been investigated in several phase II and phase III studies in patients with locally advanced or metastatic prostate cancer, in an attempt to delay time to tumour progression and reduce the side-effect burden of ADT. In selected patient groups IADT is no less effective than continuous ADT, ameliorating the impact of ADT-related side-effects, and, to a degree, their impact on patient health-related quality of life (HRQL). Further comparative study is required, particularly in relation to HRQL and long-term complications associated with ADT. © 2014 The Authors. BJU International © 2014 BJU International.


Farinha P.,Cancer Agency Center for Lymphoid Cancers | Farinha P.,Centro Hospitalar Of Lisbon Central | Al-Tourah A.,Cancer Agency Center for Lymphoid Cancers | Gill K.,Cancer Agency Center for Lymphoid Cancers | And 3 more authors.
Blood | Year: 2010

Previous studies of follicular lymphoma (FL) patients treated heterogeneously have suggested that decreased numbers of regulatory T cells correlates with improved survival. We studied advancedstage FL patients from a single institution phase 2 trial. All patients were treated uniformly with multiagent chemotherapy and radiation. Tissue microarrays were constructed using diagnostic biopsies available in 105 patients and stained with CD4, CD8, CD25, and forkhead/winged helix transcription factor 3 (FOXP3) antibodies. Both cell content and cell distribution were evaluated. For all antibodies, there were cases with a predominant intrafollicular or perifollicular localization of cells (follicular pattern) while others displayed a diffuse pattern. The median follow-up of living patients was 17.1 years. The International Prognostic Index score predicted overall survival (OS; P = .004) but not risk of transformation (RT). Cell content did not impact survival, while immunoarchitectural patterns of CD4/ CD8 were significant for progression-free survival (PFS; P = .056), CD25 for both PFS and OS (P = .002 and P = .024, respectively), and FOXP3 + predicted PFS, OS, and RT (P = .001, P < .001 and p = .002, respectively). A Cox multivariate model showed both International Prognostic Index score and FOXP3+ pattern were independent predictors of OS (P = .008 and P < .001, respectively), while only FOXP3+ pattern predicted RT (P = .004). We conclude that FOXP3+ cell distribution significantly predicts survival and RT in FL. © 2010 by The American Society of Hematology.


Camacho R.,New University of Lisbon | Teofilo E.,Centro Hospitalar Of Lisbon Central
Current Opinion in HIV and AIDS | Year: 2011

Purpose of review: This review discusses the current status of antiretroviral therapy (ART) in treatment-naïve patients. ART initiation in such patients needs to be carefully planned, as the aim of therapy has shifted from prolonging life to ensuring maintained adherence to ART and optimization of quality of life. There is a plethora of first-line antiretroviral agents available, and physicians must consider several patient-related and therapy-related factors before selecting the most appropriate initial ART. RECENT FINDINGS: Current treatment guidelines recommend the use of nonnucleoside reverse transcriptase inhibitor (NNRTI), ritonavir-boosted protease inhibitor (PI), or integrase strand transfer inhibitor (INSTI)-based regimens in treatment-naïve patients. Treatment selection and modification to achieve optimal response is based primarily on regular assessment of viral load (and resistance testing if necessary) and CD4 cell count. The use of genotypic resistance testing, on initiation of therapy and on treatment failure, is becoming more widespread. In selected patients, due to increasing transmitted drug resistance (TDR), a PI-based regimen may be a better option. Classic ART combinations are being challenged by new combinations, although there is currently insufficient evidence to recommend use of the newer over classic combinations. Co-formulations of drugs and single-tablet regimens are fast becoming available and their convenience may increase patient treatment adherence. SUMMARY: All drug classes currently available for first-line ART are efficacious and have good tolerability; however, differences between individual drugs must be carefully considered when deciding a first-line regimen. Each first-line regimen must be tailored to the individual patient to attain optimal efficacy, acceptable long-term tolerability, and good adherence to ART. © 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins.


Endoluminal reconstruction with flow diverter devices represents an innovative technique in the treatment of intracranial aneurysms.These new stents, self-expandable and of low porosity, are released through the microcatherization of the parent artery. The main goal of these systems is thereby rebuilding the vessel wall and excluding the aneurysmal formation of the arterial circulation.We show the preliminary results in treating 10 patients at Hospital de São José, Lisbon. These patients, with wide-necked (> 4 mm)or unfavorable dome/neck ratios (> 1.5) aneurysms, were treated with the PIPELINE® system, and angiographic control were made at three and six months. New control will be done at 12 months. The mean age of enrolled patients is 54.3 years; eight patients were female and two male. Aneurysms were incidentally discovered in two patients. The remaining patients were diagnosed during imaging investigation for headache (n = 3), visual field defect (n = 1), vertigo(n = 1) and at least one cranial palsy (n = 2). Only two patients had had prior subarachnoid hemorrhage and two patients underwent prior endovascular treatment with coils. The locations of aneurysms treated were the proximal segment of the middle cerebral artery(n = 1) and the paraophthalmic (n = 6), ophthalmic (n = 2) and cavernous (n = 4) internal carotid artery segments. Thirteen intracranial aneurysms were treated as three patients had multiple aneurysms. Control studies were conducted and shown an average degree of occlusion at three months of 74% and at six months of 86%. There was no reduction in size of one paraophthalmic artery aneurysm.The experience of this department is favorable to the use of flow-diverter devices to treat selected aneurysms. High occlusion rates were obtained given the existing challenges in the treatment of such aneurysms.


Thromboembolic phenomena are the most commonly reported complications during endovascular treatment of intracranial aneurysms with coils. Frequency of this complication varies in the literature, but authors reported rates ranging from 2.5 to 28%. Several mechanisms may be involved in the formation and migration of thrombus: it may be already existing inside the aneurysm and be dislocated and then migrate distally; it can be formed on the surface of the coils or catheters used, or it can appear in the remnant aneurysm sac it. Studies have shown a higher incidence of thromboembolic complications in wide neck aneurysms. In this paper we discuss the importance of prevention of thromboembolic complications during and after endovascular treatment of ruptured intracranial aneurysms. We also refer options and strategies to adopt in the event of a vascular occlusion is detected during the procedure, as the administration of inhibitors of glycoprotein IIb/IIIa or the release of an intra-cranial stent. Illustrative cases are shown. The prevention of thromboembolic complications and rapid action after the vascular occlusion is essential in order to improve the prognosis of patients undergoing endovascular treatment of ruptured intracranial aneurysms. Extensive knowledge of available options is essential to the pursuit of that goal.


Costa J.L.,University of Porto | Sousa S.,University of Porto | Justino A.,University of Porto | Kay T.,Centro Hospitalar Of Lisbon Central | And 4 more authors.
Human Mutation | Year: 2013

The introduction of the benchtop massive parallel sequencers made it possible for the majority of clinical diagnostic laboratories to gain access to this fast evolving technology. In this study, using the Ion Torrent Personal Genome Machine, we present a strategy for the molecular diagnosis of hereditary breast and ovarian cancer and respective analytical validation. The methodology relies on a multiplex PCR amplification of the BRCA1 and BRCA2 genes combined with a variant prioritization pipeline, designed to minimize the number of false-positive calls without the introduction of false-negative results. A training set of samples was used to optimize the entire process, and a second set was used to validate and independently evaluate the performance of the workflow. Performing the study in a blind manner relative to the variants in the samples and using conventional Sanger sequencing as standard, the workflow resulted in a strategy with a maximum analytical sensitivity ≥98.6% with a confidence of 95% and a specificity of 96.9%. Importantly, no true variant was missed. This study presents a comprehensive massive parallel sequencing-Sanger sequencing based strategy, which results in a high analytical sensitivity assay that provides a time- and cost-effective strategy for the identification of mutations in the BRCA1 and BRCA2 genes. In this study, using the Ion Torrent PGM, we present a comprehensive MPS-Sanger sequencing based strategy for the molecular diagnosis of hereditary breast and ovarian cancer and respective analytical validation. The methodology relies on multiplex PCR amplification of the BRCA1 and BRCA2 genes combined with a dedicated variant prioritization pipeline. The workflow resulted in a strategy with a high analytical sensitivity (≥98.6%) that provides a time- and cost-effective strategy for the identification of mutations in the BRCA1 and BRCA2 genes. © 2013 Wiley Periodicals, Inc.

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