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Sotolongo-Grau O.,Institute Catala Of Neurociencies Aplicades | Sotolongo-Grau O.,Spanish University for Distance Education (UNED) | Rodriguez-Perez D.,Spanish University for Distance Education (UNED) | Sotolongo-Costa O.,University of Habana | And 2 more authors.
Physica A: Statistical Mechanics and its Applications | Year: 2013

The biological effect of one single radiation dose on a living tissue has been described by several radiobiological models. However, the fractionated radiotherapy requires to account for a new magnitude: time. In this paper we explore the biological consequences posed by the mathematical prolongation of a previous model to fractionated treatment. Nonextensive composition rules are introduced to obtain the survival fraction and equivalent physical dose in terms of a time dependent factor describing the tissue trend towards recovering its radioresistance (a kind of repair coefficient). Interesting (known and new) behaviors are described regarding the effectiveness of the treatment which is shown to be fundamentally bound to this factor. The continuous limit, applicable to brachytherapy, is also analyzed in the framework of nonextensive calculus. Here a coefficient that rules the time behavior also arises. All the results are discussed in terms of the clinical evidence and their major implications are highlighted. © 2012 Elsevier B.V. All rights reserved.

Lovestone S.,University of Oxford | Boada M.,Institute Catala Of Neurociencies Aplicades | Dubois B.,University Pierre and Marie Curie | Hull M.,Center for Geriatric Medicine Freiburg | And 7 more authors.
Journal of Alzheimer's Disease | Year: 2015

Background: The ARGO study was a phase II, double-blind, placebo controlled, four parallel arm trial of tideglusib in Alzheimer's disease (AD). Objective: To prove the clinical efficacy of an inhibitor of glycogen synthase kinase-3 (GSK-3), in AD. Methods: Mild to moderate (Mini-Mental State Examination (MMSE) score, 14-26) AD patients on cholinesterase inhibitor and/or memantine treatment were administered tideglusib or placebo for 26 weeks. The ADAS-cog15 was the primary efficacy measure; function, cognition, behavior, and quality of life were assessed as secondary measures; cerebral atrophy in MRI and the levels of tau, amyloid-β, and BACE1 in cerebrospinal fluid (CSF) were exploratory endpoints. Results: 306 AD patients were randomized to active (1000 mg QD: n = 86, 1000 mg QOD: n = 90, and 500 mg QD: n = 50) or placebo (n = 85) in 55 sites in four European countries. There were no statistically significant differences between either active and placebo arms in the efficacy variables. However, BACE1 in CSF significantly decreased with treatment in a small subgroup of patients. Participants with mild AD in the 500 mg QD group showed significant responses on ADAS-cog15, MMSE, and word fluency. Diarrhea (14-18% in active, 11% placebo) and dose-dependent, mild to moderate, and fully reversible transaminase increase (9-16% in active, 3.5% placebo) were the most frequent adverse events. Conclusions: Short term (26 weeks) tideglusib was acceptably safe but produced no clinical benefit in this trial. However, given the non-linear dose response, especially in mildly affected patients, further dose finding studies in early disease stages and for longer duration are warranted to examine GSK-3 inhibition in AD patients. © 2015 - IOS Press and the authors.

Introduction and aims. Results from a pilot study and its 2-year extension (IG0502) performed on patients with mild or moderate Alzheimer's disease revealed a tendency towards clinical stabilization after a plasmapheresis program with plasma exchange with therapeutic albumin Human Albumin Grifols® 5%. Plasma levels of Aß40 and Aß42 presented a saw-tooth pattern associated to plasma exchanges. These findings encouraged a new randomized, controlled, parallel, blind study (IG0602) to confirm our previous working hypotheses, i.e. that Aß40 and Aß42 concentrations in plasma were modified pre- and post plasmapheresis with Human Albumin Grifols® 5% and, in the clinical area, that the cognitive capabilities of patients could be stabilized or even improved. Other aims of the study were focused on neuroimaging evaluation of structural and functional changes in the brain the by means of magnetic resonance and single-photon emission computerised tomography. Results. Preliminary results from the randomized study carried out after a follow-up of one year of the first 29 patients (80% of the recruited) show a clear difference between the treated and the control groups with regard to the levels of Aß40, both in plasma and in cerebrospinal fluid, that are associated with the plasma exchanges. This pattern is not so evident for Aß42. Regarding cognitive performance, the treated group scored better than the control group after the period study, according to the evaluation performed by using the Mini-Mental State Examination (MMSE) and Alzheimer's Disease Assessment Scale-Cog nitive (ADAS-Cog) tests. Conclusions. These preliminary results suggest that plasmapheresis with plasma exchange with Human Albumin Grifols® 5% may have a promising future as a treatment of mild-moderate Alzheimer's disease. © 2010 Revista de Neurología.

Gustavsson A.,Karolinska Institutet | Jonsson L.,i3 Innovus | McShane R.,Oxfordshire and Buckinghamshire Mental Healthcare NHS Foundation Trust | Boada M.,Institute Catala Of Neurociencies Aplicades | And 3 more authors.
International Journal of Geriatric Psychiatry | Year: 2010

Objective: To estimate the value of informal care in Alzheimer's disease using contingent valuation. Methods: A questionnaire was administered to 517 primary carers in four countries (UK, Spain, Sweden, and US). Dichotomous choice and bidding game methods were used to elicit their willingness to pay for a reduction in care burden by 1 h per day, or a total elimination of care needs. Further, the relationship between carer willingness to pay and carer and patient characteristics including disease severity and income was examined. Results: Carers spend on average about 7-9 h per day on giving care to their patient, of which 4-5 h constituted basic and instrumental ADL tasks. For a 1 h reduction in need for care per day, carers in the UK, Spain, Sweden, and US said that they were willing to pay £105, £121, £59, and £144 per month respectively. The willingness to pay was higher for carers with higher disposable income while the influence of other determinants varied across countries. About one-third of carers were not willing to pay anything for a reduction in care. Conclusions: Carers' stated willingness to pay for reductions in care giving time is substantial and comparable to the prices currently paid for treatments that achieve this benefit. Its determinants seem more directly related to carer status than directly to patient status and may vary by region and by cultural and sociologic factors. Copyright © 2009 John Wiley & Sons, Ltd.

Moreno-Grau S.,Institute Catala Of Neurociencies Aplicades | Ruiz A.,Institute Catala Of Neurociencies Aplicades
Expert Reviews in Molecular Medicine | Year: 2016

Genetic characterization of individuals at risk of Alzheimer's disease (AD), i.e. people having amyloid deposits in the brain without symptoms, people suffering from subjective cognitive decline (SCD) or mild cognitive impairment (MCI), has spurred the interests of researchers. However, their pre-dementia genetic profile remains mostly unexplored. In this study, we reviewed the loci related to phenotypes of AD, MCI and SCD from literature and performed the first meta-analyses evaluating the role of apolipoprotein E (APOE) in the risk of conversion from a healthy status to MCI and SCD. For AD dementia risk, an increased number of loci have been identified; to date, 28 genes have been associated with Late Onset AD. In MCI syndrome, APOE is confirmed as a pheno-conversion factor leading from MCI to AD, and clusterin is a promising candidate. Additionally, our meta-analyses revealed APOE as genetic risk factor to convert from a healthy status to MCI [OR = 1.849 (1.587–2.153); P = 2.80 × 10−15] and to a lesser extent from healthy status to SCD [OR = 1.151 (1.015–1.304); P = 0.028]. Thus, we believe that genetic studies in longitudinal SCD and MCI series may provide new therapeutic targets and improve the existing knowledge of AD. This type of studies must be completed on healthy subjects to better understand the natural disease resistance to brain insults and neurodegeneration. Copyright © Cambridge University Press 2016

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