Thomas X.,Hospices Civils de Lyon
European Journal of Haematology | Year: 2015
Although acute myeloid leukemia (AML) mostly occurs in older patients, it could be seen in women of childbearing age. It is therefore not surprising that in some patients, the management of AML will be complicated by a coexistent pregnancy. However, the association of leukemia and pregnancy is uncommon. Its incidence is estimated to be 1 in 75000-100000 pregnancies. During pregnancy, most leukemias are acute: two-thirds are myeloid and one-third are lymphoblastic. There is no standard approach for this clinical dilemma, in part because of variables such as the type of AML, the seriousness of the symptoms, and the patient's personal beliefs. In many cases, the diagnostic workup has to be altered because of the pregnancy, and often available treatments have varying risks to the fetus. While chemotherapy is reported to have some risks during the first trimester, it is admitted that it can be administered safely during the second and the third trimesters. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
Thomas X.,Hospices Civils de Lyon
Expert Opinion on Investigational Drugs | Year: 2012
Introduction: Inotuzumab ozogamicin (CMC-544) is a humanized anti-CD22 monoclonal antibody conjugated with calicheamicin. Preclinical data indicate activity against B-cell tumors and early results from clinical trials indicate activity against B-cell lineage acute lymphoblastic leukemia (ALL). Areas covered: This paper reviews the design, pharmacokinetic and pharmacodynamic characteristics, and preclinical and clinical experience of inotuzumab ozogamicin in adult ALL. Expert opinion: Inotuzumab ozogamicin appears as an effective salvage therapy in patients with advanced ALL, allowing more patients to receive stem cell transplant (SCT) with encouraging response rates. This agent should provide a unique opportunity to treat selected ALL patient subpopulations. © 2012 Informa UK, Ltd.
Blaise B.J.,Hospices Civils de Lyon
Analytical Chemistry | Year: 2013
Sample size determination is a key question in the experimental design of medical studies. The number of patients to include in a clinical study is actually critical to evaluate costs and inclusion requirements to achieve a sufficient statistical power of test and the identification of significant variations among the factors under study. Metabolic phenotyping is an expanding field of translational research in medicine, focusing on the identification of metabolism rearrangements due to various pathophysiological conditions. This top-down hypothesis-free approach uses analytical chemistry methods, coupled to statistical analysis, to quantify subtle and coordinated metabolite concentration variations and eventually identify candidate biomarkers. The sample size determination in metabolic phenotyping studies is difficult considering the absence of a priori metabolic target. This technical note introduces a data-driven sample size determination for metabolic phenotyping studies. Starting from nuclear magnetic resonance (NMR) spectra belonging to a small cohort, metabolic NMR variables are identified by the statistical recoupling of variables (SRV) procedure. A larger data set is then generated on the basis of Kernel density estimation of SRV variable distributions. Statistically significant variations of metabolic NMR signals identified by SRV are assessed by the Benjamini-Yekutieli correction for simulated data sets of variable sizes. Simulated model robustness is evaluated by receiver operating characteristic analysis (sensitivity and specificity) on an independent cohort and cross-validation. Sample size determination is obtained by identifying the optimal data set size, depending on the purpose of the study: at least one statistically significant variation (biomarker discovery) or a maximum of statistically significant variations (metabolic exploration). © 2013 American Chemical Society.
Agency: Cordis | Branch: H2020 | Program: RIA | Phase: PHC-22-2015 | Award Amount: 7.09M | Year: 2016
As the number of older people in Europe grows, increasing healthy life years is a priority. Cognitive decline, dementia (e.g. Alzheimers disease, AD), sleep disturbances and depression, all related to psychological distress and anxiety, are significant drivers of reduced quality of life in older adults. This project builds on evidence that lifestyle factors and meditation practice have the potential to downregulate these adverse factors and positively impact mental and neurological conditions including AD. Our main objectives are i) to improve early AD detection and understanding of physiopathological mechanisms; and to investigate ii) the impact of internal/external (e.g. genetic and lifestyle) determinants and iii) the effect and mechanisms of action of meditation training, on mental health and wellbeing in older people. This will be achieved by using pre-existing databases from European partners and conducting two randomized controlled trials (Studies 1 and 2B) and one observational study (2A). STUDY 1 will assess the short-term effects of an 8-week meditation intervention (versus cognitive training) in patients with subjective cognitive decline at risk for AD on behavioural measures including anxiety and wellbeing. STUDY 2A will assess senior expert meditators to identify neural signatures of different meditation practices on attention and emotion regulation tasks. STUDY 2B will assess long-term effects of an 18-month meditation intervention (versus an active control) on behavioural and biological markers of mental health and wellbeing in cognitively intact elderly. The cognitive and affective regulatory mechanisms underlying these effects will be investigated using the neural signatures identified in the expert meditators. High public health relevance is likely: the proposed intervention targets the most common mental and neurological conditions in the elderly and it can be scaled up within preventive programmes at a population level.
Agency: Cordis | Branch: FP7 | Program: BSG-SME | Phase: SME-2013-1 | Award Amount: 2.79M | Year: 2013
Interest in the use of naturally occurring human gut bacteria as pharmaceutical drugs has increased as knowledge about the human microbiota and its role in health and disease has advanced. The ELIMOX project proposes to develop a new drug from Oxalobacter formigenes, an anaerobic bacterium whose only carbon source is oxalate, for the treatment of primary hyperoxaluria (PH). PH is a rare and life-threatening disease, present at birth, characterised by high endogenous levels of oxalate that damage the kidney and cause renal failure. Enteric elimination of oxalate via the gut provide an alternative elimination pathway for the oxalate and treatment with pharmacological doses of O. formigenes would facilitate such enteric elimination. The treatment employs a new approach whereby bacterial breakdown of excessive oxalate occurs in the gut, inducing an alternative pathway for the oxalate, thereby protecting the kidneys from failure. The O. formigenes approach to treat PH is an ideal model for bacterial treatment of metabolic disease. The three SME participants will utilise the expertise of nine specialised research providers to increase the understanding of the characteristics of the sensitive, anaerobic and highly specialised O. formigenes, to implement the manufacturing process to obtain a clinically effective drug, to optimise drug delivery and to develop specialised analytical methods to monitor clinical effects following treatment. Technology advancements will be confirmed by clinical studies in PH patients and by mapping the presence of the bacteria before and after treatment with the O. formigenes drug. The ELIMOX project will advance current standards and methodology in i) manufacture of anaerobic bacteria for pharmaceutical use, ii) identification, quantification and tracking of microbes in the human gut and their impact on human microbiota during treatment, iii) optimisation of tools to monitor clinical effects during treatment with anaerobic bacteria.