Loirat C.,University Paris Diderot |
Fremeaux-Bacchi V.,Assistance Publique Hopitaux de Paris
Orphanet Journal of Rare Diseases | Year: 2011
Hemolytic uremic syndrome (HUS) is defined by the triad of mechanical hemolytic anemia, thrombocytopenia and renal impairment. Atypical HUS (aHUS) defines non Shiga-toxin-HUS and even if some authors include secondary aHUS due to Streptococcus pneumoniae or other causes, aHUS designates a primary disease due to a disorder in complement alternative pathway regulation. Atypical HUS represents 5 -10% of HUS in children, but the majority of HUS in adults. The incidence of complement-aHUS is not known precisely. However, more than 1000 aHUS patients investigated for complement abnormalities have been reported. Onset is from the neonatal period to the adult age. Most patients present with hemolytic anemia, thrombocytopenia and renal failure and 20% have extra renal manifestations. Two to 10% die and one third progress to end-stage renal failure at first episode. Half of patients have relapses. Mutations in the genes encoding complement regulatory proteins factor H, membrane cofactor protein (MCP), factor I or thrombomodulin have been demonstrated in 20-30%, 5-15%, 4-10% and 3-5% of patients respectively, and mutations in the genes of C3 convertase proteins, C3 and factor B, in 2-10% and 1-4%. In addition, 6-10% of patients have anti-factor H antibodies. Diagnosis of aHUS relies on 1) No associated disease 2) No criteria for Shigatoxin-HUS (stool culture and PCR for Shiga-toxins; serology for anti-lipopolysaccharides antibodies) 3) No criteria for thrombotic thrombocytopenic purpura (serum ADAMTS 13 activity > 10%). Investigation of the complement system is required (C3, C4, factor H and factor I plasma concentration, MCP expression on leukocytes and anti-factor H antibodies; genetic screening to identify risk factors). The disease is familial in approximately 20% of pedigrees, with an autosomal recessive or dominant mode of transmission. As penetrance of the disease is 50%, genetic counseling is difficult. Plasmatherapy has been first line treatment until presently, without unquestionable demonstration of efficiency. There is a high risk of post-transplant recurrence, except in MCP-HUS. Case reports and two phase II trials show an impressive efficacy of the complement C5 blocker eculizumab, suggesting it will be the next standard of care. Except for patients treated by intensive plasmatherapy or eculizumab, the worst prognosis is in factor H-HUS, as mortality can reach 20% and 50% of survivors do not recover renal function. Half of factor I-HUS progress to end-stage renal failure. Conversely, most patients with MCP-HUS have preserved renal function. Anti-factor H antibodies-HUS has favourable outcome if treated early. © 2011Loirat and Frémeaux-Bacchi; licensee BioMed Central Ltd. Source
Agency: Cordis | Branch: H2020 | Program: RIA | Phase: PHC-17-2014 | Award Amount: 6.43M | Year: 2015
Cardiovascular diseases (CVD) cause over 4 million deaths in Europe each year and mass disability: within the coming decades the disability-adjusted life years (DALYs) estimate is expected to rise from a loss of 85 million DALYs in 1990 to a loss of 150 million DALYs globally in 2020. Moreover, patient numbers are expected to rise rapidly in the next decades, due to an ageing society such that the burden of CVD for both patients and the healthcare sector will further rise. Cardiac rehabilitation (CR) is recognised as an effective approach for risk reduction and long term care of patients facing cardiovascular diseases (CVD). However, knowledge on CR in the elderly is limited, while tailoring of CR programmes to the elderly is needed. The reasons for this relates to the following aspects: 1) the elderly account for the majority of cardiac admissions and procedures, yet studies on cardiac rehabilitation have traditionally focused on younger patients , 2) many older patients who would derive benefit from CR interventions, do not participate, 3) there is a lack of commitment and adherence to CR within in the older population with only a minority completing the full programme and 4) a cardiovascular event in elderly patients could be a trigger for disability and dependence. Knowledge is lacking on effective approaches for this specific target group and moreover the specific challenges related to the target group must be addressed. With the ambition to achieve a breakthrough in cardiac care, the main objective of EU-CaRE is thus to obtain the evidence base to improve, tailor and optimise CR programmes regarding sustainable effectiveness, cost-effectiveness and participation level in the elderly. This is achieved through an comparative effectiveness analysis of current conventional cardiac rehabilitation programmes (CR), as well as new innovative mobile telemonitoring guided cardiac rehabilitation (mCR). As such, the project addresses the objectives of call PHC 17.
Agency: Cordis | Branch: H2020 | Program: RIA | Phase: PHC-13-2014 | Award Amount: 6.23M | Year: 2015
Chronic liver disease affects about 29-million Europeans accounting for about 170,000 deaths at a cost of around 15.8bn. This chronic non-communicable disease is increasing at an alarming rate due to increasing European obesity, alcohol use and ageing. The three main causes of the disease; alcohol, fatty liver and viral hepatitis are amenable to prevention and treatment. Gut-derived endotoxins and bacterial translocation are central factors implicated in the pathogenesis of fatty liver disease and, the development and progression of cirrhosis. In cirrhosis, current state-of-the-art therapy to prevent recurrent complications of advanced cirrhosis is to use poorly absorbed antibiotics but long-term antibiotic therapy has problems associated with bacterial resistance, infection with resistant organisms and the cost. Treatment of fatty liver and modulation of bacterial translocation in early cirrhosis to prevent complications is an unmet need. Our academic-industrial consortium has developed a novel, patented, safe and cheap nanoporous carbon that modulates the effects of bacterial translocation in animal models of liver disease. Our feasibility studies demonstrate that this product advances the current state-of-the-art, is a TRL 4/5 and is now ready for validation through clinical trials. We propose to investigate the safety and efficacy of this novel nanoporous carbon in patients with fatty liver disease and cirrhosis. If successful, we will be able to confirm an innovative, cost-effective and novel strategy for the management of this chronic disease in a European population. Exploitation of the results of the CARBALIVE project will support the continued development of this carbon through additional private and public sector investment. The use of this innovative therapy is expected to reduce the economic burden of the disease in Europe, allow patients to achieve enhanced quality of life, improve survival, and allow many patients to return to economic productivity.
I-MOVE-plus - I-MOVE+ Integrated Monitoring of Vaccines Effects in Europe: a platform to measure and compare effectiveness and impact of influenza and pneumococcal vaccines and vaccination strategies in the elderly
Agency: Cordis | Branch: H2020 | Program: RIA | Phase: PHC-17-2014 | Award Amount: 7.52M | Year: 2015
The I-MOVE\ Consortium includes European Union (EU) Public Health Institutes, SME and Universities. It aims at measuring and comparing the effectiveness (VE) and impact (VI) of influenza and Pneumococcal vaccines and vaccination strategies a in the elderly population in Europe. The goal is to develop a sustainable platform of primary care practices, hospitals and laboratory networks that share validated methods to evaluate post marketing vaccine performances. The objectives are to identify, pilot test, and disseminate in EU the best study designs to measure, on a real time basis, VE (direct effect) and the VI of vaccination programmes (indirect and overall effect) against laboratory confirmed cases of influenza (types/subtypes) and pneumococcal disease (serotypes), and clinical outcomes. Cost effectiveness analysis will be conducted. Results will allow to understand factors affecting specific VE, the duration of protection of influenza and pneumococcal vaccines, the interaction between vaccines, the role of repeated vaccinations, the occurrence of serotype replacement (pneumococcus); identify vaccine types and brands with low VE; guide the decision of the WHO committees on vaccine strain selection (influenza); provide robust benefit indicators (VE and VI) and cost benefit and effectiveness results; guide vaccination strategies (schedules, doses, boosters). This EU member state collaboration will respond to questions that require studies based on large sample sizes and sharing of expertise that cannot be achieved by one country alone. It will allow the best methods to be used and results to benefit to all EU countries whatever their current public health achievements. Results will be shared with international partners.
Agency: Cordis | Branch: H2020 | Program: RIA | Phase: PHC-30-2015 | Award Amount: 3.34M | Year: 2016
Breast cancer is the most common type of cancer affecting woman in the EU. Multidisciplinary Breast Units (BUs) were introduced in order to deal efficiently with breast cancer cases, setting guideline-based quality procedures and a high standard of care. However, daily practice in the BUs is hampered by the complexity of the disease, the vast amount of patient and disease data available in the digital era, the difficulty in coordination, the pressure exerted by the system and the difficulty in deciding on cases that guidelines do not reflect. DESIREE aims to alleviate this situation by providing a web-based software ecosystem for the personalized, collaborative and multidisciplinary management of primary breast cancer (PBC) by specialized BUs. Decision support will be provided on the available therapy options by incorporating experience from previous cases and outcomes into an evolving knowledge model, going beyond the limitations of the few existing guideline-based decision support systems (DSS). Patient cases will be represented by a novel digital breast cancer patient (DBCP) data model, incorporating variables relevant for decision and novel sources of information and biomarkers of diagnostic and prognostic value, providing a holistic view of the patient presented to the BU through specialized visual exploratory interfaces. The influence of new variables and biomarkers in current and previous cases will be explored by a set of data mining and visual analytics tools, leveraging large amounts of retrospective data. Iintuitive web-based tools for multi-modality image analysis and fusion will be developed, providing advanced imaging biomarkers for breast and tumor characterization. Finally, a predictive tool for breast conservative therapy will be incorporated, based on a multi-scale physiological model, allowing to predict the aesthetic outcome of the intervention and the healing process, with important clinical and psychological implications for the patients.