Reduction in keratin aggregates in epidermolysis bullosa simplex keratinocytes after pretreatment with trimethylamine N-oxide

Epidermolysis bullosa simplex (EBS) is a dominantly inherited skin disease caused by mutations in the keratin 5 (KRT5) or KRT14 genes 1. Some reports suggested that fever and/or hot weather may exacerbate EBS phenotype 2. Effective EBS therapies are still lacking. Molecular chaperones are proteins whose main function is to promote the correct folding of polypeptides (s1). Molecules such as trimethylamine N-oxide (TMAO) and sodium 4-phenylbutyrate (4-PBA) act as chemical chaperones (s2) with protein folding and stabilization activities (s3, s4, s5). Treatment of affected epidermal cells by chemical chaperones to correct the misfolded and aggregated keratins that characterize EBS seems a viable therapeutic option 3. Furthermore, the type I keratins K16 and K17 polymerize with K5, and upregulation of these proteins could replace the mutant K14 in the heterodimer and improve disease pathology (s6). Hence, chemical chaperones which can reduce keratin aggregates formation and upregulate K16 and K17 in EBS-affected cells would be ideal therapeutic candidates for EBS

Optimising patient active role with a user-centred eHealth platform (CONCERTO+) in chronic diseases management ::a study protocol for a pilot cluster randomised controlled trial

Introduction Multimorbidity increases care needs and primary care use among people with chronic diseases. The Concerto Health Program (CHP) has been developed to optimise chronic disease management in primary care services. However, in its current version, the CHP primarily targets clinicians and does not aim to answer directly patients’ and their informal caregivers’ needs for chronic disease management. Various studies have shown that interventions that increase patient activation level are associated with better health outcomes. Furthermore, educational tools must be adapted to patients and caregivers in terms of health literacy and usability. This project aims to develop, implement and evaluate a user-centred, multifunctional and personalised eHealth platform (CONCERTO+) to promote a more active patient role in chronic disease management and decision-making. Methods and analysis This project uses a collaborative research approach, aiming at the personalisation of CHP through three phases: (1) the development of one module of an eHealth platform based on scientific evidence and user-centred design; (2) a feasibility study of CONCERTO+ through a pilot cluster randomised controlled trial where patients with chronic diseases from a primary healthcare practice will receive CONCERTO+ during 6 months and be compared to patients from a control practice receiving usual care and (3) an analysis of CONCERTO+ potential for scaling up. To do so, we will conduct two focus groups with patients and informal caregivers and individual interviews with health professionals at the two study sites, as well as health care managers, information officers and representatives of the Ministry of Health. Ethics and dissemination This study received ethical approval from Ethics Committee of Université Laval. The findings will be used to inform the effectiveness of CONCERTO+ to improve management care in chronic diseases. We will disseminate findings through presentations in scientific conferences and publication in peer-reviewed journals. Trial registration number NCT03628963; Pre-results