Caregiver impact and health service use in high and low severity Dravet syndrome: A multinational cohort study.

Purpose: To estimate costs associated with the current management of Dravet syndrome (DS), explore psychosocial aspects of the disease in caregivers and siblings, and identify patient characteristics associated with higher costs in a large, predominantly European survey cohort of patients and their caregivers conducted in 2016.

Methods: Health and social care resource use, productivity and quality of life (QoL) data were summarised. Costs for European five (EU5) countries (France, Germany, Italy, Spain and UK) were calculated and patients with high and low current seizure burden compared.

The Problem of Rarity: Estimation of Prevalence in Rare Disease.

Background: From a disease's first description to its wider recognition, factors such as changes over time in diagnostic criteria, available therapies, and subsequent mortality rates may influence diagnosed prevalence of rare diseases.

Objectives: To propose a novel methodology for estimating the true prevalence of rare diseases using current incidence adjusted to changing diagnostic practice over time. This article focuses on rare diseases whose diagnosis may have changed over time, and raises the hypothesis that prevalence calculated from current incidence may be higher than diagnosed prevalence, which may lag behind the current disease definition and diagnostic methods.

Quality of life and comorbidities associated with Dravet syndrome severity: a multinational cohort survey.

Aim: To test the hypothesis that higher seizure burden in Dravet syndrome is associated with increased comorbidities and lower quality of life (QoL) in a large cohort of patients with Dravet syndrome and their caregivers in Europe.

Method: An extensive survey of caregivers of patients with Dravet syndrome on experiences of diagnosis, seizure burden, management, social and financial impact, and health services use was administered online in 10 languages.

Results: The survey received 584 unique responses from caregivers of paediatric (83%) and adult (17%) patients with Dravet syndrome (aged <1-48y).

Patient access to reimbursed biological disease-modifying antirheumatic drugs in the European region.

: Biological disease-modifying antirheumatic drugs (bDMARDs) for the treatment of rheumatoid arthritis (RA) are not always accessible to all patients in accordance with international guidelines, partly owing to their high direct costs against a background of restricted healthcare budgets. This study compares the size of RA patient populations with access to reimbursed bDMARDs across 37 European countries, Russia, and Turkey, according to their treatment eligibility defined by European League Against Rheumatism (EULAR) recommendations and national reimbursement criteria. : The size of the RA patient population eligible for bDMARD treatment was estimated in a population model using published RA epidemiological data and clinical criteria defined by 2013 EULAR recommendations along with national reimbursement criteria defined in a survey of the 39 countries in November 2015.

Ceftaroline fosamil treatment outcomes compared with standard of care among hospitalized patients with complicated skin and soft tissue infections.

Aim: Compare clinical and cost outcomes associated with ceftaroline fosamil with other commonly used antibiotics in complicated skin and soft tissue infections.

Methods: Retrospective analysis of hospital records from 2010 to 2013 in Premier's Perspective comparative database for adults with complicated skin and soft tissue infection treated with intravenous ceftaroline fosamil, vancomycin, daptomycin, linezolid or tigecycline. Length of stay, inpatient costs and mortality were compared between propensity score-matched treatment groups.

Adherence to exercise referral schemes by participants - what do providers and commissioners need to know? A systematic review of barriers and facilitators.

Background: Physical inactivity levels are rising worldwide with major implications for the health of the population and the prevalence of non-communicable diseases. Exercise referral schemes (ERS) continue to be a popular intervention utilised by healthcare practitioners to increase physical activity. We undertook a systematic review of views studies in order to inform guidance from the UK National Institute of Health and Care Excellence (NICE) on exercise referral schemes to promote physical activity.

Comparative analysis of the retinal potential of embryonic stem cells and amniotic fluid-derived stem cells.

Photoreceptors have recently been generated from mouse and human embryonic stem cells (ESCs), although ethics concerns impede their utilization for cell replacement therapy for retinal disease. Extra-embryonic tissues have received attention as alternative therapeutic sources of stem cells. Human and mouse amniotic fluid-derived stem cells (AFCs) have been reported to be multipotent and express embryonic and adult stem cell markers.

A useful approach to identify novel small-molecule inhibitors of Wnt-dependent transcription.

The Wnt signaling pathway is frequently deregulated in cancer due to mutations in genes encoding APC, beta-catenin, and axin. To identify small-molecule inhibitors of Wnt signaling as potential therapeutics, a diverse chemical library was screened using a transcription factor reporter cell line in which the activity of the pathway was induced at the level of Disheveled protein. A series of deconvolution studies was used to focus on three compound series that selectively killed cancer cell lines with constitutive Wnt signaling.

Neonatal desensitization allows long-term survival of neural xenotransplants without immunosuppression.

Preclinical development of human cells for potential therapeutic application in neurodegenerative diseases requires that their long-term survival, stability and functional efficacy be studied in animal models of human disease. Here we describe a strategy for long-term immune protection of human fetal and stem cell-derived neural cells transplanted into the adult rat brain, by desensitizing the host rat to similar cells in the neonatal period, without the need for additional immunosuppression.

A scaleable and defined system for generating neural stem cells from human embryonic stem cells.

The ability to differentiate human ESCs (hESCs) to defined lineages in a totally controlled manner is fundamental to developing cell-based therapies and studying human developmental mechanisms. We report a novel, scaleable, and widely applicable system for deriving and propagating neural stem cells from hESCs without the use of animal products, proprietary formulations, or genetic manipulation. This system provides a definitive platform for studying human neural development and has potential therapeutic implications.

Comparative proteomic analysis reveals differential expression of Hsp25 following the directed differentiation of mouse embryonic stem cells.

Murine embryonic stem (ES) cells can be committed to neural differentiation with high efficiency in culture through the use of feeder- and serum-free media. This system is proving to be an excellent model to study processes involved in ES cell commitment to neural cell fate. We used this approach to generate neurogenic embryoid bodies (NEBs) in a serum-free culture system to perform proteomic analysis of soluble fractions and identify early changes in protein expression as ES cells differentiate.

A functional domain of Dof that is required for fibroblast growth factor signaling.

Signal transduction by fibroblast growth factor (FGF) receptors in Drosophila depends upon the intracellular protein Dof, which has been proposed to act downstream of the receptors and upstream of Ras. Dof is the product of a fast-evolving gene whose vertebrate homologs, BCAP and BANK, are involved in signaling downstream of the B-cell receptor. Mapping functional domains within Dof revealed that neither of its potential interaction motifs, the ankyrin repeats and the coiled coil, is essential for the function of Dof.

Isolation of proteins that interact with the signal transduction molecule Dof and identification of a functional domain conserved between Dof and vertebrate BCAP.

Dof is a large molecule essential for signal transduction by the two FGF receptors in Drosophila. It contains two ankyrin repeats and a coiled-coil region, but has no other recognisable structural motif. Dof shares these features with its closest vertebrate relatives, the B-cell signalling molecules BCAP and BANK.