Search

Introduction A minority of school-aged children with asthma have persistent poor control and experience frequent asthma attacks despite maximal prescribed maintenance therapy. These children have higher morbidity and risk of death. The first add-on biologic therapy, omalizumab, a monoclonal antibody that blocks immunoglobulin (Ig)E, was licensed for children with severe asthma in 2005. While omalizumab is an effective treatment, non-response is common. A second biologic, mepolizumab which blocks interleukin 5 and targets eosinophilic inflammation, was licensed in 2018, but the licence was granted by extrapolation of adult clinical trial data to children. This non-inferiority (NI) trial will determine whether mepolizumab is as efficacious as omalizumab in reducing asthma attacks in children with severe therapy resistant asthma (STRA) and refractory difficult asthma (DA).Methods and analysis This is an ongoing multicentre 1:1 randomised NI open-label trial of mepolizumab and omalizumab. Up to 150 children and young people (CYP) aged 6–17 years with severe asthma will be recruited from specialist paediatric severe asthma centres in the UK. Prior to randomisation, children will be monitored for medication adherence for up to 16 weeks to determine STRA and refractory DA diagnoses. Current prescribing recommendations of serum IgE and blood eosinophils will not influence eligibility or enrolment. The primary outcome is the 52-week asthma attack rate. Bayesian analysis using clinician-elicited prior distributions will be used to calculate the posterior probability that mepolizumab is not inferior to omalizumab. Secondary outcomes include Composite Asthma Severity Index, Paediatric Asthma Quality of Life Questionnaire, lung function measures (forced expiratory volume in one second (FEV1), bronchodilator reversibility), fractional exhaled nitric oxide, Asthma Control Test (ACT), health outcomes EuroQol 5 Dimension (EQ-5D) and optimal serum IgE and blood eosinophil levels that may predict a response to therapy. These outcomes will be analysed in a frequentist framework using longitudinal models.Ethics and dissemination The study has been approved by the South Central—Berkshire Research Ethics Committee REC Number 19/SC/0634 and had Clinical Trials Authorisation from the Medicines and Healthcare Products Regulatory Agency (MHRA) (EudraCT 2019-004085-17). All parents/legal guardians will give informed consent for their child to participate in the trial, and CYP will give assent to participate. The results will be published in peer-reviewed journals, presented at international conferences and disseminated via our patient and public involvement partners.Trial registration number ISRCTN12109108; EudraCT Number: 2019-004085-17.

Background: Communication is an important clinical tool for the prevention and control of diseases, to advise and inform patients and the public, providing them with essential knowledge regarding healthcare and disease management. This study explored the experience of communication between healthcare professionals (HCPs) and people with long-term lung conditions, from the patient perspective. Methods: This qualitative study analyzed the experience of people with chronic lung disease, recruited via Asthma & Lung UK (A&LUK) and COPD research databases. A&LUK invited people who had expressed a desire to be involved in research associated with their condition via their Expert Patient Panel and associated patients' groups. Two focus group interviews (12 participants) and one individual interview (1 participant) were conducted. Thematic analysis was used for data analysis. Results: Two main themes were identified and we named them 'involving communication' and 'communication needs to be improved. 'They included seven subthemes: community-led support increased the patients' social interaction with peers; allied-HCP-led support increased patients' satisfaction; disliking being repeatedly asked the same basic information; feeling communication was unengaging, lacking personal specifics and the use of medical terminology and jargon. Conclusions: The study has identified what most matters in the process of communication with HCPs in people with long-term respiratory diseases of their healthcare management. The findings of the study can be used to improve the patient–healthcare professional relationship and facilitate a better communication flow in long-term healthcare management. [ABSTRACT FROM AUTHOR]

Problem Smartphone applications are an increasingly useful part of patients' self‐management of chronic health conditions. Asthma is a common chronic health condition for which good self‐management by patients is very helpful in maintaining stability. User‐centered design and intelligent systems that learn are steps forward in building applications that are more effective in providing quality care that is scalable and tailored to each patient. Methods: A literature and application store search to review historic and current asthma smart phone applications. User‐centered design is a methodology that involves all stakeholders of a proposed system from the beginning of the design phase to the end of installation. One aspect of this user‐centered approach involved conducting focus groups with patients and health care providers to determine what features they desire for use in applications and create a model to build smart infrastructure for a learning health care system. A simple prototype for an asthma smartphone application is designed and built with basic functionality. Outcomes Only one publication in the literature review of asthma smartphone applications describes both user‐centered design and intelligent learning systems. The authors have presented a set of user‐desired attributes for a smart health care application and a possible data flow diagram of information for a learning system. A prototype simple user‐centered designed asthma smartphone application that better assists patients in their care illustrates the value of the proposed architecture. Discussion Our user‐centered approach helped design and implement a learning prototype smart phone application to help patients better manage their asthma and provide information to clinical care providers. While popular in other industries, user‐centered design has had slow adoption in the health care area. However, the popularity of this approach is increasing and will hopefully result in mobile application that better meets the needs of both patients and their care providers. [ABSTRACT FROM AUTHOR]

The article presents the programme for the Health Services Research and Pharmacy Practice (HSRPP) Conference 2012 at the University College Cork in Ireland on April 23-24, 2012.

Phospholemman (PLM, FXYD1), abundantly expressed in the heart, is the primary cardiac sarcolemmal substrate for PKA and PKC. Evidence supports the hypothesis that PLM is part of the cardiac Na-K pump complex and provides the link between kinase activity and pump modulation. PLM has also been proposed to modulate Na/Ca exchanger activity and may be involved in cell volume regulation. This study characterized the phenotype of the PLM knockout (KO) mouse heart to further our understanding of PLM function in the heart. PLM KO mice were bred on a congenic C57/BL6 background. In vivo conductance catheter measurements exhibited a mildly depressed cardiac contractile function in PLM KO mice, which was exacerbated when hearts were isolated and Langendorff perfused. There were no significant differences in action potential morphology in paced Langendorff-perfused hearts. Depressed contractile function was associated with a mild cardiac hypertrophy in PLM KO mice. Biochemical analysis of crude ventricular homogenates showed a significant increase in Na-K-ATPase activity in PLM KO hearts compared with wild-type controls. SDS-PAGE and Western blot analysis of ventricular homogenates revealed small, nonsignificant changes in Na- K-ATPase subunit expression, with two-dimensional gel (isoelectric focusing, SDS-PAGE) analysis revealing minimal changes in ventricular protein expression, indicating that deletion of PLM was the primary reason for the observed PLM KO phenotype. These studies demonstrate that PLM plays an important role in the contractile function of the normoxic mouse heart. Data are consistent with the hypothesis that PLM modulates Na-K-ATPase activity, indirectly affecting intracellular Ca and hence contractile function. [ABSTRACT FROM AUTHOR]

The article highlights a study which investigated the use of ligandbased design strategy targeting a G protein-coupled receptor (GPCR) on platelets to identify a novel antiplatelet agent that does not prolong bleeding and can be used for more effective antiplatelet therapy. The authors compared the in vivo effects of the DG-041 compound on platelet function and bleeding time with clopidogrel. DG-041 was found to inhibit platelet aggregation with no concurrent increase in bleeding time.

The article focuses on the research on neuroprotective effects of brain-derived neurotrophic factor (BDNF) in different Alzheimer's disease models. It references a study by A.H. Nagahara et al published in the 2009 issue of "Nature Medicine." It is hypothesizes that gene therapy which involves BDNF delivery to the entorhinal region might improve Alzheimer's disease by reducing neurodegeneration. The research study uses both a transgenic mouse and aged rats in order to test the hypothesis.