Relationship between Symptoms, Exacerbations, and Treatment Response in Bronchiectasis

RATIONALE: Bronchiectasis guidelines regard treatment to prevent exacerbation and treatment of daily symptoms as separate objectives. OBJECTIVE: We hypothesized that patients with greater symptoms would be at higher risk of exacerbations and therefore a treatment aimed at reducing daily symptoms would also reduce exacerbations in highly symptomatic patients. METHODS: An observational cohort of 333 patients from the East of Scotland(2012-2016). Symptoms were either modelled as a continuous variable or patients were classified as high, moderate and low symptom burden(>70, 40-70 and <40 using the SGRQ symptom score). We hypothesised that exacerbation would be reduced in highly symptomatic patients. This was tested in a post-hoc analysis of a randomized trial of inhaled mannitol (N=461 patients) Measurement and Main Results: In the observational cohort daily symptoms were a significant predictor of future exacerbations (rate ratio [RR] 1.10, 95% confidence interval[CI] 1.03-1.17, P=0.005). Patients with high symptom scores had higher exacerbation rates (RR 1.74, 95% CI 1.12-2.72,P=0.01) over 12 months follow-up compared to those with lower symptoms. Inhaled mannitol treatment improved the time to first exacerbation (hazard ratio [HR] 0.56; 95% CI 0.40-0.77; P<0.001) and the proportion of patients remaining exacerbation free for 12 months treatment was higher in the mannitol group (32.7% vs. 14.6%; RR 2.84, 95% CI 1.40-5.76; P=0.003) only in highly symptomatic patients. In contrast no benefit was evident in patients with lower symptom burden. CONCLUSIONS: Highly symptomatic patients are at increased risk of exacerbations, and exacerbation benefit with inhaled mannitol was only evident in patients with high symptom burden

Why is it difficult to implement e-health initiatives? A qualitative study

<b>Background</b> The use of information and communication technologies in healthcare is seen as essential for high quality and cost-effective healthcare. However, implementation of e-health initiatives has often been problematic, with many failing to demonstrate predicted benefits. This study aimed to explore and understand the experiences of implementers - the senior managers and other staff charged with implementing e-health initiatives and their assessment of factors which promote or inhibit the successful implementation, embedding, and integration of e-health initiatives.<p></p> <b>Methods</b> We used a case study methodology, using semi-structured interviews with implementers for data collection. Case studies were selected to provide a range of healthcare contexts (primary, secondary, community care), e-health initiatives, and degrees of normalization. The initiatives studied were Picture Archiving and Communication System (PACS) in secondary care, a Community Nurse Information System (CNIS) in community care, and Choose and Book (C&B) across the primary-secondary care interface. Implementers were selected to provide a range of seniority, including chief executive officers, middle managers, and staff with 'on the ground' experience. Interview data were analyzed using a framework derived from Normalization Process Theory (NPT).<p></p> <b>Results</b> Twenty-three interviews were completed across the three case studies. There were wide differences in experiences of implementation and embedding across these case studies; these differences were well explained by collective action components of NPT. New technology was most likely to 'normalize' where implementers perceived that it had a positive impact on interactions between professionals and patients and between different professional groups, and fit well with the organisational goals and skill sets of existing staff. However, where implementers perceived problems in one or more of these areas, they also perceived a lower level of normalization.<p></p> <b>Conclusions</b> Implementers had rich understandings of barriers and facilitators to successful implementation of e-health initiatives, and their views should continue to be sought in future research. NPT can be used to explain observed variations in implementation processes, and may be useful in drawing planners' attention to potential problems with a view to addressing them during implementation planning

Research priorities in bronchiectasis:a consensus statement from the EMBARC Clinical Research Collaboration

Bronchiectasis is a disease of renewed interest in light of an increase in prevalence and increasing burden on international healthcare systems. There are no licensed therapies, and large gaps in knowledge in terms of epidemiology, pathophysiology and therapy. The European Multicentre Bronchiectasis Audit and Research Collaboration (EMBARC) is a European Respiratory Society (ERS) Clinical Research Collaboration, funded by ERS to promote high-quality research in bronchiectasis. The objective of this consensus statement was to define research priorities in bronchiectasis. From 2014 to 2015, EMBARC used a modified Delphi process among European bronchiectasis experts to reach a consensus on 55 key research priorities in this field. During the same period, the European Lung Foundation collected 711 questionnaires from adult patients with bronchiectasis and their carers from 22 European countries reporting important research priorities from their perspective. This consensus statement reports recommendations for bronchiectasis research after integrating both physicians and patients priorities, as well as those uniquely identified by the two groups. Priorities identified in this consensus statement provide the clearest possible roadmap towards improving our understanding of the disease and the quality of care for patients with bronchiectasis

The European Multicentre Bronchiectasis Audit and Research Collaboration (EMBARC):experiences from a successful ERS Clinical Research Collaboration

In contrast to airway diseases like chronic obstructive pulmonary disease or asthma, and rare diseases such as cystic fibrosis, there has been little research and few clinical trials in bronchiectasis. Guidelines are primarily based on expert opinion and treatment is challenging because of the heterogeneous nature of the disease. In an effort to address decades of underinvestment in bronchiectasis research, education and clinical care, the European Multicentre Bronchiectasis Audit and Research Collaboration (EMBARC) was established in 2012 as a collaborative pan-European network to bring together bronchiectasis researchers. The European Respiratory Society officially funded EMBARC in 2013 as a Clinical Research Collaboration, providing support and infrastructure to allow the project to grow. EMBARC has now established an international bronchiectasis registry that is active in more than 30 countries both within and outside Europe. Beyond the registry, the network participates in designing and facilitating clinical trials, has set international research priorities, promotes education and has participated in producing the first international bronchiectasis guidelines. This manuscript article the development, structure and achievements of EMBARC from 2012 to 2017. EDUCATIONAL AIMS: To understand the role of Clinical Research Collaborations as the major way in which the European Respiratory Society can stimulate clinical research in different disease areasTo understand some of the key features of successful disease registriesTo review key epidemiological, clinical and translational studies of bronchiectasis contributed by the European Multicentre Bronchiectasis Audit and Research Collaboration (EMBARC) project in the past 5 yearsTo understand the key research priorities identified by EMBARC for the next 5 years

Training the next generation of clinical researchers: Evaluation of a graduate podiatrist research internship in rheumatology

Background: The aim of this study was to evaluate the effectiveness of the Arthritis Research UK funded graduate internship scheme for podiatrists and to explore the experiences of interns and mentors. Methods: Nine new graduates completed the internship programme (July 2006-June 2010); six interns and two mentors participated in this study. The study was conducted in three phases. Phase 1: quantitative survey of career and research outcomes for interns. Phase 2 and 3: qualitative asynchronous interviews through email to explore the experiences of interns and mentors. Interpretive phenomenological analysis (IPA) of coded transcripts identified recurring themes. Results: Research outputs included ten peer reviewed publications with authorial contributions from interns, 23 conference abstract presentations and one subsequent 'Jewel in the Crown' award at the British Society for Rheumatology Conference. Career progression includes two National Institute for Health research (NIHR) PhD fellowships, two Arthritis Research UK PhD fellowships, one NIHR Master of Research fellowship and one specialist rheumatology clinical post. Two interns are members of NIHR and professional body committees. Seven important themes arose from the qualitative phases: perceptions of the internship pre-application; internship values; maximising personal and professional development; psychosocial components of the internship; the role of mentoring and networking; access to research career pathways; perceptions of future developments for the internship programme. The role of mentorship and the peer support network have had benefits that have persisted beyond the formal period of the scheme. Conclusions: The internship model appears to have been perceived to have been valuable to the interns' careers and may have contributed significantly to the broader building of capacity in clinical research in foot and ankle rheumatology. We believe the model has potential to be transferable across health disciplines and on national and international scales

Electrolytic ablation of the rat pancreas: a feasibility trial

BACKGROUND: Pancreatic cancer is a biologically aggressive disease with less than 20% of patients suitable for a "curative" surgical resection. This, combined with the poor 5-year survival indicates that effective palliative methods for symptom relief are required. Currently there are no ablative techniques to treat pancreatic cancer in clinical use. Tissue electrolysis is the delivery of a direct current between an anode and cathode to induce localised necrosis. Electrolysis has been shown to be safe and reliable in producing hepatic tissue and tumour ablation in animal models and in a limited number of patients. This study investigates the feasibility of using electrolysis to produce localised pancreatic necrosis in a healthy rat model. METHOD: Ten rats were studied in total. Eight rats were treated with variable "doses" of coulombs, and the systemic and local effects were assessed; 2 rats were used as controls. RESULTS: Seven rats tolerated the procedure well without morbidity or mortality, and one died immediately post procedure. One control rat died on induction of anaesthesia. Serum amylase and glucose were not significantly affected. CONCLUSION: Electrolysis in the rat pancreas produced localised necrosis and appears both safe, and reproducible. This novel technique could offer significant advantages for patients with unresectable pancreatic tumours. The next stage of the study is to assess pancreatic electrolysis in a pig model, prior to human pilot studies

The Long-Baseline Neutrino Experiment: Exploring Fundamental Symmetries of the Universe

The preponderance of matter over antimatter in the early Universe, the dynamics of the supernova bursts that produced the heavy elements necessary for life and whether protons eventually decay --- these mysteries at the forefront of particle physics and astrophysics are key to understanding the early evolution of our Universe, its current state and its eventual fate. The Long-Baseline Neutrino Experiment (LBNE) represents an extensively developed plan for a world-class experiment dedicated to addressing these questions. LBNE is conceived around three central components: (1) a new, high-intensity neutrino source generated from a megawatt-class proton accelerator at Fermi National Accelerator Laboratory, (2) a near neutrino detector just downstream of the source, and (3) a massive liquid argon time-projection chamber deployed as a far detector deep underground at the Sanford Underground Research Facility. This facility, located at the site of the former Homestake Mine in Lead, South Dakota, is approximately 1,300 km from the neutrino source at Fermilab -- a distance (baseline) that delivers optimal sensitivity to neutrino charge-parity symmetry violation and mass ordering effects. This ambitious yet cost-effective design incorporates scalability and flexibility and can accommodate a variety of upgrades and contributions. With its exceptional combination of experimental configuration, technical capabilities, and potential for transformative discoveries, LBNE promises to be a vital facility for the field of particle physics worldwide, providing physicists from around the globe with opportunities to collaborate in a twenty to thirty year program of exciting science. In this document we provide a comprehensive overview of LBNE's scientific objectives, its place in the landscape of neutrino physics worldwide, the technologies it will incorporate and the capabilities it will possess.Comment: Major update of previous version. This is the reference document for LBNE science program and current status. Chapters 1, 3, and 9 provide a comprehensive overview of LBNE's scientific objectives, its place in the landscape of neutrino physics worldwide, the technologies it will incorporate and the capabilities it will possess. 288 pages, 116 figure