Description: Introduction Increased frequency and intensity of inpatient therapy contributes to improved outcomes for stroke survivors. Differences exist in the amount of therapy provided internationally. In England, Wales and Northern Ireland it is recommended that a minimum of 45 min of each active therapy should be provided at least 5 days a week provided the therapy is appropriate and that the patient can tolerate this. Sentinel Stroke National Audit Programme (2014) data demonstrate this standard is not being achieved for most patients. No research been undertaken to explore how therapists in England manage their practice to meet time-specific therapy recommendations. The ReAcT study aims to develop an in-depth understanding of stroke therapy provision, including how the guideline of 45 min a day of each relevant therapy, is interpreted and implemented by therapists, and how it is experienced by stroke-survivors and their families. Methods and analysis A multisite ethnographic case study design in a minimum of six stroke units will include modified process mapping, observations of service organisation, therapy delivery and documentary analysis. Semistructured interviews with therapists and service managers (n=90), and with patients and informal carers (n=60 pairs) will be conducted. Data will be analysed using the Framework approach. Ethics and dissemination The study received a favourable ethical opinion via the National Research Ethics Service (reference number: 14/NW/0266). Participants will provide written informed consent or, where stroke-survivors lack capacity, a consultee declaration will be sought. ReAcT is designed to generate insights into the organisational, professional, social, practical and patient-related factors acting as facilitators or barriers to providing the recommended amount of therapy. Provisional recommendations will be debated in consensus meetings with stakeholders who have not participated in ReAcT case studies or interviews. Final recommendations will be disseminated to therapists, service managers, clinical guideline developers and policymakers and stroke-survivors and informal carers.

Description: Respiratory syncytial virus (RSV) infects epithelial cells of the respiratory tract and is a major cause of bronchiolitis and pneumonia in children and the elderly. The virus assembles and buds through the plasma membrane, forming elongated membrane filaments, but details of how this happens remain obscure. Oligomerization of the matrix protein (M) is a key step in the process of assembly and infectious virus production. In addition, it was suggested to affect the conformation of the fusion protein, the major current target for RSV antivirals, in the mature virus. The structure and assembly of M are thus key parameters in the RSV antiviral development strategy. The structure of RSV M was previously published as a monomer. Other paramyxovirus M proteins have been shown to dimerize, and biochemical data suggest that RSV M also dimerizes. Here, using size exclusion chromatography-multiangle laser light scattering, we show that the protein is dimeric in solution. We also crystallized M in two crystal forms and show that it assembles into equivalent dimers in both lattices. Dimerization interface mutations destabilize the M dimer in vitro . To assess the biological relevance of dimerization, we used confocal imaging to show that dimerization interface mutants of M fail to assemble into viral filaments on the plasma membrane. Additionally, budding and release of virus-like particles are prevented in M mutants that fail to form filaments. Importantly, we show that M is biologically active as a dimer and that the switch from M dimers to higher-order oligomers triggers viral filament assembly and virus production. IMPORTANCE Human respiratory syncytial virus (RSV) is the most frequent cause of infantile bronchiolitis and pneumonia. The enormous burden of RSV makes it a major unmet target for a vaccine and antiviral drug therapy. Oligomerization of the matrix protein is a key step in the process of assembly and production of infectious virus, but the molecular mechanism of RSV assembly is still poorly understood. Here we show that the RSV matrix protein forms dimers in solution and in crystals; the dimer is essential for formation of higher-order oligomers. Destabilizing the dimer interface resulted in the loss of RSV filament formation and a lack of budding of virus-like particles. Importantly, our findings can potentially lead to new structure-based RSV inhibitors targeting the assembly process.

Description: Introduction The transfer of patient care between the intensive care unit (ICU) and the hospital ward is associated with increased risk of medical error and adverse events. This study will describe patient transfer from ICU to hospital ward by documenting (1) patient, family and provider experiences related to ICU transfer, (2) communication between stakeholders involved in ICU transfer, (3) adverse events that follow ICU transfer and (4) opportunities to improve ICU to hospital ward transfer. Methods This is a mixed methods prospective observational study of ICU to hospital ward transfer practices in 10 ICUs across Canada. We will recruit 50 patients at each site (n=500) who are transferred from ICU to hospital ward, and distribute surveys to enrolled patients, family members, and healthcare providers (ICU and ward physicians and nurses) after patient transfer. A random sample of 6 consenting study participants (patients, family members, healthcare providers) from each study site (n=60) will be offered an opportunity to participate in interviews to further describe stakeholders’ experience with ICU to hospital ward transfer. We will abstract information from patient health records to identify clinical data and use of transfer tools, and identify adverse events that are related to the transfer. Ethics and Dissemination Research ethics board approval has been obtained at the coordinating study centre (UofC REB13-0021) and 5 study sites (UofA Pro00050646; UBC-PHC H14-01667; Sunnybrook 336-2014; QCH 14-07; Sherbrooke 14-172). Dissemination of the findings will provide a comprehensive description of transfer from ICU to hospital ward in Canada including the uptake of validated or local transfer tools, a conceptual framework of the experiences and needs of stakeholders in the ICU transfer process, a summary of adverse events experienced by patients after transfer from ICU to hospital ward, and opportunities to guide quality improvement efforts.

Description: Background and Purpose— We developed a new postdischarge system of care comprising a structured assessment covering longer-term problems experienced by patients with stroke and their carers, linked to evidence-based treatment algorithms and reference guides (the longer-term stroke care system of care) to address the poor longer-term recovery experienced by many patients with stroke. Methods— A pragmatic, multicentre, cluster randomized controlled trial of this system of care. Eligible patients referred to community-based Stroke Care Coordinators were randomized to receive the new system of care or usual practice. The primary outcome was improved patient psychological well-being (General Health Questionnaire-12) at 6 months; secondary outcomes included functional outcomes for patients, carer outcomes, and cost-effectiveness. Follow-up was through self-completed postal questionnaires at 6 and 12 months. Results— Thirty-two stroke services were randomized (29 participated); 800 patients (399 control; 401 intervention) and 208 carers (100 control; 108 intervention) were recruited. In intention to treat analysis, the adjusted difference in patient General Health Questionnaire-12 mean scores at 6 months was –0.6 points (95% confidence interval, –1.8 to 0.7; P =0.394) indicating no evidence of statistically significant difference between the groups. Costs of Stroke Care Coordinator inputs, total health and social care costs, and quality-adjusted life year gains at 6 months, 12 months, and over the year were similar between the groups. Conclusions— This robust trial demonstrated no benefit in clinical or cost-effectiveness outcomes associated with the new system of care compared with usual Stroke Care Coordinator practice. Clinical Trial Registration— URL: http://www.controlled-trials.com . Unique identifier: ISRCTN 67932305.

Description: Introduction When used appropriately, transfusion of red blood cells (RBCs) is a necessary life-saving therapy. However, RBC transfusions have been associated with negative outcomes such as infection and organ damage. Seeking explanations for the beneficial and deleterious effects of RBC transfusions is necessary to ensure the safe and optimal use of this precious resource. This study will create a framework to analyse the influence of blood donor characteristics on recipient outcomes. Methods and analysis We will conduct a multisite, longitudinal cohort study using blood donor data routinely collected by Canadian Blood Services, and recipient data from health administrative databases. Our project will include a thorough validation of primary data, the linkage of various databases into one large longitudinal database, an in-depth epidemiological analysis and a careful interpretation and dissemination of the results to assist the decision-making process of clinicians, researchers and policymakers in transfusion medicine. Our primary donor characteristic will be age of blood donors and our secondary donor characteristics will be donor–recipient blood group compatibility and blood donor sex. Our primary recipient outcome will be a statistically appropriate survival analysis post-RBC transfusion up to a maximum of 8 years. Our secondary recipient outcomes will include 1-year, 2-year and 5-year mortality; hospital and intensive care unit length of stay; rehospitalisation; new cancer and cancer recurrence rate; infection rate; new occurrence of myocardial infarctions and need for haemodialysis. Ethics and dissemination Our results will help determine whether we need to tailor transfusion based on donor characteristics, and perhaps this will improve patient outcome. Our results will be customised to target the different stakeholders involved with blood transfusions and will include presentations, peer-reviewed publications and the use of the dissemination network of blood supply organisations. We obtained approval from the Research Ethics boards and privacy offices of all involved institutions.