‘It’s not really our thing’:lessons in engaging care homes in palliative care research

Background: In England and Wales there are just under 400,000 older adults residing in care homes at any one time. Despite this, care home residents are often excluded from epidemiological studies and little routine data are collected within care homes. Data on palliative care provided by care homes is reported to the Care Quality Commission, but the quality of care is often locally determined. There is ongoing research in this area aimed at collecting representative, internationally comparable data, such as the PACE study. Aims: To discuss the challenges encountered in engaging and recruiting care homes across England in the PACE study, a retrospective, cross sectional survey of deaths over three months. The study collected questionnaire data from care home staff, general practitioners and relatives of care home residents on their experiences of palliative care. It aimed to include 200 deceased residents in fifty care homes over a one-year period. Methods: The research team reviewed the barriers and challenges encountered throughout the research process, including developing a representative sampling framework, obtaining ethical approvals, advertising the study and recruiting care homes. Results: There is a lack of clarity regarding where care homes are located within the scope of ethical approval bodies. Recruitment through random sampling was found to be less effective compared to recruitment through ENRICH networks. Barriers to care home participation included concerns regarding sharing information, fear of opening up to potential criticism, lack of resources and misunderstandings regarding confidentiality. Conclusions: The development of care home networks and informal contacts can improve the rate and extent of research involvement. Whilst representativeness can be attained, random samples and ensuring a rigorous sample through these methods of recruitment remains a challenge

Engaging nursing homes (NHs) in the PACE study:comparing recruitment in observational and intervention research designs

Background: NH residents are often excluded from epidemiological studies, demonstrating a need for representative, internationally comparable research in this area. Data on palliative care provided by NHs is reported to the Care Quality Commission in England, but the quality of care is often locally determined. Aims: To review the challenges encountered in engaging and recruiting NHs across England to the European Commission funded PACE research project; a two part study comprising of a retrospective, cross sectional survey of deaths and a cluster randomised controlled trial (RCT) of the ‘PACE Steps to Success’ end of life training intervention. Methods: Study 1 collected quantitative data from NH staff, general practitioners and relatives of 200 deceased NH residents in 50 NHs. Study 2 aimed to recruit twelve NHs, six in each arm of the RCT. The research team encountered challenges throughout the research process, including developing a representative sampling framework, obtaining ethical approvals, advertising the study and recruiting NHs. Results: Study 1 has recruited 44 NHs resulting in data on 92 deceased residents from 32 research visits made so far. Identifying NHs through random sampling resulted in fewer NHs recruited compared to advertising through the ENRICH NHs research networks. Average death rates per NH were lower than expected (3.1 per three months). Study 2 is in the process of recruiting twelve NHs with the support of local ENRICH teams by January 2016. Lack of time and resources, concerns regarding data protection and fear of opening up to potential criticism were identified as barriers to participation. Conclusions: Observational and RCT research designs in NHs require distinct recruitment processes. Whilst representativeness was attained in study 1, ensuring a rigorous random sample was not possible. In both studies, the engagement with NH research networks and informal contacts improved the rate and extent of research involvement

Comparing palliative care in care homes across Europe (PACE):protocol of a cross-sectional study of deceased residents in six EU countries

Objectives While a growing number of older people are dying in care homes, palliative care has developed in these settings only recently. Crosscountry representative comparative research hardly exists in this area. As part of a large EU-funded project, we aim to undertake representative comparative research in care homes in Europe, to describe and compare six countries in terms of 1) resident outcomes, quality and costs of palliative and end-of-life care; 2) palliative care structures and staff knowledge and attitudes towards palliative care. We also aim to explore country, facility, staff, patient and care characteristics related to better outcomes at resident level. Design and Methods To obtain a representative nationwide sample, we will conduct a large-scale cross-sectional study of deceased residents in care homes in Belgium, Finland, Italy, the Netherlands, Poland and the United Kingdom, using proportional stratified random sampling (taking into account region, facility type and bed capacity). In each country, all participating care homes retrospectively report all deaths of residents in and outside the facilities over the previous three-month period. For each case, structured questionnaires including validated instruments are sent to (1) the administrator/manager, (2) staff member most involved in care, (3) treating physician (GP or elderly care physician), and (4) a closely involved relative. It is estimated that, per country, 50 care homes are needed on average to obtain a minimum of 200 deceased residents. Collected data include clinical and socio-demographic characteristics, quality of dying, quality and costs of palliative care and end-of-life care, and palliative care structures at facility level and country level. To obtain a representative view of staff knowledge and attitudes regarding palliative care, PACE will conduct a cross-sectional study of staff working in the participating care homes. Conclusion Considering the growing challenges associated with aging in all European countries, there is an urgent need to build a robust international comparative evidence-base that can inform the development of policies to target improved palliative care in care homes. By describing this research protocol, we hope to inform international research in care homes on how to perform representative end-of-life care research in these settings and better understand which systems are associated with better outcomes

NBEAL2 is required for neutrophil and NK cell function and pathogen defense.

Mutations in the human NBEAL2 gene cause gray platelet syndrome (GPS), a bleeding diathesis characterized by a lack of α granules in platelets. The functions of the NBEAL2 protein have not been explored outside platelet biology, but there are reports of increased frequency of infection and abnormal neutrophil morphology in patients with GPS. We therefore investigated the role of NBEAL2 in immunity by analyzing the phenotype of Nbeal2-deficient mice. We found profound abnormalities in the Nbeal2-deficient immune system, particularly in the function of neutrophils and NK cells. Phenotyping of Nbeal2-deficient neutrophils showed a severe reduction in granule contents across all granule subsets. Despite this, Nbeal2-deficient neutrophils had an enhanced phagocyte respiratory burst relative to Nbeal2-expressing neutrophils. This respiratory burst was associated with increased expression of cytosolic components of the NADPH oxidase complex. Nbeal2-deficient NK cells were also dysfunctional and showed reduced degranulation. These abnormalities were associated with increased susceptibility to both bacterial (Staphylococcus aureus) and viral (murine CMV) infection in vivo. These results define an essential role for NBEAL2 in mammalian immunity

Eros is a novel transmembrane protein that controls the phagocyte respiratory burst and is essential for innate immunity

The phagocyte respiratory burst is crucial for innate immunity. The transfer of electrons to oxygen is mediated by a membrane-bound heterodimer, comprising gp91$\textit{phox}$ and p22$\textit{phox}$ subunits. Deficiency of either subunit leads to severe immunodeficiency. We describe Eros (essential for reactive oxygen species), a protein encoded by the previously undefined mouse gene $\textit{bc017643}$, and show that it is essential for host defense via the phagocyte NAPDH oxidase. Eros is required for expression of the NADPH oxidase components, gp91$\textit{phox}$ and p22$\textit{phox}$. Consequently, $\textit{Eros}$-deficient mice quickly succumb to infection. $\textit{Eros}$ also contributes to the formation of neutrophil extracellular traps (NETS) and impacts on the immune response to melanoma metastases. $\textit{Eros}$ is an ortholog of the plant protein Ycf4, which is necessary for expression of proteins of the photosynthetic photosystem 1 complex, itself also an NADPH oxio-reductase. We thus describe the key role of the previously uncharacterized protein Eros in host defense.D.C. Thomas was funded by a Wellcome Trust/CIMR Next Generation Fellowship, a National Institute for Health Research (NIHR) Clinical Lectureship, and a Starter Grant for Clinical Lecturers (Academy of Medical Sciences). K.G.C. Smith was funded by funded by the Medical Research Council (program grant MR/L019027) and is a Wellcome Investigator and a NIHR Senior Investigator. S. Clare and G. Dougan were funded by the Wellcome Trust (grant 098051). The Cambridge Institute for Medical Research is in receipt of a Wellcome Trust Strategic Award (079895). J.C.L is funded by a Wellcome Intermediate Clinical Fellowship 105920/2/14/2

Endnotes

A collection of artists’ writings, edited by Bellotto and Rewakowicz, that brings together works by 28 artists from Montreal, Toronto, Vancouver, New York and Glasgow. Includes texts in a wide range of styles (poetic, fictional, autobiographical, etc.) that touch on diverse themes, such as: sex, art, politics, childhood, longing, memory and the body. Brief biographical notes on authors (in French and English)

EROS is a selective chaperone regulating the phagocyte NADPH oxidase and purinergic signalling.

Peer reviewed: TrueEROS (essential for reactive oxygen species) protein is indispensable for expression of gp91phox, the catalytic core of the phagocyte NADPH oxidase. EROS deficiency in humans is a novel cause of the severe immunodeficiency, chronic granulomatous disease, but its mechanism of action was unknown until now. We elucidate the role of EROS, showing it acts at the earliest stages of gp91phox maturation. It binds the immature 58 kDa gp91phox directly, preventing gp91phox degradation and allowing glycosylation via the oligosaccharyltransferase machinery and the incorporation of the heme prosthetic groups essential for catalysis. EROS also regulates the purine receptors P2X7 and P2X1 through direct interactions, and P2X7 is almost absent in EROS-deficient mouse and human primary cells. Accordingly, lack of murine EROS results in markedly abnormal P2X7 signalling, inflammasome activation, and T cell responses. The loss of both ROS and P2X7 signalling leads to resistance to influenza infection in mice. Our work identifies EROS as a highly selective chaperone for key proteins in innate and adaptive immunity and a rheostat for immunity to infection. It has profound implications for our understanding of immune physiology, ROS dysregulation, and possibly gene therapy

Collected Gnommero

Collected Gnommero is a series of five thematic pamphlets independently published in Glasgow between 2008 – 2015. The pamphlets provided space for artists and writers to respond to Italo Calvino’s thoughts on the literary qualities of lightness, quickness, exactitude, visibility, multiplicity and consistency (as published in Six Memos for the Next Millennium, 1988). Gnommero was also an economic experiment in independent publishing: the pamphlets were produced collectively by the contributors who shared production costs. The copies were then divided equally and distributed at launch events featuring performances and presentations by the contributors. The five Gnommero pamphlets, one for each memo (excluding ‘Consistency’), have been gathered into a red envelope of Collected Gnommero containing works by 54 contributors over Gnommero’s six-year lifespan. Gnommero was edited by Sarah Tripp with the artists Richard Taylor and Eona McCallum. Works in the Gnommero Collection are by: Giles Bailey, Ruth Barker, Becky Beasley, Anca Benera, Tom Betteridge, Nathalie de Briey, Kimberley Bright, Jenny Brownrigg, Maria Bojanowska, Barry Burns, Neil Davidson, Rachael Disbury, Rowena Easton, Laura Edbrook, Kathryn Elkin, Stuart Fallon, Kate Grenyer, Lauren Hall, Jane Hartshorn, Jamie Hogarth, Simone Hutchinson, Ben Knight, Mhari Lafferty, Chin Li, Lila Matsumoto, Eona McCallum, Conal McStravick, Giuseppe Mistretta, Charlotte Morgan, Kate Morrell, Aniara Omann, Steven Paige, Jessica Potter, Darren Rhymes, Anthony Schrag, Laura Simpson, Carrie Skinner, Louise Shelley, Katherine Sowerby, Emily Speed, Patrick Staff, Catherine Street, Richard Taylor, Iris Tendink, Cara Tolmie, Sarah Tripp, Tom Varley, Chris Walker, Thom Walker, Daniella Watson, Lauren Wells, Rebecca Wilcox, George Ziffo