Exploring factors that influence the spread and sustainability of a dysphagia innovation: an instrumental case study

Background: Swallowing difficulties challenge patient safety due to the increased risk of malnutrition, dehydration and aspiration pneumonia. A theoretically driven study was undertaken to examine the spread and sustainability of a locally developed innovation that involved using the Inter-Professional Dysphagia Framework to structure education for the workforce. A conceptual framework with 3 spread strategies (hierarchical control, participatory adaptation and facilitated evolution) was blended with a processual approach to sustaining organisational change. The aim was to understand the processes, mechanism and outcomes associated with the spread and sustainability of this safety initiative. Methods: An instrumental case study, prospectively tracked a dysphagia innovation for 34 months (April 2011 to January 2014) in a large health care organisation in England. A train-the-trainer intervention (as participatory adaptation) was deployed on care pathways for stroke and fractured neck of femur. Data were collected at the organisational and clinical level through interviews (n = 30) and document review. The coding frame combined the processual approach with the spread mechanisms. Pre-determined outcomes included the number of staff trained about dysphagia and impact related to changes in practice. Results: The features and processes associated with hierarchical control and participatory adaptation were identified. Leadership, critical junctures, temporality and making the innovation routine were aspects of hierarchical control. Participatory adaptation was evident on the care pathways through stakeholder responses, workload and resource pressures. Six of the 25 ward based trainers cascaded the dysphagia training. The expected outcomes were achieved when the top-down mandate (hierarchical control) was supplemented by local engagement and support (participatory adaptation). Conclusions: Frameworks for spread and sustainability were combined to create a ‘small theory’ that described the interventions, the processes and desired outcomes a priori. This novel methodological approach confirmed what is known about spread and sustainability, highlighted the particularity of change and offered new insights into the factors associated with hierarchical control and participatory adaptation. The findings illustrate the dualities of organisational change as universal and context specific; as particular and amendable to theoretical generalisation. Appreciating these dualities may contribute to understanding why many innovations fail to become routine

Alterations in the gut microbiome implicate key taxa and metabolic pathways across inflammatory arthritis phenotypes

Musculoskeletal diseases affect up to 20% of adults worldwide. The gut microbiome has been implicated in inflammatory conditions, but large-scale metagenomic evaluations have not yet traced the routes by which immunity in the gut affects inflammatory arthritis. To characterize the community structure and associated functional processes driving gut microbial involvement in arthritis, the Inflammatory Arthritis Microbiome Consortium investigated 440 stool shotgun metagenomes comprising 221 adults diagnosed with rheumatoid arthritis, ankylosing spondylitis, or psoriatic arthritis and 219 healthy controls and individuals with joint pain without an underlying inflammatory cause. Diagnosis explained about 2% of gut taxonomic variability, which is comparable in magnitude to inflammatory bowel disease. We identified several candidate microbes with differential carriage patterns in patients with elevated blood markers for inflammation. Our results confirm and extend previous findings of increased carriage of typically oral and inflammatory taxa and decreased abundance and prevalence of typical gut clades, indicating that distal inflammatory conditions, as well as local conditions, correspond to alterations to the gut microbial composition. We identified several differentially encoded pathways in the gut microbiome of patients with inflammatory arthritis, including changes in vitamin B salvage and biosynthesis and enrichment of iron sequestration. Although several of these changes characteristic of inflammation could have causal roles, we hypothesize that they are mainly positive feedback responses to changes in host physiology and immune homeostasis. By connecting taxonomic alternations to functional alterations, this work expands our understanding of the shifts in the gut ecosystem that occur in response to systemic inflammation during arthritis

Learning to mark: a qualitative study of the experiences and concerns of medical markers

BACKGROUND: Although there is published research on the methods markers use in marking various types of assessment, there is relatively little information on the processes markers use in approaching a marking exercise. This qualitative paper describes the preparation and experiences of general practice (GP) teachers who undertake marking a written assessment in an undergraduate medical course. METHODS: Semi-structured interviews were conducted with seven of the 16 GP tutors on an undergraduate course. The purposive sample comprised two new markers, two who had marked for a couple of years and three experienced markers. Each respondent was interviewed twice, once following a formative assessment of a written case study, and again after a summative assessment. All interviews were audio-taped and analysed for emerging themes. A respondent validation exercise was conducted with all 16 GP tutors. RESULTS: Markers had internal concerns about their ability to mark fairly and made considerable efforts to calibrate their marking. They needed guidance and coaching when marking for the first time and adopted a variety of marking styles, reaching a decision through a number of routes. Dealing with pass/fail borderline scripts and the consequences of the mark on the student were particular concerns. Even experienced markers felt the need to calibrate their marks both internally and externally CONCLUSION: Previous experience of marking appears to improve markers' confidence and is a factor in determining the role which markers adopt. Confidence can be improved by giving clear instructions, along with examples of marking. The authors propose that one method of providing this support and coaching could be by a process of peer review of a selection of papers prior to the main marking. New markers in particular would benefit from further guidance, however they are influenced by others early on in their marking career and course organisers should be mindful of this when arranging double marking

Exploring scale-up, spread, and sustainability: an instrumental case study tracing an innovation to enhance dysphagia care

Background Adoption, adaptation, scale-up, spread, and sustainability are ill-defined, undertheorised, and little-researched implementation science concepts. An instrumental case study will track the adoption and adaptation, or not, of a locally developed innovation about dysphagia as a patient safety issue. The case study will examine a conceptual framework with a continuum of spread comprising hierarchical control or ‘making it happen’, participatory adaptation or ‘help it happen’, and facilitated evolution or ‘let it happen’. Methods This case study is a prospective, longitudinal design using mixed methods. The fifteen-month (October 2012 to December 2013) instrumental case study is set in large, healthcare organisation in England. The innovation refers to introducing a nationally recognised, inter-disciplinary dysphagia competency framework to guide workforce development about fundamental aspects of care. Adoption and adaptation will be examined at an organisational level and along two, contrasting care pathways: stroke and fractured neck of femur. A number of educational interventions will be deployed, including training a cadre of trainers to cascade the essentials of dysphagia management and developing a Dysphagia Toolkit as a learning resource. Mixed methods will be used to investigate scale-up, spread, and sustainability in acute and community settings. A purposive sample of senior managers and clinical leaders will be interviewed to identify path dependency or the context specific particularities of implementation. A pre- and post-evaluation, using mealtime observations and a survey, will investigate the learning effect on staff adherence to patient specific dysphagia recommendations and attitudes towards dysphagia, respectively. Official documents and an ethnographic field journal allow critical junctures, temporal aspects and confounding factors to be explored. Discussion Researching spread and sustainability presents methodological and practical challenges. These include fidelity, adaptation latitude, time, and organisational changes. An instrumental case study will allow these confounding factors to be tracked over time and in place. The case study is underpinned by, and will test a conceptual framework about spread, to explore theoretical generalizability

Deconvolution of monocyte responses in inflammatory bowel disease reveals an IL-1 cytokine network that regulates IL-23 in genetic and acquired IL-10 resistance.

OBJECTIVE: Dysregulated immune responses are the cause of IBDs. Studies in mice and humans suggest a central role of interleukin (IL)-23-producing mononuclear phagocytes in disease pathogenesis. Mechanistic insights into the regulation of IL-23 are prerequisite for selective IL-23 targeting therapies as part of personalised medicine. DESIGN: We performed transcriptomic analysis to investigate IL-23 expression in human mononuclear phagocytes and peripheral blood mononuclear cells. We investigated the regulation of IL-23 expression and used single-cell RNA sequencing to derive a transcriptomic signature of hyperinflammatory monocytes. Using gene network correlation analysis, we deconvolved this signature into components associated with homeostasis and inflammation in patient biopsy samples. RESULTS: We characterised monocyte subsets of healthy individuals and patients with IBD that express IL-23. We identified autosensing and paracrine sensing of IL-1α/IL-1β and IL-10 as key cytokines that control IL-23-producing monocytes. Whereas Mendelian genetic defects in IL-10 receptor signalling induced IL-23 secretion after lipopolysaccharide stimulation, whole bacteria exposure induced IL-23 production in controls via acquired IL-10 signalling resistance. We found a transcriptional signature of IL-23-producing inflammatory monocytes that predicted both disease and resistance to antitumour necrosis factor (TNF) therapy and differentiated that from an IL-23-associated lymphocyte differentiation signature that was present in homeostasis and in disease. CONCLUSION: Our work identifies IL-10 and IL-1 as critical regulators of monocyte IL-23 production. We differentiate homeostatic IL-23 production from hyperinflammation-associated IL-23 production in patients with severe ulcerating active Crohn's disease and anti-TNF treatment non-responsiveness. Altogether, we identify subgroups of patients with IBD that might benefit from IL-23p19 and/or IL-1α/IL-1β-targeting therapies upstream of IL-23

Genetic influences on attention deficit hyperactivity disorder symptoms from age 2 to 3: A quantitative and molecular genetic investigation

<p>Abstract</p> <p>Background</p> <p>A twin study design was used to assess the degree to which additive genetic variance influences ADHD symptom scores across two ages during infancy. A further objective in the study was to observe whether genetic association with a number of candidate markers reflects results from the quantitative genetic analysis.</p> <p>Method</p> <p>We have studied 312 twin pairs at two time-points, age 2 and age 3. A composite measure of ADHD symptoms from two parent-rating scales: The Child Behavior Checklist/1.5 - 5 years (CBCL) hyperactivity scale and the Revised Rutter Parent Scale for Preschool Children (RRPSPC) was used for both quantitative and molecular genetic analyses.</p> <p>Results</p> <p>At ages 2 and 3 ADHD symptoms are highly heritable (<it>h</it>^{<it>2 </it>}<it>= </it>0.79 and 0.78, respectively) with a high level of genetic stability across these ages. However, we also observe a significant level of genetic change from age 2 to age 3. There are modest influences of non-shared environment at each age independently (<it>e</it>^{<it>2 </it>}= 0.22 and 0.21, respectively), with these influences being largely age-specific. In addition, we find modest association signals in <it>DAT1 </it>and <it>NET1 </it>at both ages, along with suggestive specific effects of <it>5-HTT </it>and <it>DRD4 </it>at age 3.</p> <p>Conclusions</p> <p>ADHD symptoms are heritable at ages 2 and 3. Additive genetic variance is largely shared across these ages, although there are significant new effects emerging at age 3. Results from our genetic association analysis reflect these levels of stability and change and, more generally, suggest a requirement for consideration of age-specific genotypic effects in future molecular studies.</p

MHC class II antigen presentation by intestinal epithelial cells fine-tunes bacteria-reactive CD4 T cell responses

Although intestinal epithelial cells (IECs) can express major histocompatibility complex class II (MHC II), especially during intestinal inflammation, it remains unclear if antigen presentation by IECs favours pro- or anti-inflammatory CD4+ T cell responses. Using selective gene ablation of MHC II in IECs and IEC organoid cultures, we assessed the impact of MHC II expression by IECs on CD4+ T cell responses and disease outcomes in response to enteric bacterial pathogens. We found that intestinal bacterial infections elicit inflammatory cues that greatly increase expression of MHC II processing and presentation molecules in colonic IECs. Whilst IEC MHC II expression had little impact on disease severity following Citrobacter rodentium or Helicobacter hepaticus infection, using a colonic IEC organoid-CD4+ T cell co-culture system, we demonstrate that IECs can activate antigen-specific CD4+ T cells in an MHC II-dependent manner, modulating both regulatory and effector Th cell subsets. Furthermore, we assessed adoptively transferred H. hepaticus-specific CD4+ T cells during intestinal inflammation in vivo and report that IEC MHC II expression dampens pro-inflammatory effector Th cells. Our findings indicate that IECs can function as non-conventional antigen presenting cells and that IEC MHC II expression fine-tunes local effector CD4+ T cell responses during intestinal inflammation

Adipocyte autophagy limits gut inflammation by controlling oxylipin and IL-10

Lipids play a major role in inflammatory diseases by altering inflammatory cell functions, either through their function as energy substrates or as lipid mediators such as oxylipins. Autophagy, a lysosomal degradation pathway that limits inflammation, is known to impact on lipid availability, however, whether this controls inflammation remains unexplored. We found that upon intestinal inflammation visceral adipocytes upregulate autophagy and that adipocyte-specific loss of the autophagy gene Atg7 exacerbates inflammation. While autophagy decreased lipolytic release of free fatty acids, loss of the major lipolytic enzyme Pnpla2/Atgl in adipocytes did not alter intestinal inflammation, ruling out free fatty acids as anti-inflammatory energy substrates. Instead, Atg7-deficient adipose tissues exhibited an oxylipin imbalance, driven through an NRF2-mediated upregulation of Ephx1. This shift reduced secretion of IL-10 from adipose tissues, which was dependent on the cytochrome P450-EPHX pathway, and lowered circulating levels of IL-10 to exacerbate intestinal inflammation. These results suggest an underappreciated fat-gut crosstalk through an autophagy-dependent regulation of anti-inflammatory oxylipins via the cytochrome P450-EPHX pathway, indicating a protective effect of adipose tissues for distant inflammation

The barriers and facilitators influencing the sustainability of hospital-based interventions: a systematic review

Acknowledgements University of Stirling for providing financial support for open access costs Funding This review was funded by the Chief Scientist Office, grant number GCA/17/26. JC, PC and EAD are employed by the Nursing, Midwifery and Allied Health Professions Research Unit, which is funded by the Chief Scientist Office in Scotland.Peer reviewedPublisher PD