Empowering junior doctors: a qualitative study of a QI programme in South West England

Aim To explore how the South-West Foundation Doctor Quality Improvement programme affected foundation year 1 (F1) doctors’ attitudes and ability to implement change in healthcare. Methods Twenty-two qualitative interviews were carried out with two cohorts of doctors. The first F1 group before and after their participation in the QI programme; the second group comprised those who had completed the programme between 1 and 5 years earlier. Qualitative data were analysed using thematic analysis techniques. Results Prior to taking part in the QI programme, junior doctors’ attitudes towards QI were mixed. Although there was agreement on the importance of QI in terms of patient safety, not all shared enthusiasm for engaging in QI, while some were sceptical that they could bring about any change. Following participation in the programme, attitudes towards QI and the ability to effect change were significantly transformed. Whether their projects were considered a success or not, all juniors reported that they valued the skills learnt and the overall experience they gained through carrying out QI projects. Participants reported feeling more empowered in their role as junior doctors, with several describing how they felt ‘listened to’ and able to ‘have a voice’, that they were beginning to see things ‘at systems level’ and learning to ‘engage more critically’ in their working environment. Conclusions Junior doctors are ideally placed to engage in QI. Training in QI at the start of their medical careers may enable a new generation of doctors to acquire the skills necessary to improve patient safety and quality of care

Impact of the English Directly Enhanced Service (DES) for Learning Disability

Final Report to the Department of Healt

Glucose, cholesterol and blood pressure in type II diabetes : a longitudinal observational study comparing patients with and without severe mental illness

INTRODUCTION: Patients with both severe mental illness (SMI) and type II diabetes (T2DM) have lower life expectancy than patients with T2DM alone, partly due to poor control of cardiovascular risk factors in comorbid patients. AIM: To compare levels of cholesterol, HbA1c and blood pressure in T2DM patients with and without SMI. METHOD: We analysed longitudinal clinical records of 30,353 people with T2DM (657 with SMI;29,696 controls without SMI) between 2001 and 2013 using the Clinical Practice Research Datalink (CPRD). We used mixed effects regression models to compare cardiovascular risk factors between SMI and controls. RESULTS: Patients with SMI had lower mean systolic blood pressure (SBP) (β -2.49; SE=0.45 P=<0.01) and were more likely to have extreme (high and low) values of HbA1c and SBP (OR 1.38, 95%CI: 1.16,1.64 and 1.76:1.40,2.21 respectively). DISCUSSION: People with T2DM and SMI have similar average values of cardiovascular risk factors to people with T2DM alone but are more likely to have values of HbA1c and SBP indicating increased risk of adverse clinical outcomes. IMPLICATIONS FOR PRACTICE: Improved management of cardiovascular risk factors in general, glycaemic control in particular, is central to addressing the increased risk of adverse outcomes in people with both SMI and T2DM. This article is protected by copyright. All rights reserved

Empowering junior doctors: a qualitative study of a QI programme in South West England

Aim To explore how the South-West Foundation Doctor Quality Improvement programme affected foundation year 1 (F1) doctors’ attitudes and ability to implement change in healthcare. Methods Twenty-two qualitative interviews were carried out with two cohorts of doctors. The first F1 group before and after their participation in the QI programme; the second group comprised those who had completed the programme between 1 and 5 years earlier. Qualitative data were analysed using thematic analysis techniques. Results Prior to taking part in the QI programme, junior doctors’ attitudes towards QI were mixed. Although there was agreement on the importance of QI in terms of patient safety, not all shared enthusiasm for engaging in QI, while some were sceptical that they could bring about any change. Following participation in the programme, attitudes towards QI and the ability to effect change were significantly transformed. Whether their projects were considered a success or not, all juniors reported that they valued the skills learnt and the overall experience they gained through carrying out QI projects. Participants reported feeling more empowered in their role as junior doctors, with several describing how they felt ‘listened to’ and able to ‘have a voice’, that they were beginning to see things ‘at systems level’ and learning to ‘engage more critically’ in their working environment. Conclusions Junior doctors are ideally placed to engage in QI. Training in QI at the start of their medical careers may enable a new generation of doctors to acquire the skills necessary to improve patient safety and quality of care

The Orphan Adhesion-GPCR GPR126 Is Required for Embryonic Development in the Mouse

Adhesion-GPCRs provide essential cell-cell and cell-matrix interactions in development, and have been implicated in inherited human diseases like Usher Syndrome and bilateral frontoparietal polymicrogyria. They are the second largest subfamily of seven-transmembrane spanning proteins in vertebrates, but the function of most of these receptors is still not understood. The orphan Adhesion-GPCR GPR126 has recently been shown to play an essential role in the myelination of peripheral nerves in zebrafish. In parallel, whole-genome association studies have implicated variation at the GPR126 locus as a determinant of body height in the human population. The physiological function of GPR126 in mammals is still unknown. We describe a targeted mutation of GPR126 in the mouse, and show that GPR126 is required for embryonic viability and cardiovascular development

Synthetic chemerin-derived peptides suppress inflammation through ChemR23.

Chemerin is a chemotactic protein that binds to the G protein-coupled receptor, ChemR23. We demonstrate that murine chemerin possesses potent antiinflammatory properties that are absolutely dependent on proteolytic processing. A series of peptides was designed, and only those identical to specific C-terminal chemerin sequences exerted antiinflammatory effects at picomolar concentrations in vitro. One of these, chemerin15 (C15; A(140)-A(154)), inhibited macrophage (MPhi) activation to a similar extent as proteolyzed chemerin, but exhibited reduced activity as a MPhi chemoattractant. Intraperitoneal administration of C15 (0.32 ng/kg) to mice before zymosan challenge conferred significant protection against zymosan-induced peritonitis, suppressing neutrophil (63%) and monocyte (62%) recruitment with a concomitant reduction in proinflammatory mediator expression. Importantly, C15 was unable to ameliorate zymosan-induced peritonitis in ChemR23(-/-) mice, demonstrating that C15's antiinflammatory effects are entirely ChemR23 dependent. In addition, administration of neutralizing anti-chemerin antibody before zymosan challenge resulted in a significant exacerbation of peritoneal inflammation (up to 170%), suggesting an important endogenous antiinflammatory role for chemerin-derived species. Collectively, these results show that chemerin-derived peptides may represent a novel therapeutic strategy for the treatment of inflammatory diseases through ChemR23

SARS-CoV-2 Receptor ACE2 Is an Interferon-Stimulated Gene in Human Airway Epithelial Cells and Is Detected in Specific Cell Subsets across Tissues.

There is pressing urgency to understand the pathogenesis of the severe acute respiratory syndrome coronavirus clade 2 (SARS-CoV-2), which causes the disease COVID-19. SARS-CoV-2 spike (S) protein binds angiotensin-converting enzyme 2 (ACE2), and in concert with host proteases, principally transmembrane serine protease 2 (TMPRSS2), promotes cellular entry. The cell subsets targeted by SARS-CoV-2 in host tissues and the factors that regulate ACE2 expression remain unknown. Here, we leverage human, non-human primate, and mouse single-cell RNA-sequencing (scRNA-seq) datasets across health and disease to uncover putative targets of SARS-CoV-2 among tissue-resident cell subsets. We identify ACE2 and TMPRSS2 co-expressing cells within lung type II pneumocytes, ileal absorptive enterocytes, and nasal goblet secretory cells. Strikingly, we discovered that ACE2 is a human interferon-stimulated gene (ISG) in vitro using airway epithelial cells and extend our findings to in vivo viral infections. Our data suggest that SARS-CoV-2 could exploit species-specific interferon-driven upregulation of ACE2, a tissue-protective mediator during lung injury, to enhance infection

Allele-Specific HLA Loss and Immune Escape in Lung Cancer Evolution

Immune evasion is a hallmark of cancer. Losing the ability to present neoantigens through human leukocyte antigen (HLA) loss may facilitate immune evasion. However, the polymorphic nature of the locus has precluded accurate HLA copy-number analysis. Here, we present loss of heterozygosity in human leukocyte antigen (LOHHLA), a computational tool to determine HLA allele-specific copy number from sequencing data. Using LOHHLA, we find that HLA LOH occurs in 40% of non-small-cell lung cancers (NSCLCs) and is associated with a high subclonal neoantigen burden, APOBEC-mediated mutagenesis, upregulation of cytolytic activity, and PD-L1 positivity. The focal nature of HLA LOH alterations, their subclonal frequencies, enrichment in metastatic sites, and occurrence as parallel events suggests that HLA LOH is an immune escape mechanism that is subject to strong microenvironmental selection pressures later in tumor evolution. Characterizing HLA LOH with LOHHLA refines neoantigen prediction and may have implications for our understanding of resistance mechanisms and immunotherapeutic approaches targeting neoantigens. Video Abstract [Figure presented] Development of the bioinformatics tool LOHHLA allows precise measurement of allele-specific HLA copy number, improves the accuracy in neoantigen prediction, and uncovers insights into how immune escape contributes to tumor evolution in non-small-cell lung cancer