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

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

Capacity Enhancement in Digital Humanities in the United Kingdom and Ireland: Training and Beyond

This first discussion paper, produced by the UK-Ireland Digital Humanities Network in consultation with the wider Digital Humanities (DH) community in the two countries and beyond, summarises the findings of a) the first workshop organised by the network and b) the post-workshop survey and offers recommendations based on these findings

Communicating the Value and Impact of Digital Humanities in Teaching, Research, and Infrastructure Development

This is the second discussion paper produced by the UK-Ireland Digital Humanities Network in consultation with the wider Digital Humanities (DH) Community in the two countries and beyond. It summarises the findings of the second workshop organised by the network, and offers recommendations based on these findings

Fc-Optimized Anti-CD25 Depletes Tumor-Infiltrating Regulatory T Cells and Synergizes with PD-1 Blockade to Eradicate Established Tumors

CD25 is expressed at high levels on regulatory T (Treg) cells and was initially proposed as a target for cancer immunotherapy. However, anti-CD25 antibodies have displayed limited activity against established tumors. We demonstrated that CD25 expression is largely restricted to tumor-infiltrating Treg cells in mice and humans. While existing anti-CD25 antibodies were observed to deplete Treg cells in the periphery, upregulation of the inhibitory Fc gamma receptor (FcγR) IIb at the tumor site prevented intra-tumoral Treg cell depletion, which may underlie the lack of anti-tumor activity previously observed in pre-clinical models. Use of an anti-CD25 antibody with enhanced binding to activating FcγRs led to effective depletion of tumor-infiltrating Treg cells, increased effector to Treg cell ratios, and improved control of established tumors. Combination with anti-programmed cell death protein-1 antibodies promoted complete tumor rejection, demonstrating the relevance of CD25 as a therapeutic target and promising substrate for future combination approaches in immune-oncology

Phylogenetic ctDNA analysis depicts early-stage lung cancer evolution.

The early detection of relapse following primary surgery for non-small-cell lung cancer and the characterization of emerging subclones, which seed metastatic sites, might offer new therapeutic approaches for limiting tumour recurrence. The ability to track the evolutionary dynamics of early-stage lung cancer non-invasively in circulating tumour DNA (ctDNA) has not yet been demonstrated. Here we use a tumour-specific phylogenetic approach to profile the ctDNA of the first 100 TRACERx (Tracking Non-Small-Cell Lung Cancer Evolution Through Therapy (Rx)) study participants, including one patient who was also recruited to the PEACE (Posthumous Evaluation of Advanced Cancer Environment) post-mortem study. We identify independent predictors of ctDNA release and analyse the tumour-volume detection limit. Through blinded profiling of postoperative plasma, we observe evidence of adjuvant chemotherapy resistance and identify patients who are very likely to experience recurrence of their lung cancer. Finally, we show that phylogenetic ctDNA profiling tracks the subclonal nature of lung cancer relapse and metastasis, providing a new approach for ctDNA-driven therapeutic studies

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570