Digital Problem-Based Learning: An Innovative and Efficient Method of Teaching Medicine

Background: The breadth of knowledge assimilated by undergraduates is substantial. Time must be utilised to impart knowledge and skills to ensure optimal training. Dermatology comprises a large portion of work in primary care; yet UK undergraduate dermatology training is short. Digital problem-based learning (PBL) is an innovative teaching method incorporating clinical images into intense, interactive teaching sessions. Aim: To determine the efficacy of digital PBL sessions in teaching UK medical students during their dermatology module. Methods: In total, 59 second-year medical students at Norwich Medical School during their dermatology secondary care attachment completed two 2.5-h digital PBL sessions. One session was focused on lesions and the second on inflammatory diseases. During each session, students assessed 60 clinical cases each comprising an image with a brief history. In small groups, students discussed the cases, described the images, and agreed a diagnosis followed by a group discussion with the supervising clinician who provided feedback. Following each session, students completed a feedback questionnaire. Results: In total, 117 sets of feedback were received; 60% of students considered they learnt a great amount in a short time. The majority of students reported feeling more confident to make a dermatological diagnosis and more motivated in clinics as a result of the digital PBL; 64% of students found digital PBL more useful than real patient clinics. The most frequent negative comment was that 2.5 h was too long to concentrate. Conclusions: Digital PBL was a popular, effective, and efficient teaching method. Digital PBL sessions should be introduced alongside clinics and other teaching methods for undergraduates

Progress in the establishment of ward based outreach teams: experiences in the North West Province

This chapter briefly describes the implementation of the Ward-based Outreach Teams (WBOTs) in the North West Province. The authors then highlight some of the findings of a rapid assessment of provincial and district implementation of Ward-based Outreach Teams conducted in the province during December 2012 and January 2013. The purpose of the chapter is to describe features of implementation that enabled the early uptake of the WBOTs in the province and to identify factors impacting on sustainable implementation that have relevance across the country. There has been a steady growth in roll-out and implementation of the PHC re- engineering strategy since 2011. By March 2014, 227 WBOTs (involving 1 643 community health workers and 201 team leaders) were functioning across the province. Implementation strategies included the establishment of a provincial task team, planning which was informed by a number of data-gathering exercises, a piloting process, implementation of a monitoring and evaluation system, development of supportive partnerships, and training of teams and team leaders. The rapid assessment found high levels of knowledge and ownership of the strategy across the province, but also concerns around its future. Based on the North West experience, the authors draw out a set of factors which will influence the sustainability of the WBOT strategy across the country. These strategies include making provision for: adequate financing, evidence-informed planning and implementation, provincial and district governance, communication and dialogue, appropriate partnerships and operational research on WBOTs

Tracking genomic cancer evolution for precision medicine: The Lung TRACERx Study

The importance of intratumour genetic and functional heterogeneity is increasingly recognised as a driver of cancer progression and survival outcome. Understanding how tumour clonal heterogeneity impacts upon therapeutic outcome, however, is still an area of unmet clinical and scientific need. TRACERx (TRAcking non-small cell lung Cancer Evolution through therapy [Rx]), a prospective study of patients with primary non-small cell lung cancer (NSCLC), aims to define the evolutionary trajectories of lung cancer in both space and time through multiregion and longitudinal tumour sampling and genetic analysis. By following cancers from diagnosis to relapse, tracking the evolutionary trajectories of tumours in relation to therapeutic interventions, and determining the impact of clonal heterogeneity on clinical outcomes, TRACERx may help to identify novel therapeutic targets for NSCLC and may also serve as a model applicable to other cancer types

Clinical outcomes and response to treatment of patients receiving topical treatments for pyoderma gangrenosum: a prospective cohort study

Background: pyoderma gangrenosum (PG) is an uncommon dermatosis with a limited evidence base for treatment. Objective: to estimate the effectiveness of topical therapies in the treatment of PG. Methods: prospective cohort study of UK secondary care patients with a clinical diagnosis of PG suitable for topical treatment (recruited July 2009 to June 2012). Participants received topical therapy following normal clinical practice (mainly Class I-III topical corticosteroids, tacrolimus 0.03% or 0.1%). Primary outcome: speed of healing at 6 weeks. Secondary outcomes: proportion healed by 6 months; time to healing; global assessment; inflammation; pain; quality-of-life; treatment failure and recurrence. Results: Sixty-six patients (22 to 85 years) were enrolled. Clobetasol propionate 0.05% was the most commonly prescribed therapy. Overall, 28/66 (43.8%) of ulcers healed by 6 months. Median time-to-healing was 145 days (95% CI: 96 days, ∞). Initial ulcer size was a significant predictor of time-to-healing (hazard ratio 0.94 (0.88;80 1.00); p = 0.043). Four patients (15%) had a recurrence. Limitations: No randomised comparator Conclusion: Topical therapy is potentially an effective first-line treatment for PG that avoids possible side effects associated with systemic therapy. It remains unclear whether more severe disease will respond adequately to topical therapy alone

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

Mortality and pulmonary complications in patients undergoing surgery with perioperative SARS-CoV-2 infection: an international cohort study

Background: The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on postoperative recovery needs to be understood to inform clinical decision making during and after the COVID-19 pandemic. This study reports 30-day mortality and pulmonary complication rates in patients with perioperative SARS-CoV-2 infection. Methods: This international, multicentre, cohort study at 235 hospitals in 24 countries included all patients undergoing surgery who had SARS-CoV-2 infection confirmed within 7 days before or 30 days after surgery. The primary outcome measure was 30-day postoperative mortality and was assessed in all enrolled patients. The main secondary outcome measure was pulmonary complications, defined as pneumonia, acute respiratory distress syndrome, or unexpected postoperative ventilation. Findings: This analysis includes 1128 patients who had surgery between Jan 1 and March 31, 2020, of whom 835 (74·0%) had emergency surgery and 280 (24·8%) had elective surgery. SARS-CoV-2 infection was confirmed preoperatively in 294 (26·1%) patients. 30-day mortality was 23·8% (268 of 1128). Pulmonary complications occurred in 577 (51·2%) of 1128 patients; 30-day mortality in these patients was 38·0% (219 of 577), accounting for 81·7% (219 of 268) of all deaths. In adjusted analyses, 30-day mortality was associated with male sex (odds ratio 1·75 [95% CI 1·28–2·40], p\textless0·0001), age 70 years or older versus younger than 70 years (2·30 [1·65–3·22], p\textless0·0001), American Society of Anesthesiologists grades 3–5 versus grades 1–2 (2·35 [1·57–3·53], p\textless0·0001), malignant versus benign or obstetric diagnosis (1·55 [1·01–2·39], p=0·046), emergency versus elective surgery (1·67 [1·06–2·63], p=0·026), and major versus minor surgery (1·52 [1·01–2·31], p=0·047). Interpretation: Postoperative pulmonary complications occur in half of patients with perioperative SARS-CoV-2 infection and are associated with high mortality. Thresholds for surgery during the COVID-19 pandemic should be higher than during normal practice, particularly in men aged 70 years and older. Consideration should be given for postponing non-urgent procedures and promoting non-operative treatment to delay or avoid the need for surgery. Funding: National Institute for Health Research (NIHR), Association of Coloproctology of Great Britain and Ireland, Bowel and Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society, European Society of Coloproctology, NIHR Academy, Sarcoma UK, Vascular Society for Great Britain and Ireland, and Yorkshire Cancer Research

Periocular photodynamic therapy for squamous intra-epidermal carcinoma

Objectives: To evaluate the response of Metvix photodynamic therapy (PDT) for the treatment of periocular Bowen's disease.  Methods: Four patients with biopsy-proven Bowen' disease were treated with Metvix PDT between November 2010 and January 2012. A detailed description of the technique used is described.  Results: All of the patients tolerated the PDT well. All had some clinical response to the treatment, although there was not complete, lasting resolution beyond one year in three out of the four cases.  Conclusion: PDT can be a good treatment in its own right in selected cases of periocular Bowen's disease

Discovery of prognostic and predictive tissue biomarkers in patients with resectable esophageal cancer

45 Background: Patients with operable esophageal adenocarcinoma have a poor prognosis (median survival &lt;2 years). We aimed to discover novel prognostic and predictive biomarkers to be validated as tools for patient selection for optimal neo-adjuvant therapy. Methods: Protein levels of XPF, MUS81, Cyclins A, B1, D1 and E, and Ki67 were assessed by retrospective immunohistochemical analysis of baseline tumor biopsy samples from 3 groups of patients with operable esophageal adenocarcinoma: surgery alone (N=54), 2 cycles of cisplatin-fluorouracil chemotherapy followed by surgery (N=46), and 2 cycles of oxaliplatin-fluorouracil chemotherapy (N=38). Expression of 48,803 genes was studied by Illumina HT-12 chip array followed by functional pathway analysis in oxaliplatin-treated patients before and after chemotherapy (N=38). Results were tested for association with pathological response (Mandard regression grading) (Chi-square test), disease free survival (DFS) and overall survival (OS) (Wilcoxon test). Results: High Ki67 protein levels were associated with worse OS (P=0.034; N=93). None of the markers were predictive of clinical endpoints following cisplatin chemotherapy. In oxaliplatin-treated patients (N=38), functional pathway analysis revealed associations between overexpression of cell cycle/DNA repair genes at baseline and worse clinical outcomes. Expression of 15 DNA repair (DNAR) genes was associated with DFS, and 16 DNAR genes with OS. Expression of 21 DNAR genes significantly increased after chemotherapy. Gene expression associations were validated at the protein level: high MUS81 at baseline predicted poor DFS (P=0.036) and poor OS (P=0.015) following oxaliplatin therapy; high XPF expression was associated with lack of pathological response (P=0.032); high Cyclin B1 predicted poor DFS (P=0.017). XPF protein levels increased following oxaliplatin (P=0.001, paired t-test). Conclusions: By confirmation of mRNA findings at the protein level, XPF, MUS81, and Cyclin B1 have been discovered as predictive biomarkers for response to oxaliplatin chemotherapy that merit prospective validation as tools for patient selection. Funded by Oxford NIHR Biomedical Research Centre and ECMC. </jats:p

Strategies to Optimize Participation in Diabetes Prevention Programs following Gestational Diabetes: A Focus Group Study

<div><p>Objective</p><p>We performed a qualitative study among women within 5 years of Gestational Diabetes (GDM) diagnosis. Our aim was to identify the key elements that would enhance participation in a type 2 diabetes (DM2) prevention program.</p><p>Research Design and Methods</p><p>Potential participants received up to three invitation letters from their GDM physician. Four focus groups were held. Discussants were invited to comment on potential facilitators/barriers to participation and were probed on attitudes towards meal replacement and Internet/social media tools. Recurring themes were identified through qualitative content analysis of discussion transcripts.</p><p>Results</p><p>Among the 1,201 contacted and 79 eligible/interested, 29 women attended a focus group discussion. More than half of discussants were overweight/obese, and less than half were physically active. For DM2 prevention, a strong need for social support to achieve changes in dietary and physical activity habits was expressed. In this regard, face-to-face interactions with peers and professionals were preferred, with adjunctive roles for Internet/social media. Further, direct participation of partners/spouses in a DM2 prevention program was viewed as important to enhance support for behavioural change at home. Discussants highlighted work and child-related responsibilities as potential barriers to participation, and emphasized the importance of childcare support to allow attendance. Meal replacements were viewed with little interest, with concerns that their use would provide a poor example of eating behaviour to children.</p><p>Conclusions</p><p>Among women within 5 years of a GDM diagnosis who participated in a focus group discussion, participation in a DM2 prevention program would be enhanced by face-to-face interactions with professionals and peers, provision of childcare support, and inclusion of spouses/partners.</p></div