The PATH to PPE Mastery - Programme for Assessment and Training in HCID (High Consequence Infectious Diseases) PPE (Personal Protective Equipment), Mastery.

Background: High Consequence Infectious Diseases (HCIDs), have the potential to cause pandemics and require particular focus for preparedness due to their high mortality rates. The application of Personal Protective Equipment (PPE) for HCIDs is complex and carries significant risk of Health Care Worker (HCW) contamination if done incorrectly. Previous reviews have reported a lack of information on the nature of training provided and the ideal timing of repeat training to best retain skills. Simulation Based Mastery Learning (SBML) is a methodology for skill acquisition which encompasses deliberate practice and repeated assessment until the learner achieves a pre-set Mastery standard. SBML has been demonstrated to improve competence, skill retention and patient outcomes in other clinical procedures. SBML has not been previously studied or utilised in HCID PPE training. Aim: We aimed to increase the likelihood of safe clinical practice by evidencing that Lothian modified SBML for PPE effectively prepares our priority learners. Methods: A quasi-experimental within group post-test design was used. Learners undertook a modified SBML programme which included two-hour asynchronous and two-hour synchronous components. Findings: 11 learners (10 infectious diseases registrars and 1 infectious diseases consultant) were enrolled in the programme with 8 completing all stages, all of whom achieved the Mastery passing standard. The resources were highly rated by learners with the exemplar videos of skills highlighted as particularly useful. Self-assessed preparedness for each skill increased following pre-learning and synchronous sessions. Conclusion: Modified SBML can be used as an effective methodology for the training and assessment of HCWs in the donning and doffing of HCID PPE.

The impact of simulation-based mastery learning, booster session timing and clinical exposure on confidence in intercostal drain insertion: a survey of internal medicine trainees in Scotland.

BACKGROUND: Intercostal chest drain (ICD) insertion is a skill that medical trainees lack confidence in performing. This study explores the impact of a national programme of Simulation-Based Mastery Learning (SBML) on procedural confidence, including the impact of time intervals between booster sessions and interim clinical experience. METHODS: Internal Medicine Trainees in Scotland were surveyed about confidence and clinical experience with ICD insertion before and immediately after SBML and booster session. Data were matched and analysed using paired sample t-tests. Short interval and long interval groups were compared using Student's unpaired t-test. The impact of interim clinical experience was assessed using Analysis of Variance. RESULTS: Mean confidence in ICD insertion rose following SBML, fell between initial and booster session, and increased again following booster session (P = < 0.001). 33 of 74 trainees had successfully inserted an ICD between sessions. Fall in confidence was unaffected by the time interval between training sessions, but was mitigated by interim clinical experience. CONCLUSIONS: SBML boosts trainee confidence in ICD insertion. However, there is evidence of confidence decay, possibly due to a lack of clinical experience between sessions. More research is needed to explore barriers to transfer of skills from simulated to real-world environments.

Postgraduate medical procedural skills: attainment of curricular competencies using enhanced simulation-based mastery learning at a novel national boot camp.

INTRODUCTION: A new UK medical postgraduate curriculum prompted the creation of a novel national medical postgraduate 'boot camp'. An enhanced simulation-based mastery learning (SBML) methodology was created to deliver procedural skills teaching within this national boot camp. This study aimed to explore the impact of SBML in a UK medical boot camp. METHODS: One-hundred and two Scottish medical trainees attended a 3-day boot camp starting in August 2019. The novel enhanced SBML pathway entailed online pre-learning resources, deliberate practice, and simulation assessment and feedback. Data were gathered via pre- and post-boot camp questionnaires and assessment checklists. RESULTS: The vast majority of learners achieved the required standard of performance. Learners reported increased skill confidence levels, including skills not performed at the boot camp. CONCLUSION: An enhanced SBML methodology in a boot camp model enabled streamlined, standardised procedural skill teaching to a national cohort of junior doctors. Training curricular competencies were achieved alongside increased skill confidence.

Pulmonary embolism severity before and during the COVID-19 pandemic.

OBJECTIVES: Early in the coronavirus 2019 (COVID-19) pandemic, a high frequency of pulmonary embolism was identified. This audit aims to assess the frequency and severity of pulmonary embolism in 2020 compared to 2019. METHODS: In this retrospective audit, we compared computed tomography pulmonary angiography (CTPA) frequency and pulmonary embolism severity in April and May 2020, compared to 2019. Pulmonary embolism severity was assessed with the Modified Miller score and the presence of right heart strain was assessed. Demographic information and 30-day mortality was identified from electronic health records. RESULTS: In April 2020, there was a 17% reduction in the number of CTPA performed and an increase in the proportion identifying pulmonary embolism (26%, n = 68/265 vs 15%, n = 47/320, p < 0.001), compared to April 2019. Patients with pulmonary embolism in 2020 had more comorbidities (p = 0.026), but similar age and sex compared to 2019. There was no difference in pulmonary embolism severity in 2020 compared to 2019, but there was an increased frequency of right heart strain in May 2020 (29 vs 12%, p = 0.029). Amongst 18 patients with COVID-19 and pulmonary embolism, there was a larger proportion of males and an increased 30 day mortality (28% vs 6%, p = 0.008). CONCLUSION: During the COVID-19 pandemic, there was a reduction in the number of CTPA scans performed and an increase in the frequency of CTPA scans positive for pulmonary embolism. Patients with both COVID-19 and pulmonary embolism had an increased risk of 30-day mortality compared to those without COVID-19. ADVANCES IN KNOWLEDGE: During the COVID-19 pandemic, the number of CTPA performed decreased and the proportion of positive CTPA increased. Patients with both pulmonary embolism and COVID-19 had worse outcomes compared to those with pulmonary embolism alone.

An enhanced approach to simulation-based mastery learning: optimising the educational impact of a novel, National Postgraduate Medical Boot Camp.

BACKGROUND: Simulation-based mastery learning (SBML) is an effective, evidence-based methodology for procedural skill acquisition, but its application may be limited by its resource intensive nature. To address this issue, an enhanced SBML programme has been developed by the addition of both pre-learning and peer learning components. These components allowed the enhanced programme to be scaled up and delivered to 106 postgraduate doctors participating in a national educational teaching programme. METHODS: The pre-learning component consisted of an online reading pack and videos. The peer learning component consisted of peer-assisted deliberate practice and peer observation of assessment and feedback within the SBML session. Anonymised pre- and post-course questionnaires were completed by learners who participated in the enhanced programme. A mixture of quantitative and qualitative data was obtained. RESULTS: Questionnaires were distributed to and completed by 50 learners. Both sections of the pre-learning component were highly rated on the basis of a seven-point Likert scale. The peer learning component was also favourably received following a Likert scale rating. Peer observation of the performance and assessment process was rated similarly by first and second learners. The thematic analysis of the reasons for which peer-assisted deliberate practice was considered useful showed that familiarisation with equipment, the rehearsal of the procedure itself, the exchange of experiences and sharing of useful tips were important. The thematic analysis of the reasons why peer observation during 'performance, assessment and feedback' was useful highlighted that an ability to compare a peer's performance to their own and learning from observing a peer's mistakes were particularly helpful. CONCLUSION: The SBML programme described has been enhanced by the addition of pre-learning and peer learning components which are educationally valued and allow its application on a national scale.

Curative intent resection for loco-regionally recurrent colon cancer: Cleveland clinic experience.

BACKGROUND: Locoregional colon cancer recurrence occurs in around 10% of patients following initial curative intent primary resection. We hypothesized oncological results can vary based on the recurrence site. Our aim was to determine outcomes for patients undergoing resection with curative intent for locally recurrent colon cancer. METHODS: Patients with locoregional recurrence after curative intent resection for colon cancer were identified (1999-2017). Demographics, operative details and outcome data were recorded. Kaplan-Meier method was used to compare survival differences. RESULTS: Fifty-two patients (mean age, 62) were included. The most common recurrence site was primary anastomosis (48%). R0 resection was obtained in 68%. Major morbidity occurred in 37%. Patients with anastomotic recurrence had a statistically significant overall survival compared to other sites (71.6 vs. 40.8 months respectively with a P value of 0.05). CONCLUSIONS: Excellent outcomes are possible for curative intent recurrent colon cancer surgery. The site of loco-regional recurrence plays a significant role in outcomes. Table of Contents Summary: Colon cancer recurrence can be treated surgically with optimal outcomes. Anastomotic recurrence is associated with improved survival.

Cost-Effectiveness of Haemorrhoidal Artery Ligation versus Rubber Band Ligation for the Treatment of Grade II-III Haemorrhoids: Analysis Using Evidence from the HubBLe Trial.

AIM: Haemorrhoids are a common condition, with nearly 30,000 procedures carried out in England in 2014/15, and result in a significant quality-of-life burden to patients and a financial burden to the healthcare system. This study examined the cost effectiveness of haemorrhoidal artery ligation (HAL) compared with rubber band ligation (RBL) in the treatment of grade II-III haemorrhoids. METHOD: This analyses used data from the HubBLe study, a multicentre, open-label, parallel group, randomised controlled trial conducted in 17 acute UK hospitals between September 2012 and August 2015. A full economic evaluation, including long-term cost effectiveness, was conducted from the UK National Health Service (NHS) perspective. Main outcomes included healthcare costs, quality-adjusted life-years (QALYs) and recurrence. Cost-effectiveness results were presented in terms of incremental cost per QALY gained and cost per recurrence avoided. Extrapolation analysis for 3 years beyond the trial follow-up, two subgroup analyses (by grade of haemorrhoids and recurrence following RBL at baseline), and various sensitivity analyses were undertaken. RESULTS: In the primary base-case within-trial analysis, the incremental total mean cost per patient for HAL compared with RBL was £1027 (95% confidence interval [CI] £782-£1272, p < 0.001). The incremental QALYs were 0.01 QALYs (95% CI -0.02 to 0.04, p = 0.49). This generated an incremental cost-effectiveness ratio (ICER) of £104,427 per QALY. In the extrapolation analysis, the estimated probabilistic ICER was £21,798 per QALY. Results from all subgroup and sensitivity analyses did not materially change the base-case result. CONCLUSIONS: Under all assessed scenarios, the HAL procedure was not cost effective compared with RBL for the treatment of grade II-III haemorrhoids at a cost-effectiveness threshold of £20,000 per QALY; therefore, economically, its use in the NHS should be questioned.

Haemorrhoidal artery ligation versus rubber band ligation for the management of symptomatic second-degree and third-degree haemorrhoids (HubBLe): a multicentre, open-label, randomised controlled trial.

BACKGROUND: Optimum surgical intervention for low-grade haemorrhoids is unknown. Haemorrhoidal artery ligation (HAL) has been proposed as an efficacious, safe therapy while rubber band ligation (RBL) is a commonly used outpatient treatment. We compared recurrence after HAL versus RBL in patients with grade II-III haemorrhoids. METHODS: This multicentre, open-label, parallel group, randomised controlled trial included patients from 17 acute UK NHS trusts. We screened patients aged 18 years or older presenting with grade II-III haemorrhoids. We excluded patients who had previously received any haemorrhoid surgery, more than one injection treatment for haemorrhoids, or more than one RBL procedure within 3 years before recruitment. Eligible patients were randomly assigned (in a 1:1 ratio) to either RBL or HAL with Doppler. Randomisation was computer-generated and stratified by centre with blocks of random sizes. Allocation concealment was achieved using a web-based system. The study was open-label with no masking of participants, clinicians, or research staff. The primary outcome was recurrence at 1 year, derived from the patient's self-reported assessment in combination with resource use from their general practitioner and hospital records. Recurrence was analysed in patients who had undergone one of the interventions and been followed up for at least 1 year. This study is registered with the ISRCTN registry, ISRCTN41394716. FINDINGS: From Sept 9, 2012, to May 6, 2014, of 969 patients screened, 185 were randomly assigned to the HAL group and 187 to the RBL group. Of these participants, 337 had primary outcome data (176 in the RBL group and 161 in the HAL group). At 1 year post-procedure, 87 (49%) of 176 patients in the RBL group and 48 (30%) of 161 patients in the HAL group had haemorrhoid recurrence (adjusted odds ratio [aOR] 2·23, 95% CI 1·42-3·51; p=0·0005). The main reason for this difference was the number of extra procedures required to achieve improvement (57 [32%] participants in the RBL group and 23 [14%] participants in the HAL group had a subsequent procedure for haemorrhoids). The mean pain 1 day after procedure was 3·4 (SD 2·8) in the RBL group and 4·6 (2·8) in the HAL group (difference -1·2, 95% CI -1·8 to -0·5; p=0·0002); at day 7 the scores were 1·6 (2·3) in the RBL group and 3·1 (2·4) in the HAL group (difference -1·5, -2·0 to -1·0; p<0·0001). Pain scores did not differ between groups at 21 days and 6 weeks. 15 individuals reported serious adverse events requiring hospital admission. One patient in the RBL group had a pre-existing rectal tumour. Of the remaining 14 serious adverse events, 12 (7%) were among participants treated with HAL and two (1%) were in those treated with RBL. Six patients had pain (one treated with RBL, five treated with HAL), three had bleeding not requiring transfusion (one treated with RBL, two treated with HAL), two in the HAL group had urinary retention, two in the HAL group had vasovagal upset, and one in the HAL group had possible sepsis (treated with antibiotics). INTERPRETATION: Although recurrence after HAL was lower than a single RBL, HAL was more painful than RBL. The difference in recurrence was due to the need for repeat bandings in the RBL group. Patients (and health commissioners) might prefer such a course of RBL to the more invasive HAL. FUNDING: NIHR Health Technology Assessment programme.

CEA-targeted nanoparticles allow specific in vivo fluorescent imaging of colorectal cancer models.

Fluorescent imaging of colorectal tumor cells would improve tumor localization and allow intra-operative staging, facilitating stratification of surgical resections thereby improving patient outcomes. We aimed to develop and test fluorescent nanoparticles capable of allowing this in vivo. Dye-doped silica nanoparticles were synthesized. Anti-CEA (carcinoembryonic antigen) or control IgGs were conjugated to nanoparticles using various chemical strategies. Binding of CEA-targeted or control nanoparticles to colorectal cancer cells was quantified in vitro, and in vivo after systemic-delivery to murine xenografts. CEA-targeted, polyamidoamine dendrimer-conjugated, nanoparticles, but not control nanoparticles, allowed strong tumor-specific imaging. We are the first to demonstrate live, specific, in vivo imaging of colorectal cancer cells using antibody-targeted fluorescent nanoparticles. These nanoparticles have potential to allow intra-operative fluorescent visualization of tumor cells.

Keratins in colorectal epithelial function and disease.

Keratins are the largest subgroup of intermediate filament proteins, which are an important constituent of the cellular cytoskeleton. The principally expressed keratins (K) of the intestinal epithelium are K8, K18 and K19. The specific keratin profile of a particular epithelium provides it with strength and integrity. In the colon, keratins have been shown to regulate electrolyte transport, likely by targeting ion transporters to their correct location in the colonocytes. Keratins are highly dynamic and are subject to post-translational modifications including phosphorylation, acetylation and glycosylation. These affect the filament dynamics and hence solubility of keratins and may contribute to protection against degradation. Keratin null mice (K8(-/-) ) develop colitis, and abnormal keratin mutations have been shown to be associated with inflammatory bowel disease (IBD). Abnormal expression of K7 and K20 has been noted in colitis-associated dysplasia and cancers. In sporadic colorectal cancers (CRCs) may be useful in predicting tumour prognosis; a low K20 expression is noted in CRCs with high microsatellite instability; and keratins have been noted as dysregulated in peri-adenomatous fields. Caspase-cleaved fragment of K18 (M30) in the serum of patients with CRC has been used as a marker of cancer load and to assess response to therapy. These data suggest an emerging importance of keratins in maintaining normal function of the gastrointestinal epithelium as well as being a marker of various colorectal diseases. This review will primarily focus on the biology of these proteins, physiological functions and alterations in IBD and CRCs.

Short-chain fatty acid level and field cancerization show opposing associations with enteroendocrine cell number and neuropilin expression in patients with colorectal adenoma.

BACKGROUND: Previous reports have suggested that the VEGF receptor neuropilin-1 (NRP-1) is expressed in a singly dispersed subpopulation of cells in the normal colonic epithelium, but that expression becomes dysregulated during colorectal carcinogenesis, with higher levels in tumour suggestive of a poor prognosis. We noted that the spatial distribution and morphology if NRP-1 expressing cells resembles that of enteroendocrine cells (EEC) which are altered in response to disease state including cancer and irritable bowel syndrome (IBS). We have shown that NRP-1 is down-regulated by butyrate in colon cancer cell lines in vitro and we hypothesized that butyrate produced in the lumen would have an analogous effect on the colon mucosa in vivo. Therefore we sought to investigate whether NRP-1 is expressed in EEC and how NRP-1 and EEC respond to butyrate and other short-chain fatty acids (SCFA - principally acetate and propionate). Additionally we sought to assess whether there is a field effect around adenomas. METHODOLOGY: Biopsies were collected at the mid-sigmoid, at the adenoma and at the contralateral wall (field) of 28 subjects during endoscopy. Samples were fixed for IHC and stained for either NRP-1 or for chromogranin A (CgA), a marker of EEC. Stool sampling was undertaken to assess individuals' butyrate, acetate and propionate levels. RESULT: NRP-1 expression was inversely related to SCFA concentration at the colon landmark (mid-sigmoid), but expression was lower and not related to SCFA concentration at the field. Likewise CgA+ cell number was also inversely related to SCFA at the landmark, but was lower and unresponsive at the field. Crypt cellularity was unaltered by field effect. A colocalisation analysis showed only a small subset of NRP-1 localised with CgA. Adenomas showed extensive, weaker staining for NRP-1 which contrastingly correlated positively with butyrate level. Field effects cause this relationship to be lost. Adenoma tissue shows dissociation of the co-regulation of NRP-1 and EEC. CONCLUSION: NRP-1 is inversely associated with levels of butyrate and other SCFA in vivo and is expressed in a subset of CgA expressing cells. EEC number is related to butyrate level in the same way.

Stereoselective synthesis of allyl-C-mannosyl compounds: use of a temporary silicon connection in intramolecular allylation strategies with allylsilanes.

Methyl mannoside 16 containing an allyldimethylsilyl ether at C(2) was synthesized in nine steps from D-mannose. Reaction with TMSOTf in MeCN at room-temperature effected C-glycosylation to provide the alpha-allyl-C-mannosyl product 18 with excellent stereoselectivity. Crossover experiments over a range of reaction concentrations proved that reaction was proceeding via an intermolecular pathway rather than the hoped-for intramolecular delivery route. The exceptionally high stereoselectivity of this allylation in the presence of an acid-scavenger, 2,6-DTBMP, can be attributed to the allylsilyl ether 16 behaving as the allylating agent. Geometrical constraints in the seven-membered ring transition state account for the lack of intramolecular allyl transfer. Attaching a modified allylsilane 29a-c to C(2)OH of methyl mannoside 15 improved matters. Reaction of the tethered mannosides 27a-c with TMSOTf in the presence of 2,6-DTBMP in MeCN at rt provided a range of products, which depended on the size of the alkyl substituents at the silyl ether tether. Diene products were the major compounds irrespective of the size of the alkyl substituents at the silyl ether tether. Their formation can be understood by intramolecular allylation of the allylsilane on to the activated anomeric center, followed by collapse of the intermediate carbocation by preferential attack of an external nucleophile at the silyl ether tether, rather than at the allylic silicon center. A cascade of further reactions rationalizes the formation of the 2-dienyl-substituted tetrahydrofuran 30 and dienes 39 and 40. The desired beta-allyl-C-mannosyl products 42 and 43 were obtained, albeit in low yield, when bulky ethyl and isopropyl groups were employed at the silyl ether tether. Stereospecific oxidative cleavage of the silyl tether in 42 and 43 provided the corresponding stereodefined diols 44 and 45, respectively. Attempts to improve the yield and diastereoselectivity of the desired beta-allyl-C-mannosyls by moving to a sulfoxide mannosyl donor, which could be activated at low temperature, proved unsuccessful.