RHAMNETIN IS A BETTER INHIBITOR OF SARS-COV-2 2’-O-METHYLTRANSFERASE THAN DOLUTEGRAVIR: A COMPUTATIONAL PREDICTION

Background: The 2’-O-methyltransferase is responsible for the capping of SARS-CoV-2 mRNA and consequently the evasion of the host’s immune system. This study aims at identifying prospective natural inhibitors of the active site of SARS-CoV-2 2’O-methyltransferase (2’-OMT) through an in silico approach. Materials and Method: The target was docked against a library of natural compounds obtained from edible African plants using PyRx - virtual screening software. The antiviral agent, Dolutegravir which has a binding affinity score of -8.5 kcal mol−1 with the SARS-CoV-2 2’-OMT was used as a standard. Compounds were screened for bioavailability through the SWISSADME web server using their molecular descriptors. Screenings for pharmacokinetic properties and bioactivity were performed with PKCSM and Molinspiration web servers respectively. The PLIP and Fpocket webservers were used for the binding site analyses. The Galaxy webserver was used for simulating the time-resolved motions of the apo and holo forms of the target while the MDWeb web server was used for the analyses of the trajectory data. Results: The Root-Mean-Square-Deviation (RMSD) induced by Rhamnetin is 1.656A0 as compared to Dolutegravir (1.579A0). The average B-factor induced by Rhamnetin is 113.75 while for Dolutegravir is 78.87; the Root-Mean-Square-Fluctuation (RMSF) for Rhamnetin is 0.75 and for Dolutegravir is 0.67. Also at the active site, Rhamnetin also has a binding affinity score of -9.5 kcal mol−1 and forms 7 hydrogen bonds as compared to Dolutegravir which has -8.5 kcal mol−1 and forms 4 hydrogen bonds respectively. Conclusion: Rhamnetin showed better inhibitory activity at the target’s active site than Dolutegravir

Improving care at scale: process evaluation of a multi-component quality improvement intervention to reduce mortality after emergency abdominal surgery (EPOCH trial)

Abstract Background Improving the quality and safety of perioperative care is a global priority. The Enhanced Peri-Operative Care for High-risk patients (EPOCH) trial was a stepped-wedge cluster randomised trial of a quality improvement (QI) programme to improve 90-day survival for patients undergoing emergency abdominal surgery in 93 hospitals in the UK National Health Service. Methods The aim of this process evaluation is to describe how the EPOCH intervention was planned, delivered and received, at both cluster and local hospital levels. The QI programme comprised of two interventions: a care pathway and a QI intervention to aid pathway implementation, focussed on stakeholder engagement, QI teamwork, data analysis and feedback and applying the model for improvement. Face-to-face training and online resources were provided to support senior clinicians in each hospital (QI leads) to lead improvement. For this evaluation, we collated programme activity data, administered an exit questionnaire to QI leads and collected ethnographic data in six hospitals. Qualitative data were analysed with thematic or comparative analysis; quantitative data were analysed using descriptive statistics. Results The EPOCH trial did not demonstrate any improvement in survival or length of hospital stay. Whilst the QI programme was delivered as planned at the cluster level, self-assessed intervention fidelity at the hospital level was variable. Seventy-seven of 93 hospitals responded to the exit questionnaire (60 from a single QI lead response on behalf of the team); 33 respondents described following the QI intervention closely (35%) and there were only 11 of 37 care pathway processes that > 50% of respondents reported attempting to improve. Analysis of qualitative data suggests QI leads were often attempting to deliver the intervention in challenging contexts: the social aspects of change such as engaging colleagues were identified as important but often difficult and clinicians frequently attempted to lead change with limited time or organisational resources. Conclusions Significant organisational challenges faced by QI leads shaped their choice of pathway components to focus on and implementation approaches taken. Adaptation causing loss of intervention fidelity was therefore due to rational choices made by those implementing change within constrained contexts. Future large-scale QI programmes will need to focus on dedicating local time and resources to improvement as well as on training to develop QI capabilities. EPOCH trial registration ISRCTN80682973 https://doi.org/10.1186/ISRCTN80682973 Registered 27 February 2014 and Lancet protocol 13PRT/7655

Can emergency nurses safely and effectively insert fascia iliaca blocks in patients with a fractured neck of femur? A prospective cohort study in an Australian emergency department

Aims and objectives To compare the effectiveness and safety of ultrasound-guided fascia iliaca block (FIB) insertion in patients with fractured neck of femur by trained emergency nurses with insertion by doctors. Background The FIB is an effective and safe form of analgesia for patients with hip fracture presenting to the emergency department (ED). While it has traditionally been inserted by medical doctors, no evidence exists comparing the effectiveness and safety of FIB insertion by nurses compared with doctors. Design A prospective cohort study. Methods The study was conducted in an Australian metropolitan ED. Patients admitted to the ED with suspected or confirmed fractured neck of femur had a FIB inserted under ultrasound guidance by either a trained emergency nurse or doctor. A retrospective medical record audit was undertaken of consecutive ED patients presenting between January 2013–December 2017. Reporting of this study followed the Strengthening the Reporting of Observational Studies in Epidemiology guidelines for cohort studies. Results Of the 472 patients eligible for a FIB, 322 (68%) had one inserted. A majority were inserted by doctors (n = 207, 64.3%) with 22.4% (n = 72) by nurses and in 13.3% (n = 43) of patients the clinician was not documented. There were no differences between the nurse-inserted and doctor-inserted groups for mean pain scores 1 hr post-FIB insertion; clinically significant reduction (≥30%) in pain score 1 hr post-FIB insertion; pain score 4 hr post-FIB insertion; delirium incidence; opioid use post-FIB insertion; or time to FIB insertion. No adverse events were identified in either group. Conclusion Insertion of FIBs by trained emergency nurses is as effective and safe as insertion by doctors in patients with fractured neck of femur in the ED. Senior emergency nurses should routinely be inserting FIB as a form of analgesia for patients with hip fracture. Relevance to clinical practice Our study showed trained emergency nurses can safely and effectively insert fascia iliaca blocks in patients with hip fractures. Pain was significantly reduced in a majority of patients with no reported complications. Emergency nurses should be trained to insert fascia iliaca blocks in patients with hip fractures