Advances in Human Factors in Complex Trauma and Emergency Anaesthesia and their Implementation into Military and Civilian Trauma Systems

The role of human factors in healthcare was introduced into the mainstream medical literature following two important seminal reports, ‘To Err is Human’ from the United States and ‘An Organisation with A Memory’ from the United Kingdom. This subsequently led to work conducted by the University of Aberdeen into defining the role of non-technical skills in the Operating Theatre for Anaesthetists, Surgeons and Scrub Practitioners. This thesis is an overview of work that I have undertaken in both Military and Civilian settings exploring and defining the importance of human factors in the management of complex trauma and emergency anaesthesia. I have undertaken original research investigating the barriers that exist to challenging seniors and have created guidelines for the management of non-iatrogenic airway injuries. This thesis also discusses a novel project that I have been involved in, the development of the ‘Trauma WHO’, which is a simple checklist designed to improve patient safety during their pathway in complex trauma. I will describe how this was developed, tested in a field hospital in Afghanistan and is now embedded into military practice and some civilian centres. This thesis also describes further knowledge assimilation in the form of two published peer reviewed systematic reviews exploring the importance of human factors in the emergency department and operating theatre and the management of non-iatrogenic trauma to the airway. Additionally, I have selected five papers for inclusion that demonstrate a translation of knowledge into different trauma arenas where the importance of human factors is essential and now embedded. The implications of this thesis are that advances in human factors in complex trauma and emergency anaesthesia that were originally developed in the military setting have now been refined and adopted into certain areas of the NHS. The impact of these advances in guidelines for the management of penetrating airway injuries, streamlining communication and flattening hierarchies by awareness of barriers to challenge have been recently witnessed in the expert and successful management of seriously injured patients. Further work to promote these advances is still required to encourage further adoption in other major trauma centres in England

Common, low-frequency, rare, and ultra-rare coding variants contribute to COVID-19 severity

The combined impact of common and rare exonic variants in COVID-19 host genetics is currently insufficiently understood. Here, common and rare variants from whole-exome sequencing data of about 4000 SARS-CoV-2-positive individuals were used to define an interpretable machine-learning model for predicting COVID-19 severity. First, variants were converted into separate sets of Boolean features, depending on the absence or the presence of variants in each gene. An ensemble of LASSO logistic regression models was used to identify the most informative Boolean features with respect to the genetic bases of severity. The Boolean features selected by these logistic models were combined into an Integrated PolyGenic Score that offers a synthetic and interpretable index for describing the contribution of host genetics in COVID-19 severity, as demonstrated through testing in several independent cohorts. Selected features belong to ultra-rare, rare, low-frequency, and common variants, including those in linkage disequilibrium with known GWAS loci. Noteworthily, around one quarter of the selected genes are sex-specific. Pathway analysis of the selected genes associated with COVID-19 severity reflected the multi-organ nature of the disease. The proposed model might provide useful information for developing diagnostics and therapeutics, while also being able to guide bedside disease management. © 2021, The Author(s)

Adding 6 months of androgen deprivation therapy to postoperative radiotherapy for prostate cancer: a comparison of short-course versus no androgen deprivation therapy in the RADICALS-HD randomised controlled trial

Background Previous evidence indicates that adjuvant, short-course androgen deprivation therapy (ADT) improves metastasis-free survival when given with primary radiotherapy for intermediate-risk and high-risk localised prostate cancer. However, the value of ADT with postoperative radiotherapy after radical prostatectomy is unclear. Methods RADICALS-HD was an international randomised controlled trial to test the efficacy of ADT used in combination with postoperative radiotherapy for prostate cancer. Key eligibility criteria were indication for radiotherapy after radical prostatectomy for prostate cancer, prostate-specific antigen less than 5 ng/mL, absence of metastatic disease, and written consent. Participants were randomly assigned (1:1) to radiotherapy alone (no ADT) or radiotherapy with 6 months of ADT (short-course ADT), using monthly subcutaneous gonadotropin-releasing hormone analogue injections, daily oral bicalutamide monotherapy 150 mg, or monthly subcutaneous degarelix. Randomisation was done centrally through minimisation with a random element, stratified by Gleason score, positive margins, radiotherapy timing, planned radiotherapy schedule, and planned type of ADT, in a computerised system. The allocated treatment was not masked. The primary outcome measure was metastasis-free survival, defined as distant metastasis arising from prostate cancer or death from any cause. Standard survival analysis methods were used, accounting for randomisation stratification factors. The trial had 80% power with two-sided α of 5% to detect an absolute increase in 10-year metastasis-free survival from 80% to 86% (hazard ratio [HR] 0·67). Analyses followed the intention-to-treat principle. The trial is registered with the ISRCTN registry, ISRCTN40814031, and ClinicalTrials.gov, NCT00541047. Findings Between Nov 22, 2007, and June 29, 2015, 1480 patients (median age 66 years [IQR 61–69]) were randomly assigned to receive no ADT (n=737) or short-course ADT (n=743) in addition to postoperative radiotherapy at 121 centres in Canada, Denmark, Ireland, and the UK. With a median follow-up of 9·0 years (IQR 7·1–10·1), metastasis-free survival events were reported for 268 participants (142 in the no ADT group and 126 in the short-course ADT group; HR 0·886 [95% CI 0·688–1·140], p=0·35). 10-year metastasis-free survival was 79·2% (95% CI 75·4–82·5) in the no ADT group and 80·4% (76·6–83·6) in the short-course ADT group. Toxicity of grade 3 or higher was reported for 121 (17%) of 737 participants in the no ADT group and 100 (14%) of 743 in the short-course ADT group (p=0·15), with no treatment-related deaths. Interpretation Metastatic disease is uncommon following postoperative bed radiotherapy after radical prostatectomy. Adding 6 months of ADT to this radiotherapy did not improve metastasis-free survival compared with no ADT. These findings do not support the use of short-course ADT with postoperative radiotherapy in this patient population

Duration of androgen deprivation therapy with postoperative radiotherapy for prostate cancer: a comparison of long-course versus short-course androgen deprivation therapy in the RADICALS-HD randomised trial

Background Previous evidence supports androgen deprivation therapy (ADT) with primary radiotherapy as initial treatment for intermediate-risk and high-risk localised prostate cancer. However, the use and optimal duration of ADT with postoperative radiotherapy after radical prostatectomy remains uncertain. Methods RADICALS-HD was a randomised controlled trial of ADT duration within the RADICALS protocol. Here, we report on the comparison of short-course versus long-course ADT. Key eligibility criteria were indication for radiotherapy after previous radical prostatectomy for prostate cancer, prostate-specific antigen less than 5 ng/mL, absence of metastatic disease, and written consent. Participants were randomly assigned (1:1) to add 6 months of ADT (short-course ADT) or 24 months of ADT (long-course ADT) to radiotherapy, using subcutaneous gonadotrophin-releasing hormone analogue (monthly in the short-course ADT group and 3-monthly in the long-course ADT group), daily oral bicalutamide monotherapy 150 mg, or monthly subcutaneous degarelix. Randomisation was done centrally through minimisation with a random element, stratified by Gleason score, positive margins, radiotherapy timing, planned radiotherapy schedule, and planned type of ADT, in a computerised system. The allocated treatment was not masked. The primary outcome measure was metastasis-free survival, defined as metastasis arising from prostate cancer or death from any cause. The comparison had more than 80% power with two-sided α of 5% to detect an absolute increase in 10-year metastasis-free survival from 75% to 81% (hazard ratio [HR] 0·72). Standard time-to-event analyses were used. Analyses followed intention-to-treat principle. The trial is registered with the ISRCTN registry, ISRCTN40814031, and ClinicalTrials.gov , NCT00541047 . Findings Between Jan 30, 2008, and July 7, 2015, 1523 patients (median age 65 years, IQR 60–69) were randomly assigned to receive short-course ADT (n=761) or long-course ADT (n=762) in addition to postoperative radiotherapy at 138 centres in Canada, Denmark, Ireland, and the UK. With a median follow-up of 8·9 years (7·0–10·0), 313 metastasis-free survival events were reported overall (174 in the short-course ADT group and 139 in the long-course ADT group; HR 0·773 [95% CI 0·612–0·975]; p=0·029). 10-year metastasis-free survival was 71·9% (95% CI 67·6–75·7) in the short-course ADT group and 78·1% (74·2–81·5) in the long-course ADT group. Toxicity of grade 3 or higher was reported for 105 (14%) of 753 participants in the short-course ADT group and 142 (19%) of 757 participants in the long-course ADT group (p=0·025), with no treatment-related deaths. Interpretation Compared with adding 6 months of ADT, adding 24 months of ADT improved metastasis-free survival in people receiving postoperative radiotherapy. For individuals who can accept the additional duration of adverse effects, long-course ADT should be offered with postoperative radiotherapy. Funding Cancer Research UK, UK Research and Innovation (formerly Medical Research Council), and Canadian Cancer Society

Evaluating the fidelity of a novel part-task trainer for emergency front of neck access training

In 2015, the British Difficult Airway Society (DAS) revised its guidelines for managing an unanticipated difficult airway, recommending surgical cricothyroidotomy as the new standard emergency front of neck access (FONA).1 In the UK, the 4th National Audit Project of the Royal College of Anaesthetists recommended anaesthetists to undergo frequent FONA training using simulation.2 Fidelity in simulation has physical, functional and psychological components,3 and we feel that the Crico-Trainer (Frova; VMB Medical, Newcastle, UK), currently used in our department, could be improved. A prestudy survey (n=15) of attending (consultant) anaesthetists identified ‘ideal manikin qualities’. This confirmed that important features were high-fidelity feel of: tissue (80.0%), scalpel incision (86.7%) and surface (80.0%). The ability to intubate (60.0%), haemorrhage (46.7%) and mimic an impalpable cricothyroid membrane (46.7%) were also considered important. The Frova was deemed to lack realistic tissue planes (80.0%), component feel (66.7%) and haemorrhage (46.7%). The aim of this study was to develop and evaluate our own trainer, focusing on improved fidelity. We designed and constructed our part-task trainer (figure 1) using a wooden base, proprietary reusable plastic ‘larynx/trachea’ and a novel disposable ‘neck tissue’ prosthesis, which feels realistic and bleeds when cut. The neck was fabricated from a viscoelastic polymer (Akton; Action Products, Leek, UK) coated in acrylic paint (Daler-Rowney, Bracknell, UK) and

A systematic review of 3251 emergency department thoracotomies: is it time for a national database?

Purpose: Emergency department thoracotomy (EDT) is a potentially life-saving procedure, performed on patients suffering traumatic cardiac arrest. Multiple indications have been reported, but overall survival remains unclear for each indication. The objective of this systematic review is to determine overall survival, survival stratified by indication, and survival stratified by geographical location for patients undergoing EDT across the world. Methods: Articles published between 2000 and 2016 were identified which detailed outcomes from EDT. All articles referring to pre-hospital, delayed, or operating room thoracotomy were excluded. Pooled odds ratios (OR) were calculated comparing differing indications. Results: Thirty-seven articles, containing 3251 patients who underwent EDT, were identified. There were 277 (8.5%) survivors. OR demonstrate improved survival for; penetrating vs blunt trauma (OR 2.10; p 0.0028); stab vs gun-shot (OR 5.45; p &lt; 0.0001); signs of life (SOL) on admission vs no SOL (OR 5.36; p &lt; 0.0001); and SOL in the field vs no SOL (OR 19.39; p &lt; 0.0001). Equivalence of survival was demonstrated between cardiothoracic vs non-cardiothoracic injury (OR 1.038; p 1.000). Survival was worse for USA vs non-USA cohorts (OR 1.59; p 0.0012). Conclusions: Penetrating injury remains a robust indication for EDT. Non-cardiothoracic cause of cardiac arrest should not preclude EDT. In the absence of on scene SOL, survival following EDT is extremely unlikely. Survival is significantly higher in the non-USA publications; reasons for this are highly complex. A UK multicentre prospective study which collects standardised data on all EDTs could provide robust evidence for better patient stratification.</p

Measuring routine childhood vaccination coverage in 204 countries and territories, 1980–2019: a systematic analysis for the Global Burden of Disease Study 2020, Release 1

10.1016/s0140-6736(21)00984-3The Lancet39810299503-52

Common, low-frequency, rare, and ultra-rare coding variants contribute to COVID-19 severity

The combined impact of common and rare exonic variants in COVID-19 host genetics is currently insufficiently understood. Here, common and rare variants from whole-exome sequencing data of about 4000 SARS-CoV-2-positive individuals were used to define an interpretable machine-learning model for predicting COVID-19 severity. First, variants were converted into separate sets of Boolean features, depending on the absence or the presence of variants in each gene. An ensemble of LASSO logistic regression models was used to identify the most informative Boolean features with respect to the genetic bases of severity. The Boolean features selected by these logistic models were combined into an Integrated PolyGenic Score that offers a synthetic and interpretable index for describing the contribution of host genetics in COVID-19 severity, as demonstrated through testing in several independent cohorts. Selected features belong to ultra-rare, rare, low-frequency, and common variants, including those in linkage disequilibrium with known GWAS loci. Noteworthily, around one quarter of the selected genes are sex-specific. Pathway analysis of the selected genes associated with COVID-19 severity reflected the multi-organ nature of the disease. The proposed model might provide useful information for developing diagnostics and therapeutics, while also being able to guide bedside disease management