An E-Learning Approach to the Prevention of Venous Thromboembolism: An Educational and Human Factors Study

The research contained within this thesis submitted for the degree of Doctor of Philosophy in Medicine investigates the role of e-learning in improving knowledge mastery around venous thromboemolism prophylaxis among medical students. Following an exhaustive literature review of venous thromboembolism epidemiology, pathology and prevention, educational theory, e-learning techniques and the delivery of education about venous thromoboembolism to medical students, the key deficiencies in our understanding of this disease were identified. We found multiple small cohort studies about the use of e-learning in medical education, but a paucity of randomised controlled trial data surrounding the use of e-learning platforms, and limited information regarding the role of instructional erongomics in e-learning delivery for medical education. Conducting a randomised controlled educational trial may determine the utility of elearning for improving student’s knowledge of venous thromboembolism prophylaxis. This investigation commenced with the development of e-learning modules in surgery, medicine, oncology, obstetrics & gynaecology and orthopaedic surgery. Two further assessment modules were also developed; one to measure baseline knowledge about venous thromboembolism prophylaxis, and one to measure postintervention effect. A randomised controlled trial was conducted to measure the effect of e-learning at improving knowledge of thromboprophyaxis guidelines. Students randomised to use the e-learning module did not demonstrate any improvement in knowledge surrounding VTE prophylaxis, either in comparison to the control group, or in comparison to their own baseline scores. Interestingly, however, students demonstrated a statistically significant improvement in knowledge when they were re-tested six months after finishing the e-learning program. This result may demonstrate that e-learning is a useful tool in a blended learning model of teaching, however, there is a possibility that confounding factors had played a role. We conducted a subgroup analysis to determine whether performance in certain cases within the e-learning module were predictive of final outcome, and whether time spent on each case was associated with final performance. We demonstrated that performance in the eMedici VTE Prophylaxis Module appeared to be associated with performance in areas of medicine in which students had prior experience, or were currently rotating. Finally, we were interested in examining ergononic factors related to the use of elearning material, particularly as one member of the group had published similar research examining the use of computer-aided learning when material was presented on CD-ROM. There is limited reporting on ergonomic data in the medical education literature, and we felt that this study may also help explore the possible causes of the results of the randomised controlled trial. This study demonstrated the importance of usability testing in designing online medical education resources, and suggests the importance of supporting online learning through the provision of physical learning spaces and infrastructure within the clinical setting.Thesis (Ph.D.) -- University of Adelaide, Adelaide Medical School, 201

Nebulized Recombinant Tissue Plasminogen Activator (rt-PA) for Acute COVID-19-Induced Respiratory Failure : An Exploratory Proof-of-Concept Trial

Acknowledgments We would like to extend our sincerest gratitude to all the colleagues and hospital staff who worked tirelessly throughout the pandemic and without whom this work would not have been possible. Firstly, we would like to thank our colleagues in the intensive care unit (ICU), in particular the matrons, Sean Carroll and Sinead Hanton, and research nurses, Filipe Helder and Amitaa Maharajh for their support, and bedside nurses who bore the responsibility of drug administration. We would also like to extend our thanks to ICU consultants who acted as professional legal consultees on behalf of critical care patients. Equally, we would like to thank colleagues within the respiratory team. Their expertise was instrumental to our role in treating patients on 8N and 8E wards. A special mention to lead Nurse Mary Emerson; we were grateful for her knowledge, support and for facilitating the training for the nebulizer and drug administration on the wards. We would like to thank Aarti Nandani and all the staff in the Royal Free clinical trials pharmacy for their immense support throughout the whole pandemic, especially considering their ever-increasing workload at the time. Thanks also to the HSL coagulation laboratory, the Trust R&D department and all the staff working to cover during a very challenging time. We are also very grateful to the Royal Free charity for funding this study. Finally, we would like to thank all the clinical nurses, physiotherapists, research data managers and healthcare professionals within the Haemophilia department (and wider hospital) for all their many efforts in supporting this study. This trial was overseen by an independent data monitoring committee, chaired by Najib Rahman, Director of the Oxford Respiratory Trials Unit, University of Oxford and comprises the following committee members: Mike Makris, Jonathan Silversides and Henry Watson. Funding Royal Free Charity Trust Fund 35 provided funding for this study. The study drug was provided by Boehringer Ingelheim (BI). BI had no role in the design, analysis, or interpretation of the results. They were given the opportunity to review the manuscript for medical and scientific accuracy since it relates to BI substances and intellectual property considerations.Peer reviewedPublisher PD

Prognostic indicators and outcomes of hospitalised COVID-19 patients with neurological disease: An individual patient data meta-analysis

BACKGROUND: Neurological COVID-19 disease has been reported widely, but published studies often lack information on neurological outcomes and prognostic risk factors. We aimed to describe the spectrum of neurological disease in hospitalised COVID-19 patients; characterise clinical outcomes; and investigate factors associated with a poor outcome. METHODS: We conducted an individual patient data (IPD) meta-analysis of hospitalised patients with neurological COVID-19 disease, using standard case definitions. We invited authors of studies from the first pandemic wave, plus clinicians in the Global COVID-Neuro Network with unpublished data, to contribute. We analysed features associated with poor outcome (moderate to severe disability or death, 3 to 6 on the modified Rankin Scale) using multivariable models. RESULTS: We included 83 studies (31 unpublished) providing IPD for 1979 patients with COVID-19 and acute new-onset neurological disease. Encephalopathy (978 [49%] patients) and cerebrovascular events (506 [26%]) were the most common diagnoses. Respiratory and systemic symptoms preceded neurological features in 93% of patients; one third developed neurological disease after hospital admission. A poor outcome was more common in patients with cerebrovascular events (76% [95% CI 67-82]), than encephalopathy (54% [42-65]). Intensive care use was high (38% [35-41]) overall, and also greater in the cerebrovascular patients. In the cerebrovascular, but not encephalopathic patients, risk factors for poor outcome included breathlessness on admission and elevated D-dimer. Overall, 30-day mortality was 30% [27-32]. The hazard of death was comparatively lower for patients in the WHO European region. INTERPRETATION: Neurological COVID-19 disease poses a considerable burden in terms of disease outcomes and use of hospital resources from prolonged intensive care and inpatient admission; preliminary data suggest these may differ according to WHO regions and country income levels. The different risk factors for encephalopathy and stroke suggest different disease mechanisms which may be amenable to intervention, especially in those who develop neurological symptoms after hospital admission

Prognostic indicators and outcomes of hospitalised COVID-19 patients with neurological disease: An individual patient data meta-analysis.

BackgroundNeurological COVID-19 disease has been reported widely, but published studies often lack information on neurological outcomes and prognostic risk factors. We aimed to describe the spectrum of neurological disease in hospitalised COVID-19 patients; characterise clinical outcomes; and investigate factors associated with a poor outcome.MethodsWe conducted an individual patient data (IPD) meta-analysis of hospitalised patients with neurological COVID-19 disease, using standard case definitions. We invited authors of studies from the first pandemic wave, plus clinicians in the Global COVID-Neuro Network with unpublished data, to contribute. We analysed features associated with poor outcome (moderate to severe disability or death, 3 to 6 on the modified Rankin Scale) using multivariable models.ResultsWe included 83 studies (31 unpublished) providing IPD for 1979 patients with COVID-19 and acute new-onset neurological disease. Encephalopathy (978 [49%] patients) and cerebrovascular events (506 [26%]) were the most common diagnoses. Respiratory and systemic symptoms preceded neurological features in 93% of patients; one third developed neurological disease after hospital admission. A poor outcome was more common in patients with cerebrovascular events (76% [95% CI 67-82]), than encephalopathy (54% [42-65]). Intensive care use was high (38% [35-41]) overall, and also greater in the cerebrovascular patients. In the cerebrovascular, but not encephalopathic patients, risk factors for poor outcome included breathlessness on admission and elevated D-dimer. Overall, 30-day mortality was 30% [27-32]. The hazard of death was comparatively lower for patients in the WHO European region.InterpretationNeurological COVID-19 disease poses a considerable burden in terms of disease outcomes and use of hospital resources from prolonged intensive care and inpatient admission; preliminary data suggest these may differ according to WHO regions and country income levels. The different risk factors for encephalopathy and stroke suggest different disease mechanisms which may be amenable to intervention, especially in those who develop neurological symptoms after hospital admission

Disseminated aspergillosis with mediastinal invasion causing fatal stroke in an immunocompetent young man

Introduction: Aspergillus flavus is a common cause of aspergillosis. Case presentation: A previously fit and well, immunocompetent 27-year old male living in Australia developed disseminated Aspergillus flavus complex infection with mediastinal and cardiac invasion, superior vena cava obstruction and stroke, with fatal haemorrhagic transformation. Conclusion: Aspergillus Flavus is a rare but important cause of serious disease in the immunocompetent

Muscle Protein Synthesis after Protein Administration in Critical Illness

Rationale Dietary protein may attenuate the muscle atrophy experienced by patients in the Intensive Care Unit (ICU), yet protein handling is poorly understood. Objective To quantify protein digestion and amino acid absorption, and fasting and postprandial myofibrillar protein synthesis during critical illness. Methods Fifteen mechanically ventilated adults (12M; age 50±17y, Body Mass Index (BMI) 27±5kg·m-2) and 10 healthy controls (6M; 54±23y, BMI 27±4kg·m-2) received a primed intravenous L-[ring-2H5]-phenylalanine, L-[3,5-2H2]-tyrosine, and L-[1-13C]-leucine infusion over 9.5h, and a duodenal bolus of intrinsically-labelled (L-[1-13C]-phenylalanine and L-[1-13C]-leucine) intact milk protein (20g protein) over 60min. Arterial blood and muscle samples were taken at baseline (fasting) and for 6h following duodenal protein administration. Data are mean±SD; analysed with 2-way repeated measures ANOVA and independent samples t-test. Measurements and main results Fasting myofibrillar protein synthesis rates did not differ between ICU patients and healthy controls (0.023±0.013 vs 0.034±0.016%/h; P=0.077). Following protein administration, plasma amino acid availability did not differ between groups (ICU patients 54.2±9.1 vs healthy controls 61.8±13.1%; P=0.12), and myofibrillar protein synthesis rates increased in both groups (0.028±0.010 vs 0.043±0.018 %/h, main time effect P=0.046, P-interaction=0.584) with lower rates in ICU patients compared to healthy controls (main group effect P=0.001). Incorporation of protein-derived phenylalanine into myofibrillar protein was ~60% lower in ICU patients (0.007±0.007 vs 0.017±0.009 mole % excess (MPE); P=0.007). Conclusion The capacity for critically ill patients to use ingested protein for muscle protein synthesis is markedly blunted despite relatively normal protein digestion and amino acid absorption

Prognostic indicators and outcomes of hospitalised COVID-19 patients with neurological disease: An individual patient data meta-analysis.

BackgroundNeurological COVID-19 disease has been reported widely, but published studies often lack information on neurological outcomes and prognostic risk factors. We aimed to describe the spectrum of neurological disease in hospitalised COVID-19 patients; characterise clinical outcomes; and investigate factors associated with a poor outcome.MethodsWe conducted an individual patient data (IPD) meta-analysis of hospitalised patients with neurological COVID-19 disease, using standard case definitions. We invited authors of studies from the first pandemic wave, plus clinicians in the Global COVID-Neuro Network with unpublished data, to contribute. We analysed features associated with poor outcome (moderate to severe disability or death, 3 to 6 on the modified Rankin Scale) using multivariable models.ResultsWe included 83 studies (31 unpublished) providing IPD for 1979 patients with COVID-19 and acute new-onset neurological disease. Encephalopathy (978 [49%] patients) and cerebrovascular events (506 [26%]) were the most common diagnoses. Respiratory and systemic symptoms preceded neurological features in 93% of patients; one third developed neurological disease after hospital admission. A poor outcome was more common in patients with cerebrovascular events (76% [95% CI 67-82]), than encephalopathy (54% [42-65]). Intensive care use was high (38% [35-41]) overall, and also greater in the cerebrovascular patients. In the cerebrovascular, but not encephalopathic patients, risk factors for poor outcome included breathlessness on admission and elevated D-dimer. Overall, 30-day mortality was 30% [27-32]. The hazard of death was comparatively lower for patients in the WHO European region.InterpretationNeurological COVID-19 disease poses a considerable burden in terms of disease outcomes and use of hospital resources from prolonged intensive care and inpatient admission; preliminary data suggest these may differ according to WHO regions and country income levels. The different risk factors for encephalopathy and stroke suggest different disease mechanisms which may be amenable to intervention, especially in those who develop neurological symptoms after hospital admission