Dexmedetomidine Opioid Sparing Effect in Mechanically Ventilated Children (DOSE): Trial of Fentanyl versus Fentanyl

Objectives This article observes the mean daily dose of fentanyl required for adequate sedation in critically ill, mechanically ventilated children randomized to receive dexmedetomidine or placebo.Methods We conducted Dexmedetomidine Opioid Sparing Effect in Mechanically Ventilated Children (DOSE), a multicenter, double-blind, randomized, placebo-controlled, dose-escalating trial. We enrolled children aged 35 weeks postmenstrual to 17 years (inclusive) admitted across 13 pediatric multidisciplinary and cardiac intensive care units. Adequate sedation was based on a State Behavioral Score and Richmond Agitation-Sedation Scale of -1 or lower. Only the first two dexmedetomidine dosing cohorts opened for enrollment, due to early trial closure during the coronavirus 2019 pandemic. Thirty children were randomized over 13 months and included in the analyses.Results Demographic and baseline characteristics were not different between dexmedetomidine and placebo cohorts. Similarly, mean daily fentanyl use was not different, using an unadjusted mixed regression model that considered treatment, time, and a treatment-by-time interaction. Adverse events and safety events of special interest were not different between cohorts.Conclusion The DOSE trial revealed that dexmedetomidine added to fentanyl does not impact safety and may not spare fentanyl use in critically ill children, although the trial did not meet its recruitment goals, due to early closure during the coronavirus 2019 pandemic. More rigorous inpatient pediatric trials like DOSE that study critically ill, mechanically ventilated children are needed. Despite the many obstacles faced, the DOSE trial presents challenges from which the greater research community can learn and use to optimize future therapeutic trials in children.

Longitudinal lung function assessment of patients hospitalised with COVID-19 using 1H and 129Xe lung MRI

Introduction: The progression of pathophysiological pulmonary changes in patients following acute COVID-19 is not well established. Method(s): Patients hospitalised with COVID-19 pneumonia without signs of ILD, had MRI exams at a median of 6 (n=9), 12 (n=9), 25 (n=7), and 52 (n=3) weeks. MRI sequences included: dynamic contrast enhanced (DCE) lung perfusion,129 Xe diffusion weighted (DW-MRI), 129Xe ventilation and 129Xe 3D dissolved phase imaging. Result(s): 9 patients (age 56+/-9 years;7 male;1 required treatment in an ICU) were recruited. Median RBC:TP was abnormally low at all visits compared to reference age and sex matched data. An individual's RBC:TP was significantly and positively associated with an increase in their pulmonary blood volume (p=0.026). For patients with 52 week data available, one showed a continued increase in RBC:TP, 2 patients maintained a low RBC:TP (Figure 1). Ventilation defect percentage, and ventilation heterogeneity significantly decreased at 25 weeks compared to 6 129 129 129 weeks (p=0.010 and p=0.048). DW-MRI was normal at all visits. Dissolved phase xenon imaging showed RBC:TP significantly increased at 12 and 25 weeks compared to 6 weeks (p=0.048). Conclusion(s): In patients recovering after COVID-19, poor gas transfer is reflected by impaired xenon transfer, which improves alongside pulmonary blood volume.

A practical guide to mathematical methods for estimating infectious disease outbreak risks.

Mathematical models are increasingly used throughout infectious disease outbreaks to guide control measures. In this review article, we focus on the initial stages of an outbreak, when a pathogen has just been observed in a new location (e.g., a town, region or country). We provide a beginner's guide to two methods for estimating the risk that introduced cases lead to sustained local transmission (i.e., the probability of a major outbreak), as opposed to the outbreak fading out with only a small number of cases. We discuss how these simple methods can be extended for epidemiological models with any level of complexity, facilitating their wider use, and describe how estimates of the probability of a major outbreak can be used to guide pathogen surveillance and control strategies. We also give an overview of previous applications of these approaches. This guide is intended to help quantitative researchers develop their own epidemiological models and use them to estimate the risks associated with pathogens arriving in new host populations. The development of these models is crucial for future outbreak preparedness. This manuscript was submitted as part of a theme issue on "Modelling COVID-19 and Preparedness for Future Pandemics".

Characterization of Heart Failure Patients in an Academic Home Hospital Program and Identification of Patient Factors Requiring Escalation of Care

Background: Hospital capacity concerns exacerbated by the COVID-19 pandemic have accelerated growth of hospital at home (HaH) programs. However, for HaH admissions related to heart failure, information on patient characteristics and clinical outcomes remain sparse. We aimed to better characterize heart failure admissions in a HaH model and assess characteristics of patients who later needed escalation of care to a traditional hospitalization. Method(s): This retrospective, descriptive study examined HaH admissions for heart failure at an academic medical center between 2017 and 2022. We compared baseline characteristics and outcomes using the Chi-squared test for categorical variables and t-test for continuous variables for patients who required escalation of care to those who did not. Using the same methods, we also compared patients based on their location prior to admission (e.g. emergency department (ED), home). Result(s): Heart failure was the primary diagnosis for 32% of HaH admissions. The majority of the heart failure cohort (N=199, average age 80.6 years), 73.9%, had heart failure with preserved ejection fraction (HFpEF). Escalation of care to traditional hospitalization was required for 22.6% of patients. 9.0% of patients died within 90 days, and 20.1% and 36.2% of patients were readmitted for any reason within 30 and 90 days respectively. Patients whose care was escalated were more likely to have a history of chronic kidney disease (84.1% vs 66.9%, p=0.043), higher admission BUN (41.5 vs 31.1, p=0.004) and creatinine (1.74 vs 1.41, p=0.011), and a history of PCI (20.5% vs 5.3%, p=0.005). Patients referred directly from home compared to the ED had similar baseline characteristics and rates of 90 day inpatient readmission and mortality. Conclusion(s): Patients admitted to HaH for heart failure represent a high risk cohort who are commonly older with multiple comorbidities and more likely to have HFpEF. Among this cohort, patients with kidney dysfunction and/or history of percutaneous coronary intervention are more likely to require escalation of care. These results suggest that heart failure patients admitted to HaH who will later need traditional hospitalization could be identified prospectively using these characteristics.

Neoadjuvant Chemotherapy for Muscle-invasive Bladder Cancer - the Northern Irish Experience

Purpose: An analysis of neoadjuvant chemotherapy delivery and outcomes for patients with muscle-invasive bladder cancer prior to radical cystectomy. Neoadjuvant chemotherapy is associated with a 5 year 5% overall survival benefit in selected patients [1]. Method(s): Using a central histopathology database, all patients in Northern Ireland with newly diagnosed muscle-invasive bladder cancer between January 2017 and December 2018 were identified. This time period was selected to reflect practice prior to the COVID-19 pandemic. Investigation included MDM discussion rates, number of patients proceeding to neoadjuvant chemotherapy and survival outcomes for all patients. Result(s): 66 patients underwent a radical cystectomy during this time period. 65/66 were discussed at MDM. 39/66 (59%) were reviewed at an oncology clinic and 22/66 (33%) proceeded to neoadjuvant chemotherapy. Reasons for patients not proceeding with neoadjuvant chemotherapy included patient preference (76%), poor renal function (18%) and cardiac history (6%). 10/22 (45%) patients who received neoadjuvant chemotherapy were down-staged at the time of cystectomy showing a complete pathological response. Being reviewed at an oncology clinic for discussion regarding neoadjuvant chemotherapy did not significantly delay time to proceed to surgery if patients opted not to receive chemotherapy. 16/22 (73%) patients who received NAC are alive at the end of follow-up, compared with 25/44 (57%) who did not. There were no SACT-related deaths. Conclusion(s): Our local data show impressive outcomes for patients receiving neoadjuvant chemotherapy. In line with NICE guidelines and published data, we propose that all eligible patients should meet with an oncologist to consider the role of neoadjuvant chemotherapy before proceeding to radical cystectomy. Reference [1] Vale C. Neoadjuvant chemotherapy in invasive bladder cancer: a systematic review and meta-analysis. Lancet 2003;361(9373):1927-34. Copyright © 2022 The Royal College of Radiologists

AGEING COLLABORATIONS: CO-DESIGNING FUTURE TECHNOLOGY OPPORTUNITIES

The Ageing experience and increased longevity presents innovation opportunity for emergent technology, e.g., mobile and wearable. In turn, these technologies can enhance quality of life and independence as we age;however, they can also increase social inequalities and exclusion. The Covid-19 pandemic affected how we interact, communicate engage and interact with people and also technologies. People - across the generations were impacted and disrupted, motivating new behaviours in how they conducted everyday tasks and activities. Co-Design approaches have previously revealed successful collaborations between older adults, students, researchers, designers and other disciplines as a means to define unmet needs. Edinburgh Napier University provided funding to the PI (Principal Investigator) as a means to mobilise a 'Creative Cross-Education Team' (CCET) consisting of undergraduate students, research assistants (post-graduate researchers) and other staff colleagues of the University. The CCET worked with members from 'Tap into IT' (a local charity based in Edinburgh with a remit and focus on enhancing and enabling digital technology access for older adults). Two CoDesign workshops were conducted online titled 'Express' & 'Create.' The aim of these workshops was to explore, identify and define unmet needs/gaps expressed by older adult participants as a catalyst to create and generate future conceptual technology opportunities. The workshops were framed around Instrumental Activities of Daily Living (IADLs). The team were broken into groups whereby they were encouraged to collectively collaborate, Express and Create with the participants. This multi-generational and transdisciplinary approach created a democratized outlook where each contributor added value through expression, commentary and creativity. The findings have generated themes which are the basis for new opportunity through education and research with a focus on future technology opportunities. © Proceedings of the 24th International Conference on Engineering and Product Design Education: Disrupt, Innovate, Regenerate and Transform, E and PDE 2022. All rights reserved.

Non-generalisability of biomarkers for mortality in SARS-CoV-2

P169 Figure 1ConclusionsBiomarker effectiveness varies significantly by geographical location. To track these changes we have mapped the root studies on the following website (https://covid19.cimr.cam.ac.uk/) This has significant implications for prognosticating SARS-CoV-2 and also for future pandemics.

Effect of COVID-19 infection and preventive public health measures on haemodynamics, activity and quality of life in patients with pulmonary arterial hypertension

Introduction & ObjectivesIn patients with pulmonary arterial hypertension (PAH), cardiopulmonary haemodynamics and exercise capacity relates to clinical outcomes, and exercise training improves cardiopulmonary function. Public health measures that limit physical activity have been widely enforced to reduce COVID-19 transmission. COVID-19 infection causes endothelial dysfunction, which is central to the pathophysiology of PAH. Here, we describe the temporal effects of UK government restriction measures on daily activity and quality of life (QoL) in patients with PAH and the effect of COVID-19 infection on cardiopulmonary haemodynamics and physical activity.MethodsPatients were enrolled in FIT-PH (NCT04078243) and implanted with remote monitoring devices that provided mean pulmonary artery pressure (mPAP), cardiac output (CO;CardioMEMS, Abbott), day/night heart rate (DHR/NHR), heart rate variability (HRV), and physical activity (PA;Medtronic LinQ). Data were transmitted and reviewed in accordance with established clinical protocols. Standard questionnaires were administered remotely to assess QoL (EmPHasis-10), anxiety (GAD-7), depression (PHQ-9) and collect dates of COVID-19 infection.ResultsFollowing a lockdown, mean activity was reduced compared to pre-lockdown levels (p<0.0001, n=26). QoL was reduced (p<0.01), whereas anxiety (p<0.001) and depression scores increased (p<0.001) compared to pre-lockdown levels. During lockdown measures, there was no change in mPAP, CO, DHR, NHR, or HRV. Of the cohort, 7 patients contracted COVID-19, leading to an decreased CO, increased mPAP and total pulmonary resistance. Consistent with observed changes in haemodynamics PA, HRV, DHR were reduced and NHR increased.ConclusionsIn this cohort of patients with PAH, protective health measures resulted in reduced daily activity and QoL and were associated with increased anxiety and depression indicators. COVID-19 infection resulted in acute changes to haemodynamics and physical activity.

T and B Cell Response to 3 Dose Covid Vaccine Series for Kidney Transplant Patients on Belatacept

Purpose: Data shows COVID vaccine response after 2 doses in patients on Belatacept immunosuppression (IS) is low, with reported rates of seroconversion (as measured by COVID spike IgG antibody (IgG Ab) detection) of <10%. It is suggested that T cell immunity provides more nuanced marker of immunity. We seek to describe immune response with third dose of vaccine using T cell immunity and spike Ab as surrogate markers. Method(s): 12 kidney transplant patients on long term belatacept maintenance therapy were included. All patients received induction rabbit anti thymocyte globulin at transplant and were maintained on triple IS with mycophenolate and steroids. All patients received 3 doses of the Pfizer BioNTech SARS CoV2 mRNA vaccine. IgG Ab and T cell immunity response were monitored after 2 doses of vaccine, on the date of 3rd dose with repeat testing done about 4 weeks after 3rd dose. Due to small sample size, T cell response detection was treated qualitatively as "detected" and "negative" results based upon manufacturer instructions (Eurofins Viracor). IgG Ab response was treated qualitatively as "detected" and "negative", as many responses were too low to be reliably quantifiable. Result(s): Of the 12 included patients, 58% were female, 50% were African American, at mean of 77 months post transplant. After 2 vaccine doses, immunity was detected using the T cell based assay in 6/12 [50.0%, 95% CI: (21.1%-78.9%)];after 3 doses, T cell immunity detection remained the same (6/12). After 2 doses, IgG was detected in 2/12 patients [16.7%, 95% CI: (2.1%-48.4%)]. After 3 doses, this rate doubled to 4/12 [33.3%, 95% CI: (9.9%-65.1%)]. All IgG Ab detected patients were within the T Cell detected patients. There were statistically significant differences between patients that showed a response vs those that did not although patients with no response had been on a numerically higher duration of belatacept (mean=56 months) vs those with any response (mean=34 months;p=0.23). No patients developed a COVID 19 infection during the study period. Conclusion(s): In this cohort, T cell response identified a bigger subset of patients with vaccine response with 2 mRNA vaccine doses compared with those identified with an IgG response only. However, both T cell immunity and IgG Ab response remained low after 2 or 3 doses, and no patient in in the 2 dose group developed new T cell immunity response after third vaccination. IgG Ab response increased in half of the patients, but these were patients who already had developed a T cell immune response after second dose of vaccine. Total change in COVID spike IgG response after the third dose was up to 33% from an initial 16%, which may demonstrate improved total response to 3 doses. Further research is needed to assess if response rates improve with additional (fourth) doses of COVID vaccine or 'mix and match' strategies.

USING OBJECTIVE ELECTROCARDIOGRAPHIC DATA TO BETTER PREDICT MORTALITY IN PATIENTS HOSPITALIZED WITH COVID 19

BACKGROUND: The impact of SARS-CoV-2 infection on intrinsic myocardial conduction continues to be an area of focus amongst the medical community. Our objective was to investigate if specific myocardial conduction abnormalities were independently associated with mortality in patients hospitalized with COVID 19. METHODS: Under IRB exemption, the electronic medical records of COVID-19 patients (N=3840) undergoing index hospitalization were reviewed to extract presentation ECG conduction data, demographics, and laboratory results (within 8h). This patient cohort was then separated into two groups based on mortality vs. not (N=520). Logistical regression was used to test association of ECG conduction intervals with mortality. RESULTS: According to our nominal logistic fit for hospital mortality, Heart Rate (HR) >100 (p=0.0007;LW 4.14), QRS duration > 120 ms (p=0.0053;LW 2.27), and QTc prolongation (defined as QTc > 450ms in males;QTc > 460ms in females) (p=0.0089;LW 2.04) were independently associated with higher risk of mortality. LogWorth (LW) calculations were included in an effort to estimate the proportional effect each variable has on overall mortality. LW > 2 were shown to be statistically significant with p< 0.05 with HR > 100 (LW 4.14) having the highest proportional effect on mortality followed by QRSd (LW 2.27) then QTc prolongation (LW 2.04). PR interval> 200ms (p=0.30) and QRS axis (p=0.15) were not associated with higher risk of mortality. CONCLUSIONS: Amongst our patient cohort, HR > 100, QRSd > 120ms, and QTc prolongation (QTc > 450 in males;QTc > 460 in females) were each independently associated with higher risk of mortality in patients hospitalized with COVID 19. These findings support the use of objective ECG data in risk stratifying patients hospitalized with COVID 19.

Heterogeneity in the onwards transmission risk between local and imported cases affects practical estimates of the time-dependent reproduction number.

During infectious disease outbreaks, inference of summary statistics characterizing transmission is essential for planning interventions. An important metric is the time-dependent reproduction number (Rt), which represents the expected number of secondary cases generated by each infected individual over the course of their infectious period. The value of Rt varies during an outbreak due to factors such as varying population immunity and changes to interventions, including those that affect individuals' contact networks. While it is possible to estimate a single population-wide Rt, this may belie differences in transmission between subgroups within the population. Here, we explore the effects of this heterogeneity on Rt estimates. Specifically, we consider two groups of infected hosts: those infected outside the local population (imported cases), and those infected locally (local cases). We use a Bayesian approach to estimate Rt, made available for others to use via an online tool, that accounts for differences in the onwards transmission risk from individuals in these groups. Using COVID-19 data from different regions worldwide, we show that different assumptions about the relative transmission risk between imported and local cases affect Rt estimates significantly, with implications for interventions. This highlights the need to collect data during outbreaks describing heterogeneities in transmission between different infected hosts, and to account for these heterogeneities in methods used to estimate Rt. This article is part of the theme issue 'Technical challenges of modelling real-life epidemics and examples of overcoming these'.

SHARED DECISION-MAKING TRAINING WORKSHOPS FOR CLINICIANS WORKING IN MATERNITY CARE

Background: Shared decision-making (SDM) involves patients in making decisions about their care, informed by clinical evidence and patient values and preferences. Despite its importance to woman-centred care, effectively implemented SDM remains uncommon in maternity care. This project developed clinician SDM training to help reduce variation in planned birth (labour induction/elective Caesarean), and pilottested acceptability and feasibility. Methods: An online SDM clinician training intervention package was developed in 2020-2021 by a Sydney-based team including midwifery and medical maternity clinicians, consumers, and social scientists. The package included a preparatory online video and a two-hour practical workshop (converted to online due to COVID-19) where participants rotate roles (woman, clinician, observer/rater) in clinical scenarios devised to test SDM in planned birth. Participants completed online pre- and posttraining surveys. Results: Preliminary results (first workshop Oct 2021;second scheduled March 2022) suggest clinicians agree that SDM is easy to understand, facilitate and experiment with, compatible with current practices, enable women to make more informed decisions compared with the usual approach and produce more benefit than harm. There were mixed responses about whether SDM is better than or involves major changes to current practice, will help women make choices that align with their values, or enable partnership between women and clinicians. Conclusions: The SDM training program has potential to improve clinicians' capacity for engaging woman in decisions about their care around planned birth and its timing. Further workshops, qualitative interviews with participants and a posttraining consumer survey at each site is planned for 2022.

Emergency remote teaching and learning during COVID-19 pandemic: Efficacy of a four-stage model

The COVID-19 pandemic created the need for a global change in tertiary education. Universities that traditionally relied on contact with students in physical classrooms were forced to consider modes of remote teaching to mitigate the risks of infection due to physical proximity. This study evaluates the emergency remote teaching implemented within the Department of Information Technology at the Durban University of Technology, South Africa. An emergency remote teaching model with four stages consisting of: preparation, synchronous and asynchronous teaching and learning, e-assessments and reflections are described, analysed and evaluated with reference to both lecturers and students. The evaluation is performed using both qualitative and quantitative research methods. Qualitative analysis was performed on 29 sources using content analysis. 229 initial codes were identified and first categorized into 13 subcategories and finally to the four categories synonymous with the adopted four-stage emergency remote teaching model: preparation (135 references), asynchronous and synchronous teaching and learning (67 references), e-assessments (25 references) and reflections (8 references). Quantitative data on the use of the learning management system from 2019 to 2020 evaluated the results of the applied changes in practice. From the results, it was evident that students and lecturers invested much time in the learning management system with 13 tools being adopted by the 49 analysed subjects. The learning management system was used extensively for communication, assessment and dissemination of subject content. The comparative results of the data from the 2019 and 2020 academic years showed that the majority of the 2020 subjects' final results were statistically higher than the 2019 results. Results of analysis revealed the success of the implementation of the four-stage emergency remote teaching model.

NACVGM 2020 Retrospective Thoughts on Organizing a Digital Conference

The North American Conference on Video GameMusic (NACVGM) has been held yearly as an in-person conference. NACVGM 2020 was originally scheduled to occur in April 2020 in Ithaca, New York. As a result of the COVID-19 pandemic, many academic events in 2020 were shifted online, including game music conferences like Ludo2020 and NACVGM. The organizing committee for NACVGM decided to hold the full conference digitally as a live event. After hosting NACVGM2020 live on his personal Twitch.tv page, Ryan Thompson explains the technical means that made it possible and offers a series of recommendations for other individuals considering shifting in-person meetings to online events. This reflection provides one perspective on hosting an academic conference during lockdown. © 2021 Cultural Imperialism in Capcom’s Mega Man Series. All rights reserved.

OUTCOMES OF NEPHRECTOMY FOR RENAL CELL CARCINOMA WITH VENOUS THROMBUS FOLLOWING IMMUNE CHECKPOINT INHIBITOR THERAPY: A MULTICENTER COLLABORATIVE STUDY

INTRODUCTION AND OBJECTIVE: Nephrectomy and venous thrombectomy is a challenging procedure with potential morbidity and mortality. Despite the increasing use of immune checkpoint inhibitors (ICI) in the management of advanced renal cell carcinoma (RCC), data regarding the outcomes of venous thrombectomy following ICI is limited. We evaluated the feasibility and perioperative outcomes of nephrectomy and venous thrombectomy following ICIs. METHODS: Patients with locally advanced or metastatic RCC with venous thrombus undergoing nephrectomy following ICI therapy were evaluated in four high-volume US academic centers between June 2017 and June 2021. Clinical data, perioperative outcomes, and 90-day complications were recorded. RESULTS: Out of 79 patients who received post-ICI nephrectomy, 27 had venous thrombus. Median (IQR) age was 64 (55-71) years. ICI regimens were Nivolumab ± Ipilimumab (n=19), and Pembrolizumab± Axitinib (n=8). Nephrectomy was indicated following either a good clinical response to ICI (n=24) or as a palliative surgery (n=3). Venous thrombi levels are shown in Table-1. Among all patients, 26 (96%) underwent radical and 1 (4%) partial nephrectomy;12 (44.5%) open, 12 (44.5%) robotic and 3 (11%) laparoscopic. One robotic case converted electively to open. Vascular procedures included renal vein thrombectomy (n=6), IVC thrombectomy and primary repair (n=19), IVC patch repair (n=1), and suprarenal cavectomy (n=1). No intraoperative complications were reported. Nine patients showed no viable tumor in the thrombus, of whom 2 had complete response in the primary tumor as well (ypT0N0). 90-day complication rate was 33% (n=9), with 8 patients (30%) requiring readmission (Table-2). One death was reported within 90 days due to COVID-19 infection. CONCLUSIONS: Nephrectomy and venous thrombectomy following systemic immune checkpoint inhibitor therapy is feasible. One third of patients show no viable tumor in the thrombus. Larger studies are needed to predict pathological response.