PiMS: A Pre-ML Labelling Tool

Machine Learning (ML) techniques in clinical decision support systems are scarce due to the limited availability of clinically validated and labelled training data sets. We present a framework to (1) enable quality controls at data submission toward ML appropriate data, (2) provide in-situ algorithm assessments, and (3) prepare dataframes for ML training and robust stochastic analysis. We developed and evaluated PiMS (Pandemic Intervention and Monitoring Systems): a remote monitoring solution for patients that are Covid-positive. The system was trialled at two hospitals in Melbourne, Australia (Alfred Health and Monash Health) involving 109 patients and 15 clinicians.

PiMS: A Pre-ML Labelling Tool

Machine Learning (ML) techniques in clinical decision support systems are scarce due to the limited availability of clinically validated and labelled training data sets. We present a framework to (1) enable quality controls at data submission toward ML appropriate data, (2) provide in-situ algorithm assessments, and (3) prepare dataframes for ML training and robust stochastic analysis. We developed and evaluated PiMS (Pandemic Intervention and Monitoring Systems): a remote monitoring solution for patients that are Covid-positive. The system was trialled at two hospitals in Melbourne, Australia (Alfred Health and Monash Health) involving 109 patients and 15 clinicians. © 2022 IEEE.

COVID-19, ACE2, Plus Human Angiotensin II: The Perfect Storm

Background: SARs-CoV-2 causes a disease unlike any we have seen before. The virus is similar to some, but the resultant disease is vastly different in the short and long term. This appears to be due to the Cytokine Storm (CS). The connection between COVID and the CS is likely related to Angiotensin II. Specifically, the Angiotensin II Type 1 Receptor (AT1R) which is regulated via the ACE2 Receptor (ACE2R). The AT1R pathway is the primary pro-inflammatory pathway that promotes endothelial activation, cellular recruitment and differentiation, T and B cell co-stimulation, and complement activation. This would explain the exact findings in the Cytokine Storm. Method(s): Extensive literature search including international publications and presentations as well as clinical experience. Direct clinical observation of the impact of RAAS on pathophysiology in COVID patients. Result(s): The connection between COVID and the ACE2 Receptor (ACE2R) is the best explanation for the CS. COVID induced ACE2R endocytosis, decreased expression, and decreased transcription facilitates unchecked activation of AT1R. In addition to controlling AT1R mediated endothelial inflammation, the ACE2R is also the regulatory mechanism for the Bradykinin mediated coagulation pathway. This would enhance the explanation of not just the inflammation, but the clotting as well. Conclusion(s): The ACE2R and AT1R connection is the best explanation for the tissue damage from COVID. AT1R mediated inflammation and vascular complications would explain the laboratory findings, histology findings, and clinical symptoms found in the Cytokine Storm. Furthermore, one of the key differences between SARS-CoV-2 and other recent virus outbreaks is the affinity with which SARS-CoV-2 binds to the ACE2R. It has the highest binding affinity of all current coronaviruses. This may explain the different outcomes in certain patients also. Any patients that would be at a higher RAAS baseline (Diabetes, Kidney Disease, Heart Disease) would be more likely to have complications. This is what we have seen clinically. Finally, this pathway gives us a mechanism for certain therapies that have shown promise such as Tocilizumab and Baricitinib. It also offers further treatment potentials for RAAS. In my experience, adequate blood pressures and ongoing diuresis are beneficial. Of particular benefit is diuresis with Hypertonic Saline, which has the best RAAS suppression and diuresis capabilities of any diuretic adjunct.

Women’s experiences of accessing vaccines during pregnancy and for their babies during COVID-19 : Helen Skirrow

Background COVID-19 changed access to healthcare, including vaccinations, in the United Kingdom (UK). This study explored UK women’s experiences of accessing pertussis vaccination during pregnancy and infant vaccinations during COVID-19. Methods An online cross-sectional survey was completed, between 3rd August-11th October 2020, by 1404 women aged 16+ years who were pregnant at some point after the first UK lockdown from March 23rd 2020. Ten follow-up semi-structured interviews were conducted. Results Most women surveyed were pregnant (65.7%) and a third postnatal (34.3%). Almost all women (95.6%) were aware that pertussis vaccination is recommended in pregnancy. Most pregnant (72.1%) and postnatal women (84.0%) had received pertussis vaccination however, access issues were reported. Over a third (39.6%) of women had a pregnancy vaccination appointment changed. COVID-19 made it physically difficult to access pregnancy vaccinations for one fifth (21.5%) of women and physically difficult to access infant vaccinations for almost half of women (45.8%). Nearly half of women (45.2%) reported feeling less safe attending pregnancy vaccinations and over three quarters (76.3%) less safe attending infant vaccinations due to COVID-19. The majority (94.2%) felt it was important to get their baby vaccinated during COVID-19. Pregnant women from ethnic-minorities and lower-income households were less likely to have been vaccinated. Minority-ethnicity women were more likely to report access problems and feeling less safe attending vaccinations for both themselves and their babies. Qualitative analysis found women experienced difficulties accessing antenatal care and relied on knowledge from previous pregnancies to access vaccine appointments. Conclusions COVID-19 disrupted access to vaccinations in the UK. Vaccine services must ensure equitable access to vaccine appointments during ongoing and future pandemics including tailoring services for lower income and ethnic minority families. Key messages • Pregnancy and infant vaccines was disrupted by COVID-19 with women feeling less safe and having difficulties accessing vaccinations with ethnic minority women more likely to report access issues. • Equitable access to routine pregnancy and infant vaccine appointments must be prioritised during future pandemics, including considering tailoring services for different population groups.

SINGLE-CENTER EXPERIENCE WITH THE USE OF THE SERAPH-100 MICROBIND AFFINITY BLOOD FILTER IN-PARALLEL WITH EXTRACORPOREAL MEMBRANE OXYGENATION CIRCUIT IN SEPTIC PATIENTS

TYPE: Late Breaking Case Report TOPIC: Critical Care INTRODUCTION: Patients who require extracorporeal membrane oxygenation (ECMO) have a high mortality if they develop septic shock. With the emergence of novel and resistant pathogens, new therapies are needed to treat septic patients. The Seraph–100 Microbind Affinity Blood Filter was granted Emergency Use Authorization by the FDA to treat severe COVID-19. The Seraph-100 filter contains microbeads that can bind bacteria, fungi, viruses and cytokines. Recommended configurations for the Seraph–100 utilize hemodialysis or continuous renal replacement therapy (CRRT) machines in a stand-alone fashion or in-combination with a hemodialysis filter. In this series, we explore a new configuration for the Seraph-100 for patients requiring ECMO. CASE PRESENTATION: Five septic patients underwent treatment with the Seraph-100 in-parallel with ECMO. This configuration allowed for pressures generated by the ECMO circuit to drive blood flow through the Seraph-100. All five patients were on multiple high dose vasopressors prior to therapy with the Seraph-100. Within 12-24 hours of treatment, vasopressor support significantly decreased and repeat blood cultures showed clearance of pathogens. DISCUSSION: All our patients treated with Seraph–100 in-parallel with ECMO had significant reduction in vasopressor support. Benefits of this configuration include limiting need for additional vascular access and need for dialysis circuits, along with the associated risks of renal replacement therapy. CONCLUSIONS: The Seraph-100 represents an innovative solution for the treatment of septic patients. This case series demonstrated the effectiveness and safety of a new configuration for the Seraph-100 in patients requiring ECMO. Further studies are needed to elucidate the optimal use of the Seraph-100 blood filter. DISCLOSURE: Nothing to declare. KEYWORD: Seraph-100 Blood Filter

COVID-19 vs. Bloodstream Purification: A Targeted Therapy

Background: The use of bloodstream purification has been well studied in bacteremia but the emergence of COVID found a new target. Using blood purification in the fight against COVID we have found a potential treatment for viremia and pneumonia, cytokine storm and decompensation, and superinfections in COVID. When used at the appropriate time, blood purification has the potential to prevent further organ injury. Methods: The following case series is an individual clinical observation of patients withing the PURIFY NIH funded clinical trial. Results: 28M w/o significant PMHx, transferred to BAMC for ECMO due to severe COVID. He initially improved, but decompensated with MRSA bacteremia, was ECMO/ CRRT and quadruple pressor dependent. He was treated with the Seraph for bloodstream purification and was off all vasopressors within 6 hours. He recovered, and was ultimately discharged without ECLS depdence. 64 M w/ CAD and CKD was admitted for mild COVID PNA requiring minimal o2. On hospital day 9-11 he decompensated ultimately requiring intubation and vasopressor support with AKI and oliguria. He was treated with the Seraph for 16 hours and was off vasopressors within 10 hours, urine output recovered within 24 hours, he was extubated in 48 hours and discharged from the ICU after 96 hours. 52 M w/ CKD/COPD/CHF/CAD admitted for mild COVID PNA, decompensated on day 12, required intubation / vasopressor support / CRRT, treated for 24 hours on CRRT with the Seraph Filter and was off vasopressors with returning renal function within 24 hours. 64 M w/ CKD/CHF/CAD admitted for NSTEMI and cardiogenic shock, found to be non-obstructive and likely viral cardiomyopathy due to COVID. He was started on dobutamine / levophed and IABP. Due to oliguria he was treated with CRRT and Seraph for blood purification. Within hours he was off vasopressors, no longer needing IABP after 24 hours, and ultimately recovered renal function within 48 hours. Conclusions: While further study is needed, the use of blood purification for specific targets in COVID appears to have incredible benefits. Due to documented pathogen removal (bacteria/fungi/virions) it is likely beneficial treatment for any bloodstream infections, but especially in the susceptible COVID population it seems to have miraculous benefit. The Seraph also appears to mitigate organ injury from the cytokine storm in COVID due to attenuation of the cytokine storm.

THE SERAPH FILTER VS THE CYTOKINE STORM

TOPIC: Critical Care TYPE: Original Investigations PURPOSE: To assess a more COVID specific treatment centered around the pathophysiology of the acute decompensation due to the cytokine storm in COVID-19. When used indiscriminately, no therapies have widely accepted and widely positive outcomes. Clinically, there is rather specific timeline to COVID in most settings, and treatments in early disease may be less beneficial later. Additionally, non-specific treatments of the immune system appear to have the best evidence yet these patients are also plagued by superinfections. The ideal treatment for COVID pneumonia and the COVID cytokine storm may not be the same and patient factors may prove more useful in determining what treatment to use when. The Seraph filter is a unique Heparin Sulfate moiety dialysis filter usable with HD or CRRT. It has been shown in multiple studies to actually bind and remove pathogens from the blood (bacteria, fungi, and viruses including COVID) but more recently has also been shown to remove certain middle to large molecules such as cytokines. Specifically, when studied in COVID, the Seraph has been shown to decrease most inflammatory markers and cytokines when measured. METHODS: Case series within the PURIFY study. These patients were consented, enrolled, and treated within the PURIFY protocols and under the FDA EUA for the Seraph filter.These patients in particular were chosen to highlight the pathophysiology but are part of a much larger group. RESULTS: Of the 5 patients in the case series, all 5 exhibited some immediate or rapid hemodynamic improvements. Additionally these improvements temporally could be most likely connected to Seraph treatment alone or in combination with standard of care as all 5 patients were on maximal medical therapy up until the time of treatment. Either related or unrelated to these hemodynamic effects, 3 of the 5 patients had sustained improvement in renal function and fluid status and the other 2 were anuric. CONCLUSIONS: The optimal treatment for COVID pneumonia would likely be supportive care, dexamethasone, and possibly anti-viral therapies. Additionally, if severe, direct removal of the virus from the bloodstream would also be significant. If treated during the likely viremic phase, the Seraph can potentially remove COVID and decrease the overall viral load. The optimal treatment for the cytokine storm is likely to be much more variable due to severity. When used early in the decompensation or when coinciding bloodstream infection is present the Seraph may be the most specific treatment for severe COVID with the best risk to benefit profile. Of note, intervention prior to true "renal failure" or anuria has also consistently yielded better results, emphasizing early recognition and treatment. CLINICAL IMPLICATIONS: Possibility to attenuate the cytokine storm in COVID with simple 8 - 24 hour treatments using the Seraph filter. A safe, simple, specific therapy with good evidence of benefit. DISCLOSURES: No relevant relationships by Sean Barnett, source=Web Response no disclosure on file for Kumar Sharma;

Implementing a change in practice in a different specialty via the chief registrar (CR) role

Junior doctor feedback from the General Medical Council (GMC) survey and quality panels has consistently highlighted poor handover in Acute Medical Unit (AMU) as a concern. Neglected handover practice has been identified as a key component of poor outcomes in root cause analyses within the unit. There was no formal handover of patients between the incoming and outgoing medical teams. Resolution of this problem was tasked to the chief registrar (CR). As an obstetrics and gynaecology registrar in the CR role there were potential benefits and barriers to taking on a project in a different specialty.The information gathering occurred over six months (surveys, focus groups, incident reporting). The implementation coincided with the COVID-19 surge. All staff were notified of the finalised plans the week before handover was implemented and key staff were individually approached to be champions. Feedback was encouraged and actively sought to highlight teething problems.The results show a clear improvement in handover practice, junior doctor support and multi-professional team working. There had been resistance from some senior clinicians to attend an evening handover in the planning stages, however, implementing change at the height of the pandemic meant that staff had to adapt rapidly to new ways of working and as a result this change was widely accepted and implemented. The next stage is to incorporate more teaching into handover practice by including ‘teaching bites.’Upon starting the CR job this was presented as an unsolvable project. However, by a thorough analysis and formation of a plan for change with buy-in from the entire team we were able to affect a successful change. This demonstrates the value of seconding middle grade doctors to management roles as they can provide a crucial link between medical and management staff and coordinate vital change to improve patient safety.