COVID-19 and Beyond: Taming the Virtual Healthcare Tiger with Colored Petri Nets based Modeling and Simulation

The Coronavirus crisis has forced hospitals globally to develop new virtual service portals and systems to: 1) triage, diagnose, and manage new patients virtually for every clinical specialty at home as their symptoms emerge, avoiding COVID-19 exposure to patient or physicians, and hospitalization, as much as possible, and 2) discharge, track, and support recovered patients via homecare and virtual visits to free as many critical care beds as possible. This paper focuses on simulating and modeling an episode of care with innovative initial patient contact and triage processes using the Colored Petri Net (CPN) formalism to help optimize workflow, patient throughput, and overall system efficacy. The two patient triage programs under consideration are a health system in Australia and an orthopedic surgical program in the US. We describe our model for the US program. Our presented results establish a desired stratification of patients through a virtual musculoskeletal triage. © 2022 IEEE Computer Society. All rights reserved.

Assessing endothelial activation and risk of bleeding in patients receiving VV-ECMO supportive therapy for COVID-19 using non-standard laboratory assays

Background: Critically ill patients infected with the SARS-CoV- 2 virus are known to have a coagulopathy with a risk of thrombosis due to endothelial activation and systemic inflammation. Veno-venous extracorporeal membrane oxygenation (VV ECMO) is recommended by the World Health Organisation (WHO) as a supportive therapy for patients with severe COVID-19 infection when conventional ICU methods have proven ineffective. VV ECMO comes with haematological complications, including loss of high molecular weight von Willebrand factor multimers, consumption of clotting factors and premature activation of platelets. Laboratory methods to characterise haemostasis in these patients are required and may be clinically useful in predicting clinical outcome. Aim(s): Can non-standard methods provide clinically meaningful results in COVID-19 positive patients supported by VV ECMO? Methods: Tissue plasminogen activator and von Willebrand factor were quantified via Abcam SimpleStep ELISA in VV ECMO supported Covid-19 patients and normal controls. Fibrinogen antigen concentration was quantified via Liaphen Fibrinogen Antigen assay in VV ECMO supported Covid-19 patients and normal controls. VW Select ristocetin cofactor assay was used to assess von Willebrand Factor activity in VV ECMO supported COVID-19 patients. Result(s): Tissue plasminogen activator and von Willebrand factor concentrations are significantly increased in COVID-19 patients supported by VV ECMO compared to healthy controls, which reflects endothelial damage displayed in critically unwell COVID patients. Fibrinogen levels were not significantly different between the two patient groups. The VW Select ristocetin cofactor assay detected patients with low vWF activity that would have otherwise been overlooked by standard methods. Conclusion(s): Non-conventional laboratory methods can be used to represent the extent of endothelial damage and risk of bleeding in patients who are COVID-19 positive and anticoagulated on VV ECMO support. The assays help to characterise pathology of COVID-19 used in conjunction with standard tests by providing clinically relevant results. (Figure Presented).

Pre-analytical screening and removal of Argatroban interference for haemostasis assays

Background: Argatroban is a direct thrombin inhibitor licenced in the UK and USA for treatment of Heparin Induced Thrombocytopenia and has been utilised as alternative anticoagulation for critically ill COVID-19 patients. Interferences in specialised haemostasis assays may be clinically important when bridging anticoagulant regimens or investigating thrombotic and bleeding complications common in critically ill patients. Aim(s): * Assess effect of Argatroban on specialised haemostasis assays * Assess effectiveness of DOAC-Remove (DR) in removing Argatroban interference Methods: Argatroban calibration plasma, spanning concentrations of 0 mug/ml-2.08 mug/ml, was tested for Antithrombin (IIa activator), Factors IX, and XI, and dilute Russel's viper venom time (dRVVT) to assess Argatroban interference. Samples were treated with DOAC-Remove and re-run for these assays. A p value of <0.05 was used to assess significance using paired t-tests Results: * Antithrombin results were significantly and linearly increased by increasing Argatroban concentrations (R -0.99). * Factor IX and XI concentrations were significantly decreased by increasing Argatroban concentrations from 83.4 IU/dl at 0 mug/ml to 3.79 IU/ dL at 2.07 mug/ml Argatroban * dRVVT screen results were significantly increased by increasing Argatroban concentrations (DRVVT ratio 1.07 (no Argatroban) to 3.79 at 2.07 ng/ml Argatroban) * Pre-treatment of samples with DOAC-Remove completely removes Argatroban interference to baseline. Conclusion(s): Argatroban has significant effects on specialist haemostasis assays. Antithrombin overestimation was observed when IIa activator is used, a Xa activator should be considered in such patients. dRVVT screen ratios were significantly increased, which could lead to false positive Lupus anticoagulant results. Factors IX and XI results were significantly decreased. Similar results have been published for direct oral anticoagulants with the need for pre-analytical screening, where anticoagulant status is unknown, becoming more important. For Argatroban, dilute thrombin time can be used as a pre-analytical screening tool. (Table Presented).

Dilute thrombin time versus activated partial thromboplastin time to monitor Argatroban in critically ill patients

Background: Argatroban is a direct thrombin inhibitor currently licenced in the UK and USA for treatment of Heparin Induced Thrombocytopenia (HIT) and has been utilised as an alternative anticoagulant for critically ill COVID-19 patients. UK and US guidelines recommend Argatroban monitoring via activated partial thromboplastin time (aPTT), in critically ill patients, recommending ratios of between 1.5-3 times patient's baseline, without exceeding 100 s. This guidance is based on spiked pooled platelet poor plasma with increasing concentrations of Argatroban. Aim(s): * Does the aPTT demonstrate suitable linearity for Argatroban monitoring? * Are readily available alternatives more useful to indicate extent of Argatroban anticoagulation? Methods: From May to July 2021, 97 residual blood samples from 12 patients receiving Argatroban were processed for HemosIL APTT-SS, Thrombin time, Argatroban, and dilute thrombin time using ACL-TOP750 (Werfen, Bedford, USA). Performance was compared to commercial calibrators, across a therapeutic range from 0-2.08 mug/ml mimicking spiked plasma. Result(s): * No linearity was observed between Argatroban concentration and aPTT ratio (R2 value of 0.0778) in critically ill patient plasma compared to linearity for APTT ratios (R2 value of 0.9346) in commercial calibrators * Thrombin time produced good linearity with Argatroban (R2 value of 0.8473). Non-specific clot curve kinetic issues and exceeding acquisition times were noted. * Dilute thrombin time produced very good linearity with Argatroban (R2 value of 0.9443) Conclusion(s): In critically ill patients, aPTT ratio lacks a demonstrable linear response, unlike spiked and commercial plasmas. Non linearity is most likely due to other effects on the aPTT than Argatroban alone. 10.3% of patients exceeded an Argatroban concentration of 2.08 mug/ml with an aPTT ratio within guideline quoted ranges. Thrombin time and dTT demonstrated linearity. However, the thrombin time had non-specific clot curve kinetic abnormalities and some results exceeded acquisition time. No issues were seen with dilute thrombin time.

COVID-19 in health care workers, Australia 2020

Background: Health care workers are at increased risk of SARS-CoV-2 infection due to potential exposure to patients or staff in health care settings. Australian health care services and health care workers experienced intense pressure to prepare for and respond to SARS-CoV-2 infections. We summarise national data on health care worker infections and associated outbreaks during 2020.

Impact of COVID-19 on emergency department attendance in an Australia hospital: a parallel convergent mixed methods study.

OBJECTIVES: The COVID-19 pandemic has changed the way people are accessing healthcare. The aim of this study was to examine the impact of COVID-19 on emergency department (ED) attendance for frequent attenders and to explore potential reasons for changes in attendance. DESIGN: This convergent parallel mixed methods study comprised two parts. SETTING: An interrupted time-series analysis evaluated changes in ED presentation rates; interviews investigated reasons for changes for frequent ED users in a culturally and linguistically diverse setting. PARTICIPANTS: A total of 4868 patients were included in the time series. A subgroup of 200 patients were interviewed, mean age 66 years (range 23-99). RESULTS: Interrupted time-series analysis from 4868 eligible participants showed an instantaneous decrease in weekly ED presentations by 36% (p<0.001), with reduction between 45% and 67% across emergency triage categories. 32% did not know they could leave home to seek care with differences seen in English versus non-English speakers (p<0.001). 35% reported postponing medical care. There was a high fear about the health system becoming overloaded (mean 4.2 (±2) on 6-point scale). Four key themes emerged influencing health-seeking behaviour: fear and/or avoidance of hospital care; use of telehealth for remote assessment; no fear or avoidance of hospital care; not leaving the house for any reason. CONCLUSIONS: This study demonstrated reduced ED use by a vulnerable population of previously frequent attenders. COVID-19 has resulted in some fear and avoidance of hospitals, but has also offered new opportunity for alternative care through telehealth.

Fatal Exacerbations of Systemic Capillary Leak Syndrome Complicating Coronavirus Disease.

We report 2 fatal exacerbations of systemic capillary leak syndrome (SCLS), also known as Clarkson disease, associated with coronavirus disease (COVID-19) in the United States. One patient carried an established diagnosis of SCLS and the other sought treatment for new-onset hypotensive shock, hemoconcentration, and anasarca, classic symptoms indicative of an SCLS flare. Both patients had only mild-to-moderate symptoms of COVID-19. This clinical picture suggests that these patients succumbed to complications of SCLS induced by infection with severe acute respiratory syndrome coronavirus 2. Persons with known or suspected SCLS may be at increased risk for developing a disease flare in the setting of mild-to-moderate COVID-19 infection.

Commanding Curiosity from the Couch: MSL Remote Operations, Challenges, and Path Ahead

This paper describes how the Mars Science Laboratory (MSL) project prepared for and successfully began Curiosity rover Mars operations from their homes in response to the COVID-19 work-from-home orders. In a very short period, the team developed procedures and executed a remote operations readiness test in parallel with the team's support for nominal operations. Continuing regular rover operations with an entirely remote team had not previously been considered feasible due to a variety of factors. These included both the human factors, such as multiple concurrent person-to-person interactions of the uplink planning team, as well as technical factors, such as reliance on powerful workstations dedicated to graphically intensive software tools used for planning. The test was conducted on March 12, 2020, with both the downlink and uplink teams successfully simulating a near full planning day. The JPL administration announced the transition to mandatory telework on Monday, March 16. MSL stood down the uplink planning originally scheduled for the next day while downlink continued monitoring the rover. Full operations then resumed per schedule with nearly the entire operations team teleworking on Friday, March 20, during which the team planned rover activities for three Martian days (sols). These activities included the successful drilling of the "Edinburgh" rock target, a highly complex robotic arm contact science activity. As of October 1, 2020, the Mars Science Laboratory mission operations team has conducted 88 remote tactical uplink shifts for a total of 190 sols of planned rover activity, which accounts for more than 6% of the mission to date. In this period the rover has completed four drilling campaigns and driven over 1160 meters towards its next major science target - a sulfate bearing geologic unit at the foot of Mount Sharp. Success has not been without its challenges. Many of these have been addressed while others will remain in some form until the team can safely return to JPL, which in turn is the largest challenge for the future.

Commanding Curiosity from the Couch: MSL Remote Operations, Challenges, and Path Ahead

This paper describes how the Mars Science Laboratory (MSL) project prepared for and successfully began Curiosity rover Mars operations from their homes in response to the COVID-19 work-from-home orders. In a very short period, the team developed procedures and executed a remote operations readiness test in parallel with the team's support for nominal operations. Continuing regular rover operations with an entirely remote team had not previously been considered feasible due to a variety of factors. These included both the human factors, such as multiple concurrent person-to-person interactions of the uplink planning team, as well as technical factors, such as reliance on powerful workstations dedicated to graphically intensive software tools used for planning. The test was conducted on March 12, 2020, with both the downlink and uplink teams successfully simulating a near full planning day. The JPL administration announced the transition to mandatory telework on Monday, March 16. MSL stood down the uplink planning originally scheduled for the next day while downlink continued monitoring the rover. Full operations then resumed per schedule with nearly the entire operations team teleworking on Friday, March 20, during which the team planned rover activities for three Martian days (sols). These activities included the successful drilling of the 'Edinburgh' rock target, a highly complex robotic arm contact science activity. As of October 1, 2020, the Mars Science Laboratory mission operations team has conducted 88 remote tactical uplink shifts for a total of 190 sols of planned rover activity, which accounts for more than 6% of the mission to date. In this period the rover has completed four drilling campaigns and driven over 1160 meters towards its next major science target - a sulfate bearing geologic unit at the foot of Mount Sharp. Success has not been without its challenges. Many of these have been addressed while others will remain in some form until the team can safely return to JPL, which in turn is the largest challenge for the future. © 2021 IEEE.

Shaping applied epidemiology workforce training to strengthen emergency response: a global survey of applied epidemiologists, 2019-2020

BACKGROUND: Rapid and effective emergency response to address health security relies on a competent and suitably trained local and international workforce. The COVID-19 pandemic has highlighted that the health security workforce needs to be well equipped to tackle current and future challenges. In this study, we explored whether training in applied epidemiology was meeting the current needs of the applied epidemiology workforce. METHOD: We conducted a cross-sectional online survey that was available in English and French. We used purposive and snowballing sampling techniques to identify potential survey respondents. An online social media advertisement campaign was used to disseminate a REDCap survey link between October 2019 and February 2020 through field epidemiology networks. Survey questions included demographic details of participants, along with their technical background, level of formal education, topics studied during epidemiology training, and years of experience as an epidemiologist. We used Pearson Chi-squared (Chi²) to test the difference between categorical variables, and content analysis to evaluate responses to open-ended questions. RESULTS: In total, 282 people responded to the survey. Participants had a range of formal public health and epidemiology training backgrounds. Respondents applied epidemiology experience spanned almost 30 years, across 64 countries. Overall, 74% (n = 210) were alumni of Field Epidemiology Training Programs (FETP). Basic outbreak and surveillance training was well reported by respondents, however training in specialised techniques related to emergency response, communication, and leadership was less common. FETP graduates reported higher levels of formal training in all survey topics. CONCLUSION: It is critical for the health security workforce to be well-trained and equipped with skills needed to ensure a rapid and effective response to acute public health events. Leadership, communication, interpersonal skills, and specialist training in emergency response are lacking in current training models. Our study has demonstrated that applied epidemiology workforce training must evolve to remain relevant to current and future public health challenges.