Medicine (Austin & Northern Health) - Research Publications

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    COVID-Care - a safe and successful digital self-assessment tool for outpatients with proven and suspected coronavirus-2019
    Drewett, GP ; Holmes, NE ; Trubiano, JA ; Vogrin, S ; Feldman, J ; Rose, M (SAGE PUBLICATIONS LTD, 2021-09)
    INTRODUCTION: The coronavirus-2019 (COVID-19) pandemic and restrictions placed on movement to prevent its transmission have led to a surge in demand for remote medical care. We investigated whether COVID-Care, a patient-reported, telehealth, symptom monitoring system, was successful at delivering safe monitoring and care for these patients leading to decreased hospital presentations. METHODS: We performed a single centre, prospective, interventional cohort study with symptomatic outpatients who presented for COVID-19 screening at Austin Health, Australia. Participants were invited to take part in the COVID-Care programme, entering common COVID-19 symptoms on a purpose-built, online survey monitored by infectious diseases physicians, and matched with clinical data including date of symptom onset, hospital admission, and screening clinic presentations. RESULTS: 42,158 COVID-19 swabs were performed in 31,626 patients from March to October 2020, with 414 positive cases. 20,768 people used the COVID-Care survey at least once. COVID-Care users were significantly younger than non-users. Of the 414 positive cases, 254 (61.3%) used COVID-Care, with 160 (38.6%) non-users. Excluding presentations on the same day or prior to the COVID-19 swab, of the positive cases there were 56 hospital presentations. 4.3% (11) of COVID-Care users and 28.1% (45) non-users were admitted to hospital or the emergency department (p < 0.001), with 3.9% (10) versus 22.5% (36) requiring inpatient admission (p < 0.001). There were no deaths in COVID-Care users versus 2 deaths in non-users. CONCLUSION: COVID-Care, a digitally integrated, outpatient, symptom tracking and telemedical service for patients with COVID-19, was safe and successful at reducing hospital and emergency department admissions, suggesting a strong role for telemedicine for future healthcare delivery in this logistically challenging setting.
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    Staff to staff transmission as a driver of healthcare worker infections with COVID-19
    Gordon, CL ; Trubiano, JA ; Holmes, NE ; Chua, KYL ; Feldman, J ; Young, G ; Sherry, NL ; Grayson, ML ; Kwong, JC (ELSEVIER INC, 2021-11)
    BACKGROUND: High rates of healthcare worker (HCW) infections due to COVID-19 have been attributed to several factors, including inadequate personal protective equipment (PPE), exposure to a high density of patients with COVID-19, and poor building ventilation. We investigated an increase in the number of staff COVID-19 infections at our hospital to determine the factors contributing to infection and to implement the interventions required to prevent subsequent infections. METHODS: We conducted a single-centre retrospective cohort study of staff working at a tertiary referral hospital who tested positive for SARS-CoV-2 between 25 January 2020 and 25 November 2020. The primary outcome was the source of COVID-19 infection. RESULTS: Of 45 staff who returned a positive test result for SARS-CoV-2, 19 were determined to be acquired at our hospital. Fifteen (15/19; 79% [95% CI: 54-94%]) of these were identified through contact tracing and testing following exposures to other infected staff and were presumed to be staff-to-staff transmission, including an outbreak in 10 healthcare workers (HCWs) linked to a single ward that cared for COVID-19 patients. The staff tearoom was identified as the likely location for transmission, with subsequent reduction in HCW infections and resolution of the outbreak following implementation of enhanced control measures in tearoom facilities. No HCW contacts (0/204; 0% [95% CI: 0-2%]) developed COVID-19 infection following exposure to unrecognised patients with COVID-19. CONCLUSION: Unrecognised infections among staff may be a significant driver of HCW infections in healthcare settings. Control measures should be implemented to prevent acquisition from other staff as well as patient-staff transmission.
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    Identifying patterns in unplanned hospital admissions during the COVID-19 pandemic: a single-centre retrospective study
    Goel, V ; Chan, RK ; Smibert, OC ; Holmes, NE ; Marhoon, N ; Bach, C-AT ; Trubiano, JA ; Jones, NR (WILEY, 2021-06)
    BACKGROUND: Countries with a high prevalence of COVID-19 have identified a reduction in crude hospital admission rates for non-COVID-19 conditions during the pandemic. There remains a paucity of such data from lower prevalence countries, including Australia. AIMS: To describe the patterns of unplanned hospital daily admission rates during the COVID-19 pandemic in a major Australian metropolitan hospital, with a focus on acute medical presentations including acute coronary syndrome (ACS), stroke and falls. METHODS: This single-centre retrospective analysis analysed hospital admission episodes between 1 March and 30 April 2020 (COVID-19-era) and compared this to a historical cohort during the same period between 2017 and 2019 (pre-COVID-19). Information collected included total admission rates and patient characteristics for ACS, stroke and falls patients. RESULTS: A total of 12 278 unplanned admissions was identified across the study period. The daily admission rate was lower in the COVID-19-era compared with pre-COVID-19 (46.59 vs 51.56 days, P < 0.001). There was also a reduced average daily admission rate for falls (7.79 vs 9.95 days, P < 0.001); however, similar admission rates for ACS (1.52 vs 1.49 days, P = 0.83) and stroke (1.56 vs 1.76 days, P = 0.33). CONCLUSIONS: Public health interventions have been effective in reducing domestic cases of COVID-19 in Australia. At our tertiary metropolitan hospital, we have observed a significant reduction in unplanned hospital admission rates during the COVID-19-era, particularly for falls. Public health messaging needs to focus on educating the public how to seek medical care safely and promptly in the context of the ongoing COVID-19 crisis.
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    Asystolic cardiac arrest following liposomal amphotericin B infusion: anaphylaxis or compliment activation-related pseudoallergy?
    Drewett, GP ; Copaescu, A ; DeLuca, J ; Holmes, NE ; Trubiano, JA (BMC, 2021-07-29)
    Allergic reaction to liposomal amphotericin B is rare. We report a case of cardiac arrest in a 64-year-old woman following liposomal amphotericin B infusion, requiring resuscitation. We also present the results of subsequent skin prick and intradermal testing to liposomal amphotericin on the patient and three healthy controls, highlighting the need for further research into the immunopathogenesis of this reaction.
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    Delayed hypersensitivity associated with amoxicillin-clavulanate
    Copaescu, A ; Rose, M ; Mouhtouris, E ; Chua, KY ; Holmes, NE ; Phillips, EJ ; Trubiano, JA (WILEY, 2020-10)
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    Integrated immune dynamics define correlates of COVID-19 severity and antibody responses
    Koutsakos, M ; Rowntree, LC ; Hensen, L ; Chua, BY ; van de Sandt, CE ; Habel, JR ; Zhang, W ; Jia, X ; Kedzierski, L ; Ashhurst, TM ; Putri, GH ; Marsh-Wakefield, F ; Read, MN ; Edwards, DN ; Clemens, EB ; Wong, CY ; Mordant, FL ; Juno, JA ; Amanat, F ; Audsley, J ; Holmes, NE ; Gordon, CL ; Smibert, OC ; Trubiano, JA ; Hughes, CM ; Catton, M ; Denholm, JT ; Tong, SYC ; Doolan, DL ; Kotsimbos, TC ; Jackson, DC ; Krammer, F ; Godfrey, D ; Chung, AW ; King, NJC ; Lewin, SR ; Wheatley, AK ; Kent, SJ ; Subbarao, K ; McMahon, J ; Thevarajan, I ; Thi, HON ; Cheng, AC ; Kedzierska, K (CELL PRESS, 2021-03-16)
    SARS-CoV-2 causes a spectrum of COVID-19 disease, the immunological basis of which remains ill defined. We analyzed 85 SARS-CoV-2-infected individuals at acute and/or convalescent time points, up to 102 days after symptom onset, quantifying 184 immunological parameters. Acute COVID-19 presented with high levels of IL-6, IL-18, and IL-10 and broad activation marked by the upregulation of CD38 on innate and adaptive lymphocytes and myeloid cells. Importantly, activated CXCR3+cTFH1 cells in acute COVID-19 significantly correlate with and predict antibody levels and their avidity at convalescence as well as acute neutralization activity. Strikingly, intensive care unit (ICU) patients with severe COVID-19 display higher levels of soluble IL-6, IL-6R, and IL-18, and hyperactivation of innate, adaptive, and myeloid compartments than patients with moderate disease. Our analyses provide a comprehensive map of longitudinal immunological responses in COVID-19 patients and integrate key cellular pathways of complex immune networks underpinning severe COVID-19, providing important insights into potential biomarkers and immunotherapies.
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    COVID-MATCH65-A prospectively derived clinical decision rule for severe acute respiratory syndrome coronavirus 2
    Trubiano, JA ; Vogrin, S ; Smibert, OC ; Marhoon, N ; Alexander, AA ; Chua, KYL ; James, FL ; Jones, NRL ; Grigg, SE ; Xu, CLH ; Moini, N ; Stanley, SR ; Birrell, MT ; Rose, MT ; Gordon, CL ; Kwong, JC ; Holmes, NE ; Jin, X (PUBLIC LIBRARY SCIENCE, 2020-12-09)
    OBJECTIVES: We report on the key clinical predictors of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and present a clinical decision rule that can risk stratify patients for COVID-19. DESIGN, PARTICIPANTS AND SETTING: A prospective cohort of patients assessed for COVID-19 at a screening clinic in Melbourne, Australia. The primary outcome was a positive COVID-19 test from nasopharyngeal swab. A backwards stepwise logistic regression was used to derive a model of clinical variables predictive of a positive COVID-19 test. Internal validation of the final model was performed using bootstrapped samples and the model scoring derived from the coefficients, with modelling performed for increasing prevalence. RESULTS: Of 4226 patients with suspected COVID-19 who were assessed, 2976 patients underwent SARS-CoV-2 testing (n = 108 SARS-CoV-2 positive) and were used to determine factors associated with a positive COVID-19 test. The 7 features associated with a positive COVID-19 test on multivariable analysis were: COVID-19 patient exposure or international travel, Myalgia/malaise, Anosmia or ageusia, Temperature, Coryza/sore throat, Hypoxia-oxygen saturation < 97%, 65 years or older-summarized in the mnemonic COVID-MATCH65. Internal validation showed an AUC of 0.836. A cut-off of ≥ 1.5 points was associated with a 92.6% sensitivity and 99.5% negative predictive value (NPV) for COVID-19. CONCLUSIONS: From the largest prospective outpatient cohort of suspected COVID-19 we define the clinical factors predictive of a positive SARS-CoV-2 test. The subsequent clinical decision rule, COVID-MATCH65, has a high sensitivity and NPV for SARS-CoV-2 and can be employed in the pandemic, adjusted for disease prevalence, to aid COVID-19 risk-assessment and vital testing resource allocation.
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    Clinical evaluation of four commercial immunoassays for the detection of antibodies against established SARS-CoV-2 infection
    Chua, KYL ; Vogrin, S ; Bittar, I ; Horvath, JH ; Wimaleswaran, H ; Trubiano, JA ; Holmes, NE ; Lam, Q (ELSEVIER, 2020-12-01)
    A comparison of the clinical performance of the Elecsys Anti-SARS-CoV-2, Liaison SARS-CoV-2 S1/S2 IgG, Access SARS-CoV-2 IgG and Vitros Immunodiagnostic Products Anti-SARS-CoV-2 IgG immunoassays for the diagnosis of COVID-19 infection was performed. Patient sera were collected at least 6 weeks following onset of COVID-19 infection symptoms. Negative control specimens were stored specimens from those without COVID-19, collected in April–May 2019. Sensitivity and specificity with 95% confidence intervals (CI) were calculated. Linear regression was used to examine the relationship between the magnitude of serological response and clinical characteristics. There were 80 patients from whom 86 sera specimens were collected; six patients had duplicate specimens. There were 95 negative control specimens from 95 patients. The clinical sensitivity of the Elecsys assay was 98.84% (95% CI 93.69–99.97), specificity was 100% (95% CI 96.19–100.00); the Liaison assay clinical sensitivity was 96.51% (95% CI 90.14–99.27), specificity was 97.89% (95% CI 92.60–99.74); the Access assay clinical sensitivity was 84.88% (95% CI 75.54–91.70), specificity was 98.95% (95% CI 94.27–99.97); and the Vitros assay clinical sensitivity was 97.67% (95% CI 91.85–99.72), specificity was 100% (95% CI 96.15–100.00). A requirement for hospitalisation for COVID-19 infection was associated with a larger Vitros, Liaison and Access IgG response whilst fever was associated with a larger Elecsys response. All assays evaluated with the exception of the Access assay demonstrated similar performance. The Elecsys assay demonstrated the highest sensitivity and specificity.
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    Alterations in Smell or Taste-Classic Coronavirus Disease 2019?
    Trubiano, JA ; Vogrin, S ; Kwong, JC ; Homes, N (OXFORD UNIV PRESS INC, 2020-10-15)
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    Safety of cephalosporins in penicillin class severe delayed hypersensitivity reactions
    Trubiano, JA ; Chua, KYL ; Holmes, NE ; Douglas, AP ; Mouhtouris, E ; Goh, M ; Phillips, EJ (ELSEVIER, 2020-03)