A survey of Australian public opinion on using comorbidity to triage intensive care patients in a pandemic.

ObjectivesThis study aimed to determine which method to triage intensive care patients using chronic comorbidity in a pandemic was perceived to be the fairest by the general public. Secondary objectives were to determine whether the public perceived it fair to provide preferential intensive care triage to vulnerable or disadvantaged people, and frontline healthcare workers.MethodsA postal survey of 2000 registered voters randomly selected from the Australian Electoral Commission electoral roll was performed. The main outcome measures were respondents' fairness rating of four hypothetical intensive care triage methods that assess comorbidity (chronic medical conditions, long-term survival, function and frailty); and respondents' fairness rating of providing preferential triage to vulnerable or disadvantaged people, and frontline healthcare workers.ResultsThe proportion of respondents who considered it fair to triage based on chronic medical conditions, long-term survival, function and frailty, was 52.1, 56.1, 65.0 and 62.4%, respectively. The proportion of respondents who considered it unfair to triage based on these four comorbidities was 31.9, 30.9, 23.8 and 23.2%, respectively. More respondents considered it unfair to preferentially triage vulnerable or disadvantaged people, than fair (41.8% versus 21.2%). More respondents considered it fair to preferentially triage frontline healthcare workers, than unfair (44.2% versus 30.0%).ConclusionRespondents in this survey perceived all four hypothetical methods to triage intensive care patients based on comorbidity in a pandemic disaster to be fair. However, the sizable minority who consider this to be unfair indicates that these triage methods could encounter significant opposition if they were to be enacted in health policy.

People in intensive care with COVID-19: demographic and clinical features during the first, second, and third pandemic waves in Australia.

OBJECTIVE: To compare the demographic and clinical features, management, and outcomes for patients admitted with COVID-19 to intensive care units (ICUs) during the first, second, and third waves of the pandemic in Australia. DESIGN, SETTING, AND PARTICIPANTS: People aged 16 years or more admitted with polymerase chain reaction-confirmed COVID-19 to the 78 Australian ICUs participating in the Short Period Incidence Study of Severe Acute Respiratory Infection (SPRINT-SARI) Australia project during the first (27 February - 30 June 2020), second (1 July 2020 - 25 June 2021), and third COVID-19 waves (26 June - 1 November 2021). MAIN OUTCOME MEASURES: Primary outcome: in-hospital mortality. SECONDARY OUTCOMES: ICU mortality; ICU and hospital lengths of stay; supportive and disease-specific therapies. RESULTS: 2493 people (1535 men, 62%) were admitted to 59 ICUs: 214 during the first (9%), 296 during the second (12%), and 1983 during the third wave (80%). The median age was 64 (IQR, 54-72) years during the first wave, 58 (IQR, 49-68) years during the second, and 54 (IQR, 41-65) years during the third. The proportion without co-existing illnesses was largest during the third wave (41%; first wave, 32%; second wave, 29%). The proportion of ICU beds occupied by patients with COVID-19 was 2.8% (95% CI, 2.7-2.9%) during the first, 4.6% (95% CI, 4.3-5.1%) during the second, and 19.1% (95% CI, 17.9-20.2%) during the third wave. Non-invasive (42% v 15%) and prone ventilation strategies (63% v 15%) were used more frequently during the third wave than during the first two waves. Thirty patients (14%) died in hospital during the first wave, 35 (12%) during the second, and 281 (17%) during the third. After adjusting for age, illness severity, and other covariates, the risk of in-hospital mortality was similar for the first and second waves, but 9.60 (95% CI, 3.52-16.7) percentage points higher during the third than the first wave. CONCLUSION: The demographic characteristics of patients in intensive care with COVID-19 and the treatments they received during the third pandemic wave differed from those of the first two waves. Adjusted in-hospital mortality was highest during the third wave.

Comparison of baseline characteristics, treatment and celinical outcomes of critically ill COVID-19 patients admitted in the first and second waves in Australia.

Objective: To report longitudinal differences in baseline characteristics, treatment, and outcomes in patients with coronavirus disease 2019 (COVID-19) admitted to intensive care units (ICUs) between the first and second waves of COVID-19 in Australia. Design, setting and participants: SPRINT-SARI Australia is a multicentre, inception cohort study enrolling adult patients with COVID-19 admitted to participating ICUs. The first wave of COVID-19 was from 27 February to 30 June 2020, and the second wave was from 1 July to 22 October 2020. Results: A total of 461 patients were recruited in 53 ICUs across Australia; a higher number were admitted to the ICU during the second wave compared with the first: 255 (55.3%) versus 206 (44.7%). Patients admitted to the ICU in the second wave were younger (58.0 v 64.0 years; P = 0.001) and less commonly male (68.9% v 60.0%; P = 0.045), although Acute Physiology and Chronic Health Evaluation (APACHE) II scores were similar (14 v 14; P = 0.998). High flow oxygen use (75.2% v 43.4%; P < 0.001) and non-invasive ventilation (16.5% v 7.1%; P = 0.002) were more common in the second wave, as was steroid use (95.0% v 30.3%; P < 0.001). ICU length of stay was shorter (6.0 v 8.4 days; P = 0.003). In-hospital mortality was similar (12.2% v 14.6%; P = 0.452), but observed mortality decreased over time and patients were more likely to be discharged alive earlier in their ICU admission (hazard ratio, 1.43; 95% CI, 1.13-1.79; P = 0.002). Conclusion: During the second wave of COVID-19 in Australia, ICU length of stay and observed mortality decreased over time. Multiple factors were associated with this, including changes in clinical management, the adoption of new evidence-based treatments, and changes in patient demographic characteristics but not illness severity.

Outcomes for patients with COVID-19 admitted to Australian intensive care units during the first four months of the pandemic.

OBJECTIVES: To describe the characteristics and outcomes of patients with COVID-19 admitted to intensive care units (ICUs) during the initial months of the pandemic in Australia. DESIGN, SETTING: Prospective, observational cohort study in 77 ICUs across Australia. PARTICIPANTS: Patients admitted to participating ICUs with laboratory-confirmed COVID-19 during 27 February - 30 June 2020. MAIN OUTCOME MEASURES: ICU mortality and resource use (ICU length of stay, peak bed occupancy). RESULTS: The median age of the 204 patients with COVID-19 admitted to intensive care was 63.5 years (IQR, 53-72 years); 140 were men (69%). The most frequent comorbid conditions were obesity (40% of patients), diabetes (28%), hypertension treated with angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers (24%), and chronic cardiac disease (20%); 73 patients (36%) reported no comorbidity. The most frequent source of infection was overseas travel (114 patients, 56%). Median peak ICU bed occupancy was 14% (IQR, 9-16%). Invasive ventilation was provided for 119 patients (58%). Median length of ICU stay was greater for invasively ventilated patients than for non-ventilated patients (16 days; IQR, 9-28 days v 3 days; IQR, 2-5 days), as was ICU mortality (26 deaths, 22%; 95% CI, 15-31% v four deaths, 5%; 95% CI, 1-12%). Higher Acute Physiology and Chronic Health Evaluation II (APACHE-II) scores on ICU day 1 (adjusted hazard ratio [aHR], 1.15; 95% CI, 1.09-1.21) and chronic cardiac disease (aHR, 3.38; 95% CI, 1.46-7.83) were each associated with higher ICU mortality. CONCLUSION: Until the end of June 2020, mortality among patients with COVID-19 who required invasive ventilation in Australian ICUs was lower and their ICU stay longer than reported overseas. Our findings highlight the importance of ensuring adequate local ICU capacity, particularly as the pandemic has not yet ended.

Tocilizumab for severe COVID-19 pneumonia: Case series of 5 Australian patients.

AIM: To describe the first Australian cases of severe acute respiratory syndrome-coronavirus 2 (SARS-CoV2) disease (COVID-19) pneumonia treated with the interleukin-6 receptor antagonist tocilizumab. METHODS: Retrospective, open-label, real-world, uncontrolled, single-arm case series conducted in 2 tertiary hospitals in NSW, Australia and 1 tertiary hospital in Victoria, Australia. Five adult male patients aged between 46 and 74 years with type 1 respiratory failure due to COVID-19 pneumonia requiring intensive care unit (ICU) admission and biochemical evidence of systemic hyperinflammation (C-reactive protein greater than 100 mg/L; ferritin greater than 700 µg/L) were administered variable-dose tocilizumab. RESULTS: At between 13 and 26 days follow-up, all patients are alive and have been discharged from ICU. Two patients have been discharged home. Two patients avoided endotracheal intubation. Oxygen therapy has been ceased in three patients. Four adverse events potentially associated with tocilizumab therapy occurred in three patients: ventilator-associated pneumonia, bacteremia associated with central venous catheterization, myositis and hepatitis. All patients received broad-spectrum antibiotics, 4 received corticosteroids and 2 received both lopinavir/ritonavir and hydroxychloroquine. The time from first tocilizumab administration to improvement in ventilation, defined as a 25% reduction in fraction of inspired oxygen required to maintain peripheral oxygen saturation greater than 92%, ranged from 7 hours to 4.6 days. CONCLUSIONS: Tocilizumab use was associated with favorable clinical outcome in our patients. We recommend tocilizumab be included in randomized controlled trials of treatment for patients with severe COVID-19 pneumonia, and be considered for compassionate use in such patients pending the results of these trials.

ANZICS guiding principles for complex decision making during the COVID-19 pandemic.

The global 2019 coronavirus disease (COVID-19) pandemic has led to major challenges in clinical decision making when the demand for intensive care exceeds local capacity. In order to promote consistent, transparent, objective and ethical decision making, the Australian and New Zealand Intensive Care Society (ANZICS) formed a committee to urgently develop guidelines outlining key principles that should be utilised during the pandemic. This guidance is intended to support the practice of intensive care specialists during the COVID-19 pandemic and to promote the development of local admission policies that should be endorsed by health care organisations and relevant local authorities.

Efficient Nonviral Transfection of Human Bone Marrow Mesenchymal Stromal Cells Shown Using Placental Growth Factor Overexpression.

BACKGROUND: Human mesenchymal stromal/stem cells (hMSCs) hold great therapeutic potential due to their immunomodulatory and tissue regenerative properties. Enhancement of biological features of hMSCs by transfection has become a focus of investigation for cell- and gene-based therapies. However, many of the current transient transfection methods result in either low transfection efficiency or high cytotoxicity. METHODS: In order to find a transfection method that would address the current issues of low transfection efficiency and high cytotoxicity, 6 commercially available cationic lipid and polymer reagents were tested on human bone marrow-derived MSCs (hBM-MSCs) using GFP as a reporter gene. One transfection method using TransIT-2020 was selected and tested with an emphasis on cell quality (viability, identity, and yield), as well as efficacy with a human placental growth factor (PlGF) plasmid. RESULTS: TransIT-2020 yielded the highest fluorescence signal per cell out of the methods that did not decrease cell recovery. Transfecting GFP to 5 hBM-MSC donors using TransIT-2020 yielded 24-36% GFP-expressing cells with a viability of 85-96%. hBM-MSC identity was unaffected as CD90, CD105, and CD73 markers were retained (>95%+) after transfection. When this method was applied to PlGF expression, there was up to a 220-fold increase in secretion. Both growth and secretion of PlGF in overexpressing hBM-MSC were sustained over 7 days, confirming the sustainability and applicability of the TransIT-2020 transfection system. DISCUSSION: We report a simple and efficient method for transient transfection that has not been reported for hBM-MSCs, encompassing high levels of plasmid expression without significant changes to fundamental hBM-MSC characteristics.

A cross-sectional survey of Australian and New Zealand public opinion on methods totriage intensive care patients in an influenza pandemic.

BACKGROUND AND OBJECTIVE: An influenza pandemic has the potential to overwhelm intensive care resources, but the views of the general public on how resources should be allocated in such a scenario were unknown. We aimed to determine Australian and New Zealand public opinion on how intensive care unit beds should be allocated during an influenza pandemic. DESIGN, SETTING, AND PARTICIPANTS: A postal questionnaire was sent to 4000 randomly selected registered voters; 2000 people each from the Australian Electoral Commission and New Zealand Electoral Commission rolls. MAIN OUTCOME MEASURE: The respondents' preferred method to triage ICU patients in an influenza pandemic. Respondents chose from six methods: use a "first in, first served" approach; allow a senior doctor to decide; use pre-determined health department criteria; use random selection; use the patient's ability to pay; use the importance of the patient to decide. Respondents also rated each of the triage methods for fairness. RESULTS: Australian respondents preferred that patients be triaged to the ICU either by a senior doctor (43.2%) or by pre-determined health department criteria (38.7%). New Zealand respondents preferred that triage be performed by a senior doctor (45.9%). Respondents from both countries perceived triage by a senior doctor and by pre-determined health department criteria to be fair, and the other four methods of triage to be unfair. CONCLUSION: In an influenza pandemic, when ICU resources would be overwhelmed, survey respondents preferred that ICU triage be performed by a senior doctor, but also perceived the use of pre-determined triage criteria to be fair.

Problematic Dichotomization of Risk for Intensive Care Unit (ICU)-Acquired Invasive Candidiasis: Results Using a Risk-Predictive Model to Categorize 3 Levels of Risk From a Multicenter Prospective Cohort of Australian ICU Patients.

BACKGROUND: Delayed antifungal therapy for invasive candidiasis (IC) contributes to poor outcomes. Predictive risk models may allow targeted antifungal prophylaxis to those at greatest risk. METHODS: A prospective cohort study of 6685 consecutive nonneutropenic patients admitted to 7 Australian intensive care units (ICUs) for ≥72 hours was performed. Clinical risk factors for IC occurring prior to and following ICU admission, colonization with Candida species on surveillance cultures from 3 sites assessed twice weekly, and the occurrence of IC ≥72 hours following ICU admission or ≤72 hours following ICU discharge were measured. From these parameters, a risk-predictive model for the development of ICU-acquired IC was then derived. RESULTS: Ninety-six patients (1.43%) developed ICU-acquired IC. A simple summation risk-predictive model using the 10 independently significant variables associated with IC demonstrated overall moderate accuracy (area under the receiver operating characteristic curve = 0.82). No single threshold score could categorize patients into clinically useful high- and low-risk groups. However, using 2 threshold scores, 3 patient cohorts could be identified: those at high risk (score ≥6, 4.8% of total cohort, positive predictive value [PPV] 11.7%), those at low risk (score ≤2, 43.1% of total cohort, PPV 0.24%), and those at intermediate risk (score 3-5, 52.1% of total cohort, PPV 1.46%). CONCLUSIONS: Dichotomization of ICU patients into high- and low-risk groups for IC risk is problematic. Categorizing patients into high-, intermediate-, and low-risk groups may more efficiently target early antifungal strategies and utilization of newer diagnostic tests.

Candida colonization as a risk marker for invasive candidiasis in mixed medical-surgical intensive care units: development and evaluation of a simple, standard protocol.

Colonization with Candida species is an independent risk factor for invasive candidiasis (IC), but the minimum and most practicable parameters for prediction of IC have not been optimized. We evaluated Candida colonization in a prospective cohort of 6,015 nonneutropenic, critically ill patients. Throat, perineum, and urine were sampled 72 h post-intensive care unit (ICU) admission and twice weekly until discharge or death. Specimens were cultured onto chromogenic agar, and a subset underwent molecular characterization. Sixty-three (86%) patients who developed IC were colonized prior to infection; 61 (97%) tested positive within the first two time points. The median time from colonization to IC was 7 days (range, 0 to 35). Colonization at any site was predictive of IC, with the risk of infection highest for urine colonization (relative risk [RR]=2.25) but with the sensitivity highest (98%) for throat and/or perineum colonization. Colonization of ≥2 sites and heavy colonization of ≥1 site were significant independent risk factors for IC (RR=2.25 and RR=3.7, respectively), increasing specificity to 71% to 74% but decreasing sensitivity to 48% to 58%. Molecular testing would have prompted a resistance-driven decision to switch from fluconazole treatment in only 11% of patients infected with C. glabrata, based upon species-level identification alone. Positive predictive values (PPVs) were low (2% to 4%) and negative predictive values (NPVs) high (99% to 100%) regardless of which parameters were applied. In the Australian ICU setting, culture of throat and perineum within the first two time points after ICU admission captures 84% (61/73 patients) of subsequent IC cases. These optimized parameters, in combination with clinical risk factors, should strengthen development of a setting-specific risk-predictive model for IC.

Incidents resulting from staff leaving normal duties to attend medical emergency team calls.

OBJECTIVE: To determine the rate of adverse events and incidents occurring as a result of hospital staff leaving normal duties to attend medical emergency team (MET) calls. DESIGN, PARTICIPANTS AND SETTING: Single-centre, interview and questionnaire-based study of staff attending MET calls at a 650-bed university teaching hospital in Sydney, New South Wales, July to December 2013. MAIN OUTCOME MEASURE: The rate of adverse events and incidents directly related to MET staff leaving normal duties to attend MET calls. RESULTS: During the study period, 1490 structured interviews were conducted, and 279 written questionnaires were returned (overall response rate, 66.4%). There were no adverse events. There were 378 recorded incidents. The incident rate was 213.7 incidents per 1000 MET participant attendances (95% CI, 194.8-233.5), and 1.1 incidents per MET call. Using the severity assessment code, 99.5% of incidents were classified as minimum. The most commonly reported incidents were disruptions to normal duties, ward rounds, and patient reviews. Only 0.8% of incidents were reported on institutional incident reporting systems. CONCLUSION: Significant disruption to normal hospital routines and inconvenience to staff occurred, without causing major harm to patients, when MET staff temporarily left normal duties to attend MET calls. Normal hospital incident reporting systems cannot be used to monitor for these problems, as they are underreported.

A comparison of survival following out-of-hospital cardiac arrest in Sydney, Australia, between 2004-2005 and 2009-2010.

OBJECTIVE: To determine whether survival following out-of- hospital cardiac arrest (OHCA) in Sydney, Australia, improved between 2004-2005 and 2009-2010, and whether there was a change in incidence of OHCA. DESIGN: Retrospective study using the Ambulance Service of New South Wales and NSW Registry of Births, Deaths and Marriages databases. PARTICIPANTS AND SETTING: All patients who had an OHCA in the Sydney metropolitan area and who used the Ambulance Service of NSW between June 2009 and May 2010 (2009-2010), and between June 2004 and May 2005 (2004-2005). MAIN OUTCOME MEASURES: Survival to 90 days. Other outcome measures included the incidence of OHCA and survival to the day following OHCA, 28 days and 1 year following OHCA. Survival and incidence were also calculated according to initial electrocardiograph rhythm. RESULTS: Survival to 90 days was 12.3% in 2004-2005 and 10.2% in 2009-2010 (P = 0.015). In 2004-2005, the age standardised incidence of OHCA was 52.6 events per 100 000 person-years (95% CI, 51.6-53.6 events per 100 000 person-years), and in 2009-2010 it was 48.4 events per 100 000 person-years (95% CI, 46.3-50.4 events per 100 000 person-years). In 2004-2005, the incidence of ventricular fibrillation (VF) was 31.3% (95% CI, 28.4%- 33.9%) and in 2009-2010 it was 22.1% (95% CI, 20.0%- 24.3%). CONCLUSION: There was no improvement in survival following OHCA in Sydney between 2004-2005 and 2009- 2010. There has been a decrease in overall survival from OHCA and a decrease in the overall age-standardised incidence of OHCA. The decrease in overall survival may be due to a decline in the incidence of VF.

The effect of endotracheal tube size on voice and swallowing function in patients with thermal burn injury: an evaluation using the Australian Therapy Outcome Measures (AusTOMS).

The objective of this study was to determine if intubation using larger endotracheal tube sizes in mechanically ventilated patients with thermal burn injury adversely affects voice and swallowing function. This prospective, observational study was conducted in patients with thermal burn injuries, who were mechanically ventilated via an endotracheal tube. The primary outcome measures were changes in voice and swallowing function, assessed using the Australian Therapy Outcome Measures (AusTOMS), immediately before the burn injury, and 12 months after the removal of the endotracheal tube. Of 101 patients screened, 20 male patients were followed for 12 months. Patients intubated with size 8.0 or larger endotracheal tubes were compared to patients with size 7.5 endotracheal tubes or smaller. Patients with the larger endotracheal tubes had a significant 1.8-point (9%) decline in their AusTOMS voice score (p =.01) using the paired t-test, but there was no significant difference between the two groups using the independent samples t-test. There was no significant difference in swallowing outcome between the two groups. Male patients with thermal burn injuries, mechanically ventilated using size 8.0 endotracheal tubes or larger, had a statistically significant decline in voice outcome; however, interpretation of this result is limited by methodological considerations.

Development and evaluation of an influenza pandemic intensive care unit triage protocol.

OBJECTIVES: To develop an influenza pandemic ICU triage (iPIT) protocol that excludes patients with the highest and lowest predicted mortality rates, and to determine the increase in ICU bed availability that would result. DESIGN AND SETTING: Post-hoc analysis of a study evaluating two triage protocols, designed to determine which patients should be excluded from access to ICU resources during an influenza pandemic. ICU mortality rates were determined for the individual triage criteria in the protocols and included criteria based on the Sequential Organ Failure Assessment (SOFA) score. Criteria resulting in mortality rates outside the 25th and 75th percentiles were used as exclusion criteria in a new iPIT-1 protocol. The SOFA threshold component was modified further and reported as iPIT-2 and iPIT-3. MAIN OUTCOME MEASURE: Increase in ICU bed availability. RESULTS: The 25th and 75th percentiles for ICU mortality were 8.3% and 35.2%, respectively. Applying the iPIT-1 protocol resulted in an increase in ICU bed availability at admission of 71.7% ± 0.6%. Decreasing the lower SOFA score exclusion criteria to ≤6 (iPIT-2) and ≤4 (iPIT-3) resulted in an increase in ICU bed availability at admission of 66.9% ± 0.6% and 59.4 ± 0.7%, respectively (P < 0.001). CONCLUSION: The iPIT protocol excludes patients with the lowest and highest ICU mortality, and provides increases in ICU bed availability. Adjusting the lower SOFA score exclusion limit provides a method of escalation or de- escalation to cope with demand.

A multicentre evaluation of two intensive care unit triage protocols for use in an influenza pandemic.

OBJECTIVE: To determine the increase in intensive care unit (ICU) bed availability that would result from the use of the New South Wales and Ontario Health Plan for an Influenza Pandemic (OHPIP) triage protocols. DESIGN, SETTING AND PATIENTS: Prospective evaluation study conducted in eight Australian, adult, general ICUs, between September 2009 and May 2010. All patients who were admitted to the ICU, excluding those who had elective surgery, were prospectively evaluated using the two triage protocols, simulating a pandemic situation. Both protocols were originally developed to determine which patients should be excluded from accessing ICU resources during an influenza pandemic. MAIN OUTCOME MEASURE: Increase in ICU bed availability. RESULTS: At admission, the increases in ICU bed availability using Tiers 1, 2 and 3 of the NSW triage protocol were 3.5%, 14.7% and 22.7%, respectively, and 52.8% using the OHPIP triage protocol (P < 0.001). Re-evaluation of patients at 12 hours after admission using Tiers 1, 2 and 3 of the NSW triage protocol incrementally increased ICU bed availability by 19.2%, 16.1% and 14.1%, respectively (P < 0.001). The maximal cumulative increases in ICU bed availability using Tiers 1, 2 and 3 of the NSW triage protocol were 23.7%, 31.6% and 37.5%, respectively, at 72 hours (P < 0.001), and 65.0% using the OHPIP triage protocol, at 120 hours (P < 0.001). CONCLUSION: Both triage protocols resulted in increases in ICU bed availability, but the OHPIP protocol provided the greatest increase overall. With the NSW triage protocol, ICU bed availability increased as the protocol was escalated.