Corrigendum to "Blend to Limit OxygEN in ECMO: A RanDomised ControllEd Registry (BLENDER) trial: Study protocol and statistical analysis plan" [Crit Care Resuscit 25 (2023) 118-125].

[This corrects the article DOI: 10.1016/j.ccrj.2023.06.001.].

Mitigating Intensive Care Unit Noise: Design-Led Modeling Solutions, Calculated Acoustic Outcomes, and Cost Implications.

OBJECTIVES, PURPOSE, OR AIM: The study aimed to decrease noise levels in the ICU, anticipated to have adverse effects on both patients and staff, by implementing enhancements in acoustic design. BACKGROUND: Recognizing ICU noise as a significant disruptor of sleep and a potential hindrance to patient recovery, this study was conducted at a 40-bed ICU in Fiona Stanley Hospital in Perth, Australia. METHODS: A comprehensive mixed-methods approach was employed, encompassing surveys, site analysis, and acoustic measurements. Survey data highlighted the importance of patient sleep quality, emphasizing the negative impact of noise on work performance, patient connection, and job satisfaction. Room acoustics analysis revealed noise levels ranging from 60 to 90 dB(A) in the presence of patients, surpassing sleep disruption criteria. RESULTS: Utilizing an iterative 3D design modeling process, the study simulated significant acoustic treatment upgrades. The design integrated effective acoustic treatments within patient rooms, aiming to reduce noise levels and minimize transmission to adjacent areas. Rigorous evaluation using industry-standard acoustic software highlights the design's efficacy in reducing noise transmission in particular. Additionally, cost implications were examined, comparing standard ICU construction with acoustically treated options for new construction and refurbishment projects. CONCLUSIONS: This study provides valuable insights into design-based solutions for addressing noise-related challenges in the ICU. While the focus is on improving the acoustic environment by reducing noise levels and minimizing transmission to adjacent areas. It is important to clarify that direct measurements of patient outcomes were not conducted. The potential impact of these solutions on health outcomes, particularly sleep quality, remains a crucial aspect for consideration.

Stratification of Sepsis Patients on Admission into the Intensive Care Unit According to Differential Plasma Metabolic Phenotypes.

Delayed diagnosis of patients with sepsis or septic shock is associated with increased mortality and morbidity. UPLC-MS and NMR spectroscopy were used to measure panels of lipoproteins, lipids, biogenic amines, amino acids, and tryptophan pathway metabolites in blood plasma samples collected from 152 patients within 48 h of admission into the Intensive Care Unit (ICU) where 62 patients had no sepsis, 71 patients had sepsis, and 19 patients had septic shock. Patients with sepsis or septic shock had higher concentrations of neopterin and lower levels of HDL cholesterol and phospholipid particles in comparison to nonsepsis patients. Septic shock could be differentiated from sepsis patients based on different concentrations of 10 lipids, including significantly lower concentrations of five phosphatidylcholine species, three cholesterol esters, one dihydroceramide, and one phosphatidylethanolamine. The Supramolecular Phospholipid Composite (SPC) was reduced in all ICU patients, while the composite markers of acute phase glycoproteins were increased in the sepsis and septic shock patients within 48 h admission into ICU. We show that the plasma metabolic phenotype obtained within 48 h of ICU admission is diagnostic for the presence of sepsis and that septic shock can be differentiated from sepsis based on the lipid profile.

Non-COVID-19 intensive care admissions during the pandemic: a multinational registry-based study.

BACKGROUND: The COVID-19 pandemic resulted in a large number of critical care admissions. While national reports have described the outcomes of patients with COVID-19, there is limited international data of the pandemic impact on non-COVID-19 patients requiring intensive care treatment. METHODS: We conducted an international, retrospective cohort study using 2019 and 2020 data from 11 national clinical quality registries covering 15 countries. Non-COVID-19 admissions in 2020 were compared with all admissions in 2019, prepandemic. The primary outcome was intensive care unit (ICU) mortality. Secondary outcomes included in-hospital mortality and standardised mortality ratio (SMR). Analyses were stratified by the country income level(s) of each registry. FINDINGS: Among 1 642 632 non-COVID-19 admissions, there was an increase in ICU mortality between 2019 (9.3%) and 2020 (10.4%), OR=1.15 (95% CI 1.14 to 1.17, p<0.001). Increased mortality was observed in middle-income countries (OR 1.25 95% CI 1.23 to 1.26), while mortality decreased in high-income countries (OR=0.96 95% CI 0.94 to 0.98). Hospital mortality and SMR trends for each registry were consistent with the observed ICU mortality findings. The burden of COVID-19 was highly variable, with COVID-19 ICU patient-days per bed ranging from 0.4 to 81.6 between registries. This alone did not explain the observed non-COVID-19 mortality changes. INTERPRETATION: Increased ICU mortality occurred among non-COVID-19 patients during the pandemic, driven by increased mortality in middle-income countries, while mortality decreased in high-income countries. The causes for this inequity are likely multi-factorial, but healthcare spending, policy pandemic responses, and ICU strain may play significant roles.

National ICU Registries as Enablers of Clinical Research and Quality Improvement.

OBJECTIVES: Clinical quality registries (CQRs) have been implemented worldwide by several medical specialties aiming to generate a better characterization of epidemiology, treatments, and outcomes of patients. National ICU registries were created almost 3 decades ago to improve the understanding of case-mix, resource use, and outcomes of critically ill patients. This narrative review describes the challenges, proposed solutions, and evidence generated by National ICU registries as facilitators for research and quality improvement. DATA SOURCES: English language articles were identified in PubMed using phrases related to ICU registries, CQRs, outcomes, and case-mix. STUDY SELECTION: Original research, review articles, letters, and commentaries, were considered. DATA EXTRACTION: Data from relevant literature were identified, reviewed, and integrated into a concise narrative review. DATA SYNTHESIS: CQRs have been implemented worldwide by several medical specialties aiming to generate a better characterization of epidemiology, treatments, and outcomes of patients. National ICU registries were created almost 3 decades ago to improve the understanding of case-mix, resource use, and outcomes of critically ill patients. The initial experience in European countries and in Oceania ensured that through locally generated data, ICUs could assess their performances by using risk-adjusted measures and compare their results through fair and validated benchmarking metrics with other ICUs contributing to the CQR. The accomplishment of these initiatives, coupled with the increasing adoption of information technology, resulted in a broad geographic expansion of CQRs as well as their use in quality improvement studies, clinical trials as well as international comparisons, and benchmarking for ICUs. CONCLUSIONS: ICU registries have provided increased knowledge of case-mix and outcomes of ICU patients based on real-world data and contributed to improve care delivery through quality improvement initiatives and trials. Recent increases in adoption of new technologies (i.e., cloud-based structures, artificial intelligence, machine learning) will ensure a broader and better use of data for epidemiology, healthcare policies, quality improvement, and clinical trials.

Flattening the biological age curve by improving metabolic health: to taurine or not to taurine, that' s the question.

The aging population is an important issue around the world especially in developed countries. Although medical advances have substantially extended life span, the same cannot be said for the duration of health span. We are seeing increasing numbers of elderly people who are frail and/or have multiple chronic conditions; all of these can affect the quality of life of the elderly population as well as increase the burden on the healthcare system. Aging is mechanistically related to common medical conditions such as diabetes mellitus, ischemic heart disease, cognitive decline, and frailty. A recently accepted concept termed 'Accelerated Biological Aging' can be diagnosed when a person's biological age-as measured by biomarkers of DNA methylation-is older than their corresponding chronological age. Taurine, a conditionally essential amino acid, has received much attention in the past few years. A substantial number of animal studies have provided a strong scientific foundation suggesting that this amino acid can improve cellular and metabolic health, including blood glucose control, so much that it has been labelled one of the 'longevity amino acids'. In this review article, we propose the rationale that an adequately powered randomized-controlled-trial (RCT) is needed to confirm whether taurine can meaningfully improve metabolic and microbiome health, and biological age. This trial should incorporate certain elements in order to provide the much-needed evidence to guide doctors, and also the community at large, to determine whether this promising and inexpensive amino acid is useful in improving human metabolic health.

Protocol summary and statistical analysis plan for the low oxygen intervention for cardiac arrest injury limitation (LOGICAL) trial.

Background: The effect of conservative vs. liberal oxygen therapy on outcomes of intensive care unit (ICU) patients with hypoxic ischaemic encephalopathy (HIE) is uncertain and will be evaluated in the Low Oxygen Intervention for Cardiac Arrest injury Limitation (LOGICAL) trial. Objective: The objective of this study was to summarise the protocol and statistical analysis plans for the LOGICAL trial. Design setting and participants: LOGICAL is a randomised clinical trial in adults in the ICU who are comatose with suspected HIE (i.e., those who have not obeyed commands following return of spontaneous circulation after a cardiac arrest where there is clinical concern about possible brain damage). The LOGICAL trial will include 1400 participants and is being conducted as a substudy of the Mega Randomised registry trial comparing conservative vs. liberal oxygenation targets in adults receiving unplanned invasive mechanical ventilation in the ICU (Mega-ROX). Main outcome measures: The primary outcome is survival with favourable neurological function at 180 days after randomisation as measured with the Extended Glasgow Outcome Scale (GOS-E). A favourable neurological outcome will be defined as a GOS-E score of lower moderate disability or better (i.e. a GOS-E score of 5-8). Secondary outcomes include survival time, day 180 mortality, duration of invasive mechanical ventilation, ICU length of stay, hospital length of stay, the proportion of patients discharged home, quality of life assessed at day 180 using the EQ-5D-5L, and cognitive function assessed at day 180 using the Montreal Cognitive Assessment (MoCA-blind). Conclusions: The LOGICAL trial will provide reliable data on the impact of conservative vs. liberal oxygen therapy in ICU patients with suspected HIE following resuscitation from a cardiac arrest. Prepublication of the LOGICAL protocol and statistical analysis plan prior to trial conclusion will reduce the potential for outcome-reporting or analysis bias. Trial registration: Australian and New Zealand Clinical Trials Registry (ACTRN12621000518864).

Blend to Limit OxygEN in ECMO: A RanDomised ControllEd Registry (BLENDER) Trial: Study Protocol and Statistical Analysis Plan.

Introduction: Critically ill patients supported with venoarterial extracorporeal membrane oxygenation (VA ECMO) are at risk of developing severe arterial hyperoxia, which has been associated with increased mortality. Lower saturation targets in this population may lead to deleterious episodes of severe hypoxia. This manuscript describes the protocol and statistical analysis plan for the Blend to Limit OxygEN in ECMO: A RanDomised ControllEd Registry (BLENDER) Trial. Design: The BLENDER trial is a pragmatic, multicentre, registry-embedded, randomised clinical trial., registered at ClinicalTrials.gov (NCT03841084) and approved by The Alfred Hospital Ethics Committee project ID HREC/50486/Alfred-2019. Participants and setting: Patients supported by VA ECMO for cardiogenic shock or cardiac arrest who are enrolled in the Australian national ECMO registry. Intervention: The study compares a conservative oxygenation strategy (target arterial saturations 92-96%) with a liberal oxygenation strategy (target 97-100%). Main Outcome Measures: The primary outcome is the number of intensive care unit (ICU)-free days for patients alive at day 60. Secondary outcomes include duration of mechanical ventilation, ICU and hospital mortality, the number of hypoxic episodes, neurocognitive outcomes, and health economic analyses. The 300-patient sample size enables us to detect a 3-day difference in ICU-free days at day 60, assuming a mean ICU-free days of 11 days, with a risk of type 1 error of 5% and power of 80%. Data will be analysed according to a predefined analysis plan. Findings will be disseminated in peer-reviewed publications. Conclusions: This paper details the protocol and statistical analysis plan for the BLENDER trial, a registry-embedded, multicentre interventional trial comparing liberal and conservative oxygenation strategies in VA ECMO.

Thirty years of ANZICS CORE: A clinical quality success story.

In 2023, the Australian and New Zealand Intensive Care Society (ANZICS) Registry run by the Centre for Outcomes and Resources Evaluation (CORE) turns 30 years old. It began with the Adult Patient Database, the Australian and New Zealand Paediatric Intensive Care Registry, and the Critical Care Resources Registry, and it now includes Central Line Associated Bloodstream Infections Registry, the Extra-Corporeal Membrane Oxygenation Database, and the Critical Health Resources Information System. The ANZICS Registry provides comparative case-mix reports, risk-adjusted clinical outcomes, process measures, and quality of care indicators to over 200 intensive care units describing more than 200 000 adult and paediatric admissions annually. The ANZICS CORE outlier management program has been a major contributor to the improved patient outcomes and provided significant cost savings to the healthcare sector. Over 200 peer-reviewed papers have been published using ANZICS Registry data. The ANZICS Registry was a vital source of information during the COVID-19 pandemic. Upcoming developments include reporting of long-term survival and patient-reported outcome and experience measures.

Using machine learning to predict bleeding after cardiac surgery.

OBJECTIVES: The primary objective was to predict bleeding after cardiac surgery with machine learning using the data from the Australia New Zealand Society of Cardiac and Thoracic Surgeons Cardiac Surgery Database, cardiopulmonary bypass perfusion database, intensive care unit database and laboratory results. METHODS: We obtained surgical, perfusion, intensive care unit and laboratory data from a single Australian tertiary cardiac surgical hospital from February 2015 to March 2022 and included 2000 patients undergoing cardiac surgery. We trained our models to predict either the Papworth definition or Dyke et al.'s universal definition of perioperative bleeding. Our primary outcome was the performance of our machine learning algorithms using sensitivity, specificity, positive and negative predictive values, accuracy, area under receiver operating characteristics curve (AUROC) and area under precision-recall curve (AUPRC). RESULTS: Of the 2000 patients undergoing cardiac surgery, 13.3% (226/2000) had bleeding using the Papworth definition and 17.2% (343/2000) had moderate to massive bleeding using Dyke et al.'s definition. The best-performing model based on AUPRC was the Ensemble Voting Classifier model for both Papworth (AUPRC 0.310, AUROC 0.738) and Dyke definitions of bleeding (AUPRC 0.452, AUROC 0.797). CONCLUSIONS: Machine learning can incorporate routinely collected data from various datasets to predict bleeding after cardiac surgery.

Measuring the Impact of ICU Strain on Mortality, After-Hours Discharge, Discharge Delay, Interhospital Transfer, and Readmission in Australia With the Activity Index.

OBJECTIVES: ICU resource strain leads to adverse patient outcomes. Simple, well-validated measures of ICU strain are lacking. Our objective was to assess whether the "Activity index," an indicator developed during the COVID-19 pandemic, was a valid measure of ICU strain. DESIGN: Retrospective national registry-based cohort study. SETTING: One hundred seventy-five public and private hospitals in Australia (June 2020 through March 2022). SUBJECTS: Two hundred seventy-seven thousand seven hundred thirty-seven adult ICU patients. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Data from the Australian and New Zealand Intensive Care Society Adult Patient Database were matched to the Critical Health Resources Information System. The mean daily Activity index of each ICU (census total of "patients with 1:1 nursing" + "invasive ventilation" + "renal replacement" + "extracorporeal membrane oxygenation" + "active COVID-19," divided by total staffed ICU beds) during the patient's stay in the ICU was calculated. Patients were categorized as being in the ICU during very quiet (Activity index < 0.1), quiet (0.1 to < 0.6), intermediate (0.6 to < 1.1), busy (1.1 to < 1.6), or very busy time-periods (≥ 1.6). The primary outcome was in-hospital mortality. Secondary outcomes included after-hours discharge from the ICU, readmission to the ICU, interhospital transfer to another ICU, and delay in discharge from the ICU. Median Activity index was 0.87 (interquartile range, 0.40-1.24). Nineteen thousand one hundred seventy-seven patients died (6.9%). In-hospital mortality ranged from 2.4% during very quiet to 10.9% during very busy time-periods. After adjusting for confounders, being in an ICU during time-periods with higher Activity indices, was associated with an increased risk of in-hospital mortality (odds ratio [OR], 1.49; 99% CI, 1.38-1.60), after-hours discharge (OR, 1.27; 99% CI, 1.21-1.34), readmission (OR, 1.18; 99% CI, 1.09-1.28), interhospital transfer (OR, 1.92; 99% CI, 1.72-2.15), and less delay in ICU discharge (OR, 0.58; 99% CI, 0.55-0.62): findings consistent with ICU strain. CONCLUSIONS: The Activity index is a simple and valid measure that identifies ICUs in which increasing strain leads to progressively worse patient outcomes.

Intravenous vitamin C for vasoplegia: A double-blinded randomised clinical trial (VALENCIA trial).

PURPOSE: To determine whether intravenous vitamin C compared with placebo, reduces vasopressor requirements in patients with vasoplegic shock. METHODS: Double-blinded, randomised clinical trial (RCT) conducted in two intensive care units in Perth, Australia. Vasopressor requirements at enrolment needed to be >10 µg/min noradrenaline after hypovolaemia was clinically excluded. Patients received either intravenous 1.5 g sodium ascorbate in 100 ml normal saline every 6 h for 5 days, or placebo (100 ml normal saline). The primary outcome was duration of vasopressor usage in hours. Secondary outcomes were ICU and hospital length of stay, and 28-day, ICU and hospital mortality. RESULTS: Of the 71 patients randomised (35 vitamin C, 36 placebo group), the median vasopressor duration was 44 h [95% CI, 37-54 h] and 55 h [95% CI, 33-66 h]) in the vitamin C and placebo groups (p = 0.057). ICU and hospital length of stay, mortality outcomes were similar between groups. CONCLUSIONS: In this RCT of patients with vasoplegic shock of at least moderate severity, the use of IV vitamin C compared with placebo did not significantly reduce the duration of vasopressors. TRIAL REGISTRATION: Prospective registration - trial number ACTRN12617001392358.

Mortality data from omission of early thromboprophylaxis in critically ill patients highlights the importance of an individualised diagnosis-related approach.

BACKGROUND: Venous thromboembolism (VTE) prophylaxis is effective in reducing VTE events, however, its impact on mortality is unclear. We examined the association between omission of VTE prophylaxis within the first 24 h after intensive care unit (ICU) admission and hospital mortality. METHODS: Retrospective analysis of prospectively collected data from the Australian New Zealand Intensive Care Society Adult Patient Database. Data were obtained for adult admissions between 2009 and 2020. Mixed effects logistic regression models were used to evaluate the association between omission of early VTE prophylaxis and hospital mortality. RESULTS: Of the 1,465,020 ICU admissions, 107,486 (7.3%) did not receive any form of VTE prophylaxis within the first 24 h after ICU admission without documented contraindication. Omission of early VTE prophylaxis was independently associated with 35% increased odds of in-hospital mortality (odds ratios (OR): 1.35; 95% CI: 1.31-1.41). The associations between omission of early VTE prophylaxis and mortality varied by admission diagnosis. In patients diagnosed with stroke (OR: 1.26, 95% CI: 1.05-1.52), cardiac arrest (OR: 1.85, 95% CI: 1.65-2.07) or intracerebral haemorrhage (OR: 1.48, 95% CI: 1.19-1.84), omission of VTE prophylaxis was associated with increased risk of mortality, but not in patients diagnosed with subarachnoid haemorrhage or head injury. CONCLUSIONS: Omission of VTE prophylaxis within the first 24 h after ICU admission was independently associated with increased risk of mortality that varied by admission diagnosis. Consideration of early thromboprophylaxis may be required for patients with stroke, cardiac arrest and intracerebral haemorrhage but not in those with subarachnoid haemorrhage or head injury. The findings highlight the importance of individualised diagnosis-related thromboprophylaxis benefit-harm assessments.

Effect of intravenous fluid volume on biomarkers of endothelial glycocalyx shedding and inflammation during initial resuscitation of sepsis.

PURPOSE: To investigate the effect of IV fluid resuscitation on endothelial glycocalyx (EG) shedding and activation of the vascular endothelium and inflammation. MATERIALS AND METHODS: A planned biomarker sub-study of the REFRESH trial in which emergency department (ED) patients) with suspected sepsis and hypotension were randomised to a restricted fluid/early vasopressor regimen or IV fluid resuscitation with later vasopressors if required (usual care). Blood samples were collected at randomisation (T0) and at 3 h (T3), 6 h (T6)- and 24 h (T24) for measurement of a range of biomarkers if EG shedding, endothelial cell activation and inflammation. RESULTS: Blood samples were obtained in 95 of 99 enrolled patients (46 usual care, 49 restricted fluid). Differences in the change in biomarker over time between the groups were observed for Hyaluronan (2.2-fold from T3 to T24, p = 0.03), SYN-4 (1.5-fold from T3 to T24, P = 0.01) and IL-6 (2.5-fold from T0 to T3, p = 0.03). No difference over time was observed between groups for the other biomarkers. CONCLUSIONS: A consistent signal across a range of biomarkers of EG shedding or of endothelial activation or inflammation was not demonstrated. This could be explained by pre-existing EG shedding or overlap between the fluid volumes administered in the two groups in this clinical trial. Trial registration Australia New Zealand Clinical Trials Registry ACTRN126160000006448 Registered 12 January 2016.

Effect of Deferoxamine on Post-Transfusion Iron, Inflammation, and In Vitro Microbial Growth in a Canine Hemorrhagic Shock Model: A Randomized Controlled Blinded Pilot Study.

Red blood cell (RBC) transfusion is associated with recipient inflammation and infection, which may be triggered by excessive circulating iron. Iron chelation following transfusion may reduce these risks. The aim of this study was to evaluate the effect of deferoxamine on circulating iron and inflammation biomarkers over time and in vitro growth of Escherichia coli (E. coli) following RBC transfusion in dogs with atraumatic hemorrhage. Anesthetized dogs were subject to atraumatic hemorrhage and transfusion of RBCs, then randomized to receive either deferoxamine or saline placebo of equivalent volume (n = 10 per group) in a blinded fashion. Blood was sampled before hemorrhage and then 2, 4, and 6 h later. Following hemorrhage and RBC transfusion, free iron increased in all dogs over time (both p < 0.001). Inflammation biomarkers interleukin-6 (IL6), CXC motif chemokine-8 (CXCL8), interleukin-10 (IL10), and keratinocyte-derived chemokine (KC) increased in all dogs over time (all p < 0.001). Logarithmic growth of E. coli clones within blood collected 6 h post-transfusion was not different between groups. Only total iron-binding capacity was different between groups over time, being significantly increased in the deferoxamine group at 2 and 4 h post-transfusion (both p < 0.001). In summary, while free iron and inflammation biomarkers increased post-RBC transfusion, deferoxamine administration did not impact circulating free iron, inflammation biomarkers, or in vitro growth of E. coli when compared with placebo.

The relationship between nursing skill mix and severity of illness of patients admitted in Australian and New Zealand intensive care units.

BACKGROUND: Critically ill patients in the intensive care environment require an appropriate nursing workforce to improve quality of care and patient outcomes. However, limited information exists as to the relationship between severity of illness and nursing skill mix in the intensive care. OBJECTIVE: The aim of this study was to describe the variation in nursing skill mix across different hospital types and to determine if this was associated with severity of illness of critically ill patients admitted to adult intensive care units (ICUs) in Australia and New Zealand. DESIGN & SETTING: A retrospective cohort study using the Australia and New Zealand Intensive Care Society Adult Patient Database (to provide information on patient demographics, severity of illness, and outcome) and the Critical Care Resources Registry (to provide information on annual nursing staffing levels and hospital type) from July 2014 to June 2020. Four hospital types (metropolitan, private, rural/regional, and tertiary) and three patient groups (elective surgical, emergency surgical, and medical) were examined. MAIN OUTCOME MEASURE: The main outcome measure was the proportion of critical care specialist registered nurses (RNs) expressed as a percentage of the full-time equivalent (FTE) of total RNs working within each ICU each year, as reported annually to the Critical Care Resources Registry. RESULTS: Data were examined for 184 ICUs in Australia and New Zealand. During the 6-year study period, 770 747 patients were admitted to these ICUs. Across Australia and New Zealand, the median percentage of registered nursing FTE with a critical care qualification for each ICU (n = 184) was 59.1% (interquartile range [IQR] = 48.9-71.6). The percentage FTE of critical care specialist RNs was highest in private [63.7% (IQR = 52.6-78.2)] and tertiary ICUs [58.1% (IQR = 51.2-70.2)], followed by metropolitan ICUs [56.0% (IQR = 44.5-68.9)] with the lowest in rural/regional hospitals [55.9% (IQR = 44.9-70.0)]. In ICUs with higher percentage FTE of critical care specialist RNs, patients had higher severity of illness, most notably in tertiary and private ICUs. This relationship was persistent across all hospital types when examining subgroups of emergency surgical and medical patients and in multivariable analysis after adjusting for the type of hospital and relative percentage of each diagnostic group. CONCLUSIONS: In Australian and New Zealand ICUs, the highest acuity patients are cared for by nursing teams with the highest percentage FTE of critical care specialist RNs. The Australian and New Zealand healthcare system has a critical care nursing workforce which scales to meet the acuity of ICU patients across Australia and New Zealand.

Lower gut dysbiosis and mortality in acute critical illness: a systematic review and meta-analysis.

BACKGROUND: The human gastrointestinal tract harbours a complex multi-kingdom community known as the microbiome. Dysbiosis refers to its disruption and is reportedly extreme in acute critical illness yet its clinical implications are unresolved. The review systematically evaluates the association between gut dysbiosis and clinical outcomes of patients early in critical illness. METHODS: Following PRISMA guidelines, a prospectively registered search was undertaken of MEDLINE and Cochrane databases for observational studies undertaking metagenomic sequencing of the lower gastrointestinal tract of critically ill adults and children within 72 h of admission. Eligible studies reported an alpha diversity metric and one or more of the primary outcome, in-hospital mortality, or secondary clinical outcomes. After aggregate data were requested, meta-analysis was performed for four studies with in-hospital mortality stratified to high or low Shannon index. RESULTS: The search identified 26 studies for systematic review and 4 had suitable data for meta-analysis. No effect of alpha diversity was seen on in-hospital mortality after binary transformation of Shannon index (odds ratio 0.52, CI 0.12-4.98, I2 = 0.64) however certainty of evidence is low. Pathogen dominance and commensal depletion were each more frequently associated with in-hospital mortality, adverse clinical and ecological sequelae, particularly overabundance of Enterococcus. CONCLUSIONS: There is a paucity of large, rigorous observational studies in this population. Globally, alpha diversity was dynamically reduced in early ICU admission in adults and children and was not associated with in-hospital mortality. The abundance of taxa such as Enterococcus spp. appears to offer greater predictive capacity for important clinical and ecological outcomes.

Twelve-month mortality outcomes for Indigenous and non-Indigenous people admitted to intensive care units in Australia: a registry-based data linkage study.

OBJECTIVE: To compare longer term (12-month) mortality outcomes for Indigenous and non-Indigenous people admitted to intensive care units (ICUs) in Australia. DESIGN, SETTING, PARTICIPANTS: Retrospective registry-based data linkage cohort study; analysis of all admissions of adults (16 years or older) to Australian ICUs, 1 January 2017 - 31 December 2019, as recorded in the Australian and New Zealand Intensive Care Society (ANZICS) Adult Patient Database (APD), linked using the SLK-581 key to National Death Index data. MAIN OUTCOME MEASURES: Unadjusted and adjusted mortality risk, censored at twelve months from the start of index ICU admission. Secondary outcomes were unadjusted and adjusted mortality twelve months from admission to the ICU. RESULTS: The APD recorded 330 712 eligible ICU admissions during 2017-2019 (65% of all ICU admissions registered), of which 11 322 were of Indigenous people (3.4%). Median age at admission was lower for Indigenous patients (51.2 [IQR, 36.7-63.6] years) than for non-Indigenous patients (66.5 [IQR, 52.7-76.1] years). Unadjusted mortality risk was similar for Indigenous and non-Indigenous patients (hazard ratio, 1.01; 95% CI, 0.97-1.06), but was higher for Indigenous patients after adjusting for age, admission diagnosis, illness severity, hospital type, jurisdiction, remoteness and socio-economic status (adjusted hazard ratio, 1.20; 95% CI, 1.14-1.27). Twelve-month mortality was higher for Indigenous than non-Indigenous patients (adjusted odds ratio, 1.24; 95% CI, 1.16-1.33). CONCLUSIONS: Twelve-month mortality outcomes are poorer for people admitted to ICUs in Australia than for the general population. Further, after adjusting for age and other factors, survival outcomes are poorer for Indigenous than non-Indigenous people admitted to ICUs. Critical illness may therefore contribute to shorter life expectancy among Indigenous Australians.

Economic evaluations for intensive care unit randomised clinical trials in Australia and New Zealand: Practical recommendations for researchers.

OBJECTIVES: Economic evaluations of intensive care unit (ICU) interventions have specific considerations, including how to cost ICU stays and accurately measure quality of life in survivors. The aim of this article was to develop best practice recommendations for economic evaluations alongside future ICU randomised controlled trials (RCTs). REVIEW METHODS: We collated our experience based on expert consensus across several recent economic evaluations to provide best-practice, practical recommendations for researchers conducting economic evaluations alongside RCTs in the ICU. Recommendations were structured according to the International Society for Pharmacoeconomics and Outcomes Research (ISPOR) Consolidated Health Economic Evaluation Reporting Standards (CHEERS) Task Force Report. RESULTS: We discuss recommendations across the components of economic evaluations, including: types of economic evaluation, the population and sample size, study perspective, comparators, time horizon, choice of health outcomes, measurement of effectiveness, measurement and valuation of quality of life, estimating resources and costs, analytical methods, and the increment cost-effectiveness ratio. We also provide future directions for research with regard to developing more robust economic evaluations for the ICU. CONCLUSION: Economic evaluations should be built alongside ICU RCTs and should be designed a priori using appropriate follow-up and data collection to capture patient-relevant outcomes. Further work is needed to improve the quality of data available for linkage in Australia as well as developing costing methods for the ICU and appropriate quality of life measurements.