Medicine (Austin & Northern Health) - Research Publications

Permanent URI for this collection

Search Results

Now showing 1 - 10 of 92
  • Item
    No Preview Available
    Development and validation of the Gender-Equity Model for Liver Allocation (GEMA) to prioritise candidates for liver transplantation: a cohort study
    Rodriguez-Peralvarez, ML ; Gomez-Orellana, AM ; Majumdar, A ; Bailey, M ; McCaughan, GW ; Gow, P ; Guerrero, M ; Taylor, R ; Guijo-Rubio, D ; Hervas-Martinez, C ; Tsochatzis, EA (ELSEVIER INC, 2023-03)
    BACKGROUND: The Model for End-stage Liver Disease (MELD) and its sodium-corrected variant (MELD-Na) have created gender disparities in accessing liver transplantation. We aimed to derive and validate the Gender-Equity Model for liver Allocation (GEMA) and its sodium-corrected variant (GEMA-Na) to amend such inequities. METHODS: In this cohort study, the GEMA models were derived by replacing creatinine with the Royal Free Hospital glomerular filtration rate (RFH-GFR) within the MELD and MELD-Na formulas, with re-fitting and re-weighting of each component. The new models were trained and internally validated in adults listed for liver transplantation in the UK (2010-20; UK Transplant Registry) using generalised additive multivariable Cox regression, and externally validated in an Australian cohort (1998-2020; Royal Prince Alfred Hospital [Australian National Liver Transplant Unit] and Austin Hospital [Victorian Liver Transplant Unit]). The study comprised 9320 patients: 5762 patients for model training, 1920 patients for internal validation, and 1638 patients for external validation. The primary outcome was mortality or delisting due to clinical deterioration within the first 90 days from listing. Discrimination was assessed by Harrell's concordance statistic. FINDINGS: 449 (5·8%) of 7682 patients in the UK cohort and 87 (5·3%) of 1638 patients in the Australian cohort died or were delisted because of clinical deterioration within 90 days. GEMA showed improved discrimination in predicting mortality or delisting due to clinical deterioration within the first 90 days after waiting list inclusion compared with MELD (Harrell's concordance statistic 0·752 [95% CI 0·700-0·804] vs 0·712 [0·656-0·769]; p=0·001 in the internal validation group and 0·761 [0·703-0·819] vs 0·739 [0·682-0·796]; p=0·036 in the external validation group), and GEMA-Na showed improved discrimination compared with MELD-Na (0·766 [0·715-0·818] vs 0·742 [0·686-0·797]; p=0·0058 in the internal validation group and 0·774 [0·720-0·827] vs 0·745 [0·690-0·800]; p=0·014 in the external validation group). The discrimination capacity of GEMA-Na was higher in women than in the overall population, both in the internal (0·802 [0·716-0·888]) and external validation cohorts (0·796 [0·698-0·895]). In the pooled validation cohorts, GEMA resulted in a score change of at least 2 points compared with MELD in 1878 (52·8%) of 3558 patients (25·0% upgraded and 27·8% downgraded). GEMA-Na resulted in a score change of at least 2 points compared with MELD-Na in 1836 (51·6%) of 3558 patients (32·3% upgraded and 19·3% downgraded). In the whole cohort, 3725 patients received a transplant within 90 days of being listed. Of these patients, 586 (15·7%) would have been differently prioritised by GEMA compared with MELD; 468 (12·6%) patients would have been differently prioritised by GEMA-Na compared with MELD-Na. One in 15 deaths could potentially be avoided by using GEMA instead of MELD and one in 21 deaths could potentially be avoided by using GEMA-Na instead of MELD-Na. INTERPRETATION: GEMA and GEMA-Na showed improved discrimination and a significant re-classification benefit compared with existing scores, with consistent results in an external validation cohort. Their implementation could save a clinically meaningful number of lives, particularly among women, and could amend current gender inequities in accessing liver transplantation. FUNDING: Junta de Andalucía and EDRF.
  • Item
    Thumbnail Image
    The association between peri-operative acute risk change (ARC) and long-term survival after cardiac surgery
    Coulson, TG ; Bailey, M ; Reid, CM ; Tran, L ; Mullany, DV ; Smith, JA ; Pilcher, D (WILEY, 2017-12)
    Acute risk change has been described as the difference in calculated mortality risk between the pre-operative and postoperative periods of cardiac surgery. We aimed to assess whether this was associated with long-term survival after cardiac surgery. We retrospectively analysed 22,570 cardiac surgical patients, with minimum and maximum follow-up of 1.0 and 6.7 years. Acute risk change was calculated as the arithmetic difference between pre- and postoperative mortality risk. 'Rising risk' represented an increase in risk from pre- to postoperative phase. The primary outcome was one-year mortality. Secondary outcomes included mortality at 3 and 5 years and time to death. Univariable and multivariable analyses were undertaken to examine the relationship between acute risk change and outcomes. Rising risk was associated with higher mortality (5.6% vs. 3.5%, p < 0.001). After adjusting for baseline risk, rising risk was independently associated with increased 1-year mortality (OR 2.6, 95%CI 2.2-3.0, p < 0.001). The association of rising risk with long-term survival was greatest in patients with highest baseline risk. Cox regression confirmed rising risk was associated with shorter time to death (HR 1.86, 1.68-2.05, p < 0.001). Acute risk change may represent peri-operative clinical events in combination with unmeasured patient risk and noise. Measuring risk change could potentially identify patterns of events that may be amenable to investigation and intervention. Further work with case review, and risk scoring with shared variables, may identify mechanisms, including the interaction between miscalibration of risk and true differences in peri-operative care.
  • Item
    Thumbnail Image
    Fibrinogen concentration and use of fibrinogen supplementation with cryoprecipitate in patients with critical bleeding receiving massive transfusion: a bi-national cohort study
    McQuilten, ZK ; Bailey, M ; Cameron, PA ; Stanworth, SJ ; Venardos, K ; Wood, EM ; Cooper, DJ (WILEY, 2017-10)
    We aimed to compare hypofibrinogenaemia prevalence in major bleeding patients across all clinical contexts, fibrinogen supplementation practice, and explore the relationship between fibrinogen concentrations and mortality. This cohort study included all adult patients from 20 hospitals across Australia and New Zealand who received massive transfusion between April 2011 and October 2015. Of 3566 patients, 2829 (79%) had fibrinogen concentration recorded, with a median first and lowest concentration of 2·0 g/l (interquartile range [IQR] 1·5-2·7) and 1·8 g/l (IQR 1·3-2·4), respectively. Liver transplant (1·7 g/l, IQR 1·2-2·1), trauma (1·8, IQR 1·3-2·5) and vascular surgery (1·9 g/l, IQR 1·4-2·5) had lower concentrations. Total median fibrinogen dose administered from all products was 7·3 g (IQR 3·3-13·0). Overall, 1732 (61%) received cryoprecipitate and 9 (<1%) fibrinogen concentrate. Time to cryoprecipitate issue in those with initial fibrinogen concentration <1 g/l was 2·5 h (IQR 1·2-4·3 h). After adjustment, initial fibrinogen concentration had a U-shaped association with in-hospital mortality [adjusted odds ratios: fibrinogen <1 g/l, 2·31 (95% confidence interval (CI) 1·48-3·60); 1-1·9 g/l, 1·29 (95% CI 0·99-1·67) and >4 g/l, 2·03 (95% CI 1·35-3·04), 2-4 g/l reference category]. The findings indicate areas for practice improvement including timely administration of cryoprecipitate, which is the most common source of concentrated fibrinogen in Australia and New Zealand.
  • Item
    Thumbnail Image
    Renal effects of an emergency department chloride-restrictive intravenous fluid strategy in patients admitted to hospital for more than 48 hours
    Yunos, NM ; Bellomo, R ; Taylor, DM ; Judkins, S ; Kerr, F ; Sutcliffe, H ; Hegarty, C ; Bailey, M (WILEY, 2017-12)
    OBJECTIVE: Patients commonly receive i.v. fluids in the ED. It is still unclear whether the choice of i.v. fluids in this setting influences renal or patient outcomes. We aimed to assess the effects of restricting i.v. chloride administration in the ED on the incidence of acute kidney injury (AKI). METHODS: We conducted a before-and-after trial with 5008 consecutive ED-treated hospital admissions in the control period and 5146 consecutive admissions in the intervention period. During the control period (18 February 2008 to 17 August 2008), patients received standard i.v. fluids. During the intervention period (18 February 2009 to 17 August 2009), we restricted all chloride-rich fluids. We used the Kidney Disease: Improving Global Outcomes (KDIGO) staging to define AKI. RESULTS: Stage 3 of KDIGO-defined AKI decreased from 54 (1.1%; 95% confidence interval [CI] 0.8-1.4) to 30 (0.6%; 95% CI 0.4-0.8) (P = 0.006). The rate of renal replacement therapy did not change, from 13 (0.3%; 95% CI 0.2-0.4) to 8 (0.2%; 95% CI 0.1-0.3) (P = 0.25). After adjustment for relevant covariates, liberal chloride therapy remained associated with a greater risk of KDIGO stage 3 (hazard ratio 1.82; 95% CI 1.13-2.95; P = 0.01). On sensitivity assessment after removing repeat admissions, KDIGO stage 3 remained significantly lower in the intervention period compared with the control period (P = 0.01). CONCLUSION: In a before-and-after trial, a chloride-restrictive strategy in an ED was associated with a significant decrease in the incidence of stage 3 of KDIGO-defined AKI.
  • Item
    Thumbnail Image
    ICU mortality is increased with high admission serum osmolarity in all patients other than those admitted with pulmonary diseases and hypoxia
    Bihari, S ; Prakash, S ; Peake, SL ; Bailey, M ; Pilcher, D ; Bersten, A (WILEY, 2017-08)
    BACKGROUND AND OBJECTIVE: High serum osmolarity has been shown to be lung protective. There is lack of clinical studies evaluating the impact on outcomes such as mortality. We aimed to examine the effect of serum osmolarity on intensive care unit (ICU) mortality in critically ill patients METHODS: Data from January 2000 to December 2012 was accessed using the Australian and New Zealand Intensive Care Society (ANZICS) Clinical Outcomes and Resource Evaluation (CORE) database. A total of 509 180 patients were included. Serum osmolarity was calculated from data during the first 24 h of ICU admission. Predefined subgroups (Acute Physiology and Chronic Health Evaluation (APACHE) III diagnostic codes), including patients with acute pulmonary diagnoses, were examined. The effect of serum osmolarity on ICU mortality was assessed with analysis adjusted for illness severity (serum sodium, glucose and urea component removed) and year of admission. Results are presented as OR (95% CI) referenced against a serum osmolarity of 290-295 mmol/L. RESULTS: The ICU mortality was elevated at each extremes of serum osmolarity (U-shaped relationship). A similar relationship was found in various subgroups, with the exception of patients with pulmonary diagnoses in whom ICU mortality was not influenced by high serum osmolarity and was different from other non-pulmonary subgroups (P < 0.01). Any adverse associations with high serum osmolarity in pulmonary patients were confined to patients with a PaO2 /FiO2 ratio > 200. CONCLUSION: High admission serum osmolarity was not associated with increased odds for ICU death in pulmonary patients, unlike other subgroup of patients, and could be a potential area for future interventional therapy.
  • Item
    Thumbnail Image
    Duration of platelet storage and outcomes of critically ill patients
    Flint, A ; Aubron, C ; Bailey, M ; Bellomo, R ; Pilcher, D ; Cheng, AC ; Hegarty, C ; Reade, MC ; McQuilten, Z (WILEY, 2017-03)
    BACKGROUND: The storage duration of platelet (PLT) units is limited to 5 to 7 days. This study investigates whether PLT storage duration is associated with patient outcomes in critically ill patients. STUDY DESIGN AND METHODS: This study was a retrospective analysis of critically ill patients admitted to the intensive care unit (ICU) of two hospitals in Australia who received one or more PLT transfusions from 2008 to 2014. Storage duration was approached in several different ways. Outcome variables were hospital mortality and ICU-acquired infection. Associations between PLT storage duration and outcomes were evaluated using multiple logistic regression and also by Cox regression. RESULTS: Among 2250 patients who received one or more PLT transfusions while in the ICU, the storage duration of PLTs was available for 64% of patients (1430). In-hospital mortality was 22.1% and ICU infection rate 7.2%. When comparing patients who received PLTs of a maximum storage duration of not more than 3, 4, or 5 days, there were no significant differences in baseline characteristics. After confounders were adjusted for, the storage duration of PLTs was not independently associated with mortality (4 days vs. ≤3 days, odds ratio [OR] 0.88, 95% confidence interval [CI] 0.59-1.30; 5 days vs. ≤3 days, OR 0.97, 95% CI 0.68-1.37) or infection (4 days vs. ≤3 days, OR 0.71, 95% CI 0.39-1.29; 5 days vs. ≤3 days, OR 1.11, 95% CI 0.67-1.83). Similar results were obtained regardless of how storage duration of PLTs was approached. CONCLUSIONS: In this large observational study in a heterogeneous ICU population, storage duration of PLTs was not associated with an increased risk of mortality or infection.
  • Item
    Thumbnail Image
    Characteristics, incidence and outcome of patients admitted to intensive care because of pulmonary embolism
    Winterton, D ; Bailey, M ; Pilcher, D ; Landoni, G ; Bellomo, R (WILEY, 2017-02)
    BACKGROUND AND OBJECTIVE: Despite the clinical significance of major pulmonary embolism (PE), little is known about patients with a presentation severe enough to lead to intensive care unit (ICU) admission and nothing is known about PE requiring mechanical ventilation (MV). We aimed to examine the characteristics, incidence and outcome of patients with PE as their reason for ICU admission. METHODS: We performed a retrospective, cross-sectional study of patients admitted to Australia's and New Zealand's ICUs because of PE from 2005 to 2013. We compared survivors with non-survivors and mechanically ventilated with non-ventilated patients. We analysed variations in incidence and mortality over time. RESULTS: We studied 2797 patients. PE accounted for 0.3% of all ICU admissions and had a population incidence of 11 cases/million people/year, which increased significantly during the study period (P < 0.0001). Co-morbidities were common (24.1%) and the emergency department was the most common admission source (49.1%). However, patients who died were more commonly admitted from the wards (P < 0.0001). Overall mortality was 14.1% but reached 41.0% in patients requiring MV (P < 0.0001). Illness severity-adjusted mortality rate did not change during the study period. CONCLUSION: The incidence of PE requiring admission to ICU has increased over time; its mortality rate remains high, especially in mechanically ventilated patients, and its prognosis has not improved over time. Our findings imply the need for focused research in this high-risk patient group.
  • Item
    Thumbnail Image
    Results of the Australasian (Trans-Tasman Oncology Group) radiotherapy benchmarking exercise in preparation for participation in the PORTEC-3 trial
    Jameson, MG ; McNamara, J ; Bailey, M ; Metcalfe, PE ; Holloway, LC ; Foo, K ; Do, V ; Mileshkin, L ; Creutzberg, CL ; Khaw, P (WILEY-BLACKWELL, 2016-08)
    INTRODUCTION: Protocol deviations in Randomised Controlled Trials have been found to result in a significant decrease in survival and local control. In some cases, the magnitude of the detrimental effect can be larger than the anticipated benefits of the interventions involved. The implementation of appropriate quality assurance of radiotherapy measures for clinical trials has been found to result in fewer deviations from protocol. This paper reports on a benchmarking study conducted in preparation for the PORTEC-3 trial in Australasia. METHODS: A benchmarking CT dataset was sent to each of the Australasian investigators, it was requested they contour and plan the case according to trial protocol using local treatment planning systems. These data was then sent back to Trans-Tasman Oncology Group for collation and analysis. RESULTS: Thirty three investigators from eighteen institutions across Australia and New Zealand took part in the study. The mean clinical target volume (CTV) volume was 383.4 (228.5-497.8) cm(3) and the mean dose to a reference gold standard CTV was 48.8 (46.4-50.3) Gy. CONCLUSIONS: Although there were some large differences in the contouring of the CTV and its constituent parts, these did not translate into large variations in dosimetry. Where individual investigators had deviations from the trial contouring protocol, feedback was provided. The results of this study will be used to compare with the international study QA for the PORTEC-3 trial.
  • Item
    Thumbnail Image
    The haemodynamic effects of intravenous paracetamol (acetaminophen) in healthy volunteers: a double-blind, randomized, triple crossover trial
    Chiam, E ; Weinberg, L ; Bailey, M ; McNicol, L ; Bellomo, R (WILEY, 2016-04)
    AIM: The haemodynamic effects of intravenous paracetamol have not been systematically investigated. We compared the physiological effects of intravenous mannitol-containing paracetamol, and an equivalent dosage of mannitol, and normal saline 0.9% in healthy volunteers. METHODS: We performed a blinded, triple crossover, randomized trial of 24 adult healthy volunteers. Participants received i.v. paracetamol (1 g paracetamol +3.91 g mannitol 100 ml(-1) ), i.v. mannitol (3.91 g mannitol 100 ml(-1) ) and i.v. normal saline (100 ml). Composite primary end points were changes in mean arterial pressure (MAP), systolic blood pressure (SBP) and diastolic blood pressure (DBP) measured pre-infusion, during a 15 min infusion period and over a 45 min observation period. Systemic vascular resistance index (SVRI) and cardiac index were measured at the same time points. RESULTS: Infusion of paracetamol induced a transient yet significant decrease in blood pressures from pre-infusion values (MAP -1.85 mmHg, 95% CI -2.6, -1.1, SBP -0.54 mmHg, 95% CI -1.7, 0.6 and DBP -1.92 mmHg, 95% CI -2.6, -1.2, P < 0.0001), associated with a transient reduction in SVRI and an increase in cardiac index. Changes were observed, but to a lesser extent with normal saline (MAP -0.15 mmHg, SBP +1.44 mmHg, DBP --0.73 mmHg, P < 0.0001), but not with mannitol (MAP +1.47 mmHg, SBP +4.03 mmHg, DBP +0.48 mmHg, P < 0.0001). CONCLUSIONS: I.v. paracetamol caused a transient decrease in blood pressure immediately after infusion. These effects were not seen with mannitol or normal saline. The physiological mechanism was consistent with vasodilatation. This study provides plausible physiological data in a healthy volunteer setting, supporting transient changes in haemodynamic variables with i.v. paracetamol and justifies controlled studies in the peri-operative and critical care setting.
  • Item
    No Preview Available
    Cost-Effectiveness of Erythropoietin in Traumatic Brain Injury: A Multinational Trial-Based Economic Analysis
    Knott, RJ ; Harris, A ; Higgins, A ; Nichol, A ; French, C ; Little, L ; Haddad, S ; Presneill, J ; Arabi, Y ; Bailey, M ; Cooper, DJ ; Duranteau, J ; Huet, O ; Mak, A ; McArthur, C ; Pettila, V ; Skrifvars, MB ; Vallance, S ; Varma, D ; Wills, J ; Bellomo, R (MARY ANN LIEBERT, INC, 2019-09-01)
    The EPO-TBI multi-national randomized controlled trial found that erythropoietin (EPO), when compared to placebo, did not affect 6-month neurological outcome, but reduced illness severity-adjusted mortality in patients with traumatic brain injury (TBI), making the cost-effectiveness of EPO in TBI uncertain. The current study uses patient-level data from the EPO-TBI trial to evaluate the cost-effectiveness of EPO in patients with moderate or severe TBI from the healthcare payers' perspective. We addressed the issue of transferability in multi-national trials by estimating costs and effects for specific geographical regions of the study (Australia/New Zealand, Europe, and Saudi Arabia). Unadjusted mean quality-adjusted life-years (QALYs; 95% confidence interval [CI]) at 6 months were 0.027 (0.020-0.034; p < 0.001) higher in the EPO group, with an adjusted QALY increment of 0.014 (0.000-0.028; p = 0.04). Mean unadjusted costs (95% CI) were $US5668 (-9191 to -2144; p = 0.002) lower in the treatment group; controlling for baseline IMPACT-TBI score and regional heterogeneity reduced this difference to $2377 (-12,446 to 7693; p = 0.64). For a willingness-to-pay threshold of $US50,000 per QALY, 71.8% of replications were considered cost-effective. Therefore, we did not find evidence that EPO was significantly cost-effective in the treatment of moderate or severe TBI at 6-month follow-up.