Publications by authors named "Eldho Paul"

200 Publications

Abnormal one-year post-lung transplant spirometry is a significant predictor of increased mortality and chronic lung allograft dysfunction.

J Heart Lung Transplant 2021 Dec 21;40(12):1649-1657. Epub 2021 Aug 21.

Lung Transplant Service, Alfred Hospital, Melbourne, Australia; Department of Medicine, Central Clinical School, Monash University, Melbourne, Australia.

Background: The prognostic value of evaluating spirometry at a fixed time point using standardized population reference has not previously been evaluated. Our aim was to assess the association between spirometric phenotype at 12 months (Spiro), survival and incidence of chronic lung allograft dysfunction (CLAD) in bilateral lung transplant recipients.

Methods: We conducted a retrospective cohort study of bilateral lung transplant recipients transplanted between January 2003 and September 2012. We defined Spiro as the mean of the 2 prebronchodilator FEV measurements 12-month post-transplant. Normal spirometry was defined as FEV/FVC ≥0.7 and FEV1≥80% and FVC≥80% predicted population-based values for that recipient. Abnormal spirometry was defined as failure to attain normal function by 12-months. We used a Cox regression model to assess the association between Spiro, survival, and CLAD. We used logistic regression to assess potential pretransplant donor and recipient factors associated with abnormal Spiro RESULTS: One hundred and eleven (51%) lung transplant recipients normalized their Spiro. Normal Spiro was associated improved survival (hazard ratio [HR] 0.60, 95% confidence interval [CI] 0.41-0.88], p = 0.009. Each 10% decrement in FEV increased the risk of death in a stepwise fashion. Additionally, CLAD was reduced in those with normal Spiro (HR:0.65, 95%CI:0.46-0.92, p = 0.016). Donor smoking history (OR:2.93, 95% CI:1.21-7.09; p = 0.018) and mechanical ventilation time in hours (OR:1.03, 95% CI:1.004-1.05; p = 0.02) were identified as independent predictors of abnormal Spiro.

Conclusions: Abnormal Spiro is associated with increased mortality and the development of CLAD. The effect is dose dependent with increased dysfunction corresponding to increased risk. This assessment of phenotype at 12-months can easily be incorporated into standard of care.
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http://dx.doi.org/10.1016/j.healun.2021.08.003DOI Listing
December 2021

Physical activity decline is disproportionate to decline in pulmonary physiology in IPF.

Respirology 2021 Dec 26;26(12):1152-1159. Epub 2021 Aug 26.

Lung Fibrosis Service, Department of General Respiratory Medicine and Lung Transplantation, Alfred Hospital, Melbourne, Victoria, Australia.

Background And Objective: Patients with idiopathic pulmonary fibrosis (IPF) have reduced levels of daily physical activity (DPA); however, little is known about how DPA changes as disease progresses. We aimed to (i) describe change in DPA over 12 months, (ii) analyse its association with conventional markers of disease severity and quality of life and (iii) assess DPA as a prognostic tool.

Methods: A total of 54 patients with IPF had DPA monitored at baseline and at 6 and 12 months with a SenseWear armband for 7 consecutive days. Participants completed the Hospital Anxiety and Depression scale, St George's Respiratory Questionnaire and Leicester Cough Questionnaire at each time point and provided clinical data including forced vital capacity (FVC), diffusion capacity of carbon monoxide and 6-min walk distance (6MWD).

Results: Baseline and 12-month daily step count (DSC) were 3887 (395) and 3326 (419), respectively. A significant reduction in DSC (mean = 645 [260], p = 0.02) and total energy expenditure (mean = 486 kJ [188], p = 0.01) was demonstrated at 12 months. The decline in DSC over 12 months was proportionally larger than decline in lung function. Annual change in DPA had weak to moderate correlation with annual change in FVC % predicted and 6MWD (range r = 0.34-0.45). Change in physical activity was not associated with long-term survival.

Conclusion: In IPF, decline in DPA over 12 months is significant and disproportionate to decline in pulmonary physiology and may be a useful tool for assessment of disease progression.
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http://dx.doi.org/10.1111/resp.14137DOI Listing
December 2021

Changing Demographics of Stroke Mimics in Present Day Stroke Code Era: Need of a Streamlined Clinical Assessment for Emergency Physicians.

J Neurosci Rural Pract 2021 Jul 16;12(3):550-554. Epub 2021 Jun 16.

Department of Neurology, Rajagiri Hospital, Kochi, India.

 There is an apparently high incidence of stroke mimics in the present-day stroke code era. The reason being is the intense pressure to run with time to achieve the "time is brain"-based goals.  The present study was a retrospective analysis of the data collected over a duration of 6 months from April 2019 to September 2019. We observed the incidence of stroke mimics among the patients for whom rapid response stroke code was activated during the study period. We also performed a logistic regression analysis to identify the clinical features which can act as strong predictors of stroke and mimics.  A total of 314 stroke codes were activated of which 256 (81.5%) were stroke and 58 (18.5%) were the mimics. Functional disorders and epilepsy were the most common mimics (24.1% each). Female gender ( = 0.04; odds ratio [OR] 2.9[1.0-8.8]), isolated impairment of consciousness ( < 0.01; OR 4.3[1.5-12.6]), and isolated dysarthria ( < 0.001) were the strong independent predictors for a stroke mimic. Hemiparesis was the strong independent predictor for a stroke ( < 0.001; OR 0.0[0.0-0.1]).  In the present epoch of rapid response stroke management, a streamlined assessment by the emergency physicians based on the above clinical predictors may help in avoiding the misdiagnosis of a mimic as stroke.
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http://dx.doi.org/10.1055/s-0041-1727419DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8381026PMC
July 2021

The impact of distance on post-ICU disability.

Aust Crit Care 2021 Jul 25. Epub 2021 Jul 25.

Australian and New Zealand Intensive Care Research Centre, Melbourne, Australia; The Alfred Hospital, Melbourne, Australia; Monash Partners Academic Health Science Centre, Australia. Electronic address:

Background: Nonurban residential living is associated with adverse outcomes for a number of chronic health conditions. However, it is unclear what effect it has amongst survivors of critical illness.

Objectives: The purpose of this study is to determine whether patients living greater than 50 km from the treating intensive care unit (ICU) have disability outcomes at 6 months that differ from people living within 50 km.

Methods: This was a multicentre, prospective cohort study conducted in five metropolitan ICUs. Participants were adults admitted to the ICU, who received >24 h of mechanical ventilation and survived to hospital discharge. In a secondary analysis of these data, the cohort was dichotomised based on residential distance from the treating ICU: <50 km and ≥50 km. The primary outcome was patient-reported disability using the 12-item World Health Organization's Disability Assessment Schedule (WHODAS 2.0). This was recorded at 6 months after ICU admission by telephone interview. Secondary outcomes included health status as measured by EQ-5D-5L return to work and psychological function as measured by the Hospital Anxiety and Depression Scale (HADS). Multivariable logistic regression was used to assess the association between distance from the ICU and moderate to severe disability, adjusted for potential confounders. Variables included in the multivariable model were deemed to be clinically relevant and had baseline imbalance between groups (p < 0.10). These included marital status and hours of mechanical ventilation. Sensitivity analysis was also conducted using distance in kilometres as a continuous variable.

Results: A total of 262 patients were enrolled, and 169 (65%) lived within 50 km of the treating ICU and 93 (35%) lived ≥50 km from the treating ICU (interquartile range [IQR] 10-664 km). There was no difference in patient-reported disability at 6 months between patients living <50 km and those living ≥50 km (WHODAS total disability % [IQR] 10.4 [2.08-25] v 14.6 [2.08-20.8], P = 0.74). There was also no difference between groups for the six major life domains of the WHODAS. There was no difference in rates of anxiety or depression as measured by HADS score (HADS anxiety median [IQR] 4 [1-7] v 3 [1-7], P = 0.60) (HADS depression median [IQR] 3 [1-6] v 3 [1-6], P = 0.62); health status as measured by EQ-5D (mean [SD] 66.7 [20] v 69.8 [22.2], P = 0.24); or health-related unemployment (% (N) 39 [26] v 25 [29.1], P = 0.61). After adjusting for confounders, living ≥50 km from the treating ICU was not associated with increased disability (odds ratio 0.61, 95% confidence interval: 0.33-1.16; P = 0.13) CONCLUSIONS: Survivors of intensive care in Victoria, Australia, who live at least 50 km from the treating ICU did not have greater disability than people living less than 50 km at 6 months after discharge. Living 50 km or more from the treating ICU was not associated with disability, nor was it associated with anxiety or depression, health status, or unemployment due to health.
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http://dx.doi.org/10.1016/j.aucc.2021.05.013DOI Listing
July 2021

Comparison of clinical characteristics and outcomes between alcohol-induced and gallstone-induced acute pancreatitis: An Australian retrospective observational study.

SAGE Open Med 2021 10;9:20503121211030837. Epub 2021 Jul 10.

Department of Intensive Care Medicine, Frankston Hospital, Frankston, VIC, Australia.

Objectives: To compare the characteristics and outcomes of patients presenting to hospital with alcohol-induced and gallstone-induced acute pancreatitis.

Methods: Retrospective study of all patients with alcohol-induced or gallstone-induced pancreatitis during the period 1 June 2012 to 31 May 2016. The primary outcome measure was hospital mortality. Secondary outcome measures included hospital length of stay, requirements for intensive care unit admission, intensive care unit mortality, mechanical ventilation, renal replacement therapy, requirement of inotropes and total parenteral nutrition.

Results: A total of 642 consecutive patients (49% alcohol; 51% gallstone) were included. No statistically significant differences were found between alcohol-induced and gallstone-induced acute pancreatitis with respect to hospital mortality, requirement for intensive care unit admission, intensive care unit mortality and requirement for mechanical ventilation, renal replacement therapy, inotropes or total parenteral nutrition. There was significant difference in hospital length of stay (3.07 versus 4.84;   0.0001). On multivariable regression analysis, Bedside Index of Severity in Acute Pancreatitis score (estimate: 0.393; standard error: 0.058;  < 0.0001) and admission haematocrit (estimate: 0.025; standard error: 0.008;  = 0.002) were found to be independently associated with prolonged hospital length of stay.

Conclusion: Hospital mortality did not differ between patients with alcohol-induced and gallstone-induced acute pancreatitis. The duration of hospital stay was longer with gallstone-induced pancreatitis. Bedside Index of Severity in Acute Pancreatitis score and admission haematocrit were independently associated with hospital length of stay.
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http://dx.doi.org/10.1177/20503121211030837DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8274077PMC
July 2021

Long-Term Functional Outcome and Quality of Life Following In-Hospital Cardiac Arrest-A Longitudinal Cohort Study.

Crit Care Med 2021 Jun 24. Epub 2021 Jun 24.

Australian and New Zealand Intensive Care Research Centre (ANZIC-RC), School of Public Health and Preventive Medicine, Monash University, Melbourne, VIC, Australia. Department of Physiotherapy, St. Vincent's Hospital, Melbourne, VIC, Australia. Department of Intensive Care, The Austin Hospital, Melbourne, VIC, Australia. Department of Physiotherapy, The Alfred Hospital, Melbourne,VIC, Australia.

Objectives: To evaluate the functional outcome and health-related quality of life of in-hospital cardiac arrest survivors at 6 and 12 months.

Design: A longitudinal cohort study.

Setting: Seven metropolitan hospitals in Australia.

Patients: Data were collected for hospitalized adults (≥ 18 yr) who experienced in-hospital cardiac arrest, defined as "a period of unresponsiveness, with no observed respiratory effort and the commencement of external cardiac compressions."

Interventions: None.

Measurements And Main Results: Prior to hospital discharge, patients were approached for consent to participate in 6-month and 12-month telephone interviews. Outcomes included the modified Rankin Scale, Barthel Index, Euro-Quality of Life 5 Dimension 5 Level, return to work and hospital readmissions. Forty-eight patients (80%) consented to follow-up interviews. The mean age of participants was 67.2 (± 15.3) years, and 33 of 48 (68.8%) were male. Good functional outcome (modified Rankin Scale score ≤ 3) was reported by 31 of 37 participants (83.8%) at 6 months and 30 of 33 (90.9%) at 12 months. The median Euro-Quality of Life-5D index value was 0.73 (0.33-0.84) at 6 months and 0.76 (0.47-0.88) at 12 months. The median Euro-Quality of Life-Visual Analogue Scale score at 6 months was 70 (55-80) and 75 (50-87.5) at 12 months. Problems in all Euro-Quality of Life-5D-5 L dimension were reported frequently at both time points. Hospital readmission was reported by 23 of 37 patients (62.2%) at 6 months and 16 of 33 (48.5%) at 12 months. Less than half of previously working participants had returned to work by 12 months.

Conclusions: The majority of in-hospital cardiac arrest survivors had a good functional outcome and health-related quality of life at 6 months, and this was largely unchanged at 12 months. Despite this, many reported problems with mobility, self-care, usual activities, pain, and anxiety/depression. Return to work rates was low, and hospital readmissions were common.
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http://dx.doi.org/10.1097/CCM.0000000000005118DOI Listing
June 2021

Measured energy expenditure in mildly hypothermic critically ill patients with traumatic brain injury: A sub-study of a randomized controlled trial.

Clin Nutr 2021 06 24;40(6):3875-3882. Epub 2021 May 24.

Australian and New Zealand Intensive Care Research Centre, School of Public Health and Preventative Medicine, Monash University, St Kilda Road, Melbourne, 3004, Australia; Intensive Care Unit, The Alfred Hospital, Commercial Road, Melbourne, 3004, Australia.

Background & Aims: Prophylactic hypothermia, often used in critically ill patients with traumatic brain injury, reduces energy expenditure and may affect energy delivered by nutrition therapy. The primary objective of this study was to measure energy expenditure in hypothermic patients over the first 3 days after traumatic brain injury (TBI). Secondary objectives included comparison of measured energy expenditure and nutrition delivery to day 7.

Methods: A prospective sub-study of a randomized controlled trial conducted in patients with severe TBI, investigating prophylactic hypothermia (33-35 °C) as a neuroprotective therapy. In two centers, indirect calorimetry was initiated within 24 h of randomization and repeated up to twice daily to day 7. Data are presented as n (%), mean (standard deviation (SD)), median [interquartile range (IQR)], and mean difference (95% confidence interval (CI)).

Results: Forty patients were included (20 in each group), with 17 patients in the hypothermic and 16 in the normothermic group having an indirect calorimetry measurement in the first 3 days. Over the first 3 days, the mean temperature in the hypothermic and normothermic groups was 33.5 (0.6) ºC (n = 17) and 37 (0.5) ºC (n = 16), p < 0.0001, and the mean measured energy expenditure, was 21 (5) and 27 (4) kcal/kg, p = 0.002, representing a mean difference of 5 (95% CI: 2-8) kcal/kg. Energy expenditure was 20% (95% CI: 9.5-29%) less in hypothermia patients compared to normothermia patients. Hypothermia patients also had higher gastric residual volumes across the 7 day study period (438 (237) mls vs 184 (103) mls, p < 0.0001) and higher use of metoclopramide and erythromycin as prokinetics. Despite enteral nutrition intolerance, hypothermia patients received 93% of measured energy expenditure over 7 days.

Conclusion: In TBI patients, energy expenditure was 20% less when receiving prophylactic hypothermia compared to normothermia. Greater gastric residual volumes, use of prokinetics and energy delivery that approximated measured energy expenditure was also observed in hypothermia patients.

Trial Registry Number: POLAR-RCT: clinicaltrials.gov Identifier: NCT00987688; Anzctr.org.au Identifier: ACTRN12609000764235. This sub-study was not registered separately.
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http://dx.doi.org/10.1016/j.clnu.2021.05.012DOI Listing
June 2021

Gelfoam slurry tract occlusion after computed tomography-guided percutaneous lung biopsy: Does it prevent major pneumothorax?

J Med Imaging Radiat Oncol 2021 Oct 13;65(6):678-685. Epub 2021 Jun 13.

Monash Medical Centre, Melbourne, Victoria, Australia.

Introduction: Computed tomography (CT)-guided lung biopsy is a frequently performed procedure in the diagnostic workup for suspicious lung nodules that can be complicated by pneumothorax. This retrospective study assessed the efficacy of biopsy tract occlusion with a gelatin sponge slurry for preventing post-biopsy pneumothorax.

Methods: Retrospective analysis was conducted on consecutive adult patients who underwent CT-guided lung biopsy over a 10-year period. Age, gender, existing chronic obstructive pulmonary disease (COPD), evidence of emphysema on CT, location of the lesion and the presence of pneumothorax on post-procedure CT and 4-h chest radiograph were recorded.

Results: Two hundred and ninety-six patients were included (126 patients in the non-gelfoam group and 170 in the gelfoam group). When gelfoam was used, risk of developing an immediate pneumothorax was lower (P = 0.032). Patients with emphysema were 2.4 times more likely to develop a delayed pneumothorax without gelfoam (P = 0.034). There was a significantly higher risk of both immediate and delayed pneumothorax in non-peripheral lesions without gelfoam (P = 0.001 and P = 0.002, respectively). The frequency of requiring a chest tube to treat a pneumothorax was 86% lower when gelfoam was used (P = 0.012).

Conclusion: Gelfoam is effective in preventing immediate pneumothorax. In patients with emphysema, there was a significantly higher risk of delayed pneumothorax without gelfoam. Additionally, non-peripheral lesions were more likely to develop pneumothorax when gelfoam was not used. The use of gelfoam was especially important in preventing the development of major pneumothoraces that would require drainage with a chest tube.
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http://dx.doi.org/10.1111/1754-9485.13256DOI Listing
October 2021

Routine Frailty Screening in Critical Illness: A Population-Based Cohort Study in Australia and New Zealand.

Chest 2021 Oct 4;160(4):1292-1303. Epub 2021 Jun 4.

Australian and New Zealand Intensive Care Research Centre, Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, VIC, Australia; Department of Intensive Care, Alfred Hospital, Melbourne, VIC, Australia; Centre for Outcome and Resource Evaluation, Australian and New Zealand Intensive Care Society, Melbourne, VIC, Australia.

Background: Frailty is associated with poor outcomes in critical illness. However, it is unclear whether frailty screening on admission to the ICU can be conducted routinely at the population level and whether it has prognostic importance.

Research Question: Can population-scale frailty screening with the Clinical Frailty Scale (CFS) be implemented for critically ill adults in Australia and New Zealand (ANZ) and can it identify patients at risk of negative outcomes?

Study Design And Methods: We conducted a binational prospective cohort study of critically ill adult patients admitted between July 1, 2018, and June 30, 2020, in 175 ICUs in ANZ. We classified frailty with the CFS on admission to the ICU. The primary outcome was in-hospital mortality; secondary outcomes were length of stay (LOS), discharge destination, complications (delirium, pressure injury), and duration of survival.

Results: We included 234,568 critically ill patients; 45,245 (19%) were diagnosed as living with frailty before ICU admission. Patients with vs without frailty had higher in-hospital mortality (16% vs 5%; P < .001), delirium (10% vs 4%; P < .001), longer LOS in the ICU and hospital, and increased new chronic care discharge (3% vs 1%; P < .001), with worse outcomes associated with increasing CFS category. Of patients with very severe frailty (CFS score, 8), 39% died in hospital vs 2% of very fit patients (CFS score, 1; multivariate categorical CFS score, 8 [reference, 1]; OR, 7.83 [95% CI, 6.39-9.59]; P < .001). After adjustment for illness severity, frailty remained highly significantly predictive of mortality, including among patients younger than 50 years, with improvement in the area under the receiver operating characteristic curve of the Acute Physiology and Chronic Health Evaluation III-j score to 0.882 (95% CI, 0.879-0.885) from 0.868 (95% CI, 0.866-0.871) with the addition of frailty (P < .001).

Interpretation: Large-scale population screening for frailty degree in critical illness was possible and prognostically important, with greater frailty (especially CFS score of ≥ 6) associated with worse outcomes, including among younger patients.
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http://dx.doi.org/10.1016/j.chest.2021.05.049DOI Listing
October 2021

Treatable traits in an English cohort: prevalence and predictors of future decline in lung function and quality of life in COPD.

ERJ Open Res 2021 Apr 31;7(2). Epub 2021 May 31.

Centre for Medicine Use and Safety, Faculty of Pharmacy and Pharmaceutical Sciences, Monash University, Melbourne, Australia.

Background: "Treatable traits (TTs)" is a precision medicine approach for facilitating multidimensional assessment of every patient with chronic airway disease, in order to determine the core traits associated with disease outcomes where targeted treatments may be applied.

Objectives: To determine the prevalence of TTs in chronic obstructive pulmonary disease (COPD) and which traits predict future decline in lung function and quality of life (QoL).

Methods: A 4-year longitudinal evaluation was conducted using data from 3726 participants in the English Longitudinal Study of Ageing (ELSA). TTs were identified based on published recommendations. Traits that predicted decline in lung function and QoL were analysed using generalised estimating equations.

Results: Overall, 21 TTs, including pulmonary (n=5), extra-pulmonary (n=13) and behavioural/lifestyle risk-factors (n=3) were identified. In multivariate analyses, the traits of chronic bronchitis (β -0.186, 95% CI -0.290 to -0.082), breathlessness (β -0.093, 95% CI -0.164 to -0.022), underweight (β -0.216, 95% CI -0.373 to -0.058), sarcopenia (β -0.162, 95% CI -0.262 to -0.061) and current smoking (β -0.228, 95% CI -0.304 to -0.153) predicted decline in forced expiratory volume in 1 s (FEV). Of the seven traits that predicted decline in QoL, depression (β -7.19, 95% CI -8.81 to -5.57) and poor family and social support (β -5.12, 95% CI -6.65 to -3.59) were the strongest.

Conclusion: The core TTs of COPD associated with a decline in lung function and QoL were identified. Targeting these impactful traits with individualised treatment using a precision medicine approach may improve outcomes in people with COPD.
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http://dx.doi.org/10.1183/23120541.00934-2020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8165376PMC
April 2021

Mobilization During Critical Illness: A Higher Level of Mobilization Improves Health Status at 6 Months, a Secondary Analysis of a Prospective Cohort Study.

Crit Care Med 2021 09;49(9):e860-e869

Australian and New Zealand Intensive Care Research Centre, Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, VIC, Australia.

Objectives: To determine the influence of active mobilization during critical illness on health status in survivors 6 months post ICU admission.

Design: Post hoc secondary analysis of a prospective cohort study conducted between November 2013 and March 2015.

Setting: Two tertiary hospital ICU's in Victoria, Australia.

Patients: Of 194 eligible patients admitted, mobility data for 186 patients were obtained. Inclusion and exclusion criteria were as per the original trial.

Interventions: The dosage of mobilization in ICU was measured by: 1) the Intensive Care Mobility Scale where a higher Intensive Care Mobility Scale level was considered a higher intensity of mobilization or 2) the number of active mobilization sessions performed during the ICU stay. The data were extracted from medical records and analyzed against Euro-quality of life-5D-5 Level version answers obtained from phone interviews with survivors 6 months following ICU admission. The primary outcome was change in health status measured by the Euro-quality of life-5D-5 Level utility score, with change in Euro-quality of life-5D-5 Level mobility domain a secondary outcome.

Measurements And Main Results: Achieving higher levels of mobilization (as per the Intensive Care Mobility Scale) was independently associated with improved outcomes at 6 months (Euro-quality of life-5D-5 Level utility score unstandardized regression coefficient [β] 0.022 [95% CI, 0.002-0.042]; p = 0.033; Euro-quality of life-5D-5 Level mobility domain β = 0.127 [CI, 0.049-0.205]; p = 0.001). Increasing the number of active mobilization sessions was not found to independently influence health status. Illness severity, total comorbidities, and admission diagnosis also independently influenced health status.

Conclusions: In critically ill survivors, achieving higher levels of mobilization, but not increasing the number of active mobilization sessions, improved health status 6 months after ICU admission.
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http://dx.doi.org/10.1097/CCM.0000000000005058DOI Listing
September 2021

Smoking cessation intervention in Australian general practice: a secondary analysis of a cluster randomised controlled trial.

Br J Gen Pract 2021 06 27;71(707):e458-e464. Epub 2021 May 27.

Centre for Medicine Use and Safety, Faculty of Pharmacy and Pharmaceutical Sciences.

Background: GPs have limited capacity to routinely provide smoking cessation support. New strategies are needed to reach all smokers within this setting.

Aim: To evaluate the effect of a pharmacist-coordinated interdisciplinary smoking cessation intervention delivered in Australian general practice.

Design And Setting: Secondary analysis of a cluster randomised controlled trial (RCT) conducted in 41 Australian general practices.

Method: In all, 690 current smokers were included in this study: 373 from intervention clinics ( = 21) and 317 from control clinics ( = 18). A total of 166 current smokers had spirometry-confirmed chronic obstructive pulmonary disease (COPD). In the intervention clinics, trained pharmacists provided smoking cessation support plus Quitline referral. Control clinics provided usual care plus Quitline referral. Those with COPD in the intervention group ( = 84) were referred for home medicines review (HMR) and home-based pulmonary rehabilitation (HomeBase), which included further smoking cessation support. Outcomes included carbon monoxide (CO)-validated smoking abstinence, self-reported use of smoking cessation aids, and differences between groups in readiness-to-quit score at 6 months.

Results: Intention-to-treat analysis showed similar CO-validated abstinence rates at 6 months in the intervention (4.0%) and control clinics (3.5%). No differences were observed in readiness-to-quit scores between groups at 6 months. CO-validated abstinence rates were similar in those who completed HMR and at least six sessions of HomeBase to those with COPD in usual care.

Conclusion: A pharmacist-coordinated interdisciplinary smoking cessation intervention when integrated in a general practice setting had no advantages over usual care. Further research is needed to evaluate the effect of HMR and home-based pulmonary rehabilitation on smoking abstinence in smokers with COPD.
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http://dx.doi.org/10.3399/BJGP.2020.0906DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8103929PMC
June 2021

Diagnostic tools used for melanoma: A survey of Australian general practitioners and dermatologists.

Australas J Dermatol 2021 Aug 16;62(3):300-309. Epub 2021 Apr 16.

Victorian Melanoma Service, Alfred Health, Melbourne, Victoria, Australia.

Background/objective: Diagnostic tools such as dermoscopy, sequential digital dermoscopy imaging (SDDI), total body photography (TBP) and automated diagnostic tools are available to assist in early melanoma diagnosis. The use, accessibility and barriers of dermoscopy have been well studied; however, there are few similar studies regarding SDDI, TBP and automated diagnostic tools. We aim to understand the use of these diagnostic aids amongst Australian general practitioners (GPs) and dermatologists.

Methods: Between June 2019 and January 2020, GPs and dermatologists across Australia were invited to participate in an online survey. Surveys were distributed through GP and dermatology organisations.

Results: A total of 227 survey responses were received, 175 from GPs and 52 from dermatologists. Amongst GPs, 44.6% worked in a skin cancer clinic. Dermoscopy was used at least occasionally by 98.9% of all GPs. SDDI was used by 93.6% of skin cancer GPs, 80.8% of dermatologists and 45.3% of generalist GPs. TBP was used or recommended by 77.1% of generalist GPs, 82.3% of skin cancer GPs and 86.5% of dermatologists. The most common barriers to the use of TBP were cost, limited accessibility, poor patient compliance, and time required for both patients and doctors. Very few clinicians reported using automated diagnostic tools. There was an interest in future diagnostic aids for melanoma in 88% of GPs and dermatologists.

Conclusion: Dermoscopy, SDDI and TBP were commonly used by responding Australian skin cancer GPs and dermatologists in this survey. Automated diagnostic tools were not reported to be used routinely. Several barriers were identified for use of TBP.
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http://dx.doi.org/10.1111/ajd.13595DOI Listing
August 2021

Risk factors for invasive fungal infection in 5-azacytidine treated patients with acute myeloid leukemia and myelodysplastic syndrome.

Eur J Haematol 2021 Aug 27;107(2):181-189. Epub 2021 May 27.

Monash Haematology, Monash Health, Clayton, Vic., Australia.

The rate of invasive fungal infection (IFI) in patients with myelodysplasia (MDS) and acute myeloid leukemia (AML) receiving 5-azacytidine is incompletely defined and published recommendations for mold-active fungal prophylaxis in such patients vary according to source. We performed a retrospective cohort study in order to identify contemporary IFI rates and infection-related mortality in relation to known risk factors and the use of antifungal prophylaxis. One hundred and seventeen patients receiving 5-azacytidine for MDS and low blast count AML were identified, of whom 71 (61%) received antifungal prophylaxis. The IFI rate was 7.7% across the entire cohort: 5.6% in those receiving prophylaxis vs 10.9% in the subgroup who did not (P = .30). The presence of neutropenia at three months of treatment was associated with increased IFI risk (hazard ratio [HR] 8.29; (95% confidence interval [CI)] 1.61-42.6; P = .01), and on multivariate analysis, IFI was independently associated with increased all-cause mortality risk (HR 8.37; 95% CI 3.67 - 19.11; P < .0001). These data further highlight the risk of IFI in this population and support the use of mold-active prophylaxis in neutropenic patients receiving 5-azacytidine for MDS and AML.
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http://dx.doi.org/10.1111/ejh.13631DOI Listing
August 2021

Comparison of clinical outcomes between nurse practitioner and registrar-led medical emergency teams: a propensity-matched analysis.

Crit Care 2021 03 22;25(1):117. Epub 2021 Mar 22.

Department of Intensive Care Medicine, Peninsula Health, Melbourne, Australia.

Objective: Medical emergency teams (MET) are mostly led by physicians. Some hospitals are currently using nurse practitioners (NP) to lead MET calls. These are no studies comparing clinical outcomes between these two care models. To determine whether NP-led MET calls are associated with lower risk of acute patient deterioration, when compared to intensive care (ICU) registrar (ICUR)-led MET calls.

Methods: The composite primary outcome included recurrence of MET call, occurrence of code blue or ICU admission within 24 h. Secondary outcomes were mortality within 24 h of MET call, length of hospital stay, hospital mortality and proportion of patients discharged home. Propensity score matching was used to reduce selection bias from confounding factors between the ICUR and NP group.

Results: A total of 1343 MET calls were included (1070 NP, 273 ICUR led). On Univariable analysis, the incidence of the primary outcome was higher in ICUR-led MET calls (26.7% vs. 20.6%, p = 0.03). Of the secondary outcome measures, mortality within 24 h (3.4% vs. 7.7%, p = 0.002) and hospital mortality (12.7% vs. 20.5%, p = 0.001) were higher in ICUR-led MET calls. Propensity score-matched analysis of 263 pairs revealed the composite primary outcome was comparable between both groups, but NP-led group was associated with reduced risk of hospital mortality (OR 0.57, 95% CI 0.35-0.91, p = 0.02) and higher likelihood of discharge home (OR 1.55, 95% CI 1.09-2.2, p = 0.015).

Conclusion: Acute patient deterioration was comparable between ICUR- and NP-led MET calls. NP-led MET calls were associated with lower hospital mortality and higher likelihood of discharge home.
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http://dx.doi.org/10.1186/s13054-021-03534-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7986296PMC
March 2021

Outcomes Following ATG Therapy for Chronic Lung Allograft Dysfunction.

Transplant Direct 2021 Apr 16;7(4):e681. Epub 2021 Mar 16.

Lung Transplant Service, Alfred Hospital, Melbourne, VIC, Australia.

Chronic lung allograft dysfunction (CLAD) is the major factor limiting survival post lung transplantation (LTx) with limited effective therapeutic options. We report our 12-y experience of antithymocyte globulin (ATG) as second-line CLAD therapy.

Methods: Clinical and lung function data were collected on LTx patients receiving ATG. Rate of FEV1 decline (mL/d) was calculated before and after ATG. Partial response to ATG was defined by rate of FEV1 decline improving 20%. Complete response was defined by an absolute improvement or stability in baseline FEV1.

Results: Seventy-six patients received ATG for CLAD. Of these, 5 patients who had a clinical diagnosis of antibody-mediated rejection and were treated with plasmapheresis before or after ATG were excluded from analysis. Sixteen (23%) were complete responders, 29 (40%) were partial responders, and 26 (37%) did not respond. Those with CLAD stage 2 or 3 and younger age were more likely to respond. Partial responders had a 65% lower risk of death or retransplant (HR, 0.35;  = 0.003), whereas complete responders reduced their risk by 70% (HR, 0.30;  = 0.006).

Conclusions: ATG appears to stabilize or attenuate lung function decline in CLAD, which may lead to improved retransplant-free survival. Although certain predictors of response have been identified in this large single-center review, these findings need to be confirmed by a multicenter randomized-controlled trial to determine predictors of response to ATG for CLAD.
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http://dx.doi.org/10.1097/TXD.0000000000001134DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7969305PMC
April 2021

Acidemia subtypes in critically ill patients: An international cohort study.

J Crit Care 2021 08 26;64:10-17. Epub 2021 Feb 26.

Australian and New Zealand Intensive Care Research Centre, Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Victoria, Australia; Department of Intensive Care, Austin Hospital, Heidelberg, Victoria, Australia; Department of Intensive Care, Royal Melbourne Hospital, Melbourne, Victoria, Australia; Centre for Integrated Critical Care, Department of Medicine, The University of Melbourne, Parkville, Victoria, Australia; Data Analytics Research and evaluation Centre, The University of Melbourne and Austin Hospital, Melbourne, Australia.

Purpose: To study the prevalence, characteristic, outcome, and acid-base biomarker predictors of outcome for different acidemia subtypes.

Methods: We used national intensive care databases from three countries and classified acidemia subtypes as metabolic (standard base excess [SBE] < -2 mEq/L only), respiratory (PaCO > 42 mmHg only), and combined (both SBE < -2 mEq/L and PaCO > 42 mmHg) based on blood gas analysis in the first 24 h after ICU admission. To investigate acid-base predictors for hospital mortality, we applied the area under the receiver operating characteristic curve approach.

Results: We screened 643,689 ICU patients (2014-2018) and detected acidemia in 57.8%. The most common subtype was metabolic (42.9%), followed by combined (30.3%) and respiratory (25.9%). Combined acidemia had a mortality of 12.7%, compared with 11% for metabolic and 5.5% for respiratory. For combined acidemia, the best predictor of hospital mortality was pH. However, for metabolic or respiratory acidemia, it was SBE or PaCO, respectively.

Conclusions: In ICU patients with acidemia, mortality differs according to subtype and is highest in the combined subtype. Best acid-base predictors of mortality also differ according to subtype with best performance for pH in combined, SBE in metabolic, and PaCO in respiratory acidemia.
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http://dx.doi.org/10.1016/j.jcrc.2021.02.006DOI Listing
August 2021

Utility of computed tomography angiography in traumatic lower limb injury: Review of clinical impact in level 1 trauma centre.

Injury 2021 Oct 21;52(10):3064-3067. Epub 2021 Feb 21.

Department of Radiology and Nuclear Medicine, Alfred Health, 55 Commercial Rd., Melbourne, Vic, Australia (T.I.J., P.R., W.C.); Department of Epidemiology and Preventive Medicine, School of Public Health and Preventive Medicine, Monash University, 553 St Kilda Road (E.P) and Department of Surgery, Monash University, Melbourne, Vic., Australia (W.C.); National Trauma Research Institute Monash University, Australia (W.C.).

Introduction: CT angiography (CTA) is efficient and accurate in detecting lower limb vascular injury in the setting of trauma (1-6). Less clear is the in-practice correlation between appropriate indications for these examinations and subsequent clinical impacts.

Materials And Methods: All CT leg angiography acquired from January 2016 through April 2019 were reviewed via retrospective search. Studies not acquired for trauma were excluded. Imaging and reports were reviewed to assess for vascular injury. Electronic medical records were reviewed to assess the presence or absence of classical 'hard' or 'soft' signs of vascular injury and whether vascular intervention was undertaken.

Results: A total of 347 lower limb injuries were identified in 273 men and 74 women. Mean age was 41.5 years ranging from 15-95 years. 268 cases were fractures with 177 open injuries. 301 of injuries were secondary to blunt trauma, 31 penetrating injury occurred and 15 cases were ascribed to blast/gunshot injury. 74 (21.3%) studies were deemed to have a positive finding of vascular injury, 249 (71.8%) were reported as negative and 24 (6.9%) were indeterminate. Of the cases with positive findings, 26 underwent intervention (7.4% of all patients undergoing CTA). No patients with negative CTA required intervention, while three (3, 0.8% of total) with indeterminate findings required intervention. Where there were no clinical signs (absence of any hard or soft signs) 249 CTA's were performed and none required any form of intervention.

Conclusion: In the absence of clinical signs of vessel injury, CT angiography is unlikely to demonstrate vascular injury requiring intervention in the setting of lower limb trauma.
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http://dx.doi.org/10.1016/j.injury.2021.02.047DOI Listing
October 2021

Imaging triage of acute stroke patients for endovascular clot retrieval: Effect of increased therapeutic window on the utilization of CT perfusion.

J Med Imaging Radiat Oncol 2021 Apr 8;65(2):152-159. Epub 2020 Dec 8.

Monash Imaging, Monash Health, Melbourne, Victoria, Australia.

Introduction: Recent randomized trials showing improved outcomes for later-presenting acute ischaemic stroke (AIS) patients with large vessel occlusion (LVO) treated with endovascular clot retrieval (ECR) may result in substantial increases in CTP utilization. This 3-hospital, single-institution cohort study aimed to compare 2017 and 2018 patient cohorts for the following: CTP use in AIS. Prevalence of LVO in all patients having CTP. Number and clinical characteristics of patients triaged to ECR. Number of patients receiving CTP relative to similar-acuity total ED presentations.

Methods: Inclusion criteria: Consecutive adult emergency (ED) patients receiving CTP for suspected AIS. Study period 1:1 January-30 June 2017; Period 2:1 January-30 June 2018.

Data Collection: age, gender, triage category, NIHSS (National Institute of Health Stroke Score), symptoms/signs, time elapsed since last seen well (TESLSW) to triage, disposition (home/other).

Results: A 38.7 % increase in CTP (512 in 2017, 710 in 2018) occurred with 39/512 (7.6%) and 72/710 (10.1%) having intended ECR. CTPs per intended ECR declined from 13.1 to 9.9. 36/512 (7.0%) and 58/710 (8.2%) patients had ECR (61.1% increase) and 22/36 (61.1%) and 25/58 (43.1%) of these were discharged home in 2017 and 2018, respectively, an increase of 3/22(14%).

Conclusion: Despite a 38.7% increase in CTP utilization, we experienced a reduction in the number of CTPs performed/patient triaged to ECR. This did not reflect higher LVO prevalence among later presenters but may reflect changed selection criteria for CTP and/or decision making about suitability for ECR.
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http://dx.doi.org/10.1111/1754-9485.13122DOI Listing
April 2021

Lumacaftor/ivacaftor-associated health stabilisation in adults with severe cystic fibrosis.

ERJ Open Res 2021 Jan 1;7(1). Epub 2021 Feb 1.

Cystic Fibrosis Service, Dept of Respiratory Medicine, Alfred Hospital, Melbourne, Australia.

Introduction: Lumacaftor/ivacaftor (LUM/IVA) has been shown to improve clinical outcomes in cystic fibrosis (CF) patients homozygous for Phe508del with forced expiratory volume in 1 s (FEV) % pred >40%. We assessed the clinical utility of LUM/IVA in all eligible adult CF patients with FEV % pred <40% treated for at least 1 year under a single-centre managed access programme.

Methods: Following clinical optimisation, eligible patients (n=40) with FEV % pred <40% were commenced on LUM/IVA and monitored for tolerance and clinical outcomes, including health service utilisation, pulmonary function, weight and body composition. 24 patients reached 1 year of treatment by the time of evaluation. Six patients discontinued due to adverse events (five for increased airways reactivity) and three underwent lung transplantation.

Results: In comparison with the year prior to LUM/IVA commencement, significant reductions (median per year) were observed in the treatment year in the number of pulmonary exacerbations requiring hospitalisation (from 3 to 1.5; p=0.0002), hospitalisation days (from 27 to 17; p=0.0002) and intravenous antibiotic (IVAB) usage days (from 45 to 27; p=0.0007). Mean±sd change in FEV % pred was -2.10±1.18% per year in the year prior, with the decline reversed in the year following (+1.45±1.13% per year; p=0.035), although there was significant heterogeneity in individual responses. Mean±sd weight gain at 1 year was 2.5±4.1 kg (p=0.0007), comprising mainly fat mass (mean 2.2 kg). The proportion of patients severely underweight (body mass index <18.5 kg·m) decreased from 33% at baseline to 13% at 1 year (p=0.003).

Conclusion: This real-world evaluation study demonstrated benefits over several clinical domains (infective exacerbations requiring hospitalisation, IVABs, pulmonary function decline and nutritional parameters) in CF patients with severe lung disease.
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http://dx.doi.org/10.1183/23120541.00203-2020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7861032PMC
January 2021

Treatment of Anaemia in Patients with Acute Burn Injury: A Study of Blood Transfusion Practices.

J Clin Med 2021 Jan 27;10(3). Epub 2021 Jan 27.

Victorian Adult Burns Service, Alfred Hospital 55 Commercial Road, Melbourne, VIC 3004, Australia.

: To determine blood transfusion practices, risk factors, and outcomes associated with the use of blood products in the setting of the acute management of burn patients at the Victorian Adult Burn Service. : Patients with burn injuries have variable transfusion requirements, based on a multitude of factors. We reviewed all acute admissions to the Victorian Adult Burns Service (VABS) between 2011 and 2017: 1636 patients in total, of whom 948 had surgery and were the focus of our analysis. : Patient demographics, surgical management, transfusion details, and outcome parameters were collected and analyzed. A total of 175 patients out of the 948 who had surgery also had a blood transfusion, while 52% of transfusions occurred in the perioperative period. The median trigger haemoglobin in perioperative was 80mg/dL (IQR = 76-84.9 mg/dL), and in the non-perioperative setting was 77 mg/dL (IQR = 71.61-80.84 mg/dL). Age, gender, % total body surface area (TBSA) burn, number of surgeries, and intensive care unit and hospital length of stay were associated with transfusion. : The use of blood transfusions is an essential component of the surgical management of major burns. As observed in our study, half of these transfusions are related to surgical procedures and may be influenced by the employment of blood conserving strategies. Furthermore, transfusion trigger levels in stable patients may be amenable to review and reduction. Risk adjusted analysis can support the implementation of blood transfusion as a useful quality indicator in burn care.
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http://dx.doi.org/10.3390/jcm10030476DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7865424PMC
January 2021

Multiparametric MR evaluation of uterine leiomyosarcoma and STUMP versus leiomyoma in symptomatic women planned for high frequency focussed ultrasound: accuracy of imaging parameters and interobserver agreement for identification of malignancy.

Br J Radiol 2021 Mar 28;94(1119):20200483. Epub 2021 Jan 28.

Royal Women's Hospital, Parkville, Victoria, Australia.

Objective: To assess accuracy of and interobserver agreement on multiparametric MR findings to distinguish uterine leiomyoma (LM) from uterine leiomyosarcoma (LMS) and soft tissue tumour of unknown malignant potential.

Methods: Inclusion criteria: All females over 18 years with least one uterine mass measuring 5 cm or more in at least one of the three standard orthogonal dimensions on MR with histopathological confirmation of LM, LMS, or soft tissue tumour of unknown malignant potential (STUMP) in the 3 months following MR. Patients with LMS were drawn from a larger cohort being assessed for MR-guided focussed ultrasound (MRgFUS) suitability. Image evaluation: Assessed variables were: lesion margin, margin definition, T2 signal homogeneity, >50% of lesion with T2 signal brighter than myometrium, haemorrhage, restricted diffusion, contrast enhancement (CE), CE pattern, local lymphadenopathy and ascites.

Results: 32 LM, 10 LMS and 1 STUMP were evaluated. Ill-defined (-value = 0.0003-0.0004) or irregular ( = 0.003-0.004) lesion margin, T2 hyperintensity >50% ( = 0.001-0.004), and peripheral CE ( = 0.02-0.05) were significantly more common in LMS/STUMP than LM for both radiologists. 10/11 (Reader 2) and 11/11 (Reader 1) LMS/STUMP displayed restricted diffusion but so did 63-80% of LM. Agreement was greatest for margin characteristics (κ = 0.73-0.81).

Conclusion: Irregular/ill-defined lesion margin best distinguished LMS/STUMP from LM with good interrater reliability.

Advances In Knowledge: Assessment of agreement regarding MR parameters distinguishing LM from LMS and STUMP has not previously been undertaken in a cohort including a large number of patients with LMS. This will help inform evaluation of females considering minimally invasive LM treatment.
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http://dx.doi.org/10.1259/bjr.20200483DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8011260PMC
March 2021

A 4-tier Protocolized Radiological Classification System for Leaks Following Sleeve Gastrectomy.

Ann Surg 2021 Jan 19. Epub 2021 Jan 19.

Monash University Department of Surgery, Central Clinical School, Monash University, Melbourne, Australia Oesophago-gastric and Bariatric Surgical Unit, Department of General Surgery, The Alfred Hospital, Melbourne, Australia Department of Epidemiology and Preventive Medicine, School of Public Health and Preventative Medicine, Monash University, Melbourne, Australia Department of Radiology, The Alfred Hospital, Melbourne, Australia.

Objectives: To develop and validate a classification of sleeve gastrectomy leaks able to reliably predict outcomes, from protocolized computed tomography (CT) findings and readily available variables.

Summary Of Background Data: Leaks post sleeve gastrectomy remain morbid and resource-consuming. Incidence, treatments, and outcomes are variable, representing heterogeneity of the problem. A predictive tool available at presentation would aid management and predict outcomes.

Methods: From a prospective database (2009-2018) we reviewed patients with staple line leaks. A Delphi process was undertaken on candidate variables (80-20). Correlations were performed to stratify 4 groupings based on outcomes (salvage resection, length of stay, and complications) and predictor variables. Training and validation cohorts were established by block randomization.

Results: A 4-tiered classification was developed based on CT appearance and duration postsurgery. Interobserver agreement was high (κ=0.85, P<0.001). There were 59 patients, (training: 30, validation: 29). Age 42.5±10.8 versus 38.9±10.0 years (P=0.187); female 65.5% versus 80.0% (P=0.211), weight 127.4±31.3 versus 141.0±47.9 kg, (P=0.203). In the training group, there was a trend toward longer hospital stays as grading increased (I=10.5 d; II=24 d; III=66.5 d; IV=72 d; P= 0.005). Risk of salvage resection increased (risk ratio grade 4=9; P=0.043) as did complication severity (P=0.027). Findings were reproduced in the validation group: risk of salvage resection (P=0.007), hospital stay (P=0.001), complications (P=0.016).

Conclusion: We have developed and validated a classification system, based on protocolized CT imaging that predicts a step-wise increased risk of salvage resection, complication severity, and increased hospital stay. The system should aid patient management and facilitate comparisons of outcomes and efficacy of interventions.
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http://dx.doi.org/10.1097/SLA.0000000000003984DOI Listing
January 2021

Impacts of multidisciplinary meeting case discussion on palliative care referral and end-of-life care in lung cancer: a retrospective observational study.

Intern Med J 2021 Sep;51(9):1450-1456

Department of Palliative Care, Alfred Health, Melbourne, Victoria, Australia.

Background: Multidisciplinary meeting (MDM) discussion and early palliative care are recommended in lung cancer management. The literature is unclear whether MDM discussion leads to early palliative care and improved end-of-life care.

Aims: To evaluate impacts of discussion at an Australian lung MDM on palliative care referral, and MDM and early palliative care on aggressive end-of-life care.

Methods: A retrospective, cross-sectional study was conducted of 352 patients diagnosed with primary lung cancer from 2017 to 2019 at the Alfred Hospital, Melbourne. The primary question was whether MDM discussion influenced palliative care referrals. Secondary questions were whether MDM discussion and early palliative care reduced aggressive treatment (chemotherapy, hospitalisation, emergency department visits, intensive care admission and in-hospital death) during the last 30 days of life. Multivariable logistic regression was used to determine independent association between MDM discussion and palliative care referral.

Results: MDM discussion did not independently impact palliative care referral. There was reduced likelihood of MDM presentation in patients with metastatic disease (P < 0.0001) and poorer performance status (P = 0.025), and higher likelihood of palliative care referral in these patients (both P < 0.001). MDM discussion reduced end-of-life intensive care unit (ICU) admission in patients with metastatic disease (P = 0.04). A palliative care referral-to-death interval of ≥30 days was associated with reduced hospitalisation at the end of life (P < 0.0001) and hospital deaths (P = 0.001).

Conclusion: Discussion at lung MDM did not increase palliative care referral, but did reduce ICU admission among metastatic patients at the end of life. Longer palliative care referral-to-death interval was associated with reduced aggressive end-of-life care. Further research is needed in these areas.
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http://dx.doi.org/10.1111/imj.15215DOI Listing
September 2021

Health-related quality of life in necrotising soft tissue infection survivors: perspective from an Australian tertiary referral centre.

ANZ J Surg 2021 09 12;91(9):1733-1738. Epub 2021 Jan 12.

John Anstee Research Group, Department of Plastic, Hand and Faciomaxillary Surgery, Alfred Health, Melbourne, Victoria, Australia.

Background: Necrotising soft tissue infection (NSTI) is a life-threatening disease with widespread tissue destruction. Immediate and aggressive surgical debridement remains the main focus of treatment. This results in disfiguring scars, functional limitation and psychological sequelae for survivors. As mortality rate declines with improvements in care, a greater focus should be placed upon the psychological and functional outcomes of survivors. This study aims to assess the health-related quality of life (HRQoL) of patients following NSTI using the Short Form-36 (SF-36) and Derriford Appearance Scale-24 (DAS-24).

Methods: All NSTI patients admitted at our tertiary referral centre between 1 January 2013 and 31 December 2019 were invited to complete the DAS-24 and SF-36 surveys. A retrospective chart review was also performed.

Results: A total of 30 participants responded to the surveys. On comparison against the general Australian population, the NSTI cohort demonstrated significantly reduced physical and mental HRQoL as measured by the SF-36 (P < 0.001). Increased age was significantly associated with a reduced physical HRQoL (P = 0.002), while dysfunction with appearance as measured by the DAS-24 form correlated with both reduced physical and mental HRQoL (P = 0.020). A total of 79.3% of patients expressed concern regarding their appearance with a significantly higher level of distress at their appearance compared to a non-clinical population (P = 0.120).

Conclusion: Despite the rarity of NSTI, this study demonstrates that this disease has a large and persistent burden for survivors, who report significantly reduced HRQoL and distress with appearance. Further research into comprehensive physical and psychosocial services for NSTI survivors is required.
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http://dx.doi.org/10.1111/ans.16540DOI Listing
September 2021

Venous thromboembolism in burns patients: Are we underestimating the risk and underdosing our prophylaxis?

J Plast Reconstr Aesthet Surg 2021 08 13;74(8):1814-1823. Epub 2020 Dec 13.

Department of Surgery, Central Clinical School, Monash University, 99 Commercial Road, Melbourne, Victoria 3004, Australia; Victorian Adult Burns Service, The Alfred, 55 Commercial Road, Melbourne, Victoria 3004, Australia.

Background: Burns patients exhibit all factors of Virchow's triad and are thus at high theoretical risk of venous thromboembolism (VTE). At our tertiary referral burns unit, a standard dose of low molecular weight heparin, which acts primarily by inhibiting Factor Xa, is given for thromboprophylaxis. However, the pharmacokinetics of enoxaparin are altered following a burn injury, and thus burns patients are likely underdosed on their thromboprophylaxis. The objectives of this study were to determine the incidence and risk factors for VTE among burns patients at the Victorian Adult Burns Service (VABS) and to determine the adequacy of the current enoxaparin thromboprophylaxis regimen through measurement of anti-factor Xa (AFXa) levels and comparison with established reference ranges.

Methods: This study consisted of two parts. In part 1, the Burns Registry of Australia and New Zealand (BRANZ) was reviewed for cases of VTE in burns patients admitted to the VABS from 2013 - 2018. Part 2 was a prospective study that determined peak and trough AFXa levels in patients admitted to the VABS with >10% total body surface area (TBSA) burns.

Results: Part 1. Totally, 1,475 patients were admitted to the VABS between 2013 - 2018. There were 20 cases of VTE (1.36%). Percent TBSA of burn (OR = 1.04, 95% CI: 1.03 - 1.06), full thickness burns (OR = 2.78, 95% CI: 1.15 - 6.73), ICU admission (OR = 15.08, 95% CI: 5.01 - 45.44), mechanical ventilation (OR = 10.62, 95% CI: 4.05 - 27.91), operative procedures (OR = 1.43, 95% CI: 1.29 - 1.59), and a longer hospital stay (OR = 1.05, 95% CI: 1.04 - 1.07) were all associated with an increased VTE risk. Part 2. A total of 20 participants with >10% TBSA burns were recruited to the prospective study. Peak anti Factor Xa (AFXa) levels were measured for all 20 participants with 15% recording an initial prophylactic peak AFXa level within reference range. Upon subsequent measurements, 50% of participants reached a prophylactic peak AFXa level. Trough AFXa levels were measured for 17 participants with no participant recording an initial or subsequent trough AFXa level at or above the prophylactic threshold.

Conclusion: Our study demonstrates a high incidence of VTE among burns patients at the VABS, especially among the major burns patients, and a thromboprophylaxis protocol that is ineffective in achieving prophylactic levels of AFXa level. The evidence suggests a need to evaluate different dosing protocols among burns patients in order to improve AFXa levels, with the aim of decreasing incidence of VTE in high-risk patients.
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http://dx.doi.org/10.1016/j.bjps.2020.12.011DOI Listing
August 2021

Impact of rosuvastatin on atherosclerosis in people with HIV at moderate cardiovascular risk: a randomised, controlled trial.

AIDS 2021 03;35(4):619-624

Division of Infectious Diseases, HIV/AIDS Unit, Geneva University Hospitals, Geneva, Switzerland.

Background: People living with HIV-1 (PLHIV) are at increased risk for cardiovascular disease.

Objective: This study aimed to determine if PLHIV would benefit from starting statins at a lower threshold than currently recommended in the general population.

Design: A double-blind multicentre, randomised, placebo-controlled trial was performed.

Methods: Participants (n = 88) with well controlled HIV, at moderate cardiovascular risk (Framingham score of 10-15%), and not recommended for statins were recruited from Australia and Switzerland. They were randomized 1 : 1 to rosuvastatin (n = 44) 20 mg daily, 10 mg if co-administered with ritonavir/cobicistat-boosted antiretroviral therapy, or placebo (n = 40) for 96 weeks. Assessments including fasting blood collection and carotid--intima media thickness (CIMT) were performed at baseline, and weeks 48 and 96. The primary outcome was the change from baseline to week 96 in CIMT (clinicaltrials.gov: NCT01813357).

Results: Participants were predominantly men [82 (97.6%); mean age 54 years (SD 6.0)]. At 96 weeks, there was no difference in the progression of CIMT between the rosuvastatin (mean 0.004 mm, SE 0.0036) and placebo (0.0062 mm, SE 0.0039) arms (P = 0.684), leading to no difference in CIMT levels between groups at week 96 [rosuvastatin arm, 0.7232 mm (SE 0.030); placebo arm 0.7785 mm (SE 0.032), P = 0.075].Adverse events were common (n = 146) and predominantly in the rosuvastatin arm [108 (73.9%)]. Participants on rosuvastatin were more likely to cease study medication because of an adverse event [7 (15.9%) vs. 2 (5.0%), P = 0.011].

Conclusion: In PLHIV, statins prescribed at a lower threshold than guidelines did not lead to improvements in CIMT but was associated with significant adverse events.
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http://dx.doi.org/10.1097/QAD.0000000000002764DOI Listing
March 2021

The Utility of Prophylactic Zoledronic Acid in Patients Undergoing Lung Transplantation.

J Clin Densitom 2021 Oct-Dec;24(4):581-590. Epub 2020 Oct 21.

Department of Endocrinology and Diabetes, Alfred Health, Victoria, Australia; Central Clinical School, Faculty of Medicine, Nursing and Health Sciences, Monash University, Victoria, Australia; School of Public Health and Preventive Medicine, Monash University, Victoria, Australia.

Osteoporosis is prevalent among lung transplant candidates and is exacerbated post-transplant by immunosuppressive therapy. Low bone mineral density (BMD) is a well-recognized surrogate for fragility fracture risk, which is associated with significant morbidity and mortality. Intravenous zoledronic acid (ZA) effectively reduces BMD loss and prevents fractures in postmenopausal osteoporosis. Many groups, ours included, prophylactically treat lung transplant recipients (LTR) with bisphosphonates, but no documented consensus currently exists. Our protocol comprises ZA every 6-months from transplant wait-listing, with interval reassessment to guide ongoing treatment. We evaluate the impact of a dose of ZA within 6 months of transplantation on BMD and fracture occurrence. A retrospective analysis was performed on all adult LTR from April 2012 to October 2014, of which 60 met our inclusion criteria. LTR who received ZA within 6 months of transplantation (n = 37) were compared to those who did not (n = 23), and followed up for a minimum of three years. Outcome measures were BMD change at the lumbar spine and femur (primary), and fracture occurrence (secondary). LTR treated with ZA within 6 months of transplantation experienced a median BMD change of +8.11% at the lumbar spine and +1.39% at the femur, compared to -1.20% and -3.92%, respectively, in LTR who did not receive a ZA dose within 6 months of transplantation (p = 0.002 & p = 0.008 respectively). Our findings indicate that prophylactic ZA within 6 months of transplantation prevents BMD loss in LTR.
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http://dx.doi.org/10.1016/j.jocd.2020.10.003DOI Listing
November 2021

Effect of oral tranexamic acid on erythema index in patients with melasma.

Australas J Dermatol 2021 May 30;62(2):206-209. Epub 2020 Oct 30.

Chroma Dermatology, Pigment and Skin of Colour Centre, Wheelers Hill, Victoria, Australia.

Melasma is a common disorder of hyperpigmentation that presents a therapeutic challenge for clinical dermatologists. The pathogenesis is complex, but previous studies have demonstrated vascular proliferation is a key factor in the development of the classic hyperpigmented patches. Studies have revealed reduction of erythema by oral tranexamic acid; however, there has been no direct comparison to placebo. This 24-week randomised placebo-controlled trial demonstrates oral tranexamic acid may improve erythema in melasma. This mechanism of action may be the reason for the success of tranexamic acid in complex and difficult to treat melasma.
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http://dx.doi.org/10.1111/ajd.13482DOI Listing
May 2021

The efficacy and safety of varenicline alone versus in combination with nicotine lozenges for smoking cessation among hospitalised smokers (VANISH): study protocol for a randomised, placebo-controlled trial.

BMJ Open 2020 10 6;10(10):e038184. Epub 2020 Oct 6.

Centre for Medicine Use and Safety, Faculty of Pharmacy and Pharmaceutical Sciences, Monash University, Parkville, Victoria, Australia

Introduction: Smoking is a leading cause of premature deaths globally. The health benefits of smoking cessation are many. However, majority of quit attempts are unsuccessful. One way to potentially improve success rates is to evaluate new combinations of existing smoking cessation therapies that may work synergistically to decrease the intensity of withdrawal symptoms and cravings.

Aims: To evaluate the feasibility, efficacy and safety of the combination of varenicline and nicotine replacement therapy (NRT) lozenges versus varenicline alone in assisting hospitalised smokers to quit.

Methods And Analysis: This is a multicentre, randomised, placebo-controlled trial. Adults with a history of smoking ≥10 cigarettes per day on average in the 4 weeks prior to their hospitalisation will be recruited. Participants will be randomly assigned to either the intervention group and will receive varenicline and NRT lozenges, or the control group and will receive varenicline and placebo lozenges. All participants will be actively referred to behavioural support from telephone Quitline. Participants are followed up at 1 and 3 weeks and 3, 6 and 12 months from the start of treatment. The primary outcome is carbon monoxide validated prolonged abstinence from 2 weeks to 6 months after treatment initiation. Secondary outcomes include self-reported and biochemically validated prolonged and point prevalence abstinence at 3, 6 and 12 months, self-reported adverse events, withdrawal symptoms and cravings, adherence to treatment, Quitline sessions attended and others. According to the Russell Standard, all randomised participants will be accounted for in the primary intention-to-treat analysis.

Ethics And Dissemination: The trial will be conducted in compliance with the protocol, the principles of Good Clinical Practice, the National Health and Medical Research Council National Statement on Ethical Conduct in Human Research (updated 2015) and the Australian Code for the Responsible Conduct of Research (2018). Approval will be sought from the Human Ethics Committees of all the participating hospitals and the university. Written informed consent will be obtained from each participant at the time of recruitment.

Trial Registration Number: Australia New Zealand Clinical Trials Registry (ACTRN12618001792213).
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http://dx.doi.org/10.1136/bmjopen-2020-038184DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7539569PMC
October 2020
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