Medicine (Austin & Northern Health) - Research Publications

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    A systematic review: Cost-effectiveness of continuous glucose monitoring compared to self-monitoring of blood glucose in type 1 diabetes.
    Jiao, Y ; Lin, R ; Hua, X ; Churilov, L ; Gaca, MJ ; James, S ; Clarke, PM ; O'Neal, D ; Ekinci, EI (Wiley, 2022-11)
    Continuous glucose monitoring (CGM) is rapidly becoming a vital tool in the management of type 1 diabetes. Its use has been shown to improve glycaemic management and reduce the risk of hypoglycaemic events. The cost of CGM remains a barrier to its widespread application. We aimed to identify and synthesize evidence about the cost-effectiveness of utilizing CGM in patients with type 1 diabetes. Studies were identified from MEDLINE, Embase and Cochrane Library from January 2010 to February 2022. Those that assessed the cost-effectiveness of CGM compared to self-monitored blood glucose (SMBG) in patients with type 1 diabetes and reported lifetime incremental cost-effectiveness ratio (ICER) were included. Studies on critically ill or pregnant patients were excluded. Nineteen studies were identified. Most studies compared continuous subcutaneous insulin infusion and SMBG to a sensor-augmented pump (SAP). The estimated ICER range was [$18,734-$99,941] and the quality-adjusted life year (QALY) gain range was [0.76-2.99]. Use in patients with suboptimal management or greater hypoglycaemic risk revealed more homogenous results and lower ICERs. Limited studies assessed CGM in the context of multiple daily injections (MDI) (n = 4), MDI and SMBG versus SAP (n = 2) and three studies included hybrid closed-loop systems. Most studies (n = 17) concluded that CGM is a cost-effective tool. This systematic review suggests that CGM appears to be a cost-effective tool for individuals with type 1 diabetes. Cost-effectiveness is driven by reducing short- and long-term complications. Use in patients with suboptimal management or at risk of severe hypoglycaemia is most cost-effective.
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    Healthy Life-Year Costs of Treatment Speed From Arrival to Endovascular Thrombectomy in Patients With Ischemic Stroke A Meta-analysis of Individual Patient Data From 7 Randomized Clinical Trials
    Almekhlafi, MA ; Goyal, M ; Dippel, DWJ ; Majoie, CBLM ; Campbell, BCV ; Muir, KW ; Demchuk, AM ; Bracard, S ; Guillemin, F ; Jovin, TG ; Mitchell, P ; White, P ; Hill, MD ; Brown, S ; Saver, JL (AMER MEDICAL ASSOC, 2021-05-03)
    Importance: The benefits of endovascular thrombectomy (EVT) are time dependent. Prior studies may have underestimated the time-benefit association because time of onset is imprecisely known. Objective: To assess the lifetime outcomes associated with speed of endovascular thrombectomy in patients with acute ischemic stroke due to large-vessel occlusion (LVO). Data Sources: PubMed was searched for randomized clinical trials of stent retriever thrombectomy devices vs medical therapy in patients with anterior circulation LVO within 12 hours of last known well time, and for which a peer-reviewed, complete primary results article was published by August 1, 2020. Study Selection: All randomized clinical trials of stent retriever thrombectomy devices vs medical therapy in patients with anterior circulation LVO within 12 hours of last known well time were included. Data Extraction/Synthesis: Patient-level data regarding presenting clinical and imaging features and functional outcomes were pooled from the 7 retrieved randomized clinical trials of stent retriever thrombectomy devices (entirely or predominantly) vs medical therapy. All 7 identified trials published in a peer-reviewed journal (by August 1, 2020) contributed data. Detailed time metrics were collected including last known well-to-door (LKWTD) time; last known well/onset-to-puncture (LKWTP) time; last known well-to-reperfusion (LKWR) time; door-to-puncture (DTP) time; and door-to-reperfusion (DTR) time. Main Outcomes and Measures: Change in healthy life-years measured as disability-adjusted life-years (DALYs). DALYs were calculated as the sum of years of life lost (YLL) owing to premature mortality and years of healthy life lost because of disability (YLD). Disability weights were assigned using the utility-weighted modified Rankin Scale. Age-specific life expectancies without stroke were calculated from 2017 US National Vital Statistics. Results: Among the 781 EVT-treated patients, 406 (52.0%) were early-treated (LKWTP ≤4 hours) and 375 (48.0%) were late-treated (LKWTP >4-12 hours). In early-treated patients, LKWTD was 188 minutes (interquartile range, 151.3-214.8 minutes) and DTP 105 minutes (interquartile range, 76-135 minutes). Among the 298 of 380 (78.4%) patients with substantial reperfusion, median DTR time was 145.0 minutes (interquartile range, 111.5-185.5 minutes). Care process delays were associated with worse clinical outcomes in LKW-to-intervention intervals in early-treated patients and in door-to-intervention intervals in early-treated and late-treated patients, and not associated with LKWTD intervals, eg, in early-treated patients, for each 10-minute delay, healthy life-years lost were DTP 1.8 months vs LKWTD 0.0 months; P < .001. Considering granular time increments, the amount of healthy life-time lost associated with each 1 second of delay was DTP 2.2 hours and DTR 2.4 hours. Conclusions and Relevance: In this study, care delays were associated with loss of healthy life-years in patients with acute ischemic stroke treated with EVT, particularly in the postarrival time period. The finding that every 1 second of delay was associated with loss of 2.2 hours of healthy life may encourage continuous quality improvement in door-to-treatment times.
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    Tenecteplase versus Alteplase for Stroke Thrombolysis Evaluation Trial in the Ambulance (Mobile Stroke Unit-TASTE-A): protocol for a prospective randomised, open-label, blinded endpoint, phase II superiority trial of tenecteplase versus alteplase for ischaemic stroke patients presenting within 4.5 hours of symptom onset to the mobile stroke unit
    Bivard, A ; Zhao, H ; Coote, S ; Campbell, B ; Churilov, L ; Yassi, N ; Yan, B ; Valente, M ; Sharobeam, A ; Balabanski, A ; Dos Santos, A ; Ng, F ; Langenberg, F ; Stephenson, M ; Smith, K ; Bernard, S ; Thijs, V ; Cloud, G ; Choi, P ; Ma, H ; Wijeratne, T ; Chen, C ; Olenko, L ; Davis, SM ; Donnan, GA ; Parsons, M (BMJ PUBLISHING GROUP, 2022-04-01)
    INTRODUCTION: Mobile stroke units (MSUs) equipped with a CT scanner are increasingly being used to assess and treat stroke patients' prehospital with thrombolysis and transfer them to the most appropriate hospital for ongoing stroke care and thrombectomy when indicated. The effect of MSUs in both reducing the time to reperfusion treatment and improving patient outcomes is now established. There is now an opportunity to improve the efficacy of treatment provided by the MSU. Tenecteplase is a potent plasminogen activator, which may have benefits over the standard of care stroke lytic alteplase. Specifically, in the MSU environment tenecteplase presents practical benefits since it is given as a single bolus and does not require an infusion over an hour like alteplase. OBJECTIVE: In this trial, we seek to investigate if tenecteplase, given to patients with acute ischaemic stroke as diagnosed on the MSU, improves the rate of early reperfusion. METHODS AND ANALYSIS: TASTE-A is a prospective, randomised, open-label, blinded endpoint (PROBE) phase II trial of patients who had an ischaemic stroke assessed in an MSU within 4.5 hours of symptom onset. The primary endpoint is early reperfusion measured by the post-lysis volume of the CT perfusion lesion performed immediately after hospital arrival. ETHICS AND DISSEMINATION: The study was approved by the Royal Melbourne Hospital Human Ethics committee. The findings will be published in peer-reviewed journals, presented at academic conferences and disseminated among consumer and healthcare professional audiences. TRIAL REGISTRATION NUMBER: NCT04071613.
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    The Association Between Sarcopenia and Functional Improvement in Older and Younger Patients Who Completed Inpatient Rehabilitation: A Prospective Cohort Study.
    Churilov, I ; Churilov, L ; Brock, K ; Murphy, D ; MacIsaac, RJ ; Ekinci, EI (Frontiers Media SA, 2021)
    Objective: To investigate the association between sarcopenia and functional improvement in patients older and younger than 65 years upon completion of an inpatient rehabilitation program. Design: Prospective cohort study. Participants: Adult consecutive patients who completed the inpatient rehabilitation program at a metropolitan tertiary referral hospital general inpatient rehabilitation unit. Methods: Sarcopenia status was determined using the European Working Group on Sarcopenia in Older People 2 algorithm, using muscle mass measured by BioImpedance Analysis and grip strength. Progress in rehabilitation was measured using change in the Functional Independence Measure and Goal Attainment Scaling score. To investigate the age group by sarcopenia status interaction we used quantile regression models with bootstrapped standard error estimation for functional improvement and linear regression model with robust standard error estimation for GAS score. Results: 257 participants [128 (50%) male, median age 63 years (IQR: 52-72)], 33(13%) with sarcopenia, completed inpatient rehabilitation [median length of stay 16 days (IQR: 11-27.5)]. Participants' median Functional Independence Measure change was 24 (IQR 15-33.5) and mean total Goal Attainment Scaling score was 57.6 (SD 10.2). Adjusting for admission Functional Independence Measure score, the median difference in Functional Independence Measure change between participants with and without sarcopenia was: -4.3 (95% CI: -10.6, 1.9); p = 0.17 in participants 65 years and younger, and 4.6 (95% CI: 1.0, 8.2); p = 0.01 in participants older than 65; age-by-sarcopenia interaction p = 0.02. Conclusions: Unlike younger people, older people with sarcopenia have greater functional improvement in inpatient rehabilitation than those without sarcopenia.
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    Early Brain Volume Changes After Stroke: Subgroup Analysis From the AXIS-2 Trial
    Bu, N ; Churilov, L ; Khlif, MS ; Lemmens, R ; Wouters, A ; Fiebach, JB ; Chamorro, A ; Ringelstein, EB ; Norrving, B ; Laage, R ; Grond, M ; Wilms, G ; Brodtmann, A ; Thijs, V (FRONTIERS MEDIA SA, 2022-01-28)
    BACKGROUND AND PURPOSE: The evolution of total brain volume early after stroke is not well understood. We investigated the associations between age and imaging features and brain volume change in the first month after stroke. METHODS: We retrospectively studied patients with acute ischemic stroke enrolled in the AXIS-2 trial. Total brain volume change from hyperacute MRI data to the first month after stroke was assessed using unified segmentation in SPM12. We hypothesized that age, ischemic brain lesion size, and white matter (WM) changes were associated with larger brain volume change. Enlarged perivascular spaces (EPVSs) and white matter hyperintensities (WMHs) were rated visually and the presence of lacunes was assessed. RESULTS: We enrolled 173 patients with a mean age of 67 ± 11 years, 44% were women. There was a median 6 ml decrease in volume (25th percentile -1 ml to 75th percentile 21 ml) over time, equivalent to a median 0.5% (interquartile range [IQR], -0.07%-1.4%), decrease in brain volume. Age was associated with larger brain volume loss (per 10 years of age, 5 ml 95% CI 2-8 ml). Baseline diffusion weighted imaging (DWI) lesion volume was not associated with greater volume loss per 10 ml of lesion volume, change by 0 ml (95% CI -0.1 to 0.1 ml). Increasing Fazekas scores of deep WMH were associated with greater tissue loss (5 ml, 95% CI 1-10 ml). CONCLUSIONS: Total brain volume changes in a heterogenous fashion after stroke. Volume loss occurs over 1 month after stroke and is associated with age and deep WM disease. We did not find evidence that more severe strokes lead to increased early tissue loss.
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    Feasibility of using self-reported ethnicity in pregnancy according to the gestation-related optimal weight classification: a cross-sectional study
    Lockie, E ; McCarthy, EA ; Hui, L ; Churilov, L ; Walker, SP (WILEY, 2018-05-01)
    OBJECTIVE: To evaluate the feasibility of self-reported ethnicity using the gestation-related optimal growth (GROW) classification in a contemporary multicultural antenatal population. DESIGN: Cross-sectional study. SETTING: Tertiary obstetric hospital in Melbourne, Australia. POPULATION: Pregnant women attending the antenatal clinic. METHODS: We surveyed pregnant women during April-June 2016 regarding their understanding of the term 'ethnicity', and how they would classify the ethnicity of themselves, their partner, and family members according to the Australian GROW classification. RESULTS: Two hundred and thirty-five women completed the survey. When describing 'ethnicity', most women (103, 44%) chose multiple descriptors, most frequently country of birth (54%) and region of ancestry (47%). Interpretation of 'ethnicity' varied significantly between ethnic groups: those choosing 'country of birth' were more likely to identify as Indian (odds ratio, OR 3.5, P = 0.03), whereas those choosing 'physical appearance' were more likely to identify as Chinese (OR 3.0, P = 0.047). Thirty participants (13%) were unable to describe their ethnicity from the available GROW options. Sixty-one (26%) respondents' ethnicity was inconsistent with that of their parents' heritage. A further 35% had a partner of different ethnicity. The agreement between country of birth and self-reported ethnicity was only fair (kappa 0.73, 95% confidence interval, 95% CI 0.64-0.82). CONCLUSION: This study confirms the complexity of defining ethnicity in contemporary multicultural settings. Self-reported ethnicity is often inaccurate, concepts of ethnicity vary by ethnic group, and country of birth is a poor descriptive surrogate. Adjustment for maternal ethnicity should be undertaken with caution in the customised assessment of fetal growth. TWEETABLE ABSTRACT: Is self-reported maternal ethnicity reliable? We think not.
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    A novel immune function biomarker identifies patients at risk of clinical events early following liver transplantation
    Sood, S ; Haifer, C ; Yu, L ; Pavlovic, J ; Churilov, L ; Gow, PJ ; Jones, RM ; Angus, PW ; Visvanathan, K ; Testro, AG (WILEY, 2017-04-01)
    Balancing immunosuppression after liver transplant is difficult, with clinical events common. We investigate whether a novel immune biomarker based on a laboratory platform with widespread availability that measures interferon γ (IFNγ) after stimulation with a lyophilized ball containing an adaptive and innate immune stimulant can predict events following transplantation. A total of 75 adult transplant recipients were prospectively monitored in a blinded, observational study; 55/75 (73.3%) patients experienced a total of 89 clinical events. Most events occurred within the first month. Low week 1 results were significantly associated with risk of early infection (area under the receiver operating characteristic curve [AUROC], 0.74; P = 0.008). IFNγ ≤ 1.30 IU/mL (likelihood ratio positive, 1.93; sensitivity, 71.4%; specificity, 63.0%) was associated with the highest risk for infection with minimal rejection risk. Nearly half the cohort (27/60, 45.0%) expressed IFNγ ≤ 1.30 IU/mL. Moreover, an elevated week 1 result was significantly associated with the risk of rejection within the first month after transplant (AUROC, 0.77; P = 0.002), but no episodes of infection. On multivariate logistic regression, IFNγ ≥ 4.49 IU/mL (odds ratio, 4.75) may be an independent predictor of rejection (P = 0.05). In conclusion, low IFNγ suggesting oversuppression is associated with infections, whereas high IFNγ indicating undersuppression is associated with rejection. This assay offers the potential to allow individualization and optimization of immunosuppression that could fundamentally alter the way patients are managed following transplantation. Liver Transplantation 23 487-497 2017 AASLD.
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    Epilepsy in families: Age at onset is a familial trait, independent of syndrome
    Ellis, CA ; Churilov, L ; Epstein, MP ; Xie, SX ; Bellows, ST ; Ottman, R ; Berkovic, SF (WILEY, 2019-07-01)
    OBJECTIVE: We tested 2 hypotheses regarding age at onset within familial epilepsies: (1) family members with epilepsy tend to have similar ages at onset, independent of epilepsy syndrome; and (2) age at onset is younger in successive generations after controlling for sampling bias. METHODS: We analyzed clinical data collected by the Epi4K Consortium (303 multiplex families, 1,120 individuals). To test hypothesis 1, we used both linear mixed models commonly used for heritability analysis and Cox regression models with frailty terms to assess clustering of onset within families after controlling for other predictors. To test hypothesis 2, we used mixed effects models, pairwise analyses, and survival analysis to address sampling-related bias that may mimic anticipation. RESULTS: Regarding hypothesis 1, age at seizure onset was significantly heritable (intraclass correlation coefficient = 0.17, p < 0.001) after adjusting for epilepsy type, sex, site, history of febrile seizure, and age at last observation. This finding remained significant after adjusting for epilepsy syndromes, and was robust across statistical methods in all families and in generalized families. Regarding hypothesis 2, the mean age at onset decreased in successive generations (p < 0.001). After adjusting for age at last observation, this effect was not significant in mixed effects models (p = 0.14), but remained significant in pairwise (p = 0.0003) and survival analyses (p = 0.02). INTERPRETATION: Age at seizure onset is an independent familial trait, and may have genetic determinants distinct from the determinants of particular epilepsy syndromes. Younger onsets in successive generations can be explained in part by sampling bias, but the presence of genetic anticipation cannot be excluded. ANN NEUROL 2019.
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    Health economic implications of postoperative complications following liver resection surgery: a systematic review.
    Cosic, L ; Ma, R ; Churilov, L ; Nikfarjam, M ; Christophi, C ; Weinberg, L (Wiley, 2019-12)
    BACKGROUND: Limited data exists concerning the health economics of liver resection, with even less information on the costs emerging from complications, despite this remaining an important target from a health economic perspective. Our objective was to describe the financial burden of complications following liver resection. METHODS: We conducted a systematic search and included studies reporting resource use of in-hospital complications during the index liver resection admission. All indications for liver resection were considered. All techniques were considered. Data was collected using a data extraction table and a narrative synthesis was performed. RESULTS: We identified 12 eligible articles. There was considerable heterogeneity in study designs, patient populations and outcome definitions. We found weak evidence of increased costs associated with major liver resection compared to minor resections. We found robust evidence supporting the increasing economic burden arising from complications after liver resection. Acceptable evidence for increased cost due to the presence and grade of complication was found. Strong evidence concerning the association of length of stay with costs was demonstrated. CONCLUSIONS: The presence and grade of complications increase hospital cost across diverse settings. The costing methodology should be transparent and complication grading systems should be consistent in future studies.
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    Timing of diagnosis of gestational diabetes and pregnancy outcomes: A retrospective cohort
    Shub, A ; Chee, T ; Templeton, A ; Boyce, D ; McNamara, C ; Houlihan, C ; Churilov, L ; McCarthy, EA (WILEY, 2019-02-01)
    BACKGROUND: Recent guidelines suggest screening high-risk women in early pregnancy for gestational diabetes (GDM); however, there is little evidence to support this. AIMS: To compare pregnancy outcomes associated with diabetes for women with risk factors for GDM according to gestation of diagnosis. Early GDM was defined as a positive test before 20 weeks gestation, late GDM as a positive test at 20 or more weeks and no GDM when both tests were negative. MATERIALS AND METHODS: Retrospective analysis in an Australian tertiary hospital of women who underwent a glucose tolerance test in pregnancy prior to 20 weeks gestation, and a repeat test after 20 weeks gestation if the initial test was negative. Results were adjusted for maternal demographics. RESULTS: Women with early GDM (n = 170) were no more likely to experience the obstetric composite outcome than women with late GDM (n = 171) or no GDM (n = 547) (early odds ratio (OR) 1.16, 95%CI 0.79-1.71; late OR 0.78, 95%CI 0.53-1.12). Infants of women with early GDM, but not late GDM, were more likely (early OR 1.8, 95%CI 1.15-2.92; late OR 1.4, 95%CI 0.90-2.23) to have the neonatal composite outcome than infants of women without GDM, predominantly due to an increase in neonatal hypoglycaemia. CONCLUSIONS: This result may be due to careful management of GDM, or because, after adjustment for maternal demographics, the early diagnosis of GDM does not substantially increase rates of adverse outcomes compared to GDM diagnosed in later pregnancy or no GDM in women with risk factors for GDM.