ORCID Profile
0000-0003-3817-4885
Current Organisations
Monash University
,
WA Country Health Service
,
Seoul National University Hospital
,
University of Melbourne
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Publisher: Springer Science and Business Media LLC
Date: 05-04-2023
DOI: 10.1007/S00262-023-03430-6
Abstract: CD73 upregulation in tumors leads to local immunosuppression. This phase I, first-in-human study evaluated oleclumab (MEDI9447), an anti-CD73 human IgG1λ monoclonal antibody, alone or with durvalumab in patients with advanced colorectal cancer (CRC), pancreatic ductal adenocarcinoma (PDAC), or epidermal growth factor receptor-mutant non-small-cell lung cancer (NSCLC). Patients received oleclumab 5–40 mg/kg (dose-escalation) or 40 mg/kg (dose-expansion) intravenously every 2 weeks (Q2W), alone (escalation only) or with durvalumab 10 mg/kg intravenously Q2W. 192 patients were enrolled, 66 during escalation and 126 (42 CRC, 42 PDAC, 42 NSCLC) during expansion. No dose-limiting toxicities occurred during escalation. In the monotherapy and combination therapy escalation cohorts, treatment-related adverse events (TRAEs) occurred in 55 and 54%, respectively, the most common being fatigue (17 and 25%). In the CRC, PDAC, and NSCLC expansion cohorts, 60, 57, and 45% of patients had TRAEs, respectively the most common were fatigue (15%), diarrhea (9%), and rash (7%). Free soluble CD73 and CD73 expression on peripheral T cells and tumor cells showed sustained decreases, accompanied by reduced CD73 enzymatic activity in tumor cells. Objective response rate during escalation was 0%. Response rates in the CRC, PDAC, and NSCLC expansion cohorts were 2.4% (1 complete response [CR]), 4.8% (1 CR, 1 partial response [PR]), and 9.5% (4 PRs), respectively 6-month progression-free survival rates were 5.4, 13.2, and 16.0%. Oleclumab ± durvalumab had a manageable safety profile, with pharmacodynamic activity reflecting oleclumab’s mechanism of action. Evidence of antitumor activity was observed in tumor types that are generally immunotherapy resistant. Clinicaltrials.gov, NCT02503774 date of registration, July 17, 2015.
Publisher: Elsevier BV
Date: 10-2017
DOI: 10.1016/J.CARDFAIL.2017.06.002
Abstract: The aim of this work was to understand the pattern and outcomes for heart failure (HF)-related hospitalization among Indigenous and non-Indigenous patients living in Central Australia. A retrospective analysis of administrative data for patients presenting with a primary or secondary diagnosis of HF to Central Australia's Alice Springs Hospital during 2008-2012 was performed. The population rate of admission and subsequent outcomes (including mortality and readmission) during the 5-year study period were examined. A total of 617 patients, aged 55.8 ± 17.5 years and 302 (49%) female constituted the study cohort. The 446 Indigenous patients (72%) were significantly younger (50.8 ± 15.9 vs 68.7 ± 14.9 P < .001) and clinically more complex compared with the non-Indigenous patients. Annual prevalence of any HF hospitalization was markedly higher in the Indigenous population (1.9%, 95% CI 1.7-2.1) compared with the non-Indigenous population (0.5%, 95% CI 0.4-0.6) the greatest difference being for women. Overall, non-Indigenous patients had poorer outcomes and were significantly more likely to die (P < .0001), but this was largely driven by age differences. Alternatively, Indigenous patients were significantly more likely to have a higher number of hospitalizations, although indigeneity was not a predictor for 30- or 365-day rehospitalization from the index admission. The pattern of HF among Indigenous Australians in Central Australia is characterized by a younger population with more clinically complex cases and greater health care utilization.
Publisher: MDPI AG
Date: 19-05-2018
DOI: 10.3390/NU10050644
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 21-09-2021
Abstract: The natural history of latent rheumatic heart disease (RHD) detected by echocardiography remains unclear. We aimed to assess the accuracy of a simplified score based on the 2012 World Heart Federation criteria in predicting mid‐term RHD echocardiography outcomes in children from 4 different countries. Patient‐level baseline and follow‐up data of children with latent RHD from 4 countries (Australia, n=62 Brazil, n=197 Malawi, n=40 New Zealand, n=94) were combined. A simplified echocardiographic scoring system previously developed from Brazilian and Ugandan cohorts, consisting of 5 point‐based variables with respective weights, was applied: mitral valveanterior leaflet thickening (weight=3), excessive leaflet tip motion (3), regurgitation jet length ≥2 cm (6), aortic valve focal thickening (4), and any regurgitation (5). Unfavorable outcome was defined as worsening diagnostic category, persistent definite RHD or development/worsening of valve regurgitation/stenosis. The score model was updated using methods for recalibration. 393 patients (314 borderline, 79 definite RHD) with median follow‐up of 36 (interquartile range, 25–48) months were included. Median age was 14 (interquartile range, 11–16) years and secondary prophylaxis was prescribed to 16%. The echocardiographic score model applied to this external population showed significant association with unfavorable outcome (hazard ratio, 1.10 95% CI, 1.04–1.16 P =0.001). Unfavorable outcome rates in low (≤5 points), intermediate (6–9), and high‐risk (≥10) children at 3‐year follow‐up were 14.3%, 20.8%, and 38.5% respectively ( P .001). The updated score model showed good performance in predicting unfavorable outcome. The echocardiographic score model for predicting RHD outcome was updated and validated for different latent RHD populations. It has potential utility in the clinical and screening setting for risk stratification of latent RHD.
Publisher: American Society of Clinical Oncology (ASCO)
Date: 20-06-2023
DOI: 10.1200/JCO.22.02524
Abstract: Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported. In the longest follow-up, to our knowledge, for a KRAS G12C inhibitor, we assessed the long-term efficacy, safety, and biomarkers of sotorasib in patients with KRAS G12C-mutated advanced non–small-cell lung cancer (NSCLC) from the CodeBreaK 100 clinical trial (ClinicalTrials.gov identifier: NCT03600883 ). This multicenter, single-group, open-label phase I hase II trial enrolled 174 patients with KRAS G12C-mutated, locally advanced or metastatic NSCLC after progression on prior therapies. Patients (N = 174) received sotorasib 960 mg once daily with the primary end points for phase I of safety and tolerability and for phase II of objective response rate (ORR). Sotorasib produced an ORR of 41%, median duration of response of 12.3 months, progression-free survival (PFS) of 6.3 months, overall survival (OS) of 12.5 months, and 2-year OS rate of 33%. Long-term clinical benefit (PFS ≥ 12 months) was observed in 40 (23%) patients across PD-L1 expression levels, in a proportion of patients with somatic STK11 and/or KEAP1 alterations, and was associated with lower baseline circulating tumor DNA levels. Sotorasib was well tolerated, with few late-onset treatment-related toxicities, none of which led to treatment discontinuation. These results demonstrate the long-term benefit of sotorasib, including in subgroups with poor prognosis.
Publisher: Informa UK Limited
Date: 02-2021
DOI: 10.2147/COPD.S287172
Publisher: MDPI AG
Date: 12-09-2019
Abstract: Smoking cessation remains a health promotion target. Applying the Transtheoretical Model to Australian Burden of Obstructive Lung Diseases (BOLD) data, we examined differences in stages of change (SoC) and readiness to quit decisional behaviours. Factors were identified likely to influence readiness of smokers, ≥40 years old, to quit. Analysis was restricted to current smokers classified to one of three stages: pre-contemplation (PC), contemplation (C) or preparation (P) to quit. Their ability to balance positive and negative consequences was measured using decisional balance. Among 314 smokers, 43.0% females and 60.8% overweight/obese, the distribution of SoC was: 38.1% PC, 38.3% C and 23.5% P. Overweight/obesity was associated with readiness to quit in stages C and P and there were more negative than positive attitudes towards smoking in those stages. Males were significantly heavier smokers in PC and C stages. Females used smoking cessation medication more frequently in PC stage, were more embarrassed about smoking and had greater negative reinforcements from smoking. Age started smoking and factors related to smoking history were associated with readiness to quit and increased the odds of being in stage C or P. An overweight/obese smoker was likely to be contemplating or preparing to quit. In these stages, smokers have more negative attitudes toward smoking. Starting smoking later, taking advice on cessation from health providers and using quit medications indicate increased readiness to quit. Evaluating these factors in smokers and developing cessation gain-framed messages may prove useful to healthcare providers.
No related grants have been discovered for Graeme Maguire.