Australian e-Health Research Centre

Summary‘Chemobrain’ language symptoms are commonly reported by adults receiving intensive chemotherapy for acute myeloid leukaemia (AML), but real‐time detection eludes clinical imaging modalities. We performed a prospective, observational, longitudinal cohort study employing serial comprehensive neurocognitive assessment and brain functional MRI (fMRI) in 20 adults receiving intensive chemotherapy for newly diagnosed AML. At chemotherapy completion, fMRI demonstrated significantly reduced functional connectivity between the salience (anterior cingulate cortex [ACC]) and the left language (inferior frontal gyrus [IFG] and posterior superior temporal gyrus [pSTG]) networks (p = 0.008), supported by significant decreases in white matter fibre density in the corpus callosum (p = 0.009) and in the tract connecting the ACC and left IFG (p = 0.037). Increasing cytarabine dose significantly correlated with decreasing ACC–IFG connectivity (R2 = 0.51, p = 0.021). Correlative analyses identified significant associations between worse brain imaging findings (language region connectivity and volume); worse verbal fluency scores; and increasing treatment intensity (cytarabine dose, transfusions and serum ferritin) (R2 > 0.5, p < 0.05). Taken together, this study provides novel evidence that AML chemotherapy induces measurable alterations in brain microstructure and functional connectivity, particularly affecting salience and language networks, and suggests a dose‐dependent effect with escalating cytarabine and transfusion exposure.

High-quality, culturally safe, secondary prevention care has the potential to improve the cardiovascular health of Aboriginal and Torres Strait Islander People in Australia (hereafter collectively referred to as First NationsPeoples). Despite this, there is a paucity of comprehensive data on cardiac rehabilitation (CR) participation among First Nations Peoples. The Queensland Cardiac Outcome Registry is a clinical registry that routinely collects point-of-care CR data. Therefore, the aim of this study is to (i) describe the First Nations populations referred to CR across Queensland, (ii) quantify rates of participation, and (iii) determine factors associated with CR attendance and completion. The cohort comprised 2,383 patients who identified as Aboriginal and/or Torres Strait Islander and were referred to one of 56 Queensland CR service extracted from Queensland Cardiac Outcome Registry (2020-2022). Bivariate and multivariable logistic regression analyses were used to identify factors associated with CR attendance and completion. Over the study period, 50% (n=1,185) of First Nations patients in Queensland participated in at least one CR session. Of those who attended, 28% (n=333) completed CR (14% of the total cohort). The strongest predictors of CR attendance were having a coronary artery bypass graft or percutaneous coronary intervention procedure, living regionally (as opposed to remotely/very remotely), and coming from areas of higher socio-economic advantage. CR completion was more likely among men, those in older age groups (particularly 55-64 years), living in a major city, and non-smokers. This study provides the first known large-scale analysis of the uptake of CR programs among First Nations cardiac patients in Australia. We demonstrate that rates of attendance are higher among this cohort than previously reported. Barriers to attendance are described and highlight an important socio-economic gradient. There are clear opportunities for improving access to evidence-based secondary prevention programs for First Nations Peoples and benefits in collectively considering how unmet needs can be supported.

To compare the symptomatology of Aboriginal and Torres Strait Islander and non-Indigenous patients presenting to an emergency department (ED) with suspected acute coronary syndrome (ACS) and to determine whether specific symptoms increased the odds of ACS diagnosis and whether traditional groupings of typical or atypical symptoms are relevant in these populations. Prospectively collected symptom data from 1643 adult patients presenting at two Queensland emergency departments between 2011-2014 and 2016-2019 who were assessed for suspected ACS were analysed according to self-reported Indigenous status. ACS diagnosis was the primary outcome. In 1643 patients investigated for suspected ACS, chest pain (92.1%), diaphoresis (47.8%), and shortness of breath (52.2%) were the most reported symptoms. For the 194 patients diagnosed with ACS, chest pain was reported less frequently in Aboriginal and Torres Strait Islander patients compared with non-Indigenous patients (81.5% vs. 94.2%, p = 0.009). For Aboriginal and Torres Strait Islander patients, vomiting and indigestion were associated with increased odds of ACS; left-sided chest pain or sharp pain was associated with decreased odds. Aboriginal and Torres Strait Islander patients with ACS were more likely to present atypically than non-Indigenous patients, but typicality was not associated with ACS. Clinicians must have a high index of suspicion for ACS in Aboriginal and Torres Strait Islander people with chest pain who present with symptoms of gastrointestinal upset such as indigestion or vomiting. Typical or atypical groupings of ACS symptoms are of limited value or relevance in Australian populations, and these terms should be phased out. ANZCRN12617000756325.

In 2022, Australia saw an unprecedented outbreak of Japanese encephalitis virus genotype IV (JEV GIV). The outbreak involved 42 human cases with 7 fatalities, as well as affecting >80 pig farms in New South Wales and Queensland. Herein, we designed, constructed, and tested two JEV GIV mRNA vaccines encoding prME, which provided protection against a lethal JEV GIV challenge in an Ifnar-/- mouse model. The vaccines were not codon optimized and included either the Native (full-length) or a Shorter signal peptide, with the latter missing the N-terminal n-region. Two vaccinations with 5 µg of the Shorter vaccine provided neutralizing antibody responses that were significantly lower but overlapped with those seen after vaccination with Imojev, a live attenuated vaccine approved for use in humans. Both mRNA vaccines provided approximately a five to six log reduction in viremia, ≥80% protection against overt disease and weight loss, and mortality. The paper illustrates in-country mRNA vaccine generation in response to a local outbreak, with JEV mRNA vaccines potentially emerging to be easier to manufacture, cheaper, and more suitable for immunocompromised individuals.

BackgroundThere is increasing evidence for an association between white matter hyperintensities (WMH) and brain beta‐amyloid deposition. WMH are not exclusive correlates of a single etiology, and the spatial topography can associate with different pathologic markers of vascular or neurodegenerative disease. How WMH are longitudinally associated with brain beta‐amyloid burden requires further investigation, particularly with respect to co‐existent vascular risk factors and differences across brain regions.MethodWe retrospectively measured WMH on MRI and vascular risk factors in a combined neuroimaging data set comprised of the ADNI, AIBL and OASIS3 studies, which included harmonized centiloid estimates of beta‐amyloid burden from PET imaging. WMH were measured using the TrUE‐Net algorithm. Vascular risk factors were extracted from provided clinical data and used to calculate individual revised Framingham Stroke Risk Profile (FSRP) scores. Five established data‐driven WM regions (juxtacortical, deep frontal, periventricular, parietal, posterior) were used for regional relationships with WMH volume and growth. Linear mixed effects modelling was used to determine the relationship between the growth rate of normalized regional WMH volumes and baseline beta‐amyloid burden, controlling for age, sex, APOE4 status, and vascular risk factors.Result1245 participants [48.7% female, mean age 71.7 y (SD 7.6 y)] had at least 3 brain MRIs suitable for WMH volume measurement. Linear mixed models demonstrate robust independent cross‐sectional relationships between WMH and baseline beta‐amyloid burden (p <0.001), age (p <0.001) and FSRP (p <0.001). Growth rates of WMH increased with baseline beta‐amyloid burden (p <0.05) and decreased with vascular risk (p <0.001), above and beyond age, sex, and APOE4 status. Regional analyses revealed both baseline beta‐amyloid burden and FSRP associated with the juxtacortical deep frontal and periventricular regions, but the parietal region was unique to beta‐amyloid (p <0.05). Longitudinally, the association for beta‐amyloid burden (p <0.005) persisted in only the parietal WMH and no normalized regional values associated longitudinally with FSRP.ConclusionOur study suggests that in Alzheimer disease research cohorts, WMH progression is associated with beta‐amyloid burden, particularly in parietal white matter. Vascular risk associated WMH were influential for WMH volume but did not associate with WMH progression in a regionally specific manner.

Automated contour quality assurance (QA) has the potential to reduce resource and cost requirements for clinical trial QA. While several studies have developed such models, few have been translated for use in prospective real-world trials. This study aimed to implement a contour QA tool using a previously developed model and evaluate its performance during deployment within the TROG 18.01 NINJA prostate cancer trial. A software tool was developed using an existing prostate clinical target volume (CTV) QA model and integrated into the trial QA workflow. A pilot study was conducted over an 18-month period, during which 56 CTVs were assessed. Reports generated by the tool flagged cases for review and were provided to radiation oncologists to support QA processes. All five protocol-violating CTVs were correctly identified during deployment, yielding a sensitivity of 1.0. However, a higher-than-expected false positive rate resulted in an accuracy of 0.46 and specificity of 0.41. Retrospective analysis showed that many cases submitted deviated from the model's training distribution, primarily due to inconsistencies in MRI acquisition and variation in submitted CTV definitions. Incorporating out-of-distribution detection based on histogram correlation and model uncertainty improved accuracy to 0.69 for in-distribution cases. Radiation oncologists reported time savings of up to 60min per case. However, preparation of data remained time intensive for QA coordinators, highlighting the need for further workflow automation. These findings support the feasibility of automated contour QA in multicentre trials and offer guidance for future implementation at scale.

Background/Objective: Despite available SARS-CoV-2 vaccines, coverage gaps persist due to unequal distribution and limited access. Microarray patches offer a promising solution to address these challenges, providing a safer and easier-to-use alternative. We present a randomised, double-blind Phase I clinical trial evaluating the SARS-CoV-2 spike protein subunit vaccine, HexaPro, delivered via a high-density microarray patch (HD-MAP). Methods: Forty-four healthy adults aged 18–50 years were assigned to receive either 0 µg, 15 µg, or 45 µg of HexaPro via the HD-MAP, with the primary objective of assessing safety and tolerability. Results: The HD-MAP HexaPro vaccine was found to be safe and well tolerated, with only mild adverse events reported. Following vaccination significant increases in spike-specific IgG titers were observed by 7 days and remained stable through day 90. This IgG response effectively neutralised multiple SARS-CoV-2 variants. Additionally, the HexaPro HD-MAP was stable for up to 12 months at 40 °C. Conclusions: These findings support the continued clinical development of HD-MAPs as an alternative vaccination strategy.