Medicine (Austin & Northern Health) - Research Publications
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ItemDevelopments in systemic therapies for the management of lung cancer(WILEY, 2021-12)Lung cancer accounts for approximately 1 in 10 new cancer diagnoses annually and is responsible for the most cancer-associated deaths in Australia. Despite such figures, there is reason for optimism with many practice-changing developments to report for the management of patients with thoracic malignancies over the last few years. We outline such changes, including the emerging role of immunotherapy in the neoadjuvant and adjuvant setting for patients with localised non-small-cell lung cancer, as well as the established standard of consolidation immunotherapy following definitive chemoradiotherapy for those with locally advanced disease. In the metastatic setting, combination chemotherapy-immunotherapy approaches have become the new paradigm for most patients in the absence of a recognised driver mutation. A range of novel targeted therapies now exist and are Pharmaceutical Benefits Scheme (PBS)-subsidised for targets such as EGFR, ALK and ROS1, with many others, such as KRAS G12C, NTRK, MET, RET and HER2, also with therapies rapidly being developed. Even among patients with small-cell lung cancer, who account for the worst prognoses and until recently have received a chemotherapy regimen that has remained unchanged in over 20 years, there is a new standard-of-care in combination chemotherapy-immunotherapy. Furthermore, immunotherapy and potentially anti-vascular endothelial growth factor agents now also play a role in mesothelioma treatment. Last, given recent developments in immunotherapy, targeted therapy and combination approaches in the non-small-cell lung cancer space, there is an increasing recognition of the diversity of lived experience for such patients and need for survivorship programmes to acknowledge such nuances.
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ItemFenofibrate, which reduces risk of sight-threatening diabetic retinopathy in type 2 diabetes, is associated with early narrowing of retinal venules: a FIELD trial substudy(WILEY, 2022-04)Retinal vessel calibre metrics were evaluated at baseline and 2 years in a FIELD substudy (n = 208). Central retinal venule calibre was significantly reduced by fenofibrate and unchanged by placebo. Arteriole metrics did not change. Larger studies relating retinal vessel calibre to future diabetes complications and response to therapy are merited.
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ItemThe Patient Voice in Neovascular Age-Related Macular Degeneration: Findings from a Qualitative Study(SPRINGER INT PUBL AG, 2023-02)INTRODUCTION: Visual impairment resulting from diseases such as neovascular age-related macular degeneration (nAMD) may cause behavioural, environmental, psychological, and logistical challenges that could act as barriers to effective uptake and sustainability of treatment with anti-vascular endothelial growth factor agents (anti-VEGFs). Understanding emotions and experiences of patients with nAMD may help inform the determinants of adherence, and could contribute to improvements in ophthalmic outcomes and quality of life. METHODS: Seventeen patients with nAMD receiving anti-VEGF injections were enrolled from three clinics: one each in France (n = 5), Germany (n = 6), and the UK (n = 6). Patients' health information and treatment characteristics were collected. Individual phone interviews were conducted by experienced health care interviewers. Transcripts were analysed thematically. RESULTS: Patients (53% female) had a mean age of 77 years. Bilateral anti-VEGF injections were received by 24% (n = 4); and most (76%, n = 13) were adherent to their treatment. Patient emotions at diagnosis ranged from happiness at learning about the treatment for nAMD to being terrified of receiving an injection in the eye. Most patients mentioned feeling anxious and fearful before their first injection despite receiving reassurance. After the first injection, these feelings and apprehension abated for many, but not all. With the goal of maintaining the best possible vision, few (24%, n = 4) patients reported more than one missed appointment, and most had never considered stopping treatment. No patient reported additional assistance beyond family support; however, many had difficulties with recreational and domestic activities and had developed coping strategies. CONCLUSION: This study provides insights on patients' emotions related to their experience of nAMD and its management, highlighting the varying experiences between individuals. It shows the importance of the patient's voice when considering patient care and management, and how the nature and timing of interventions can improve the experience of living with and managing nAMD.
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ItemAssociation Between Visual Acuity and Fluid Compartments with Treat-and-Extend Intravitreal Aflibercept in Neovascular Age-Related Macular Degeneration: An ARIES Post Hoc Analysis(SPRINGER INT PUBL AG, 2022-06)INTRODUCTION: Recently, there has been growing interest in exploring the relationship between visual acuity and fluid localization in different retinal compartments. This post hoc analysis of the ARIES study explores the relationship between the presence of intraretinal fluid (IRF) and subretinal fluid (SRF), both at baseline and throughout treatment, and best-corrected visual acuity (BCVA) in patients with neovascular age-related macular degeneration (nAMD) treated with intravitreal aflibercept (IVT-AFL) in a treat-and-extend regimen. METHODS: ARIES (NCT02581891) was a multicenter, randomized, phase 3b/4 study comparing the efficacy of two IVT-AFL treat-and-extend regimens over 2 years in patients with treatment-naïve nAMD. This post hoc analysis explores the relationship between the presence of SRF/IRF and absolute BCVA (letter score) at baseline and fixed visits. RESULTS: In 210 patients (treat-and-extend treatment arms combined), SRF presence at baseline was associated at every time point with a numerically higher mean BCVA than if absent, with 10 more letters at week 104. IRF presence at baseline was associated at all but one time point with a numerically lower mean BCVA than if absent (week 104, 8-letter difference). Baseline SRF+IRF was associated with lower BCVA (week 104, 7-letter difference) than if only SRF was present, but higher BCVA (week 104, 8-letter difference) than if only IRF was present. Absence of SRF+IRF was not associated with better BCVA at any time point during the study. CONCLUSION: In ARIES, in patients with nAMD treated with IVT-AFL, the presence of SRF was associated with better visual acuity, whereas IRF was associated with poorer visual acuity. The findings of this post hoc analysis suggest that differentiating IRF from SRF may offer better prognostic value in guiding treatment-extension decisions than the use of combined or "any" IRF and SRF. Prospective trials are needed to validate these results and determine their clinical relevance. TRIAL REGISTRATION NUMBER (CLINICALTRIALS.GOV): NCT02581891. Association between Visual Acuity and Fluid Compartments with Treat-and-Extend Intravitreal Aflibercept in Neovascular Age-Related Macular Degeneration: An ARIES Post Hoc Analysis: A Video Abstract (MP4 308264 KB).
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ItemComparison of experiences and preferences following non-invasive cardiovascular risk procedures: a cross-sectional survey in participants with and without diabetes mellitus(SPRINGER INT PUBL AG, 2022-06)AIMS: Endothelial dysfunction is an early risk marker of cardiovascular disease in diabetes mellitus. Timely screening is important in reducing cardiovascular disease-associated morbidity and mortality. This cross-sectional study investigates the acceptability and preferability of non-invasive cardiovascular risk procedures (EndoPAT2000 system and the ECG-gated fundoscope) in participants with diabetes mellitus compared to controls. METHODS: A self-administered Likert scale-based questionnaire was completed by 106 controls and 117 participants with diabetes mellitus, identified through stratified random sampling, upon conclusion of an Australian Heart Eye sub-study conducted at Westmead Hospital, NSW, Australia from 2012 to 2014. Pearson's χ 2 test, independent-samples t-test and regression analysis were performed. RESULTS: Study participants who responded to the questionnaire had no preference for procedures (controls: 2.4 ± 1.1 vs diabetes mellitus: 2.5 ± 0.9, p = 0.38) but had an overall more negative experience with most aspects of the ECG-gated fundoscope than the EndoPAT2000 system. Of those with diabetes mellitus, participants who provided poorer self-rated health expressed discomfort with the mydriatic drops (ß 0.27, 95%CI 0.001 - 0.54, p = 0.049) and the fundoscope's green light filter (ß 0.27, 95%CI 0.07 - 0.47, p = 0.009), as well as maintaining still (ß 0.40, 95%CI 0.08 - 0.72, p = 0.02) and not blinking (ß 0.38, 95%CI 0.07 - 0.70, p = 0.02) during photo acquisition. These participants were also less willing to repeat the ECG-gated fundoscope procedure (ß 0.29, 95%CI 0.07 - 0.52, p = 0.01). CONCLUSIONS: Participants with diabetes mellitus, especially with poorer self-rated health, had a more negative experience with the ECG-gated fundoscope than the EndoPAT2000 system. Difficulties experienced under examination by the ECG-gated fundoscope appear related to the procedural design, which requires amendments improving patient comfort and compliance.
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ItemPatients with Neovascular Age-Related Macular Degeneration Requiring Intensive Intravitreal Aflibercept Treatment: An ARIES Post Hoc Analysis(SPRINGER INT PUBL AG, 2022-10)INTRODUCTION: The aim of this post hoc analysis of the ARIES study is to explore the requirement for intravitreal aflibercept (IVT-AFL) treatment intervals of < 8 weeks (w) in patients with neovascular age-related macular degeneration (nAMD), and to assess vision and anatomic outcomes in such patients who require more intensive treatment. METHODS: ARIES was a multicenter, randomized, phase 3b/4 study that investigated the efficacy of two IVT-AFL proactive, individualized, treat-and-extend regimens over 2 years in treatment-naïve patients with nAMD. Patients were determined as injection-intensive if the study investigator identified that a treatment interval of < 8 w was needed and if they had ≥ 1 interval of < 8 w after three initial monthly doses. Treatment intervals could be extended subsequently if extension criteria were met. This is a post hoc analysis of patients enrolled in ARIES and statistical analysis is descriptive. RESULTS: Of 269 patients in the combined treatment arms, 23.0% (n = 62) were injection-intensive (Year 1: 13.8% [n = 37]; Year 2: 9.3% [n = 25]). Time from IVT-AFL initiation to injection-intensive determination varied (range, 16-100 w; median: 43.2 w). Mean treatment interval was 8.4 w before and 6.1 w after injection-intensive determination. Overall, 59.7% achieved treatment intervals of ≥ 8 w following injection-intensive determination. Vision improvements from baseline to Week 104 were smaller for injection-intensive patients than non-injection-intensive patients (mean [SD] best-corrected visual acuity change: + 2.3 [15.6] vs. + 5.9 [12.3] letters). Anatomic outcomes were similar between injection-intensive and non-injection-intensive patients (central retinal thickness change from baseline to Week 104: - 160 [154] vs. - 167 [136] µm). CONCLUSIONS: In ARIES, 23% of treatment-naïve patients with nAMD experienced at least one treatment interval of < 8 w. Injection-intensive patients showed improved vision and anatomic outcomes. For most, treatment intervals could be extended to ≥ 8 w following injection-intensive determination. CLINICALTRIALS: gov Identifier: NCT02581891.
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ItemA stronger association of diabetes mellitus with impaired hyperaemia using a novel ECG-gated device compared with peripheral arterial tonometry(SPRINGER, 2022-09)PURPOSE: Impaired digital reactive hyperaemia and flicker-stimulated retinal vascular response are commonly reported risk markers of cardiovascular disease. This is the first study to determine the correlation of these risk markers with diabetes mellitus by comparing our novel flicker-modulated ECG-gated fundoscope with the EndoPAT2000 system. METHODS: In total, 119 controls and 120 participants with diabetes mellitus partook in this cross-sectional study. The EndoPAT2000 system assessed digital reactive hyperaemia under fasting conditions. A mydriatic ECG-gated fundoscope with a novel flicker module acquired digital retinal images of the left eye before, during and after flicker stimulation. An inhouse semi-automated software measured retinal vessel diameters using a validated protocol with two observers repeating measurements in a subset of 10 controls and 10 participants with diabetes mellitus. Intra- and inter-observer reliability analyses occurred by the interclass correlation coefficient. A receiver operating characteristic curve established associations of variables with diabetes mellitus. RESULTS: Diabetes mellitus was more strongly associated with flicker-stimulated retinal arteriolar calibre change from baseline (AUC 0.81, 95% CI 0.75-0.87, p < 0.0001) than reactive hyperaemia index. Median flicker-stimulated arteriolar calibre change from baseline (controls: 2.74%, IQR 1.07 vs diabetes mellitus: 1.64%, IQR 1.25, p < 0.0001) and reactive hyperaemia index (controls: 1.87, IQR 0.81 vs diabetes mellitus: 1.60, IQR 0.81, p = 0.003) were lower in diabetes mellitus than controls. Intra- and inter-observer reliability coefficients were high from 0.87 to 0.93. CONCLUSIONS: Impaired flicker-stimulated retinal arteriolar calibre change from baseline is more highly correlated with diabetes mellitus in this study than a reduced reactive hyperaemia index.
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ItemThe longitudinal association between coffee and tea consumption and the risk of metabolic syndrome and its component conditions in an older adult population.(Cambridge University Press (CUP), 2022)The present study aimed to assess the longitudinal associations of coffee and tea consumption with metabolic syndrome and its component conditions in a group of Australian older adults who participated in the Blue Mountains Eye Study (n 2554, mean age: 64 years, 43 % female). Participants' coffee and tea intake were measured using a validated food frequency questionnaire. Hazard ratios (HRs) over a 10-year period were estimated using Cox hazard regression models adjusting for lifestyle factors. Results showed that coffee consumption was not associated with the incidence of metabolic syndrome, high fasting glucose, high triglycerides, central obesity, high blood pressure and low HDL-cholesterol (HDL-C). Tea consumption was not associated with incidence of metabolic syndrome and the component conditions except for the risk of having low HDL-C, in which a nominally inverse association was observed (multivariate-adjusted HR at 2-3 cups/d: 0⋅48, 95 % CI 0⋅26, 0⋅87, P = 0⋅016; 4 cups/d or more: 0⋅50, 95 % CI 0⋅27, 0⋅93, P = 0⋅029). After stratifying for fruit consumption (P interaction between tea and fruit = 0⋅007), consuming four cups of tea per day was nominally associated with lower incidence of metabolic syndrome among those with high fruit consumption (multivariable-adjusted HR: 0⋅44, 95 % CI 0⋅20, 0⋅93, P = 0⋅033). Our results did not support a significant association between tea and coffee consumption and metabolic syndrome. Tea consumption may be associated with a lower risk of having low HDL-C, while high tea and fruit consumption together may be associated with a lower risk of developing metabolic syndrome.
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ItemAntenatal Seroprevalence of Zika and Chikungunya Viruses, Kingston Metropolitan Area, Jamaica, 2017-2019(CENTERS DISEASE CONTROL & PREVENTION, 2022-02)To determine the extent of exposure to Zika virus (ZIKV) and chikungunya virus (CHIKV) in Jamaica, we collected serum from 584 pregnant women during 2017-2019. We found that 15.6% had antibodies against ZIKV and 83.6% against CHIKV. These results indicate potential recirculation of ZIKV but not CHIKV in the near future.
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