Medicine (St Vincent's) - Research Publications
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ItemNo Preview AvailableHyponatraemia and hypopituitarism: an easily missed entity(AUSTRALASIAN MED PUBL CO LTD, 2017-10-02)
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ItemNo Preview AvailableEstimated insulin sensitivity in Type 1 diabetes adults using clinical and research biomarkers(ELSEVIER IRELAND LTD, 2020-09)AIMS: Insulin resistance in people with type 1 diabetes (T1D) is associated with increased risk of chronic complications and death. The gold standard to quantify insulin sensitivity, a euglycaemic hyperinsulinaemic clamp, is not applicable to clinical practice. We have employed clamp studies to develop a panel of formulae to estimate insulin sensitivity in adults with T1D for use in clinical practice and trials. METHODS: Clamps were conducted in 28 adults with T1D, who were also characterised with 38 clinical and research biomarkers. Exhaustive search analysis was used to derive equations correlating with clamp-quantified glucose disposal rate (GDR), GDR/plasma insulin (M/I) and log10M/I. RESULTS: Measured insulin sensitivity correlated with BMI, WHR, HDL-C, adipokines and inflammation markers on univariate analysis. Exhaustive search analysis derived three formulae correlating with clamp-derived GDR and logM/I (p < 0.0001), accounting for ≈62% of their variability. A formula using gender, age, HDL-C, pulse pressure and WHR performed as well as those containing inflammation and adipokine measures. CONCLUSIONS: The performance of formulae using routinely available parameters with/without research biomarkers in clinical studies and trials, particularly related to future complications, relevant lifestyle interventions, insulin delivery modes and insulin sensitisers is merited.
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ItemNo Preview AvailableCytoreductive Surgery of the Primary Tumor in Metastatic Adrenocortical Carcinoma: Impact on Patients' Survival(ENDOCRINE SOC, 2022-03-24)CONTEXT: The role of cytoreduction of adrenocortical carcinoma (ACC) remains poorly understood. OBJECTIVE: To analyze the impact of cytoreductive surgery of the primary tumor in patients with metastatic ACC. DESIGN AND SETTING: We performed a multicentric, retrospective paired cohort study comparing the overall survival (OS) in patients with metastatic ACC who were treated either with cytoreductive surgery (CR group) or without cytoreductive surgery (no-CR group) of the primary tumor. Data were retrieved from 9 referral centers in the American-Australian-Asian Adrenal Alliance collaborative research group. PATIENTS: Patients aged ≥18 years with metastatic ACC at initial presentation who were treated between January 1, 1995, and May 31, 2019. INTERVENTION: Performance (or not) of cytoreductive surgery of the primary tumor. MAIN OUTCOME AND MEASURES: A propensity score match was done using age and the number of organs with metastasis (≤2 or >2). The main outcome was OS, determined from the date of diagnosis until death or until last follow-up for living patients. RESULTS: Of 339 patients pooled, 239 were paired and included: 128 in the CR group and 111 in the no-CR group. The mean follow-up was 67 months. Patients in the no-CR group had greater risk of death than did patients in the CR group (hazard ratio [HR] = 3.18; 95% CI, 2.34-4.32). Independent predictors of survival included age (HR = 1.02; 95% CI, 1.00-1.03), hormone excess (HR = 2.56; 95% CI, 1.66-3.92), and local metastasis therapy (HR = 0.41; 95% CI, 0.47-0.65). CONCLUSION: Cytoreductive surgery of the primary tumor in patients with metastatic ACC is associated with prolonged survival.
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ItemNo Preview AvailableIndependent euglycaemic hyperinsulinaemic clamp studies validate clinically applicable formulae to estimate insulin sensitivity in people with type 1 diabetes(ELSEVIER SCI LTD, 2023-01)BACKGROUND AND AIM: Low insulin sensitivity (IS) increases Type 1 diabetes (T1D) complication risk and can be estimated by simple formulae developed from complex euglycemic hyperinsulinaemic clamp studies. We aimed to validate these formulae using independent clamp data. METHODS: Clamps were performed in 104 T1D adults. Measured glucose disposal rate (GDR) was correlated with eGDR and eLog10 M/I calculated by five IS formulae. RESULTS: Correlations ranged between 0.23-0.40. Two IS formulae (by the authors), using age, sex, HDL-C, HbA1c, pulse pressure, BMI, and waist-hip-ratio had the highest correlation with measured GDR and the best performance in detecting low IS.
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ItemNo Preview AvailableIndependent euglycaemic hyperinsulinaemic clamp studies validate clinically applicable formulae to estimate insulin sensitivity in people with type 1 diabetes (vol 17, 102691, 2023)(ELSEVIER SCI LTD, 2023-01)The authors regret that in the original article, on the second page, in the section with eGDR equations, variables “sex” and “hypertension” were missing categorical values indicators (“F = 0, M = 1”; “Yes = 1, No = 0”, respectively) required to calculate eGDR. It should be corrected by adding “F = 0, M = 1” in two instances and “Yes = 1, No = 0” in one instance. Also, please note that Miller at al. defined “hypertension” as BP ≥140/90mmHg or use of any anti-hypertensive (drug) treatment. The authors apologise for any inconvenience caused.
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ItemImaging for assessment of cancer treatment response to immune checkpoint inhibitors can be complementary in identifying hypophysitis(FRONTIERS MEDIA SA, 2023-11-29)INTRODUCTION: Hypophysitis is reported in 8.5%-14% of patients receiving combination immune checkpoint inhibition (cICI) but can be a diagnostic challenge. This study aimed to assess the role of routine diagnostic imaging performed during therapeutic monitoring of combination anti-CTLA-4/anti-PD-1 treatment in the identification of hypophysitis and the relationship of imaging findings to clinical diagnostic criteria. METHODS: This retrospective cohort study identified patients treated with cICI between January 2016 and January 2019 at a quaternary melanoma service. Medical records were reviewed to identify patients with a documented diagnosis of hypophysitis based on clinical criteria. Available structural brain imaging with magnetic resonance imaging (MRI) or computed tomography (CT) of the brain and 2-deoxy-2-[18F]fluoro-D-glucose positron emission tomography with computed tomography (FDG-PET/CT) were assessed retrospectively. The main radiological outcome measures were a relative change in pituitary size or FDG uptake temporally attributed to cICI. RESULTS: There were 162 patients (median age 60 years, 30% female) included. A total of 100 and 134 had serial CT/MRI of the brain and FDG-PET/CT, respectively. There were 31 patients who had a documented diagnosis of hypophysitis and an additional 20 who had isolated pituitary imaging findings. The pituitary gland enlargement was mild, and the largest absolute gland size was 13 mm, with a relative increase of 7 mm from baseline. There were no cases of optic chiasm compression. Pituitary enlargement and increased FDG uptake were universally transient. High-dose glucocorticoid treatment for concurrent irAEs prevented assessment of the pituitary-adrenal axis in 90% of patients with isolated imaging findings. CONCLUSION: Careful review of changes in pituitary characteristics on imaging performed for assessment of therapeutic response to iICI may lead to increased identification and more prompt management of cICI-induced hypophysitis.
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ItemIncreased Thyroidal Activity on Routine FDG-PET/CT after Combination Immune Checkpoint Inhibition: Temporal Associations with Clinical and Biochemical Thyroiditis(MDPI, 2023-12)BACKGROUND: FDG-PET/CT used for immune checkpoint inhibitor (ICI) response assessment can incidentally identify immune-related adverse events (irAEs), including thyroiditis. This study aimed to correlate the time course of FDG-PET/CT evidence of thyroiditis with clinical and biochemical evolution of thyroid dysfunction. METHODS: A retrospective review was performed by two independent blinded nuclear medicine physicians (NMPs) of thyroidal FDG uptake in 127 patients who underwent PET/CT between January 2016 and January 2019 at baseline and during treatment monitoring of combination ICI therapy for advanced melanoma. Interobserver agreement was assessed and FDG-PET/CT performance defined by a receiver-operating characteristic (ROC) curve using thyroid function tests (TFTs) as the standard of truth. Thyroid maximum standardized uptake value (SUVmax) and its temporal changes with respect to the longitudinal biochemistry were serially recorded. RESULTS: At a median of 3 weeks after commencing ICI, 43/127 (34%) had a diagnosis of thyroiditis established by abnormal TFTs. FDG-PET/CT was performed at baseline and at a median of 11 weeks (range 3-32) following the start of therapy. ROC analysis showed an area under the curve of 0.87 (95% CI 0.80, 0.94) for FDG-PET/CT for detection of thyroiditis with a positive predictive value of 93%. Among patients with biochemical evidence of thyroiditis, those with a positive FDG-PET/CT were more likely to develop overt hypothyroidism (77% versus 35%, p < 0.01). In the evaluation of the index test, there was an almost perfect interobserver agreement between NMPs of 93.7% (95% CI 89.4-98.0), kappa 0.83. CONCLUSION: Increased metabolic activity of the thyroid on routine FDG-PET/CT performed for tumoral response of patients undergoing ICI therapy is generally detected well after routine biochemical diagnosis. Elevation of FDG uptake in the thyroid is predictive of overt clinical hypothyroidism and suggests that an ongoing robust inflammatory response beyond the initial thyrotoxic phase may be indicative of thyroid destruction.
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ItemA qualitative study of patients with Cancer of Unknown Primary: Perceptions of communication, understanding of diagnosis and genomic testing, and information needs(WILEY, 2023-04)OBJECTIVE: Patients with Cancer of Unknown Primary (CUP) commonly report poor understanding of their illness and high levels of psychological distress. Despite the potential benefits to CUP patients, there is a paucity of research exploring the reasons behind poor understanding of a CUP diagnosis. The aim of this study was to understand patients' experiences of communication with doctors, their understanding of diagnosis and the role of genomic testing, as well as their information needs. METHODS: Semi-structured interviews explored CUP patients' perceptions of communication with their doctors, understanding of their illness, and their needs regarding medical information. Qualitative inductive thematic analysis of transcribed audio-recordings was employed. SETTING/PARTICIPANTS: Nineteen patients were recruited from within a prospective cohort study involving routine genomic testing of CUP patients. RESULTS: CUP patients had varied perceptions of communication with doctors as well as different levels of need, readiness, and capacity for information. Some patients felt well understood and supported by their doctors while others did not. Many patients reported feeling overwhelmed and shocked when receiving their cancer diagnosis and emphasized the importance of family support in receiving and understanding medical information. While patients understood the implications of genomic testing for treatment and diagnosis, few had a detailed understanding of genomic testing. CONCLUSIONS: Patients' experience of communication and understanding of CUP could be potentially improved by clinicians' assessment of the communication style preferred by each patient and their family and the development of online resources to meet their evolving information needs.
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ItemAssociation of the CHEK2 c.1100delC variant, radiotherapy, and systemic treatment with contralateral breast cancer risk and breast cancer-specific survival(WILEY, 2023-08)BACKGROUND: Breast cancer (BC) patients with a germline CHEK2 c.1100delC variant have an increased risk of contralateral BC (CBC) and worse BC-specific survival (BCSS) compared to non-carriers. AIM: To assessed the associations of CHEK2 c.1100delC, radiotherapy, and systemic treatment with CBC risk and BCSS. METHODS: Analyses were based on 82,701 women diagnosed with a first primary invasive BC including 963 CHEK2 c.1100delC carriers; median follow-up was 9.1 years. Differential associations with treatment by CHEK2 c.1100delC status were tested by including interaction terms in a multivariable Cox regression model. A multi-state model was used for further insight into the relation between CHEK2 c.1100delC status, treatment, CBC risk and death. RESULTS: There was no evidence for differential associations of therapy with CBC risk by CHEK2 c.1100delC status. The strongest association with reduced CBC risk was observed for the combination of chemotherapy and endocrine therapy [HR (95% CI): 0.66 (0.55-0.78)]. No association was observed with radiotherapy. Results from the multi-state model showed shorter BCSS for CHEK2 c.1100delC carriers versus non-carriers also after accounting for CBC occurrence [HR (95% CI): 1.30 (1.09-1.56)]. CONCLUSION: Systemic therapy was associated with reduced CBC risk irrespective of CHEK2 c.1100delC status. Moreover, CHEK2 c.1100delC carriers had shorter BCSS, which appears not to be fully explained by their CBC risk.
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ItemComparing Video-Based, Telehealth-Delivered Exercise and Weight Loss Programs With Online Education on Outcomes of Knee Osteoarthritis : A Randomized Trial(American College of Physicians, 2022-02)Background: Scalable knee osteoarthritis (OA) programs are needed to deliver recommended education, exercise and weight loss interventions. Objective: Evaluate two 6-month telehealth-delivered exercise programs, with and without dietary intervention. Design: Three-arm parallel randomized (5:5:2) trial. Setting: Australian private health insurance members. Participants: 415 people with symptomatic knee OA, body mass index 28-40 kg/m2, aged 45-80. Interventions: All groups received access to electronic OA information (Control). The Exercise program comprised six videoconferencing physiotherapist consultations for exercise, self-management advice and behavioral counselling plus exercise equipment and resources. The Diet+Exercise program included an additional six dietitian consultations for a ketogenic very low-calorie diet (two formulated meal replacements and low carbohydrate meal daily) then transition to healthy eating, and nutrition and behavioral resources. Measurements: Primary outcomes were changes in knee pain (0-10 numeric rating scale, higher worse) and physical function (0-68 WOMAC, higher worse) at 6- (primary time-point) and 12-months. Secondary outcomes were weight, physical activity, quality-of-life, mental health, global change, satisfaction, willingness for surgery, orthopaedic appointments, and knee surgery. Results: 379 (91%) and 372 (90%) participants provided 6- and 12-month primary outcomes respectively. At 6-months, both programs were superior to Control for pain (between-group mean differences: Diet+Exercise, -1.5 [95% CI, -2.1 to -0.8]; Exercise, -0.8 [CI, -1.5 to -0.2]) and function (Diet+Exercise, -9.8 [CI, -12.5 to -7.0]; Exercise, -7.0 [CI -9.7 to -4.2]) while Diet+Exercise was superior to Exercise (pain, -0.6 [CI, -1.1 to -0.2]; function, -2.8 [CI -4.7 to -0.8]). Similar findings occurred at 12-months. Limitations: Unblinded participants and clinicians. Conclusion: Telehealth-delivered exercise and diet programs improved pain and function in people with knee OA and overweight/obesity. Dietary intervention conferred modest additional pain and function benefits to exercise.