St. Vincent's Hospital Sydney

Background Nearly 20% of women will be confronted with anxiety or depressive disorders during the perinatal period and this may lead to adverse outcomes for both mother and child. Cognitive behavioural therapy (CBT) is the psychological intervention with the most empirical support for the clinical management of anxiety and depressive disorders. Anxiety and depression frequently occur in women during the perinatal period, and there is growing evidence that internet-delivered CBT (iCBT) could be an acceptable and effective intervention. THIS WAY UP, an Australian digital mental health service, has developed a program for postnatal anxiety and depression. This study protocol aims to examine the acceptability and efficacy of a French-Canadian adaptation of the program. Methods/design The research team propose to conduct a mixed hybrid type 1 pragmatic randomized clinical trial and implementation study to replicate the findings of the trial conducted in Australia by Loughnan et al. (2019), as well as explore barriers and facilitators to potential large-scale implementation. Treatment and control conditions a) postnatal anxiety and depression iCBT program with three lessons to complete in a six-week period, added to treatment-as-usual (TAU); b) TAU. Participants will include French-speaking women with probable postnatal depression or anxiety as per the Generalized Anxiety Disorder-7 (GAD-7) or the Edinburgh Postnatal Depression Scale (EPDS). The primary outcome measures will be the GAD-7 and the EPDS. Secondary outcome measures will comprise self-reported instruments to evaluate psychological distress, quality of life, mother–child experience, and treatment experience. Qualitative interviews with participants and health professionals will provide insights on acceptability and delivery of the iCBT program. Statistical analysis Statistical analysis will follow intent-to-treat principles. A mixed model regression approach will be used to account for between- and within-subject variations in the analysis of the effects of iCBT compared to TAU only intervention. Discussion The study will generate important data of efficacy and acceptability to patients, clinicians, and decision-makers to inform the scaling-up of the postnatal iCBT intervention in Canada. Trial registration ClinicalTrials.gov: NCT06778096, prospectively registered on 2025/01/16.

Purpose of Review This review aims to provide a comprehensive update to healthcare providers on the assessment and subsequent management of low-flow aortic stenosis. Recent Findings An aging population with a greater burden of cardiovascular risk factors has contributed to an increasing prevalence of aortic stenosis. The classification of the discordant low-flow cohort of aortic stenosis remains difficult and sub-optimal in the face of a heterogeneous disease population. Recent research has investigated use of echocardiographic flow parameters to categorise and prognosticate the low-flow aortic stenosis cohort. There is an increased awareness of the overlap between cardiac amyloidosis and the low-flow aortic stenosis group which has treatment implications. TAVI holds promise as a safer alternative to SAVR in this multimorbid, high-risk patient cohort. Summary Assessment and management of the low-flow aortic stenosis group needs to be highly individualised according to phenotype and comorbidities. This is best managed within the multidisciplinary Heart Team approach.

Prostate cancer (PCa) is highly heritable, with men of African ancestry at greatest risk and associated lethality. Lack of representation in genomic data means germline testing guidelines exclude for Africans. Established that structural variations (SVs) are major contributors to human disease and prostate tumourigenesis, their role is under-appreciated in familial and therapeutic testing. Utilising clinico-methodologically matched deep-sequenced whole-genome data for 113 African versus 57 European PCa patients, we interrogate 42,966 high-quality germline SVs using a best-fit pathogenicity prediction workflow. We identify 15 potentially pathogenic SVs representing 12.4% African and 7.0% European patients, of which 72% and 86% met germline testing standard-of-care recommendations, respectively. Notable African-specific loss-of-function gene candidates include DNA damage repair MLH1 and BARD1 and tumour suppressors FOXP1, WASF1 and RB1. Representing only a fraction of the vast African diaspora, this study raises considerations with respect to the contribution of kilo-to-mega-base rare variants to PCa pathogenicity and African-associated disparity.

Background Faecal calprotectin is a reliable biomarker for lower gastrointestinal inflammation. However, there are limited data on the utility of calprotectin from stoma effluent. Aim The aim of this study was to determine the performance of stomal calprotectin in identifying Crohn's disease activity in those with a stoma. Methods Patients with Crohn's disease and an ileostomy or colostomy were identified from three sites in Australia using a clinical management software. Disease activity was classified based on the presence of inflammation on imaging and/or endoscopy within 3 months of the sample. The primary outcome was the median stomal calprotectin in people with active versus inactive Crohn's disease. Other clinical indices, such as C‐reactive protein and Harvey Bradshaw Index, were evaluated as a surrogate biomarker for disease activity. Results Thirty stomal calprotectin results were identified for 23 patients with paired investigations. Of 30 cases, six had active disease. The median stomal calprotectin in active versus inactive disease were 17 μg/g (interquartile range (IQR) 5–211) and 61 μg/g (IQR 19–105, P = 0.38) respectively. Accordingly, stomal calprotectin demonstrated poor sensitivity for active disease (33% at cut‐off of 50 μg/g). C‐reactive protein was higher for active disease (25, IQR 5–199) compared with inactive disease (5, IQR 2–17, P = 0.06), but there was no difference in the Harvey Bradshaw Index (9 (IQR 7–11) vs 5 (3–7), P = 0.10). Conclusion Stomal calprotectin did not reliably distinguish between active and inactive Crohn's disease. C‐reactive protein is a more reliable biomarker for disease activity in the setting of ileostomy/colostomy. Further prospective studies are needed to identify more robust biomarkers for detecting inflammation in stoma patients.

Coronary artery disease (CAD) is a leading cause of morbidity worldwide. Although non‐invasive testing for CAD aims at reducing future disease burden, testing can often be associated with significant economic and other health‐related costs, at both an individual and societal level. Although there is an established role for screening symptomatic patients for CAD, there is still considerable debate as to the best approach for individuals who are asymptomatic. In this review, various non‐invasive tests commonly used in clinical practice will be discussed, including their potential utility, known limitations, and other considerations regarding their use. The use of such testing requires careful consideration of their diagnostic accuracy, availability, cost and patient‐specific factors that may limit their utility and safety. Future recommendations for CAD screening, especially for lower‐risk or asymptomatic individuals, should offer clinicians and patients some degree of flexibility and take into account the nuanced clinical approach that is often required to address the variability of each individual patient's biopsychosocial context and other factors relating to the suitability and accessibility of screening (e.g. financial cost and geographic location). Recommendations that are well suited to certain geographic locations or societal groups may be less appropriate for other populations, especially those that are marginalised, less well resourced or experiencing significant socioeconomic disadvantage. Screening for CAD should therefore endeavour to ensure equity and aim to improve outcomes in all patient groups, including those who are disadvantaged and most at risk.

Purpose Pituitary surgery is the mainstay treatment for most pituitary adenomas, but many questions remain about perioperative and long-term management and outcomes. This study aimed to identify the most pressing research priorities in pituitary surgery with input from patients, caregivers, and healthcare professionals. Methods An initial survey of patients, caregivers, and healthcare professionals assembled priorities related to preoperative care, surgical techniques, and postoperative management in pituitary surgery. Priorities were thematically grouped into summary priorities, and those answered by existing evidence were omitted following a literature review. An interim survey asked patients, caregivers, and healthcare professionals to select their top 10 priorities from the remaining list. The highest-ranked priorities advanced to a consensus meeting, where the top 10 questions were prioritized. Results In the initial survey, 147 participants—60.5% of whom were patients, caregivers, or patient support group representatives—submitted 785 priorities, which were then condensed into 52 summary priorities. After a literature review, 33 unanswered priorities were included in the interim survey, completed by 155 respondents, of whom 54.2% were patients, caregivers, or patient support group representatives. The top-ranked priorities were discussed by 14 participants (7 patients and 7 healthcare professionals) during a consensus meeting. The top 10 priorities covered a variety of themes including enhancing diagnosis and management of pituitary adenomas, advancing surgical techniques and technologies, optimizing the prediction of outcomes and complications, and improving patient support and follow-up. Conclusions The top 10 research priorities in pituitary surgery aim to align researchers and direct funding in order to maximize impact and champion patient representation.

Acne vulgaris is a globally prevalent dermatological disease, with its severity ranging from mild to severe. While moderate to severe acne often requires topical or systemic pharmaceutical therapy, mild to moderate acne may be managed with dermocosmetics, which are over‐the‐counter skincare agents with active ingredients that target acne pathophysiology. Dermocosmetics can also be effective as adjunct therapy for the management of more severe acne. For example, they can be used to complement the mode of action of pharmaceuticals or to mitigate side effects and improve treatment compliance. This review discusses the roles of commonly available dermocosmetics in the context of both mild and severe acne management protocols.

Background Liberation from sedation may be beneficial for patients with acute respiratory distress syndrome supported by veno-venous (VV) extracorporeal membrane oxygenation (ECMO). Currently, there is limited evidence to support this approach. Therefore, this study aimed to compare the 90-day patient mortality of different sedation strategies in COVID-19 patients supported with VV ECMO. Methods Retrospective, observational sub-study of the COVID-19 Critical Care Consortium database including COVID-19 patients supported with VV ECMO. Two cohorts were compared: high sedation patients who received neuromuscular blocking agents (NMBAs) throughout ECMO and low sedation patients who did not receive NMBA consistently. Patients’ level of sedation during ECMO was also considered. The primary outcome was 90-day in-hospital mortality and was assessed using cause-specific Cox proportional hazard models. Results 224 low and 104 high sedation patients were included. Pre-ECMO respiratory condition prior was similar between groups, except for the ratio of partial pressure of oxygen to inspired fraction of oxygen, which was lower in the high sedation group at 93 [61–130] than the low sedation group at 106 [69–140]. No difference was observed in disease severity scores between cohorts. Low sedation patients had longer ECMO runs, more circuit changes, but lower infectious and hemorrhagic complications. Higher sedation was associated with a hazard ratio for death of 3.23 (95% CI 2.16–4.83) compared to low sedation. Conclusions Reduced sedation in COVID-19 ECMO patients is feasible and may be associated with improved survival and reduced complications compared to continuous paralysis, albeit with longer ECMO runs.

Introduction Post Tuberculosis Lung Disease (PTLD) is increasingly recognised as a significant cause of morbidity internationally, but has not been described in an Australian setting. We aimed to determine the prevalence of PTLD among adult TB survivors from an Australian TB service and describe the pattens of lung function abnormalities and pulmonary disease, including pulmonary hypertension. Methods We conducted a single-centre retrospective cohort study in Sydney, Australia, including all adults who successfully completed TB treatment between January 2013 and December 2022. Baseline characteristics, post treatment pulmonary function, and thoracic computed tomography (CT) data were analysed to determine the prevalence and patterns of PTLD, defined as any lung function and/or radiological abnormality attributable to TB. Results Among 119 confirmed TB patients (mean age 46 ± 21 years, 61% males) PTLD was identified in 81/119 (68%). Pulmonary function testing was available for 51/119 (43%), of whom 38/51(75%) exhibited abnormalities. Obstructive deficits were found in 25/51 (49%), restrictive deficits in 11/51 (22%), and impaired gas transfer capacity in 26/51 (51%). Chest CT scans were completed in 76/119 (64%), with 70/76 (92%) demonstrating significant abnormalities, including pulmonary fibrosis 43/76 (57%), bronchiectasis 22/76 (29%), and emphysema 11/76 (15%). Pulmonary hypertension was suspected in 52/76 (68%) patients based on radiological findings. Conclusion Despite successful treatment, PTLD was frequently observed among our cohort of Australian TB survivors. Further research into optimal screening practices to diagnose chronic pulmonary diseases and pulmonary hypertension could provide opportunities for earlier intervention and management.

Background Androgen deprivation therapy (ADT) improves outcomes in men undergoing definitive radiotherapy for prostate cancer but carries significant toxicities. Clinical parameters alone are insufficient to accurately identify patients who will derive the most benefit, highlighting the need for improved patient selection tools to minimize unnecessary exposure to ADT’s side effects while ensuring optimal oncological outcomes. The ArteraAI Prostate Test, incorporating a multimodal artificial intelligence (MMAI)-driven digital histopathology-based biomarker, offers prognostic and predictive information to aid in this selection. However, its clinical utility in real-world settings has yet to be measured prospectively. Methods This multicentre implementation trial aims to collect real-world data on the use of the previously validated Artera MMAI-driven prognostic and predictive biomarkers in men with intermediate-risk prostate cancer undergoing curative radiotherapy. The prognostic biomarker estimates the 10-year risk of metastasis, while the predictive biomarker determines the likely benefit from short-term ADT (ST-ADT). A total of 800 participants considering ST-ADT in conjunction with curative radiotherapy will be recruited from multiple Australian centers. Eligible patients with intermediate-risk prostate cancer, as defined by the National Comprehensive Cancer Network, will be asked to participate. The primary endpoint is the percentage of patients for whom testing led to a change in the shared ST-ADT recommendation, analyzed using descriptive statistics and McNemar’s test comparing recommendations before and after biomarker testing. Secondary endpoints include the impact on quality of life and 5-year disease control, assessed through linkage with the Prostate Cancer Outcomes Registry. The sample size will be re-evaluated at an interim analysis after 200 patients. Discussion ASTuTE will determine the impact of a novel prognostic and predictive biomarker on shared decision-making in the short term, and both quality of life and disease control in the medium term. If the biomarker demonstrates a significant impact on treatment decisions, it could lead to more personalized treatment strategies for men with intermediate-risk prostate cancer, potentially reducing overtreatment and improving quality of life. A potential limitation is the variability in clinical practice across different centers inherent in real-world studies. Trial Registration Australian New Zealand Clinical Trials Registry, ACTRN12623000713695p. Registered 5 July 2023.

Introduction Methamphetamine use disorder is a significant public health concern. No pharmacological treatment options currently exist for methamphetamine use disorder, and psychotherapy is only moderately effective. Preliminary evidence suggests that ketamine-assisted psychotherapy produces sustained improvements in substance use and mental health symptomatology. In addition to direct antidepressant properties, ketamine is hypothesised to increase synaptogenesis and facilitate neuroplasticity, in turn prolonging and enhancing the effects of psychotherapy. Given the withdrawal-associated dysphoria and neurocognitive impairments characterising methamphetamine use disorder, ketamine-assisted psychotherapy may improve the efficacy of psychotherapy alone by addressing these features and facilitating therapeutic engagement. This pilot study aims to investigate the safety and feasibility (time taken to recruit sample, proportion of ineligible participants at pre-screening and screening, number of participants who complete four sessions of psychotherapy, retention rate over full duration of study, acceptability of the intervention) of subanaesthetic ketamine in combination with psychotherapy (cognitive behavioural therapy) for adults with methamphetamine use disorder. Changes in methamphetamine use, cravings and withdrawal, quality of life, and treatment satisfaction will also be explored. Methods and analysis This is an open-label, single-arm clinical trial. 20 adults meeting DSM-5-TR criteria for methamphetamine use disorder who are seeking to reduce or cease methamphetamine use will be enrolled in the study through a single-site specialist outpatient stimulant treatment service in inner Sydney (St Vincent’s Hospital, Sydney). A 4-week course with three subcutaneous ketamine doses (0.75 mg/kg to 0.9 mg/kg, titrated according to tolerability) at weekly intervals and four sessions of cognitive behavioural therapy (one at treatment initiation and three within 24–48 hours following each ketamine administration session) will be delivered. Safety and feasibility will be assessed over an 8-week period. Secondary outcomes (changes in methamphetamine use, cravings, withdrawal, quality of life and treatment satisfaction) will be assessed over a 24-week period. Ethics and dissemination This study has been approved by the St Vincent’s Hospital Human Research Ethics Committee, reference 2023/ETH00530. Study findings will be disseminated through articles in scientific, peer-reviewed journals, and at national and international conferences. Trial registration number ANZCTR: ACTRN12624000895583. Protocol version The trial protocol (Version 4.0) was approved on 24 June 2024.

Introduction All grade 2/3 gliomas are incurable and at the time of inevitable relapse, patients have significant unmet needs with few effective treatments. This study aims to improve outcomes by molecular profiling of patients at relapse, then matching them with the best available drug based on their molecular profile, maximising the chances of patient benefit while simultaneously testing multiple novel drugs. Methods and analysis Low & Anaplastic Grade Glioma Umbrella Study of MOlecular Guided TherapieS (LUMOS-2) will be an international, phase 2, multicentre, open-label, biomarker-directed, umbrella clinical trial for recurrent isocitrate dehydrogenase mutant, histologically grade 2/3 gliomas. Investigational treatment will be assigned based on molecular profiling of contemporaneous tissue obtained at disease relapse using next-generation sequencing. LUMOS-2 will begin with three therapeutic treatment arms: paxalisib, cadonilimab and selinexor. Patient molecular profiles will be assessed by an expert, multidisciplinary Molecular Tumour Advisory Panel. Patients whose molecular profile is considered suitable for a targeted agent like paxalisib will be allocated to that arm, others will be randomised to the available arms of the trial. The primary endpoint is progression-free survival at 6 months. Secondary objectives include assessment of overall survival, response rate, safety and quality of life measures. Two additional therapeutic arms are currently in development. Ethics and dissemination Central ethics approval was obtained from the Sydney Local Health District Ethics Review Committee, Royal Prince Alfred Hospital Zone, Sydney, Australia (Approval: 2022/ETH02230). Other clinical sites will provide oversight through local governance processes, including obtaining informed consent from suitable participants. A report describing the results of the study will be submitted to international meetings and peer-reviewed journals. Trial registration number ACTRN12623000096651.