Royal Prince Alfred Hospital

Background The number of people diagnosed with chronic intestinal failure (CIF) worldwide is low. The condition is clinically complex to manage and resource intense. Guidance on best‐practice staffing levels is lacking. This paper proposes a methodology for determining dietetic staffing levels for adult CIF to estimate dietetic staffing levels allowing patients access to best‐practice care. Methods After undertaking a literature search, a novel method for developing recommended adequate dietetic staffing within adult CIF services was utilized. This included (1) mapping the current patient journey and best‐practice dietetic care throughout the journey, (2) allocating clinical and nonclinical hours at each phase of the patient journey, and (3) calculating percentage clinical time, and (4) finalizing estimated dietetic staffing requirements per patient. Results Current literature informed mapping the patient journey and dietetic best practice for CIF. Australian data were included where possible to reflect patient care locally. Direct and indirect clinical hours were allocated to each activity. Allowing for nonclinical activity of 40% for a senior clinician, total hours required to provide best‐practice care per patient was calculated as 0.028 of a full‐time dietitian per adult with CIF. This equates to the management of 36 people with CIF per full‐time dietitian. Conclusion Use of a bottom‐up methodology allows calculation of staffing to meet best practice. Proposed dietetic staffing levels obtained from this study are far greater than current allocated staffing within the Australian adult CIF setting. Adequate dietetic resourcing may reduce patient complications and improve quality of life, resulting in enhanced patient and clinical outcomes.

Background Sickle cell disease (SCD) is an inherited condition that impairs red blood cell function, posing a substantial health burden on patients. As the prevalence of SCD in Australia rises due to migration, discussions surrounding treatment and management strategies are becoming more prominent. Aims Australia lacks a dedicated study on the prevalence and economic implications of SCD. In this study, we estimate the economic burden of SCD in Australia from the perspective of the Australian healthcare system. Methods We performed a cost‐of‐illness study by using a bottom‐up approach to estimate resource use per patient from a national registry with unit costs from national sources, and a top‐down estimate of the prevalence of SCD in Australia using stratification by ancestry. Results We estimated the prevalence of SCD in Australia in 2021 to be 8485 patients, the cost per patient per year to be AU$13 975 and the total cost to the Australian healthcare system to be approximately AU$119 million per year. Factors influencing costs were age, interventions and frequency of hospital visits for vaso‐occlusive crises. Prevalence had the greatest influence on results in the sensitivity analysis. Conclusions While the estimated prevalence of SCD in Australia resulted in a relatively small total cost, the per patient annual cost of SCD remains high. This cost of SCD is anticipated to increase alongside migration and improved treatment. There are policies that could enhance patients' quality of life, thereby mitigating both economic and health burdens.

The aim of this research was to investigate the pathogenesis of the bone cancer chordoma and the role of the germline rs2305089 SNP in TBXT . Using medical imaging and genotyping studies, we observed that benign notochordal cell tumours (BNCTs) were associated with chordomas and with the variant rs2305089 A‐allele with enrichment of the AA genotype compared to controls. We engineered in vitro mesoderm models, representing notochord, which showed higher expression of TBXT and activation of its regulatory network in the presence of the variant A allele. Heterozygotes (GA) displayed enrichment of Wnt/β‐catenin and epithelial mesenchymal transition pathways, faster cell migratory capacity, and altered expression of endoplasmic reticulum and intracellular transport mediators. WT lines (GG) were enriched for metabolic pathways and MTORC1 signalling, suggesting that rs2305089 genotype regulates notochord vacuoles during notochord regression. By leveraging patient‐derived data and functional studies, we show that the variant rs2305089 A‐allele predisposes to BNCTs and ultimately to chordomas. © 2025 The Author(s). The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

Background Sleep disturbances are common in dementia but rarely studied in memory clinics. Objective In a memory clinic setting we aimed to (1) identify rates of obstructive sleep apnea (OSA), abnormal sleep duration, circadian phase shift, insomnia, poor sleep quality, and REM sleep behavior disorder (RBD); (2) assess concordance between self-reported and actigraphy-derived measures; investigate associations between sleep disturbances; and (3) neuropsychological performance and (4) cognitive status. Methods Adults over 50 at a memory clinic between 2009–2024 were included. OSA was assessed via polysomnography and prior history. Sleep duration and circadian phase were measured by self-report and actigraphy. Self-report questionnaires evaluated insomnia, sleep quality, and RBD. Global cognition, processing speed, memory, and executive function were assessed. Analysis of Covariance and multinomial logistic regression examined the impact of OSA, sleep duration, insomnia, and sleep quality on cognition and cognitive status. Results 1234 participants (Mage 67.2, 46%M) were included. 75.3% had OSA, while 12.7% were previously diagnosed. Insomnia affected 12.0%, 54.3% had poor sleep quality, and 14.2% endorsed RBD symptoms. Self-reported short (30.5%) and long (10.2%) sleep exceeded actigraphy rates (8.5% and 5.1%) with poor concordance between measures. OSA was linked to impaired global cognition and memory (p < 0.05). Prolonged sleep predicted deficits in global cognition, processing speed, memory, and executive function and a higher risk of aMCI (all p < 0.05). Poor sleep quality was linked to better memory (p < 0.05). Conclusions Despite discrepancies between self-reported and objective prevalence rates, sleep disturbances are highly prevalent in memory clinics and impact cognition, necessitating further examination.

Background Allogeneic haemopoietic stem cell transplantation (HSCT) is an effective therapy with curative potential for patients with high‐risk or relapsed/refractory chronic lymphocytic leukaemia (CLL). There are limited data on the use and outcomes of HSCT in the modern era of CLL treatment. Aims The aim of this study was to examine the use of HSCT performed for CLL in Australia and New Zealand, including patients exposed to pathway inhibitors (PIs) prior to transplant. Methods Data were collected through the Australian and New Zealand Transplant and Cellular Therapy Registry for all patients who underwent HSCT for CLL between January 2009 and December 2018. Transplant outcomes were compared between two 5‐year time periods: 2009–2013 and 2014–2018. Results Ninety‐four patients underwent HSCT during 2009–2013 and 50 during 2014–2018. There was a significant reduction in non‐relapse mortality (NRM) from 42% (95% confidence interval (CI): 31–52) to 23% (95% CI: 12–35, P = 0.02) between the periods; however, overall survival (OS), progression‐free survival (PFS) and relapse were unchanged. Within the 2014–2018 cohort, 22 patients were PI exposed prior to transplant. At 3 years, these patients demonstrated a median OS of 54% (95% CI: 35–82), PFS of 44% (95% CI: 27–71), NRM of 25% (95% CI: 8–45) and cumulative incidence of relapse of 32% (95% CI: 14–52). In multivariate analysis, only disease in complete remission at the time of HSCT was associated with improved OS (hazard ratio: 2.54, 95% CI: 1.04–6.18). Conclusion Allogeneic HSCT remains a viable treatment option for select patients with CLL.

Objectives Presentations to ED are growing, worsening pressure on the health system. A discrete choice experiment (DCE) was undertaken to determine the factors that influence why patients choose the ED over primary care for low-acuity presentations. Methods A DCE was carried out at two tertiary hospital EDs between October 2022 and February 2023 in adult patients with lower triage scores. Attributes included waiting time, cost, facility, care type and provider. Participant preferences were estimated using mixed multinomial logit (MMNL) and latent class models. Willingness to pay and policy simulations were also carried out. Results 281 participants were recruited. The MMNL model revealed that patients preferred care with 30 min waiting times (β=0.75, 95% CI 0.59 to 0.91), no out-of-pocket payments (β=1.18, 95% CI 0.97 to 1.39), in-person delivery (β=0.62, 95% CI 0.51 to 0.73) and the availability of on-site investigations (β=0.83, 95% CI 0.68 to 0.98). A latent class analysis revealed three distinct cohorts of patients: those who would choose the ED regardless of other options (26% of the sample), those swayed largely by cost (29%) and those who would go elsewhere if another option was offered (45%). Conclusion The study showed patient preferences for various health service options and the strength of those preferences. A latent class analysis showed distinct subgroups within this cohort, each likely to respond differently to various policy scenarios and health service options. There was heterogeneity within the responses, which should be a target for policy. This information could be used to design services that more adequately meet patient preferences.

Aims There have been few studies that have investigated the effect of surgical approach on femoral component version in total hip arthroplasty (THA). The purpose of this study was to investigate the influence of the direct anterior approach (DAA) and the posterior approach (PA) on femoral component version in THA. Methods A retrospective database review of 807 THAs in 807 patients who had both preoperative and postoperative CT scans was performed. Femoral component version was measured in the second CT scan and compared to the native neck axis measured in the first CT scan, using the posterior femoral condyles as the reference for both. Operations were performed using either a DAA (n = 291) or a PA (n = 516), with one of four femoral component designs: quadrangular taper, calcar-guided short stem, flat taper, or fit-and-fill. Subgroup analyses investigated changes in version for low (≤ 5°), neutral (5° to 25°), and high (≥ 25°) native version subgroups and for the different femoral component types. Results Overall, DAA components had more mean anteversion relative to the native neck axis versus PA components (6.0° (SD 9.8°) vs 1.3° (SD 10.1°); p < 0.001). Predictors of increased femoral component anteversion postoperatively on multivariable regression analyses were approach (DAA), decreased native version preoperatively, decreased femoral sagittal bow angle, and component type (quadrangular taper). DAA components had greater mean anteversion relative to native than PA in hips with high native version (3.5° (SD 11.1°) vs -5.8° (SD 10.5°); p < 0.001) and neutral native version (5.2° (SD 9.3°) vs 1.3° (SD 9.4°); p < 0.001), but did not reach significance in the low native version subgroup (9.0° (SD 10.3°) vs 5.9° (SD 9.6°); p = 0.109). Quadrangular taper and calcar-guided short-component types had significantly more mean anteversion than native for DAA versus PA. Conclusion Femoral components implanted with a DAA had more mean anteversion than those implanted with a PA. Future studies should aim to investigate the effect of femoral component version on postoperative clinical outcomes. Cite this article: Bone Joint J 2025;107-B(5 Supple A):55–61.

Background Abbreviation use remains a significant cause of miscommunication among healthcare practitioners worldwide, creating uncertainty in interpretation and leading to poorer patient outcomes. This study aimed to assess the effectiveness of implementing auto-expansion prompts to reduce abbreviation use in electronic discharge letters (eDLs). Methods Observational pre- and post-intervention study conducted in 2019 at a tertiary referral hospital in Western Sydney. Participants Junior medical officers (JMOs) in postgraduate years 1 and 2. Intervention The intervention consisted of an email invitation to JMOs, outlining the risks of abbreviation use in eDLs, and providing instructions on how to use auto-expand prompts for 11 commonly used abbreviations in Cerner Powerchart. Primary outcome measure Reduction in the frequency of use of 11 commonly used abbreviations selected for auto-expansion, measured by a 200 eDL audit pre- and post-intervention. Secondary outcome measures Reduction in the total number of abbreviations used and the mean number of abbreviations per eDL in the post-intervention audit compared to pre-intervention. Results The baseline audit identified 1668 abbreviation uses in 200 eDLs, consisting of 350 different abbreviations. In the post-intervention audit, use of the 11 auto-expand abbreviations decreased by 43.6%, with decreased frequency of use for 9 of the 11 abbreviations. Post-intervention there was a 34.4% reduction in the total number of abbreviations used, with 1093 abbreviations identified in 200 eDLs. Conclusions Advising JMOs to implement auto-expansion prompts for specific abbreviations, in combination with education on the risks of abbreviation use, is a cheap and effective solution to reducing abbreviation use in eDLs. This approach could significantly improve clarity of communication between hospital doctors and community healthcare professionals during patient care transition, potentially reducing medical errors.

Background Medical care for sleep-disordered breathing (SDB) in severe mental illness (SMI) is often ignored or poorly delivered. Here we describe an oximetry screening and management pathway for obstructive sleep apnoea (OSA) and assess the night-to-night reliability in a specialist cardiometabolic disease management clinic for patients with SMI. Objective The implementation and evaluation of a sleep service for patients living with SMI. Design Prospective evaluation of a translational programme. Setting A multidisciplinary outpatient clinic for patients with SMI. Methods The clinic was prospectively evaluated between May 2019 and December 2020. We used questionnaires and three nights of oximetry to screen patients for OSA. A project coordinator managed the testing-treatment pathway while liaising with health care providers. We also evaluated the agreement between two nights of oximetry. Results It is feasible to integrate sleep service into a cardiometabolic clinic for patients with SMI. Oximetry data were collected from 140/153 patients and 129/140 had at least adequate oximetry data for one night, and 107 (82%) had two nights. Oximetry indicated likely moderate-to-severe OSA in 33 patients and severe OSA in 22 patients. A total of 96/140 patients were referred to the SMI sleep clinic, and 40 (42%) recommended polysomnography (PSG) and 31 (78%) completed PSG. Of the 44 patients recommended continuous positive airway pressure (CPAP) therapy, 38 initiated CPAP and 20 (51.3%) demonstrated adherence (>4 hours 70% of nights over 30 days). Bland-Altman analysis of two nights of oxygen desaturation events greater than 4% per hour found a mean difference of −0.2 (95% CI −14.0 to 14.0). Misclassification of OSA severity was seen in 12 patients (18.7%). Conclusions Our recount shows the feasibility and effectiveness of implementing a sleep service in a cardiometabolic clinic for patients with SMI, and using oximetry is an effective diagnostic test of SDB. Having a dedicated project coordinator to oversee the clinical pathway avoids fragmentation of clinical services.

BACKGROUND Long-term outcomes and quality of life have been identified as core patient-centered outcomes for venoarterial extracorporeal membrane oxygenation (VA-ECMO) research. The aim of this study is to investigate the incidence of death or new disability at 12 months after the initiation of VA-ECMO. METHODS Prospective, multicenter, registry-embedded cohort study in 26 hospitals in Australia and New Zealand from February 2019 through April 2023. Adult patients admitted to a participating ICU and who underwent VA-ECMO were included. The primary outcome was death or new disability at 6 and 12 months. All results were adjusted for patient characteristics at the time of ECMO initiation. RESULTS Among 389 patients who received VA-ECMO (median age, 57 [44–65] years; 35% female), the incidence of death or new disability at 12 months was 70.6% compared with 70.8% at 6 months (adjusted odds ratio for 12 versus 6 months, 0.61 [95% CI, 0.25–1.49]; P =0.27). Compared with 6 months, at 12 months after VA-ECMO more patients were independent in activities of daily living (62.1% versus 48.2%; adjusted odds ratio, 2.84 [95% CI, 1.50–5.36]; P =0.001), and fewer patients were unemployed due to health reasons (32.7% versus 47.4%; adjusted odds ratio, 0.29 [95% CI, 0.13–0.65]; P <0.001). Differences in outcomes were found according to the reason for VA-ECMO initiation. CONCLUSIONS At 12 months after VA-ECMO, 30% of patients are alive and without disability, with differences in outcome associated with the reason for VA-ECMO initiation. The major burden of disability appears to develop in the first 6 months after VA-ECMO initiation and is sustained between 6 and 12 months. REGISTRATION URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03793257.

Background This study explored the lived experience of patients with colorectal peritoneal metastases undergoing cytoreductive surgery and their carers, including the decision to undergo radical surgery, recovery, and long-term survivorship. Methods This qualitative study was conducted in a tertiary cytoreductive surgery center. Semi-structured interviews were conducted with an experienced researcher to explore participants’ experiences, challenges, and reflections during different treatment stages. In-depth thematic analysis was performed on interview transcripts using a phenomenological approach to identify key major and minor themes. Results Thirteen interviews were conducted, with 5 major themes and 11 minor themes identified . Understanding diagnosis and treatment implications— survival was a key driver in decision making, although many did not feel they had a choice or understood the magnitude of the intervention. Adjustment to uncertainly— uncertainties regarding surgical intervention, its impacts and long-term recurrence, led to significant burden. Unmet supportive care needs— psychology services and patient-led support groups have key roles in addressing long-term support needs. A positive impact from multidisciplinary care teams— allied health involvement pre- and postoperatively was associated with a positive experience. Unexpected long-term physical effects— unexpected physical effects impacted quality of life during long-term survivorship. Conclusions Patients and carers undergoing cytoreductive surgery for colorectal peritoneal metastases endure a difficult journey and decision-making process; an understanding of their lived experience can improve the informed consent process and target supportive care endeavors to areas of need.

Background Melanoma of the ear accounts for approximately 1% of cutaneous melanomas. Management recommendations are based on small retrospective series and case reports. Resection of melanoma of the ear requires a delicate balance between disease clearance, preservation of function, and aesthetics. The role of cartilage resection in the wide excision of melanoma of the ear remains unclear. We aimed to compare outcomes in patients having wide excision of ear melanoma who had cartilage resected with those who had a cartilage-sparing approach. Methods Data were obtained from the Melanoma Institute Australia (MIA) prospectively maintained database. All patients diagnosed with invasive melanoma involving the ear between 1990 and 2022 were included. Data analysis was performed to assess the association between cartilage resection and recurrence-free survival (RFS), melanoma-specific survival (MSS), and overall survival (OS). Results Overall, 411 patients were included in the study, of whom 330 (80%) had cartilage resected and 81 (20%) had a cartilage-sparing resection. The cartilage resection group had a higher mean Breslow thickness (1.9 vs. 1.4 mm; p = 0.0002), whereas the cartilage-sparing group had a higher proportion of stage IA disease (60.5 vs. 39.7%; p = 0.041). Five (1.2%) patients had melanoma invading into perichondrium but not deeper. Cartilage resection had no impact on RFS {hazard ratio [HR] 0.82 (0.52–1.29); p = 0.39} or MSS (HR 0.89 (0.30–2.62); p = 0.83). Conclusion The decision to resect cartilage as part of the wide excision of invasive ear melanoma should be tailored to the needs of the individual patient, however a cartilage-sparing approach does not appear to compromise MSS outcomes, particularly in early-stage disease.

Aims Amlodipine poisoning is a leading cause of cardiovascular medication‐related deaths, commonly managed with high‐dose insulin (HDI) therapy. However, HDI is a vasodilator that is counterproductive in managing vasoplegia. We aim to study HDI therapy in patients with hypotension following dihydropyridine calcium channel antagonist (CCA) overdose. Methods This retrospective study includes adult patients (≥15 years) with deliberate dihydropyridine CCA overdose and hypotension (mean arterial pressure <65 mmHg or systolic blood pressure <90 mmHg) managed by two Poisons Information Centres and three toxicology units in Australia (2020‐2023). Patients who received HDI were compared with those who did not receive HDI therapy. Results There were 50 patients (31 female [62%], median age 57 years). Forty‐one (82%) coingested a renin–angiotensin system antagonist. Ten (20%) received HDI (median bolus dose of 1 U/kg and infusion 1.25 U/kg/h, interquartile range: 0.9–5.5) and 40 (80%) did not receive HDI therapy. Eight patients in the HDI had echocardiogram, 4 showed left ventricular dysfunction. There were no differences in the 2 groups regarding age, sex, median dose of dihydropyridine and renin–angiotensin system antagonists. Median minimal systolic blood pressure (P = .0007) and mean arterial pressure (P = .0006) were significantly lower prior to starting HDI. There were increased maximal concomitant number of vasopressors/inotropes used (median difference: 1.5; P = .0002) and at higher doses in the HDI group. Median dose of noradrenaline used was 1.15 μg/kg/min in the HDI group vs. 0.27 μg/kg/min in the non‐HDI group (P = .003). One fatality occurred in the non‐HDI group. Conclusion Dihydropyridine CCA poisoning with associated hypotension was treated primarily with vasopressor therapy. The inodilator HDI was not commonly used, and it was primarily administered in low doses, utilized mainly in patients with left ventricular dysfunction.

Background Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that primarily affects the motor neurons, causing progressive muscle weakness and paralysis. While research has focused on understanding pathological mechanisms in the motor cortex and spinal cord, there is growing evidence that extra-motor brain regions may also play a role in the pathogenesis or progression of ALS. Methods We generated 165 sample-matched post-mortem brain transcriptomes from 22 sporadic ALS patients with pTDP-43 pathological staging and 11 non-neurological controls. For each individual, five brain regions underwent mRNA sequencing: motor cortex (pTDP-43 inclusions always present), prefrontal cortex and hippocampus (pTDP-43 inclusions sometimes present), and occipital cortex and cerebellum (pTDP-43 inclusions rarely present). We examined gene expression, cell-type composition, transcript usage (% contribution of a transcript to total gene expression) and alternative splicing, comparing ALS-specific changes between brain regions. We also considered whether post-mortem pTDP-43 pathological stage classification defined ALS subgroups with distinct gene expression profiles. Results Significant gene expression changes were observed in ALS cases for all five brain regions, with the cerebellum demonstrating the largest number of total (> 3,000) and unique (60%) differentially expressed genes. Pathway enrichment and predicted activity were largely concordant across brain regions, suggesting that ALS-linked mechanisms, including inflammation, mitochondrial dysfunction and oxidative stress, are also dysregulated in non-motor brain regions. Switches in transcript usage were identified for a small set of genes including increased usage of a POLDIP3 transcript, associated with TDP-43 loss-of-function, in the cerebellum and a XBP1 transcript, indicative of unfolded protein response activity, in the motor cortex. Extensive variation in RNA splicing was identified in the ALS brain, with 26–41% of alternatively spliced genes unique to a given brain region. This included detection of TDP-43-associated cryptic splicing events such as the STMN2 cryptic exon which was shown to have a pTDP-43 pathology-specific expression pattern. Finally, ALS patients with stage 4 pTDP-43 pathology demonstrated distinct gene and protein expression changes in the cerebellum. Conclusions Together our findings highlighted widespread transcriptome alterations in ALS post-mortem brain and showed that, despite the absence of pTDP-43 pathology in the cerebellum, extensive and pTDP-43 pathological stage-specific RNA changes are evident in this brain region.

Pharmacogenomic testing for CYP2C19 helps personalise clopidogrel therapy and reduces the risk of experiencing a secondary myocardial infarction in individuals with impaired CYP2C19 function. Routine testing, however, is uncommon and it is proposed that the key requirements and processes of testing services are poorly understood. This scoping review aimed to explore the literature for CYP2C19 testing services for clopidogrel and identify their commonalities to inform the design and delivery of future services. In total, 37 eligible studies describing services across hospital and community settings were retrieved. Key elements of delivery included a multi-disciplinary approach involving physicians and pharmacists, provision of pre-implementation training and education, and electronic communication of test results. Result integration into clinical decision support systems improved the practical application of pharmacogenomic testing. The identification of the key requirements and processes may be used by institutions looking to design and deliver CYP2C19 testing services to guide clopidogrel therapy.