People with malignancy of undefined primary origin (MUO) have a poor prognosis and may undergo a protracted diagnostic workup causing patient distress and high cancer related costs. Not having a primary diagnosis limits timely site-specific treatment and access to precision medicine. There is a need to improve the diagnostic process, and healthcare delivery and support for these patients. This trial aims to implement and evaluate an optimal model of care for people presenting with MUO to reduce time to diagnosis, improve patient experiences and reduce healthcare costs.This is a pragmatic stepped-wedge cluster randomised trial comparing a control phase of standard practice with an intervention phase. Patient inclusion criteria are: 1) age 18 years or older, 2) presenting with suspected metastatic malignancy without an obvious primary site on imaging, 3) clinically appropriate to undergo diagnostic work-up and 4) able to provide written or verbal consent. The intervention is a new model of care comprising four key components: standardised diagnostic workup, dedicated cancer care coordinators, virtual multidisciplinary meetings and a website resource for patients, carers and clinicians. The primary endpoint is the time to completion of minimum diagnostic workup. Secondary outcomes are whether the type of tumour is diagnosed, clinical trial participation, referral to palliative care, patient-reported physical, social and mental health, patient-reported understanding and uncertainty. Implementation outcomes include acceptability, feasibility, fidelity and adoption and health care use and costs. Intervention implementation will be supported using clinical leadership, education and reinforcement. Patients who consent to having their data collected will receive the model of care active at the site at the time of recruitment. Patients will complete a patient-reported outcomes questionnaire four months after study enrolment. A health economic analysis will be included. Across 15 hospitals, a total sample size of 240 is planned.There is a lack of intervention research for people presenting with MUO. The stepped-wedge design seeks to mitigate the potential challenge of enrolling people with a poor prognosis and high symptom burden in trials. This research will generate important evidence with scalability for future research at trial completion.ACTRN12622001504707.

Details of the pediatric population with end-stage kidney disease (ESKD) in Australia and New Zealand have been published previously. There is, however, a paucity of studies exploring the trends in incidence, etiology, renal replacement therapy (RRT) modality, and transplant access among the Aboriginal and Torres Strait Islander children and young adults (ATCYAs) residing in Australia.An observational study was undertaken and data on Australian patients who commenced RRT at ≤24 years of age between 1963 and 2017 were extracted from the Australian and New Zealand Dialysis and Transplant Registry (ANZDATA). The incidence and prevalence rates were restricted from 1997 to 2017 because of the unavailability of Aboriginal- and Torres Strait Islander status-specific census data before 1997.A total of 3629 children and young adults received RRT during the observation period, including 178 (4.9%) who identified as ATCYAs and 3451 (95.1%) other children and young adults (OCYAs). Compared with OCYAs, incident rates have risen among ATCYAs since 2000, with the biggest rise for young adults 20 to 24 years of age. Fewer ATCYAs received a kidney transplant compared with OCYAs (56.2% vs. 89.3%,  < 0.001). Pre-emptive kidney transplants were less common in ATCYAs compared with OCYAs (3.4% vs. 16.8%,  < 0.001). Living related donor transplants were less common among ATCYAs than OCYAs (10.7% vs. 35.9%,  < 0.001).Our study shows rising incident rates and poorer access to kidney transplantation among ATCYAs in Australia. The reasons for this health care disparity and barriers to transplantation need to be explored further and must be addressed.

Rheumatic heart disease remains prevalent in some regions of Australia and New Zealand. Echocardiography is the gold standard for detection and diagnosis using the 2023 World Heart Federation guidelines. The guidelines describe specific features of mitral and aortic valve morphology and define pathological regurgitation associated with RHD. The aim of this education piece was to assist cardiac sonographers and reporting specialists in the accurate detection, diagnosis, and classification of RHD findings. We present the echocardiographic features of RHD as defined by the 2023 WHF guidelines, including a poster summarising the individual criteria for diagnosis.

To determine the incidence of therapeutic target attainment using a three-times per week protocol for vancomycin therapy given during the last hour of intermittent hemodialysis (HD).A single-center retrospective cohort study was conducted of patient medical records in a remote dialysis center from January 2017 to July 2023. Adult patients with chronic kidney disease stage 5 on ≥3 months of intermittent HD who had received a course of vancomycin therapy with ≥1 serum vancomycin concentration recorded were included. Demographic and dosing data were collected. Clinician adherence with the dosing protocol and attainment of the therapeutic target (trough concentration within 15-20 mg/L) following the loading and maintenance doses were assessed. Factors associated with target nonattainment following the loading dose were analyzed, and the 48- and 72-h maintenance dosing intervals were analyzed for target nonattainment.A total of 98 vancomycin courses (67 patients) were available for analysis. Only 38% of the loading doses were prescribed as per protocol. Following the loading dose, 25% of trough concentrations achieved the therapeutic target concentration (15-20 mg/L), 25% returned a supra-therapeutic concentration (>20 mg/L) and 50% were sub-therapeutic (<15 mg/L). When compared with those achieving target, sub-therapeutic concentrations were associated with a lower loading dose (median 16.6 vs 20.0 mg/kg, P < 0.002), and supra-therapeutic concentrations had a shorter dosing interval between the loading dose and first maintenance dose (median 31.5 vs 39.0 h, P = 0.06). Of the 201 maintenance trough concentrations collected, 65% were therapeutic, 21% were sub-therapeutic and 14% were supra-therapeutic, with an overall median trough concentration of 17.3 mg/L. As the treatment duration increased, an increase was seen in the number of dose adjustments required to achieve the target trough concentration. The 48-h dosing interval was associated with more supra-therapeutic concentrations and the 72-h interval was associated with more sub-therapeutic concentrations (df = 2, P = 0.022).We have identified a high rate of target nonattainment for HD patients on a three times a week vancomycin dosing regimen. We recommend a loading dose of 20 to 25 mg/kg irrespective of the indication and a better-defined dosing interval after the loading dose. A higher maintenance dose should be prescribed when the time to next dialysis session is 72 h. Further pharmacokinetic studies are needed to assess factors influencing target concentration attainment following the maintenance doses and to determine an optimal dosing regimen.

PS5 Standard for Pharmacy Based Immunisation Programs

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