St. Vincent's Hospital Melbourne

Background To determine the relationship between gastroesophageal reflux disease (GORD) and its treatment and interstitial lung disease in patients with systemic sclerosis (SSc). Methods SSc patients from the Australian Scleroderma Cohort Study (ASCS) were included. GORD was defined as self-reported GORD symptoms, therapy with a proton pump inhibitor (PPI) or histamine 2 receptor antagonist (H2RA) and/or the presence of reflux oesophagitis diagnosed endoscopically. The impact of GORD and its treatment on ILD features (including severity and time to ILD development) and survival was evaluated. Results GORD was a common manifestation affecting 1539/1632 (94%) of SSc patients. GORD affected 450/469 (96%) of those with SSc-ILD cohort. In SSc-ILD, there was no relationship between the presence of GORD or its treatment and time to ILD development or ILD severity. However, GORD treatment was associated with improved survival in those with ILD (p = 0.002). Combination therapy with both a PPI and a H2RA was associated with a greater survival benefit than single agent therapy with PPI alone (HR 0.3 vs 0.5 p < 0.050 respectively). Conclusion GORD is a common SSc disease manifestation. While the presence or treatment of GORD does not influence the development or severity of ILD, aggressive GORD treatment, in particular with a combination of PPI and H2RA, is associated with improved survival in those with SSc-ILD.

Objective To inform the design and implementation of osteoarthritis (OA) education for people with knee and hip OA, this review investigated: i) the impact of OA education on knowledge, beliefs and behavior, ii) how and why these changes occur. Methods Five databases ‐ MEDLINE, Excerpta Medica Database (Embase), Cumulative Index to Nursing and Allied Health Literature (CINAHL), Scopus, Physiotherapy Evidence Database (PEDro) ‐ were searched in August 2023. Eligible studies were quantitative, qualitative and mixed‐methods, involving OA education interventions, assessing knowledge, beliefs and/or behavioral outcomes. An interpretivist analytic process guided data evaluation, synthesis and description of meta‐themes. Results Ninety‐eight studies were included (80 quantitative, 12 qualitative, 6 mixed‐methods). OA education was heterogeneous in content and delivery. Outcome measures varied, with poor distinction between knowledge, beliefs and behavior constructs. Trends toward short‐term knowledge improvement were observed, but there were no clear trends in beliefs or behavior change. Intrinsic factors (e.g. pre‐existing beliefs) and extrinsic factors (e.g. socioeconomic factors) appeared to influence change. Three meta‐themes described how and why changes may occur: i) Engagement ‐ how individuals relate with education content and delivery, ii) Embodiment – the role of experiential factors in learning, and iii) Empowerment ‐ the level of agency education generates. Conclusion Beyond the provision of information and instruction, OA education is a complex, relational process influenced by multidimensional factors. This review identifies potentially important strategies at individual, interpersonal and community levels to support the design and delivery of engaging education that promotes holistic, embodied learning, and facilitates meaningful, empowering change. image

Purpose Contraction-induced H reflexes are a late neurophysiologic response elicited with submaximal nerve stimulation during isometric muscle contraction. Mediated by spinal pathways, like other H reflexes, their use has remained somewhat limited despite a long history of development dating back to the original description by Hoffman. There is a paucity of data on normal reference ranges, which this article aims to add to. Methods Contraction-induced H reflexes were elicited from the first dorsal interosseous, flexor carpi radialis, and tibialis anterior bilaterally in 100 healthy volunteers. Reference values, including side-to-side variation, were calculated. Pearson test and multiple regression were used to evaluate the relationship of H-reflex latency to height, age, and sex of participants. Results The mean onset latencies of 28.00, 17.44, and 31.10 ms were seen for first dorsal interosseous, flexor carpi radialis, and tibialis anterior muscles, respectively. The calculated allowable side-to-side latency difference in individual participants was 3 to 4 ms. A correlation to participant height was seen. Conclusions This work provides normal reference values of contraction-induced H reflexes to three muscles, including allowable side-to-side variation. The latter suggests that bilateral testing evaluating for asymmetry within an individual is likely to be optimally sensitive. The relationship to height is also confirmed.

In a cardiac output (CO) sub-study of the Restrictive versus Liberal Fluid Therapy in Major Abdominal Surgery (RELIEF) trial, it was shown that restrictive fluid management was associated with lower cardiac index at the end of surgery. However, the association of the fluid protocol with intraoperative blood pressure was less clear. This paper primarily compares rates of hypotension between the two fluid regimens. The haemodynamic effects of these protocols may increase our understanding of perioperative fluid prescription. Using a data set of arterial pressure and cardiac output measurements, this observational cohort study primarily compares intraoperative hypotension rates defined by a mean arterial pressure < 65 mmHg between liberal and restrictive fluid protocols. Secondary analyses explore predictors of invasive mean arterial pressure and doppler-derived cardiac output, including fluid volume regimens and surgical duration. 105 patients had a combined total of 835 haemodynamic data capture events from the beginning to the end of the surgery. Here we report that a restrictive regimen is not associated with a greater proportion of participants who experience at least one episode of hypotension than the liberal regimen 64.1% vs. 61.5% (mean difference 2.6%, 95% CI − 15.9% to 21%, p = 0.78). Duration of surgery was associated with an increased risk of hypotension (OR 1.05, 1 to 1.1, p = 0.038). A fluid restriction protocol compared to liberal fluid administration is not associated with lower blood pressure.

Background Despite recent advances, optimal therapeutic approaches applicable to subpopulations with primary central nervous system (CNS) lymphoma outside of clinical trials remain to be determined. Methods We performed a retrospective study of immunocompetent, adult patients with histologically confirmed diffuse large B‐cell lymphoma of the CNS (PCNSL). 190/204 (93%) patients (median age: 65) received one of five high‐dose methotrexate (HD‐MTX) containing chemotherapy regimens: MPV/Ara‐C (HD‐MTX, procarbazine, and vincristine, followed by cytarabine [Ara‐C]) ( n = 94, 50%), MATRix (HD‐MTX, Ara‐C, thiotepa, and rituximab) ( n = 19, 10%), HD‐MTX/Ara‐C ( n = 31, 16%), HD‐MTX monotherapy ( n = 35, 18%) and MBVP (HD‐MTX, carmustine, teniposide, prednisolone) ( n = 11, 6%). Results Cumulative median HD‐MTX and Ara‐C doses were 17 g/m ² (range: 1–64 g/m ² ) and 12 g/m ² (0–32 g/m ² ) respectively. Using 14 g/m ² as the reference dose, the median HD‐MTX relative dose intensity (HD‐MTX‐RDI) was 1.25 (0.27‐4.57) with 84% receiving > 0.75. The overall response rate (ORR) was 72% (complete response: 50%) after completing HD‐MTX. At a median follow‐up of 3.41 years (0.06–9.42), progression‐free survival (PFS) and overall survival (OS) were different between chemotherapy cohorts, with the best outcomes achieved in the MPV/Ara‐C cohort (2‐year PFS 74%, 2‐year OS 82%; p = 0.0001 and p = 0.0024 respectively). On multivariate analysis, MPV/Ara‐C administration and HD‐MTX‐RDI > 0.75 were associated with longer PFS and OS. Conclusion Sequential, response‐adapted approaches can improve outcomes, even in older patients who are ineligible for a high‐intensity concurrent chemotherapy approach and do not undergo traditional consolidative strategies.

Loneliness is recognised as a risk factor for cardiovascular disease development. However, it is unclear whether loneliness itself or other closely related mental health symptoms, such as depression and social anxiety, are associated with the development of cardiovascular disease. In the present study, we examined the relationship between loneliness and several early cardiovascular disease markers in young adults, after controlling for depression and social anxiety. Sixty-six young adults (18–35 years old, Mage = 22.70; 75.8% females) completed psychological questionnaires and took part in several physiological tests assessing cardiovascular health (e.g., vascular function). Results revealed higher loneliness was significantly associated with shorter pulse transit time (β = − 0.70, p = 0.002; shorter pulse transit time is a subclinical marker for arterial stiffness). Additionally, results show that while loneliness and depression were both related to vascular dysfunction in young adults, the underlining physiological mechanisms through which they affect vascular function may be different. Specifically, higher loneliness was associated with increased arterial stiffness, whereas depression was associated with increased endothelial dysfunction (β = − 0.43, p = 0.04). Our findings indicate that presence of loneliness and depression in young adults may be accompanied by early indicators of poor cardiovascular health, such as arterial stiffness and endothelial dysfunction. Results from the study further support the link between loneliness and cardiovascular disease development.

Melasma is a chronic, acquired disorder of focal hypermelanosis that carries significant psychosocial impact and is challenging for both the patient and the treating practitioner to manage in the medium to long term. Multiple treatments have been explored, often in combination given the many aetiological factors involved in its pathogenesis. Therapeutic discoveries to treat melasma are a focal topic in the literature and include a range of modalities, with recent developments including updates on visible light photoprotection, non-hydroquinone depigmenting agents, oral tranexamic acid, chemical peels, and laser and energy-based device therapy for melasma. It is increasingly important yet challenging to remain up-to-date on the arsenal of treatments available for melasma to find an efficacious and well-tolerated option for our patients.

The aim of this article is to provide education to clinicians about certain barriers restricting the use of advanced targeted treatments in Australian health care. For illustrative purposes, the article focuses on dermatological conditions, but the content is relevant to all specialties that treat inflammatory and chronic diseases. Barriers to care discussed result in a lower than necessary standard of care for patients in Australia despite important advancements in medicine.

Serious infection is common in patients with multiple myeloma due to immune deficiency from the underlying disease and/or its treatment. Immunoglobulin replacement is one approach to reduce infection risk in these patients. However, few real‐world data exist on its use in patients with myeloma. We investigated immunoglobulin use in Australia, New Zealand and Asia‐Pacific using registry data and explored its association with survival outcomes. A total of 2374 patients with a median follow‐up time of 29.5 months (interquartile range 13.3–54.3 months) were included in the analysis – 1673 from Australia, 313 Korea, 281 New Zealand and 107 Singapore. Overall, 7.1% of participants received immunoglobulin replacement within 24 months of diagnosis. Patients who received immunoglobulin replacement were likely to be younger, had lower baseline IgG levels (excluding paraprotein), were more likely to have baseline hypogammaglobulinaemia, baseline severe hypogammaglobulinaemia and abnormal baseline fluorescent in‐situ hybridisation status, receive first‐line myeloma treatment with immunomodulatory drugs or anti‐CD38 therapy and undergo upfront autologous stem cell transplant. In our patient cohort, the use of immunoglobulin was not associated with overall survival benefit at the time of last follow‐up (adjusted hazard ratio 0.72, 95% CI 0.46–1.14, p = 0.16). Understanding treatment approaches in clinical practice can help support future planning and provision of immunoglobulin resources.

Background Clinical trials using Bayesian adaptive designs can be more efficient than those using traditional fixed designs, but there is a vast range of possible design approaches described in literature. We performed virtual re-executions of a breast cancer clinical trial with a delayed binary outcome to demonstrate what would have happened if the trial had used various Bayesian adaptive designs instead, and to explore which specific designs yielded the most benefits. Methods We retrospectively “re-executed” a randomised controlled trial that compared two chemotherapy regimens for women with metastatic breast cancer (ANZ 8614) using Bayesian adaptive designs. We used computer simulations to estimate the power and sample sizes of a large number of different candidate designs and shortlisted designs with the either highest power or the lowest average sample size. Using the real-world data, we explored what would have happened had ANZ 8614 been conducted using these shortlisted designs. Results Adaptive designs that prioritised small sample size reduced the average sample size by up to 50% when there was no clinical effect and by up to 21% at the target clinical effect. Adaptive designs that prioritised high power yielded up to an absolute increase of 6.5% in power without a corresponding increase in type I error. The performance of the adaptive designs when applied to the real-world ANZ 8614 data was consistent with the simulations. Conclusion Bayesian adaptive designs improved power or lowered the average sample size substantially when applied to this data set. When designing new oncology trials, researchers should consider whether a Bayesian adaptive design may be beneficial.

Background Unprofessional behaviours between healthcare workers are highly prevalent. Evaluations of large-scale culture change programs are rare resulting in limited evidence of intervention effectiveness. We conducted a multi-method evaluation of a professional accountability and culture change program “Ethos” implemented across eight Australian hospitals. The Ethos program incorporates training for staff in speaking-up; an online system for reporting co-worker behaviours; and a tiered accountability pathway, including peer-messengers who deliver feedback to staff for ‘reflection’ or ‘recognition’. Here we report the final evaluation component which aimed to measure changes in the prevalence of unprofessional behaviours before and after Ethos. Methods A survey of staff (clinical and non-clinical) experiences of 26 unprofessional behaviours across five hospitals at baseline before (2018) and 2.5–3 years after (2021/2022) Ethos implementation. Five of the 26 behaviours were classified as ‘extreme’ (e.g., assault) and 21 as incivility/bullying (e.g., being spoken to rudely). Our analysis assessed changes in four dimensions: work-related bullying; person-related bullying; physical bullying and sexual harassment. Change in experience of incivility/bullying was compared using multivariable ordinal logistic regression. Change in extreme behaviours was assessed using multivariable binary logistic regression. All models were adjusted for respondent characteristics. Results In total, 3975 surveys were completed. Staff reporting frequent incivility/bullying significantly declined from 41.7% (n = 1064; 95% CI 39.7,43.9) at baseline to 35.5% (n = 505; 95% CI 32.8,38.3; χ²(1) = 14.3; P < 0.001) post-Ethos. The odds of experiencing incivility/bullying declined by 24% (adjusted odds ratio [aOR] 0.76; 95% CI 0.66,0.87; P < 0.001) and odds of experiencing extreme behaviours by 32% (aOR 0.68; 95% CI 0.54,0.85; P < 0.001) following Ethos. All four dimensions showed a reduction of 32–41% in prevalence post-Ethos. Non-clinical staff reported the greatest decrease in their experience of unprofessional behaviour (aOR 0.41; 95% CI 0.29, 0.61). Staff attitudes and reported skills to speak-up were significantly more positive at follow-up. Awareness of the program was high (82.1%; 95% CI 80.0, 84.0%); 33% of respondents had sent or received an Ethos message. Conclusion The Ethos program was associated with significant reductions in the prevalence of reported unprofessional behaviours and improved capacity of hospital staff to speak-up. These results add to evidence that staff will actively engage with a system that supports informal feedback to co-workers about their behaviours and is facilitated by trained peer messengers.

LBA105 Background: Use of triplet/quadruplet therapies for 1L MM raises the need for novel combinations at first relapse, which belantamab mafodotin (belamaf) combos may address. In DREAMM-7, BVd led to a significant improvement in progression-free survival (PFS) and a strong trend in improved overall survival (OS) vs daratumumab-Vd in patients (pts) with ≥1 prior therapy. We report results from DREAMM-8 (NCT04484623), which tested a different belamaf combo (BPd) and met its primary endpoint of independent review committee–assessed PFS at a prespecified interim analysis. Methods: DREAMM-8 is a phase 3, open-label, randomized, multicenter trial evaluating the efficacy and safety of BPd vs PVd in RRMM pts who received ≥1 prior line of therapy (LoT), including lenalidomide. Pts were randomly assigned 1:1 to BPd (28-d cycles): belamaf 2.5 mg/kg IV (D1, C1), 1.9 mg/kg (D1, C2+) + pom 4 mg (D1-21, all C) + dex 40 mg (D1, QW, all C), or PVd (21-d cycles): pom 4 mg (D1-14, all C) + bortezomib 1.3 mg/m ² SC (D1, 4, 8, 11 [C1-8]; and D1, 8 [C9+]) + dex 20 mg (day of and 1 day after bortezomib dose). Results: 155 pts were randomly assigned to BPd and 147 to PVd. With a median (range) follow-up of 21.78 mo (0.03-39.23), median PFS (95% CI) was not reached (NR; 20.6-NR) with BPd vs 12.7 mo (9.1-18.5) with PVd (HR, 0.52; 95% CI, 0.37-0.73; P<0.001). 12-month PFS rate (95% CI) was 71% (63-78%) with BPd vs 51% (42-60%) with PVd. ORR (95% CI) was 77% (70.0-83.7%) with BPd vs 72% (64.1-79.2%) with PVd; rate of complete response or better (95% CI) was 40% (32.2-48.2%) with BPd vs 16% (10.7-23.3%) with PVd. Median duration of response (95% CI) was NR (24.9-NR) with BPd vs 17.5 mo (12.1-26.4) with PVd. A positive trend favoring BPd was seen for OS (HR, 0.77; 95% CI, 0.53-1.14); follow up for OS is ongoing. Adverse events (AEs) were reported in >99% and 96% of pts in the BPd and PVd arms, respectively. Of pts treated with BPd, 89% had ocular AEs (CTCAE grade 3/4, 43%) vs 30% (grade 3/4, 2%) in the PVd arm. AEs were generally manageable, and broadly consistent with known safety profile of individual agents. Conclusions: The DREAMM-8 study demonstrated a statistically significant and clinically meaningful PFS benefit with BPd vs PVd in RRMM with >1 prior LoT. BPd also led to deeper and more durable responses, showed a favorable OS trend, and had a manageable safety profile. Clinical trial information: NCT04484623 . [Table: see text]

In Australia, bortezomib‐based induction (V‐IND) is used in >90% of newly diagnosed transplant‐eligible multiple myeloma (MM) patients. Four cycles of V‐IND with bortezomib–cyclophosphamide–dexamethasone or bortezomib–lenalidomide–dexamethasone are available via the Pharmaceutical Benefits Scheme prior to autologous stem cell transplantation (ASCT). Patients who demonstrate suboptimal response or who are refractory to V‐IND demonstrate inferior survival, representing a subgroup of MM where an unmet need persists. We evaluated an early, response‐adapted approach in these patients by switching to an intensive sequential therapeutic strategy incorporating daratumumab–lenalidomide–dexamethasone‐based (DRd) salvage, high‐dose melphalan ASCT followed by DRd consolidation and R maintenance. The overall response rate following four cycles of DRd salvage was 72% (95% credible interval: 57.9–82.4); prespecified, dual, Bayesian proof‐of‐concept criteria were met. Euro‐flow minimal residual disease (MRD) negativity was 46% in the intention‐to‐treat population and 79% in the evaluable population following 12 cycles of DRd consolidation. At the 24‐month follow‐up, median progression‐free survival and overall survival were not reached. DRd salvage was well tolerated with grade 3 and 4 events reported in 24% and 8% respectively. Response‐adapted DRd combined with ASCT achieves high rates of MRD negativity and durable disease control in this functional high‐risk group.