Royal Hobart Hospital

Jack Jumper ant (JJA) venom immunotherapy (VIT) is highly efficacious but the lowest effective dose is unknown. Delta-inulin adjuvant (Advax) is known to enhance honeybee VIT immunogenicity. This phase 1/2 single-blind, randomised controlled trial aimed to compare the efficacy and safety of JJA VIT with different doses of venom ± Advax. Adults aged 18-65 with a history of immediate systemic reaction (SR) to JJA stings were randomised to receive JJA VIT at a maintenance dose of 25 mcg or 50 mcg ± Advax; participants were blinded to treatment allocation. Primary outcomes were the response to sting challenges after 12 months and venom-specific IgE and IgG4 responses to treatment. Forty-nine of 50 screened subjects met inclusion criteria and were randomised; 44 started treatment (25 mcg n = 12; 25 mcg + Advax n = 13; 50mcg n = 12, 50 mcg + Advax n = 12). Subsequently, two withdrew due to SRs to treatment, and two withdrew due to unrelated factors. The higher JJA venom maintenance dose was associated with reduced likelihood of SRs (OR 0.53 (95% CI, 0.28-0.98)), while Advax did not have an effect (OR 1.17 (95% CI, 0.59-2.32)). Forty proceeded to sting challenge, with six developing SRs. There was no difference between groups for sting challenge outcome (p = 0.98), and the ORs for 25 mcg vs. 50 mcg venom dose (0.89, 95% CI, 0.38-2.09) and Advax vs. no Advax (0.99, 95% CI 0.42-2.33) indicated no effect. There were no differences between groups for venom sIgE (p = 0.78), sIgG4 (p = 0.25), sIgE/IgG4 ratio (p = 0.42), intradermal (p = 0.77), and basophil activation test (BAT) (p = 0.69) responses to treatment. Subjects with high baseline BAT sensitivity, which reduced markedly in response to treatment, were less likely to have a positive sting challenge (p = 0.006). Challenge outcomes were similar for all groups, with no significant difference found between 25 and 50 mcg maintenance dose or between treatment with and without Advax. Further research of low dose JJA VIT is warranted to confirm its efficacy and tolerability. NCT03066986.

ABSTRACT Introduction Overweight and obesity are increasing rapidly in most countries. Underweight body mass index (BMI), though much less common, is also associated with adverse health outcomes. There is poor understanding of the implications of BMI in lymphoma patients. Recent international guidelines indicate that curative‐intent cancer treatment should not be modified for obesity alone, with no specific recommendations for low BMI patients. Our aim was to examine the impact of BMI on outcomes in a contemporary cohort of lymphoma patients. Methods We examined BMI in relation to baseline clinical features and outcomes in an Australasian cohort of 4686 lymphoma cases from the national registry. Results Patients with an overweight or obese BMI had no significant decrement in overall survival (OS) or progression free survival (PFS) compared to those with a normal BMI for any of the histological subtypes examined in this study. However, the minority of patients with underweight BMI demonstrated inferior OS for Hodgkin lymphoma (adjHR = 2.55, 95% CI = 1.05–6.19, p = 0.04) and OS (adjHR = 1.54, 95% CI = 1.02–2.32, p = 0.04) in diffuse large B‐cell lymphoma compared to patients with a normal BMI. Conclusion These findings support continued standard dosing in overweight and obese patients and identify poor outcomes requiring careful management in underweight populations. Trial Registration The authors have confirmed clinical trial registration is not needed for this submission.

Knee osteoarthritis (OA) is disabling, with few effective treatments. Anti-inflammatory treatments may be effective for patients with an inflammatory phenotype. To evaluate the efficacy of the interleukin-1β blocker diacerein, compared with placebo, on knee pain in people with knee OA who have substantial knee pain and inflammation (effusion-synovitis on magnetic resonance imaging). This multicenter, randomized, double-blind, placebo-controlled clinical trial was conducted in 4 Australian centers. Participants with clinical knee OA, substantial knee pain, and effusion-synovitis on magnetic resonance imaging were enrolled from June 2019 to September 2022. Final follow-up occurred on February 6, 2023. Data analysis began on July 7, 2023. Participants were randomized (1:1) to diacerein, 50 mg, once daily or identical placebo for the first 2 weeks, which increased to 50 mg, twice daily until 24 weeks if adverse effects were tolerable. The primary outcome was change in knee pain as assessed by the visual analogue scale (range, 0-100 mm; minimal clinically important improvement, 15) over 24 weeks. Of 262 participants randomized (mean [SD] age, 54.9 [6.1] years; 147 [56.1%] female and 115 [43.9%] male), 231 (88.2%) completed the trial. Compared with placebo, diacerein did not improve knee pain over 24 weeks (-19.9 mm [diacerein] vs -18.6 mm [placebo]; between-group mean difference, -1.3 mm; 95% CI, -9.8 to 7.3). The most common adverse events were gastrointestinal symptoms, which occurred in 55 participants (41.7%) in the diacerein group and 33 (25.4%) in the placebo group, most commonly diarrhea (51 [38.6%] in the diacerein group vs 29 [22.3%] in the placebo group). Change in urine color was observed among 13 participants (9.8%) who received diacerein. This randomized clinical trial found that, in patients with symptomatic knee OA and effusion-synovitis, diacerein (50 mg, twice daily) over 24 weeks resulted in no greater improvement in knee pain compared with placebo. These findings do not support diacerein for treating knee pain in this population. Australian New Zealand Clinical Trials Registry: ACTRN12618001656224.

Although frailty appears higher in rural and socioeconomically disadvantaged areas, existing evidence often lacks adjustment for possible population confounders. This study examined the independent associations between geographic remoteness and area-level socioeconomic status with frailty. We constructed a 33-item frailty index using data from 5740 participants of the Island Study Linking Ageing and Neurodegenerative Disease (ISLAND), a web-based longitudinal cohort of adults aged 50 years and over in Tasmania, Australia. After linking participant postcodes to Modified Monash Model remoteness and Index of Relative Socioeconomic Advantage and Disadvantage, we examined frailty distribution and its associations with geographic and sociodemographic factors using descriptive statistics, spatial mapping and multivariable linear regression models. The analytical sample mean age was 69.3 years (SD = 8.0) and most were women (72%). Frailty index scores followed a gamma distribution (mean score = 0.16, SD = 0.09), increased with age and were highest in central and western areas of Tasmania. After adjustment for age, gender, education, retirement and migrant status, frailty index scores were significantly higher in rural towns (β = 0.011 [95% confidence interval, CI = 0.005, 0.016]) and remote communities (β = 0.023 [95% CI = 0.009, 0.038]) than regional centres. Similarly, after full adjustment, compared with areas of the highest socioeconomic advantage, frailty was significantly higher in areas of middle (β = 0.013 [95% CI = 0.007, 0.018]) or low (β = 0.024 [95% CI = 0.018, 0.030]) socioeconomic advantage. The distribution of frailty across Tasmania varied by geographic remoteness and socioeconomic disadvantage. Integrating frailty assessment into regional health planning may support targeted interventions for vulnerable subpopulations, particularly in rural and disadvantaged communities.

Background: Prostate cancer (PrCa) outcomes are inferior in regional and rural areas compared to metropolitan centres. We evaluated patterns of care in PrCa patients treated in public and private healthcare facilities in regional Tasmania. Methods: This retrospective study used clinicopathological data for 2180 PrCa patients diagnosed between 2015-2022. Descriptive statistics and regression analyses determined associations between treatment facility (public vs. private) and diagnostic and treatment factors. Results: A significantly greater proportion of public patients were from outer regional/remote areas (prevalence ratio (PR) = 1.25, 95% CI: 1.19-1.31), presented with higher-risk disease (PR = 1.56, 95% CI: 1.22-2.00) and underwent active treatment compared to private patients (PR = 1.07, 95% CI: 1.03-1.11). Men treated privately were most likely to have low-risk PrCa (p < 0.001) and be managed with active surveillance (AS, 52.9%). When stratified by disease risk, public patients with intermediate (p < 0.001) or very high-risk/metastatic disease (p = 0.003) were still significantly more likely to receive active treatment than private patients. Furthermore, except for very high-risk/metastatic patients, public patients took significantly longer to commence treatment, ranging between a mean difference of 40 to 59 days depending on risk category. Conclusions: In Tasmania, treatment pathways for PrCa patients differ significantly between public and private healthcare sectors and may contribute to poorer outcomes in regional and remote areas.

BackgroundDual decline in gait and cognition is associated with an increased risk of dementia, with the strongest association seen between gait speed and delayed memory. However, the underlying brain correlates remain unknown. This study aimed to explore the associations between regional brain volumes and dual decline in gait speed and delayed memory.MethodParticipants over 60 years were randomly selected from the Southern Tasmanian electoral roll (Australia). Baseline brain MRI and three serial gait speed and delayed memory assessments were performed on average 2.5 years apart. Participants were classified into four groups depending on tertiles of annual decline in gait speed and memory: non‐decline, gait only, cognition only, and dual decline. Twenty‐one regional brain volumes (in frontal, parietal, temporal, subcortical, brain stem and cerebellar areas) were preselected based on previous studies of gait and memory. Multinomial logistic regression was used to examine the associations between baseline regional brain volumes and the four groups.ResultThe mean age of participants was 70.9 ± SD 6.7 years (n = 266). Lower volume in six brain regions (superior frontal gyrus, anterior cingulate cortex, middle frontal gyrus, thalamus, orbitofrontal cortex, hippocampus) were associated with a higher risk of dual decline. Lower volumes in the thalamus and cerebellum were associated with a higher risk of gait only and cognitive only decline respectively. However, these associations did not remain significant after correction for multiple comparisons.ConclusionIn this exploratory study regions related to memory, executive function, motor, and sensory motor integration were found to have associations with dual decline. Larger studies investigating a wider range of brain pathologies are required to fully understand the mechanisms underlying dual decline.