We need to identify novel, tractable therapeutic targets for anxiety disorders. Converging evidence suggests the endogenous opioid system plays a role in modulating affective processing, but its contribution to regulation of threat processing in humans remains unclear.

We investigated the neural correlates of non-specific opioid antagonism on explicit and implicit regulation of threatening stimuli in healthy volunteers, using functional magnetic resonance imaging (fMRI).

In a randomised, double-blind, placebo-controlled, crossover design, 38 healthy participants received the opioid antagonist naltrexone (50 mg) or placebo before completing two tasks during fMRI: (a) a cognitive emotional reappraisal task probing explicit regulation and (b) a face-viewing task probing implicit processing.

Contrary to our hypothesis, we found naltrexone reduced distress ratings during the reappraisal task (p = 0.044) without impairing regulation success. Explicit regulation in the reappraisal task engaged lateral prefrontal regions similarly across drug conditions. However, naltrexone attenuated ventromedial prefrontal cortex, thalamus and caudate activation when viewing negative images. Naltrexone additionally altered ventromedial prefrontal cortex activity and in task-positive regions including right premotor area and frontal pole compared with placebo when viewing emotional faces. In particular, naltrexone increased left middle frontal gyrus activity when viewing fearful faces.

Our results support a role for opioid signalling in automatic emotional regulation, but not in explicit regulation. Furthermore, naltrexone appeared to diminish activity in task-positive regions in response to emotional faces. These findings are consistent with a model where endogenous opioids ‘fine-tune’ affective responses to both negative and positive stimuli. Future research should explore dose–response effects, kappa-opioid contributions and whether similar results are seen in clinical populations.

Ontologies support transparent and reproducible conceptual modeling in Health Technology Assessment (HTA), but their population remains resource-intensive and reliant on expert input. This study evaluates the feasibility, reliability, and methodological implications of using generative artificial intelligence (GenAI) to populate ontology individuals for HTA applications.

A factorial experimental framework was developed using the Ontology for Simulation Modeling (OSDi) and three HTA-relevant use cases of varying complexity. Two GenAI systems were evaluated under multiple experimental conditions, including prompting strategy, serialization format, and provision of supporting information. Generated ontology individuals were validated by an HTA expert and assessed across four quality dimensions: consistency, relevance, completeness, and adequacy. Multivariate and regression analyses were conducted to examine the effects of experimental factors on quality outcomes and hallucination likelihood.

GenAI systems successfully generated ontology individuals across use cases, although performance varied by quality dimension and experimental condition. Iterative prompting significantly improved completeness, while serialization format strongly influenced reliability, with Turtle serialization associated with substantially lower hallucination likelihood compared with XML. Other factors showed dimension-specific effects, highlighting the multidimensional nature of ontology quality. Errors occurred more frequently in structurally complex ontology components, suggesting a relationship between ontological complexity and generative performance.

GenAI-assisted ontology population can enhance the efficiency and scalability of HTA conceptual modeling, enhancing the agility of HTA agencies in exploratory phases. Its effective use requires structured prompting, appropriate representation formats, and expert validation. Further research should evaluate its impact on HTA decision modeling workflows and validation frameworks.

The ryanodine receptor 2 gene mutation associated with catecholaminergic polymorphic ventricular tachycardia is one of the aetiologies of cardiac syncope and has the risk of sudden cardiac death. This study reported two novel ryanodine receptor 2 gene variants.

We described two 9-year-old girls with recurrent syncope during exercise or stress presenting two novel ryanodine receptor 2 gene variants (c.6938T>G/p. Val2313Gly and c.12263A>C/p. His4088Pro) associated with catecholaminergic polymorphic ventricular tachycardia through a comprehensive review of medical history, examination findings and genetic testing. Propranolol was used for treatment, and the two patients didn’t experience episodes of syncope during follow-up for 6 months. Besides, literature associated with catecholaminergic polymorphic ventricular tachycardia and ryanodine receptor 2 mutations was reviewed.

Recurrent syncope during exertion or stress should be focused on catecholaminergic polymorphic ventricular tachycardia caused by ryanodine receptor 2 gene mutations. The genetic testing is a crucial tool in confirming the mutation of catecholaminergic polymorphic ventricular tachycardia. Early recognition of this disease, timely diagnosis of ryanodine receptor 2 gene mutations, and administration of appropriate pharmacological agents or ICD implantation are critical to ensure favourable clinical outcomes.

Prevention of child maltreatment – incorporating physical abuse, sexual abuse, emotional abuse, neglect and exposure to domestic violence – is a clearly defined global policy priority. Global Burden of Disease studies have focused on estimating burden attributable to childhood sexual abuse omitting other forms of child maltreatment. This study aims to estimate burden attributable to child maltreatment using data from the first comprehensive national study, the Australian Child Maltreatment Study (ACMS), accounting for the co-occurrence of multiple forms, the complex impact of multi-type maltreatment and the contribution of interrelated factors.

We estimated burden attributable to child maltreatment by age and gender for Australia in 2021. Risk–outcome pairs that met criteria for sufficient evidence for a causal relationship were included. Relative risks were estimated as a function of exposure based on data from the ACMS incorporating increased risk with multi-type maltreatment and adjustment for confounding. Levels of exposure in each of the 32 mutually exclusive combinations or patterns of child maltreatment were estimated based on ACMS data by age and gender. The theoretical minimum risk exposure level was determined as no exposure to child maltreatment in the population and population attributable fractions (PAFs) were calculated. Attributable mortality, years of life lost, years lived with disability and disability-adjusted life years (DALYs) were estimated by multiplying PAFs by the relevant burden of disease estimates by age and gender for Australia in 2021. Sensitivity analyses were conducted to assess the robustness of the results. Uncertainty was propagated into attributable burden estimates using Monte Carlo simulation methods.

Overall, child maltreatment accounted for 6.6% (95% uncertainty interval (UI), 6.2–6.9%) of all DALYs for women and 6.4% (95% UI, 6.0–6.7%) of all DALYs for men in Australia in 2021. An estimated 71.2% of self-harm, 57.1% of anxiety disorders and 49.3% of major depressive disorder (MDD) DALYs in women, and 63.8% of self-harm, 55.9% of anxiety disorders and 42.9% of MDD DALYs in men were attributable to child maltreatment.

Child maltreatment contributes to a substantial proportion of burden of disease in Australia, equivalent to leading lifestyle-related risk factors such as high body mass index, high blood pressure and smoking. This research significantly advances knowledge of the disease burden attributable to child maltreatment and provides novel methodology for measuring the impact of all five forms of child maltreatment combined on mental health and health risk behaviours nationally and globally.

Early engagement in palliative and supportive care is widely promoted as a marker of insight, acceptance, and readiness for shared decision-making. Clinicians, however, frequently observe a paradoxical longitudinal pattern in which patients who initially demonstrate high emotional, cognitive, and decisional engagement later become withdrawn or fatigued despite preserved insight. This case report illustrates such a pattern and interprets it using the concept of capacity debt.

A longitudinal case description is presented, integrating clinical observation with interpretive analysis informed by literature on patient capacity, emotional labor, cumulative complexity, and serious illness communication.

The patient demonstrated high early engagement in goals-of-care discussions, advance care planning, and emotionally demanding conversations. Over time, she developed marked conversational fatigue and withdrawal without evidence of depression, demoralization, denial, or cognitive impairment. Disengagement appeared temporally related to cumulative engagement demands rather than disease progression alone.

This case illustrates how early intensive engagement may contribute to later disengagement through cumulative depletion of patient capacity. Interpreting this pattern as capacity debt provides a non-pathologizing and ethically grounded explanation, highlighting pacing as a core clinical skill in palliative care.

Reducing stigma and discrimination towards people with mental ill-health is a key priority in Australian mental health policy. Population-based surveys conducted in Australia between 2003 and 2011 showed some improvement in stigmatising attitudes, but also a deterioration in attitudes about dangerousness and unpredictability, particularly in relation to schizophrenia. This study aimed to investigate whether stigmatising attitudes have changed since the 2011 national survey.

Two large, nationally representative samples of Australian adults were surveyed in 2011 (n = 1967) and 2024 (n = 1984). At each time point, participants were presented with vignettes of a person in the early stages of depression or schizophrenia and completed questionnaires about stigmatising attitudes towards the person in the vignette (Personal Stigma Scale) and willingness to interact with them (Social Distance Scale). Using weighted data, logistic regressions assessed change from 2011 to 2024 while controlling for sociodemographic characteristics. Results were considered significant at p < .01.

There were significant reductions in endorsement of stigmatising attitudes towards depression and early schizophrenia. Notably, there were large reductions in beliefs about dangerousness (depression 22.5–4.8% and schizophrenia 37.1–18.1%). Conversely, the willingness to interact with a person with depression remained unchanged and had worsened for schizophrenia, with the odds of being unwilling to interact approximately doubling (11.0–26.9% unwilling to make friends and 18.8–33.2% unwilling to work closely with them).

The data show mixed findings regarding change in stigma in the Australian population. Despite negative beliefs diminishing over time, this has not translated into greater willingness to interact with people with depression or schizophrenia. Key action is needed on understanding the barriers to interacting with people with mental health conditions and reducing perceptions of unpredictability, particularly for schizophrenia, which remains more highly stigmatised.

Understanding trends in end-of-life care for bladder cancer patients is essential in improving palliative care planning. This study analyzes trends in preferred place of death among bladder cancer patients in the United States from year 2000 to 2020.

Data from the CDC WONDER database were used to identify 293,906 deaths caused by bladder cancer. Further data on patient place of death, age, demographics, census geographic region, and year of death were recorded. Place of death was used as a proxy for preferred place of death. A multivariable binary logistic regression analysis was performed to determine associations between preferred place of death and other variables.

At-home deaths were most common among individuals aged 75–84 years of age (42,644 deaths) and 85+ years of age (32,806 deaths). Hospice use was highest among the 75–84 age group (8,754 deaths) and 85+ age group (7,358 deaths). Nursing home deaths were highest in the 85+ age group (26,216 deaths), with significant age-related differences (p < 0.001). In terms of racial variations, White individuals accounted for 93.6% of all deaths. Black individuals were less likely to utilize hospice care (p < 0.001). Overall, race differences were significantly associated with place of death (p < 0.001). The number of home deaths rose from 4,281 in 2000 to 8,554 in 2020, and hospice deaths also rose significantly during this time period. Interestingly, younger individuals were more likely to die in hospice compared to those aged 85 years or older, though the odds decreased with age. Black individuals had significantly lower odds of hospice use than White patients (OR = 0.699, p < 0.001) and hospice use increased annually by an average of 13.4% (p < 0.001).

The results indicate that utilization of hospice care and home-based end-of-life care have risen in prominence though disparities are present across racial and regional groups. Further studies are needed to better understand potential barriers to end-of-life care among bladder cancer patients.