Predicting anxiety treatment outcome in community mental health services using linked health administrative data.

Anxiety disorders is ranked as the most common class of mental illness disorders globally, affecting hundreds of millions of people and significantly impacting daily life. Developing reliable predictive models for anxiety treatment outcomes holds immense potential to help guide the development of personalised care, optimise resource allocation and improve patient outcomes. This research investigates whether community mental health treatment for anxiety disorder is associated with reliable changes in Kessler psychological distress scale (K10) scores and whether pre-treatment K10 scores and past health service interactions can accurately predict reliable change (improvement). The K10 assessment was administered to 46,938 public patients in a community setting within the Western Australia dataset in 2005-2022; of whom 3794 in 4067 episodes of care were reassessed at least twice for anxiety disorders, obsessive-compulsive disorder, or reaction to severe stress and adjustment disorders (ICD-10 codes F40-F43). Reliable change on the K10 was calculated and used with the post-treatment score as the outcome variables. Machine learning models were developed using features from a large health service administrative linked dataset that includes the pre-treatment K10 assessment as well as community mental health episodes of care, emergency department presentations, and inpatient admissions for prediction. The classification model achieved an area under the receiver operating characteristic curve of 0.76 as well as an F1 score, precision and recall of 0.69, and the regression model achieved an R2 of 0.37 with mean absolute error of 5.58 on the test dataset. While the prediction models achieved moderate performance, they also underscore the necessity for regular patient monitoring and the collection of more clinically relevant and contextual patient data to further improve prediction of treatment outcomes.

Rewiring protein binding specificity in paralogous DRG/DFRP complexes.

Eukaryotes have two paralogous developmentally regulated GTP-binding (DRG) proteins: DRG1 and DRG2, both of which have a conserved binding partner called DRG family regulatory protein 1 and 2 (DFRP1 and DFRP2), respectively. DFRPs are important for the function of DRGs and interact with their respective DRG via a conserved region called the DFRP domain. Despite being highly similar, DRG1 and DRG2 have strict binding specificity for their respective DFRP. Using AlphaFold generated structure models of the human DRG/DFRP complexes, we have biochemically characterized their interactions and identified interface residues involved in determining specificity. This analysis revealed that as few as five mutations in DRG1 can switch binding from DFRP1 to DFRP2. Moreover, while DFRP1 binding confers increased stability and GTPase activity to DRG1, DFRP2 binding only supports increased stability. Overall, this work provides new insight into the structural determinants responsible for the binding specificities of the DRG/DFRP complexes.

Patterns of Mental Health Service Utilisation: A Population-Based Linkage of Over 17 Years of Health Administrative Records.

A cross-sectoral partnership was formed in 2021 in support of the recommendations in an audit on access to state-funded mental health services. In this first paper, we aimed to describe the demographic and service utilisation of adults with a mental health diagnosis in the Western Australian state-funded health system from 2005 to 2021. Inpatient, emergency department, specialised (ambulatory) community mental health service, and death records were linked in individuals aged ≥ 18 years with a mental health diagnosis in Western Australia. Altogether, 392,238 individuals with at least one mental health service contact between 1st January 2005 and 31st December 2021 were included for analysis. Females, Aboriginal and/or Torres Strait Islander people, and those who lived outside major cities or in the most disadvantaged areas were more likely to access state-funded mental health services. While the number of individuals who accessed community mental health services increased over time (from 28,769 in 2005 to 50,690 in 2021), the percentage increase relative to 2005 was notably greater for emergency department attendances (127% for emergency department; 76% for community; and 63% for inpatient). Conditions that contributed to the increase for emergency department were mainly alcohol disorder, reaction to severe stress and adjustment disorders, and anxiety disorders. Sex differences were observed between conditions. The pattern of access increased for emergency department and the community plus emergency department combination. This study confirmed that the patterns of access of state-funded mental health services have changed markedly over time and the potential drivers underlying these changes warrant further investigation.

Deficiency of factor-inhibiting HIF creates a tumor-promoting immune microenvironment.

Hypoxia signaling influences tumor development through both cell-intrinsic and -extrinsic pathways. Inhibiting hypoxia-inducible factor (HIF) function has recently been approved as a cancer treatment strategy. Hence, it is important to understand how regulators of HIF may affect tumor growth under physiological conditions. Here we report that in aging mice factor-inhibiting HIF (FIH), one of the most studied negative regulators of HIF, is a haploinsufficient suppressor of spontaneous B cell lymphomas, particular pulmonary B cell lymphomas. FIH deficiency alters immune composition in aged mice and creates a tumor-supportive immune environment demonstrated in syngeneic mouse tumor models. Mechanistically, FIH-defective myeloid cells acquire tumor-supportive properties in response to signals secreted by cancer cells or produced in the tumor microenvironment with enhanced arginase expression and cytokine-directed migration. Together, these data demonstrate that under physiological conditions, FIH plays a key role in maintaining immune homeostasis and can suppress tumorigenesis through a cell-extrinsic pathway.

GP perspectives on a psychiatry phone line in Western Australia's Great Southern region: implications for addressing rural GP workload.

BACKGROUND: Mental illness is a public health challenge disproportionately affecting rural Australians. GPs provide most of the mental health care, and they report increasing levels of burnout and unsustainable workload in the context of increased patient complexity. This may be more salient in rural settings characterised by resource constraints. In this paper, we use evaluation data from a GP psychiatry phone line established in Western Australia's Great Southern region in 2021 to describe GPs' perspectives on the service and reflect on how it may help alleviate rural GP workload. METHODS: The sample was recruited among GPs practicing in the region. Data were collected through an online survey and semistructured interviews. Descriptive statistics were used to analyse the survey data. Interview data were subjected to thematic analysis; qualitative survey data were used for triangulation. RESULTS: A total of 45GPs completed the survey and 14 were interviewed. Interview data yielded three themes: the criticality of timeliness; the building blocks of confidence; and trust. GPs were highly satisfied with the service, and timeliness and trust were the characteristics underpinning its effectiveness. The service built GPs' confidence in managing mental health and alcohol and other drug use issues through strengthening knowledge and providing reassurance. CONCLUSIONS: Our results suggest that a telephone line operated by trusted, local psychiatrists with knowledge of the local mental health ecosystem of support can reduce rural GP workload through building confidence and strengthening personal agency, helping GPs navigate the ethical and clinical labyrinth of managing patient complexity in rural settings.

Western Australia remote aeromedical substance use disorders outcomes.

INTRODUCTION: Substance use disorders (SUDs) cause significant harm to regional Australians, who are more likely to misuse alcohol and other drugs (AODs) and encounter difficulty in accessing treatment services. The primary aims of this study were to describe the demographics of patients aeromedically retrieved from regional locations and compare hospital outcomes with a metropolitan-based cohort. AIMS: Retrospective case-controlled cohort study. Participants were aeromedically retrieved within Western Australia for SUDs between 1 July 2014 and 30 June 2019. Retrieved patients were case-matched based on age and hospital discharge diagnosis. Descriptive statistics and χ2 analysis were used to summarise the findings. RESULTS: One hundred thirty-six (91.3%) aeromedical retrievals were found, with the majority being male (n = 95; 69.9%). These were case-matched to 427 metropolitan patients, the majority male (n = 321; 75.2%). Retrieved patients were more likely (all P < 0.05) Indigenous (odds ratio [OR], 9.35 [95% confidence interval (CI), 5.96-14.85]), unemployed (OR, 2.9 [95% CI, 1.41-6.80]), referred to a tertiary hospital (OR, 2.18 [95% CI, 1.24-3.86]) and to stay longer in hospital (OR, 1.08 [95% CI, 1.02-1.14]). DISCUSSION: Findings highlight that unmarried and/or unemployed males were overrepresented in the retrieval group, with over half identifying as Indigenous. Regional variation in retrievals was noted, while amphetamine-type stimulants featured prominently in the retrieval cohort, who experienced longer hospital stays and more restrictive treatment. CONCLUSIONS: Comparing clinical outcomes for retrieved regional patients experiencing SUDs, service design and delivery should focus on offering culturally safe care for Indigenous people, catering for regional health care catchment areas, while ideally adopting collaborative and integrated approaches between AODs and mental health services.

5-Substituted Pyridine-2,4-dicarboxylate Derivatives Have Potential for Selective Inhibition of Human Jumonji-C Domain-Containing Protein 5.

Jumonji-C domain-containing protein 5 (JMJD5) is a 2-oxoglutarate (2OG)-dependent oxygenase that plays important roles in development, circadian rhythm, and cancer through unclear mechanisms. JMJD5 has been reported to have activity as a histone protease, as an Nε-methyl lysine demethylase, and as an arginine residue hydroxylase. Small-molecule JMJD5-selective inhibitors will be useful for investigating its (patho)physiological roles. Following the observation that the broad-spectrum 2OG oxygenase inhibitor pyridine-2,4-dicarboxylic acid (2,4-PDCA) is a 2OG-competing JMJD5 inhibitor, we report that 5-aminoalkyl-substituted 2,4-PDCA derivatives are potent JMJD5 inhibitors manifesting selectivity for JMJD5 over other human 2OG oxygenases. Crystallographic analyses with five inhibitors imply induced fit binding and reveal that the 2,4-PDCA C5 substituent orients into the JMJD5 substrate-binding pocket. Cellular studies indicate that the lead compounds display similar phenotypes as reported for clinically observed JMJD5 variants, which have a reduced catalytic activity compared to wild-type JMJD5.

The impact of facilitators and rural immersion on medical student engagement during a child and adolescent mental health videoconference workshop.

OBJECTIVE: Child and adolescent mental health (CAMH) disorders are a major public health problem in Australia, especially outside metropolitan areas. The issue is compounded by a shortage of child and adolescent psychiatrists (CAPs). CAMH receives minimal coverage in health professional training, training opportunities are scarce, and support for generalist health professionals, who treat most cases, is lacking. Novel approaches to early medical education and teaching are required to strengthen the available skilled workforce in rural and remote settings. METHOD: This qualitative study explored the factors influencing medical student engagement in a CAMH videoconferencing workshop as part of the Rural Clinical School of WA. RESULTS: Our results confirm the priority of personal characteristics of medical educators, over clinical and subject matter expertise, on student learning. This research affirms that general practitioners are well-placed to facilitate recognition of learning experiences, especially given that students may not readily recognise exposure to CAMH cases. CONCLUSION: Our findings support the effectiveness, efficiencies, and benefits of utilising general medical educators in supporting child and adolescent psychiatry expertise in delivering subspecialty training within medical school curricula.

Inactivation of DRG1, encoding a translation factor GTPase, causes a recessive neurodevelopmental disorder.

PURPOSE: Developmentally regulated Guanosine-5'-triphosphate-binding protein 1 (DRG1) is a highly conserved member of a class of GTPases implicated in translation. Although the expression of mammalian DRG1 is elevated in the central nervous system during development, and its function has been implicated in fundamental cellular processes, no pathogenic germline variants have yet been identified. Here, we characterize the clinical and biochemical consequences of DRG1 variants. METHODS: We collate clinical information of 4 individuals with germline DRG1 variants and use in silico, in vitro, and cell-based studies to study the pathogenicity of these alleles. RESULTS: We identified private germline DRG1 variants, including 3 stop-gained p.Gly54∗, p.Arg140∗, p.Lys263∗, and a p.Asn248Phe missense variant. These alleles are recessively inherited in 4 affected individuals from 3 distinct families and cause a neurodevelopmental disorder with global developmental delay, primary microcephaly, short stature, and craniofacial anomalies. We show that these loss-of-function variants (1) severely disrupt DRG1 messenger RNA/protein stability in patient-derived fibroblasts, (2) impair its GTPase activity, and (3) compromise its binding to partner protein ZC3H15. Consistent with the importance of DRG1 in humans, targeted inactivation of mouse Drg1 resulted in preweaning lethality. CONCLUSION: Our work defines a new Mendelian disorder of DRG1 deficiency. This study highlights DRG1's importance for normal mammalian development and underscores the significance of translation factor GTPases in human physiology and homeostasis.

Impaired protein hydroxylase activity causes replication stress and developmental abnormalities in humans.

Although protein hydroxylation is a relatively poorly characterized posttranslational modification, it has received significant recent attention following seminal work uncovering its role in oxygen sensing and hypoxia biology. Although the fundamental importance of protein hydroxylases in biology is becoming clear, the biochemical targets and cellular functions often remain enigmatic. JMJD5 is a "JmjC-only" protein hydroxylase that is essential for murine embryonic development and viability. However, no germline variants in JmjC-only hydroxylases, including JMJD5, have yet been described that are associated with any human pathology. Here we demonstrate that biallelic germline JMJD5 pathogenic variants are deleterious to JMJD5 mRNA splicing, protein stability, and hydroxylase activity, resulting in a human developmental disorder characterized by severe failure to thrive, intellectual disability, and facial dysmorphism. We show that the underlying cellular phenotype is associated with increased DNA replication stress and that this is critically dependent on the protein hydroxylase activity of JMJD5. This work contributes to our growing understanding of the role and importance of protein hydroxylases in human development and disease.

Developing fit-for-purpose funding models for rural settings: Lessons from the evaluation of a step-up/step-down service in regional Australia.

Introduction: Sub-acute mental health community services provide a bridging service between hospital and community care. There is limited understanding of the local factors that influence success, and of the funding implications of delivering services in rural areas. Methods: This paper draws from quantitative and qualitative evaluation data from a regional Western Australian service to explore these issues. Results: Consumers satisfaction with the service was high and, overall, admission to the service resulted in positive outcomes. High re-admission rates may be linked to limited community support services following discharge. Discussion: Our results suggest that outcomes may be enhanced by implementing flexible approaches that address the resource limitations of the rural context, and that the current funding model for sub-acute mental health services in rural Australian may not be fit for purpose. More needs to be understood about how these services can be better integrated with existing support services, and how they can be better funded.

Quality improvement through audit: Zuclopenthixol acetate prescribing, monitoring and patient outcomes in a regional health service.

OBJECTIVE: Prescribers' expectations of Zuclopethixol Acetate's (ZA) efficacy and tolerability are shaped by clinical experience and organisational culture; however, these expectations may not be consistent with current evidence and best practice. METHODS: Quality improvement project (QIP) through a process audit of ZA prescribing, monitoring and patient outcomes (adverse events) in order to identify issues requiring intervention to align with service standards and practices. RESULTS: QIP interventions resulted in a statistically significant shift in psychiatrist oversight, identifying high dose ZA with adverse outcomes and cessation of prescribing/administration within the Emergency Department. Clinically significant changes in patterns of prescribing were observed between pre-post intervention audits. CONCLUSION: Entrenching an evidence-based QIP approach to clinical practice can effect clinically significant patterns of practice change to improve safe prescribing and drug monitoring.

Using social network analysis approach in developing rural psychiatrist workforce.

OBJECTIVE: This study examines how rural and remote junior doctors career decisions are influenced by highly connected principles within a discipline. METHODS: Social network analysis was completed with data collected, by structured interview, with five psychiatry trainees and three early career psychiatrists in a rural location rated MM3 using the Modified Monash Model. UNICET software was used to determine the interactions between individual networks to look for overlap and common influencers. RESULTS: A single central, highly connected, psychiatrist was found at the core of the entire social network. This connector was instrumental in recruitment and retention in rural psychiatry workforce. CONCLUSION: Improving the understanding of human capital can encourage innovative solutions in developing sustainable strategies for recruiting and retaining rural psychiatry workforces.

Rural workforce challenges: Why not rural psychiatry?

OBJECTIVE: The Australian psychiatry workforce is under-subscribed and highly urbanised. Currently, 90% of psychiatrists work in the cities, and there are significant projected workforce shortages of psychiatrists throughout Australia, particularly in rural and remote locations. This qualitative study explores factors influencing medical students and junior doctors' decisions to pursue a career in rural psychiatry. METHOD: Using a phenomenological approach, data were collected through semi-structured interviews and focus groups and subjected to thematic analysis. RESULTS: Sixteen participants were interviewed, 11 interviewees and five participants from two focus groups. This study identified enablers and challenges in pursuing rural psychiatry training in Australia. Clinical exposure to rural psychiatry, personal factors, rural lifestyle and workforce shortage awareness were identified as enablers. The lack of rural infrastructure, the attractiveness of urban psychiatry and the stigma toward rural psychiatry were identified as barriers. CONCLUSIONS: Australian rural psychiatry workforce remains a complex issue. Reinforcing enablers and addressing barriers identified in this study would benefit future rural workforce initiatives.

Remoteness and socioeconomic status reduce access to specialist mental health care across Australia.

OBJECTIVE: Estimate impact of socioeconomic factors and remoteness from tertiary hospital on incidence/duration of Australian mental health admissions. METHODS: Retrospective analysis of incidence/duration of public mental health unit admissions (2018-19). Covariates included Indigenous population, potentially preventable hospitalisations (PPH) and socioeconomic disadvantage. RESULTS: Regional distance from hospital was correlated with socioeconomic disadvantage (ρ: p < 0.01). Population identifying as Aboriginal or Torres Strait Islander was associated with distance from hospital, socioeconomic disadvantage and PPH (ρ: p < 0.01). Bed days per capita was explained (R2adj: 0.48) by distance and socioeconomic disadvantage (p < 0.0001). A 1% increase in distance from hospital was associated with a 0.37% decrease in per capita bed days. Admission rate per capita across Queensland and WA was explained (R2adj: 0.36) by distance, education/occupation and state (p < 0.05). Across Queensland and WA a 1% increase in distance from hospital was associated with a 0.05% decreased incidence of admission. CONCLUSIONS: Rural Australians face high mental illness burden, socioeconomic disadvantage and limited service provision. Overcoming the additional disadvantages of reduced likelihood of admission to and reduced time in hospital with increasing distance from hospital will require increased outreach proportional to remoteness.

Rurality as a predictor of perinatal mental health and well-being in an Australian cohort.

OBJECTIVE: Perinatal emotional well-being is more than the presence or absence of depressive and anxiety disorders; it encompasses a wide range of factors that contribute to emotional well-being. This study compares perinatal well-being between women living in metropolitan and rural regions. DESIGN: Prospective, longitudinal cohort. PARTICIPANTS/SETTING: Eight hundred and six women from Victoria and Western Australia recruited before 20 weeks of pregnancy and followed up to 12 months postpartum. MAIN OUTCOME MEASURES: Rurality was assessed using the Modified Monash Model (MM Model) with 578 in metropolitan cities MM1, 185 in regional and large rural towns MM2-MM3 and 43 in rural to remote MM4-MM7. The Structured Clinical Interview for DSM-IV (SCID-IV) was administered at recruitment to assess depression, and symptoms of depression and anxiety were measured using the Edinburgh Post-natal Depression Scale and the State and Trait Anxiety Scale, respectively. Other measures included stressful events, diet, exercise, partner support, parenting and sleep. RESULTS: The prevalence of depressive disorders did not differ across rurality. There was also no difference in breastfeeding cessation, exercise, sleep or partner support. Women living in rural communities and who also had depression reported significantly higher parenting stress than metropolitan women and lower access to parenting activities. CONCLUSIONS: Our study suggests while many of the challenges of the perinatal period were shared between women in all areas, there were important differences in parenting stress and access to activities. Furthermore, these findings suggest that guidelines and interventions designed for perinatal mental health should consider rurality.

Remote supervision in psychiatry training: Unlocking capacity and technology.

OBJECTIVE: This paper explores the literature regarding remote supervision in the context of training in psychiatry with contemporary pedagogic theory and practice and utilising telephonic and videoconference technologies to enhance education outcomes. CONCLUSION: Remote supervision may provide psychiatry trainees with a balance between autonomy and support, promote clinical and professional independence in addition to developing a specific subset of telehealth skills whilst unlocking supervisory capacity to grow the psychiatry workforce, particularly in rural and remote settings.

An evaluation of junior doctors' experience in smoking cessation training in a rural mental health setting.

Introduction: Smoking prevalence remains high amongst people with mental illness, however, they are less likely to be screened for tobacco dependence and offered treatment to quit. Smoking cessation and education training are insufficient in medical schools, despite a positive relationship between training and practice once qualified. However, the question as to whether there is adequate skill and expertise to address smoking in people with mental illness within Australian mental health settings is unclear. Furthermore, people living in rural and remote areas smoke at higher rates, quit at lower rates than those in urban areas, and experience limitations in their ability to access smoking cessation supports. The Smokers' Clinic is an initiative established in a rural Australian mental health service offering a smoking cessation service to patients and staff employed by the service. Aim: This study aims to assess the change in the knowledge and confidence of resident medical officers in their understanding of nicotine dependence, smoking cessation strategies and prescribing nicotine replacement therapy in a community mental health setting. It was hypothesized that providing education and supervised clinical experience would improve knowledge, increasing confidence and motivation in managing smoking cessation in mental health patients. The research was undertaken using data collected through a questionnaire obtained from surveying resident medical officers administering the Smokers' Clinic following a 10-week rural community mental health rotation. Materials and methods: Twenty resident medical officers completed the 10-week rotation, with 14 completing the questionnaire. Knowledge of tobacco smoking, nicotine dependence and smoking cessation interventions improved with the experience of the Smokers' Clinic during the clinical rotation. Resident medical officers were motivated to spend additional time engaged in self-directed learning and all reported continued use of acquired experience and information in their clinical work after the rotation. Conclusion: This study indicates the utility of a novel approach in delivering education, training, building clinical expertise, and facilitating sustained clinical capacity amongst junior medical staff for smoking cessation in a rural community mental health setting. It offers an efficient approach for mental health services to deliver smoking cessation services to reduce the morbidity and mortality burden associated with tobacco smoking.

Megahertz pulse trains enable multi-hit serial femtosecond crystallography experiments at X-ray free electron lasers.

The European X-ray Free Electron Laser (XFEL) and Linac Coherent Light Source (LCLS) II are extremely intense sources of X-rays capable of generating Serial Femtosecond Crystallography (SFX) data at megahertz (MHz) repetition rates. Previous work has shown that it is possible to use consecutive X-ray pulses to collect diffraction patterns from individual crystals. Here, we exploit the MHz pulse structure of the European XFEL to obtain two complete datasets from the same lysozyme crystal, first hit and the second hit, before it exits the beam. The two datasets, separated by <1 µs, yield up to 2.1 Å resolution structures. Comparisons between the two structures reveal no indications of radiation damage or significant changes within the active site, consistent with the calculated dose estimates. This demonstrates MHz SFX can be used as a tool for tracking sub-microsecond structural changes in individual single crystals, a technique we refer to as multi-hit SFX.