Mental health reform in Australia - unfinished business.

Australia was one of the first countries to develop a national mental health strategy. This article reviews the progress of reform, outlining some strengths, weaknesses and prospective challenges.

The Next-Generation Oral Selective Estrogen Receptor Degrader Camizestrant (AZD9833) Suppresses ER+ Breast Cancer Growth and Overcomes Endocrine and CDK4/6 Inhibitor Resistance.

Oral selective estrogen receptor degraders (SERD) could become the backbone of endocrine therapy (ET) for estrogen receptor-positive (ER+) breast cancer, as they achieve greater inhibition of ER-driven cancers than current ETs and overcome key resistance mechanisms. In this study, we evaluated the preclinical pharmacology and efficacy of the next-generation oral SERD camizestrant (AZD9833) and assessed ER-co-targeting strategies by combining camizestrant with CDK4/6 inhibitors (CDK4/6i) and PI3K/AKT/mTOR-targeted therapy in models of progression on CDK4/6i and/or ET. Camizestrant demonstrated robust and selective ER degradation, modulated ER-regulated gene expression, and induced complete ER antagonism and significant antiproliferation activity in ESR1 wild-type (ESR1wt) and mutant (ESR1m) breast cancer cell lines and patient-derived xenograft (PDX) models. Camizestrant also delivered strong antitumor activity in fulvestrant-resistant ESR1wt and ESR1m PDX models. Evaluation of camizestrant in combination with CDK4/6i (palbociclib or abemaciclib) in CDK4/6-naive and -resistant models, as well as in combination with PI3Kαi (alpelisib), mTORi (everolimus), or AKTi (capivasertib), indicated that camizestrant was active with CDK4/6i or PI3K/AKT/mTORi and that antitumor activity was further increased by the triple combination. The response was observed independently of PI3K pathway mutation status. Overall, camizestrant shows strong and broad antitumor activity in ER+ breast cancer as a monotherapy and when combined with CDK4/6i and PI3K/AKT/mTORi. SIGNIFICANCE: Camizestrant, a next-generation oral SERD, shows promise in preclinical models of ER+ breast cancer alone and in combination with CDK4/6 and PI3K/AKT/mTOR inhibitors to address endocrine resistance, a current barrier to treatment.

Patterns of mental healthcare provision in rural areas: A demonstration study in Australia and Europe.

Introduction: Mental healthcare systems are primarily designed to urban populations. However, the specific characteristics of rural areas require specific strategies, resource allocation, and indicators which fit their local conditions. This planning process requires comparison with other rural areas. This demonstration study aimed to describe and compare specialized rural adult mental health services in Australia, Norway, and Spain; and to demonstrate the readiness of the healthcare ecosystem approach and the DESDE-LTC mapping tool (Description and Evaluation of Services and Directories of Long Term Care) for comparing rural care between countries and across areas. Methods: The study described and classified the services using the DESDE-LTC. The analyses included context analysis, care availability, placement capacity, balance of care, and diversity of care. Additionally, readiness (Technology Readiness Levels - TRL) and impact analyses (Adoption Impact Ladder - AIL) were also assessed by two independent raters. Results: The findings demonstrated the usability of the healthcare ecosystem approach and the DESDE-LTC to map and identify differences and similarities in the pattern of care of highly divergent rural areas. Day care had a greater weight in the European pattern of care, while it was replaced by social outpatient care in Australian areas. In contrast, care coordination was more common in Australia, pointing to a more fragmented system that requires navigation services. The share between hospital and community residential care showed no differences between the two regions, but there were differences between catchment areas. The healthcare ecosystem approach showed a TRL 8 (the tool has been demonstrated in a real-world environment and it is ready for release and general use) and an AIL of 5 (the target public agencies provided resources for its completion). Two experts evaluated the readiness of the use of DESDE-LTC in their respective regional studies. All of them were classified using the TRL. Discussion: In conclusion, this study strongly supports gathering data on the provision of care in rural areas using standardized methods to inform rural service planning. It provides information on context and service availability, capacity and balance of care that may improve, directly or through subsequent analyses, the management and planning of services in rural areas.

The NSW Emergency Psychiatry Network.

Emergency Psychiatry is evolving. In an environment that lacks a clear evidence base, and where a constellation of factors is driving up Emergency Department presentation rates and lengths of stay, several stakeholders are working towards and clamouring for change. With the goal of collaborating with such parties, we believe Emergency Psychiatrists should position themselves to establish and advocate for best-practice change in culture, research, clinical care and training, and funding in the provision of mental health crisis care. To this end, we have formed the NSW Emergency Psychiatry Network, a group of Emergency Psychiatrists with a broad experience in a range of settings, from tertiary metropolitan emergency facilities with access to subspecialty psychiatric services, to rural and remote emergency settings with sporadic in-reach from local mental health services and telehealth. We unanimously recognise the need to upskill both Emergency Department and Mental Health clinicians in crisis care, and the need for committed, evidence-based Mental Health resourcing within Emergency Departments.

Co-leadership to co-design in mental health-care ecosystems: what does it mean to us?

PURPOSE: This study aims to demonstrate how service providers, service users and their families should be able to share the co-leadership, co-auspicing, co-ownership, and co-governance, of a the mental health-care ecosystem, at every level, as it develops upwards and wider, in a process of inclusivity, conviviality and polyphonic discourse, via the overlapping phases of co-creativity, codesign, co-production, co-delivery, co-evaluation, co-research and co-replication, to achieve outcomes of co-communal or organisational well-being. DESIGN/METHODOLOGY/APPROACH: "Co-design" is shorthand code for encouraging multiple pathways and trajectories toward forming and sustaining a sparkling web or vibrant network of inclusive opportunities for stakeholder participation and a collaborative partnership in organizational development, in these circumstances, for more effective mental health services (MHSs). FINDINGS: In a co-design framework, all partners should be entitled to expect and "to have and to hold" an ongoing equal stake, voice and power in the discourse from start to finish, in a bottom-up process which is fostered by an interdisciplinary leadership group, providing the strong foundation or nutrient-rich and well-watered soil and support from which a shared endeavor can grow, blossom and generate the desired fruit in ample quality and quantity. ORIGINALITY/VALUE: The authors should be working toward co-design and co-production of contemporary MHSs in a mental health-care ecosystem.

Exploring the impact of suicide care experiences and post-intervention supports sought among community pharmacists: a cross-sectional survey.

BACKGROUND: There is a need to appropriately train, support and remunerate pharmacists for their expanding roles in mental healthcare. Pharmacists often care for people experiencing mental health crises, including suicidal thoughts and behaviours, but little is known about pharmacists' suicide care experiences. AIM: This cross-sectional study aimed to explore the impact of professional experiences with people at risk of suicide and support accessed, among community pharmacists. METHOD: A survey exploring pharmacists' experiences with people at risk of suicide and post-intervention support-seeking was disseminated through Australian and Canadian professional associations, conferences and social media (June 2016-May 2017). Quantitative data were analysed using Chi-squared, Fisher's exact and independent t-tests, where appropriate. Qualitative data exploring the impact of these experiences were thematically analysed, and reasons for not seeking help post-intervention were identified. RESULTS: Among 378 respondents, 84% had encountered patients at risk of suicide and 28% had lost patients to suicide. Some were negatively affected personally and/or professionally (11%), of which 88% did not seek professional support, mainly due to uncertainty about available services. Pharmacists were significantly more negatively affected if they had a personal mental health diagnosis (p = 0.017) and previous suicide care experiences (p = 0.001). Qualitative themes included: expanding knowledge and skills, role limitation and emotional impact and response. CONCLUSION: A large proportion of pharmacists have interacted with suicidal patients and are impacted by these experiences, yet few seek help due to lack of awareness and access. There is a need to recognize pharmacists' roles in suicide care, and develop pharmacist-specific post-intervention support.

Open Dialogue, need-adapted mental health care, and implementation fidelity: A discussion paper.

Open Dialogue is a need-adapted approach to mental health care that was originally developed in Finland. Like other need-adapted approaches, Open Dialogue aims to meet consumer's needs and promote collaborative person-centred dialogue to support recovery. Need-adapted mental health care is distinguished by flexibility and responsiveness. Fidelity, defined from an implementation science perspective as the delivery of distinctive interventions in a high quality and effective fashion is a key consideration in health care. However, flexibility presents challenges for evaluating fidelity, which is much easier to evaluate when manualization and reproducible processes are possible. Hence, it remains unclear whether Open Dialogue and other need-adapted mental health interventions can be meaningfully evaluated for fidelity. The aim of this paper was to critically appraise and advance the evaluation of fidelity in need-adapted mental health care, using Open Dialogue as a case study. The paper opens a discussion about how fidelity should be evaluated in flexible, complex interventions, and identifies key questions that need to be asked by practitioners working in need-adapted mental health care to ensure they deliver these interventions as intended and in an evidence-based fashion.

Improving metabolic stability and removing aldehyde oxidase liability in a 5-azaquinazoline series of IRAK4 inhibitors.

In this article, we report our efforts towards improving in vitro human clearance in a series of 5-azaquinazolines through a series of C4 truncations and C2 expansions. Extensive DMPK studies enabled us to tackle high Aldehyde Oxidase (AO) metabolism and unexpected discrepancies in human hepatocyte and liver microsomal intrinsic clearance. Our efforts culminated with the discovery of 5-azaquinazoline 35, which also displayed exquisite selectivity for IRAK4, and showed synergistic in vitro activity against MyD88/CD79 double mutant ABC-DLBCL in combination with the covalent BTK inhibitor acalabrutinib.

The future of community psychiatry and community mental health services.

PURPOSE OF REVIEW: The aim of this article is to provide a framework and analysis of a series of critical components to inform the future design, development, sustaining, and monitoring of community mental health services. RECENT FINDINGS: Many mental health services remain too hospital-centric, often without adequate outreach services. On the basis of outcome evidence, we need to shift the balance of mental health services from hospital-centered with community outreach when convenient for staff, to community-centered and mobile, with in-reach to hospital only when necessary. Too few training programs those with emphasize the macroskills of public advocacy, working with service users, families, social movements, and the media to improve mental health and wellbeing of regional and local communities. SUMMARY: We should adopt a health ecosystems approach to mental healthcare and training, encompassing nano to macrolevels of service in every region. Catchment mental health services should be rebuilt as community-centric mental health services, integrating all community and inpatient components, but led and integrated from community sites. Community psychiatrists and mental health professionals of the future will need to be well trained in the nano to macroskills required to take responsibility for the mental health and wellbeing of their catchment communities and to provide leadership in service-planning, management, and continuing revision on the basis of rigorous evaluation. These approaches should be the core of all training in psychiatry and all mental health professions prior to any subspecialization.

Human rights implications of introducing a new mental health act - principles, challenges and opportunities.

OBJECTIVE: The United Nations Convention on the Rights of Persons with Disabilities (CRPD), 2006 has influenced the evolution of mental health legislation to protect and promote human rights of individuals with mental illness. This review introduces how the human rights agenda can be systematised into mental health services. Exploration is made of how some principles of CRPD have been incorporated into Queensland's Mental Health Act 2016. CONCLUSION: Although progress has been made in some areas, e.g. heavier reliance on capacity assessment and new supported decision-making mechanisms, MHA 2016 has continued to focus on involuntary treatment. A Human Rights Act 2019 has been passed by the Queensland parliament, which may fill in the gap by strengthening positive rights.

Survey of Australian and Canadian Community Pharmacists' Experiences With Patients at Risk of Suicide.

OBJECTIVE: The study's objective was to examine Canadian and Australian community pharmacists' experiences with people at risk of suicide. METHODS: A survey was developed and administered online. Countries were compared by Fisher's exact and t tests. Multivariable logistic-regression analysis was used to identify variables associated with preparedness to help someone in a suicidal crisis. RESULTS: The survey was completed by 235 Canadian and 161 Australian pharmacists. Most (85%) interacted with someone at risk of suicide at least once, and 66% experienced voluntary patient disclosure of suicidal thoughts. More Australians than Canadians had mental health crisis training (p<0.001). Preparedness to help in a suicidal crisis was negatively associated with being Canadian, having a patient who died by suicide, lacking training and confidence, and permissive attitudes toward suicide. CONCLUSIONS: Several perceived barriers impede pharmacists' abilities to help patients who voluntarily disclose suicidal thoughts. Gatekeeper and related suicide prevention strategy training for community pharmacists is warranted.

Discovery of a Series of 5-Azaquinazolines as Orally Efficacious IRAK4 Inhibitors Targeting MyD88L265P Mutant Diffuse Large B Cell Lymphoma.

In this article, we report the discovery of a series of 5-azaquinazolines as selective IRAK4 inhibitors. From modestly potent quinazoline 4, we introduced a 5-aza substitution to mask the 4-NH hydrogen bond donor (HBD). This allowed us to substitute the core with a 2-aminopyrazole, which showed large gains in cellular potency despite the additional formal HBD. Further optimization led to 6-cyanomethyl-5-azaquinazoline 13, a selective IRAK4 inhibitor, which proved efficacious in combination with ibrutinib, while showing very little activity as a single agent up to 100 mg/kg. This contrasted to previously reported IRAK4 inhibitors that exhibited efficacy in the same model as single agents and was attributed to the enhanced specificity of 13 toward IRAK4.

"Language Breathes Life"-Barngarla Community Perspectives on the Wellbeing Impacts of Reclaiming a Dormant Australian Aboriginal Language.

Traditional languages are a key element of Indigenous peoples' identity, cultural expression, autonomy, spiritual and intellectual sovereignty, and wellbeing. While the links between Indigenous language loss and poor mental health have been demonstrated in several settings, little research has sought to identify the potential psychological benefits that may derive from language reclamation. The revival of the Barngarla language on the Eyre Peninsula, South Australia, offers a unique opportunity to examine whether improvements in mental health and social and emotional wellbeing can occur during and following the language reclamation process. This paper presents findings from 16 semi-structured interviews conducted with Barngarla community members describing their own experienced or observed mental health and wellbeing impacts of language reclamation activities. Aligning with a social and emotional wellbeing framework from an Aboriginal and Torres Strait Islander perspective, key themes included connection to spirituality and ancestors; connection to Country; connection to culture; connection to community; connection to family and kinship; connection to mind and emotions; and impacts upon identity and cultural pride at an individual level. These themes will form the foundation of assessment of the impacts of language reclamation in future stages of the project.

Stigma and discrimination in individuals with severe and persistent mental illness in an assertive community treatment team: Perceptions of families and healthcare professionals.

AIM: To explore family member and staff perceptions of clients' experiences of stigma and discrimination, in those living with severe and persistent mental illness in an Assertive Community Treatment Team. METHOD: This qualitative study used the Discrimination and Stigma Scale to conduct structured face-to-face and telephone interviews of family members and healthcare professionals, working with the Assertive Outreach Team (AOT) (an Assertive Community Treatment Team) of a northern inner suburban catchment of Sydney, New South Wales, Australia. RESULTS: Forty-one people participated in the study (23 AOT clinical staff members and 18 family members). Family and clinical staff commonly reported stigma and discrimination amongst their relatives and clients, respectively. Four overarching themes emerged from the data: (1) appearance and behaviour, (2) avoidance and being shunned, (3) key areas of life affected by discrimination and (4) impacts of discrimination and skills to cope with discrimination. CONCLUSION: Reports of stigma and discrimination were common, yet varied between groups with clinical staff commonly witnessing experiences and impacts of discrimination in everyday life, with families' reports being substantially less. Due to the strong advocacy and support provided by the AOT model, clinical staff often buffered experiences of stigma and discrimination. Further research is needed to explore effective interventions to reduce experiences of discrimination in this population group.

Service availability and capacity in rural mental health in Australia: Analysing gaps using an Integrated Mental Health Atlas.

OBJECTIVE: Access to services and workforce shortages are major challenges in rural areas worldwide. In order to improve access to mental health care, it is imperative to understand what services are available, what their capacity is and where existing funds might be spent to increase availability and accessibility. The aim of this study is to investigate mental health service provision in a selection of rural and remote areas across Australia by analysing service availability, placement capacity and diversity. METHOD: This research studies the health regions of Western New South Wales and Country Western Australia and their nine health areas. Service provision was analysed using the DESDE-LTC system for long-term care service description and classification that allows international comparison. Rates per 100,000 inhabitants were calculated to compare the care availability and placement capacity for children and adolescents, adults and older adults. RESULTS: The lowest diversity was found in northern Western Australia. Overall, Western New South Wales had a higher availability of non-acute outpatient services for adults, but hardly any acute outpatient services. In Country Western Australia, substantially fewer non-acute outpatient services were found, while acute services were much more common. Acute inpatient care services were more common in Western New South Wales, while sub-acute inpatient services and non-acute day care services were only found in Western New South Wales. CONCLUSION: The number and span of services in the two regions showed discrepancies both within and between regions, raising issues on the equity of access to mental health care in Australia. The standard description of the local pattern of rural mental health care and its comparison across jurisdictions is critical for evidence-informed policy planning and resource allocation.

A survey of Canadian and Australian pharmacists' stigma of suicide.

BACKGROUND: There is limited information available regarding community pharmacists' stigma of suicide. Pharmacists regularly interact with people at risk of suicide and stigmatizing attitudes may impact care. OBJECTIVE: To measure community pharmacists' stigma of suicide. METHOD: Pharmacists in Canada and Australia completed an online survey with the Stigma of Suicide Scale-Short Form. Data were analysed descriptively and with univariate and multivariate analyses. RESULTS: Three hundred and ninety-six pharmacists returned completed surveys (Canada n = 235; Australia n = 161; female 70%; mean age = 38.6 ± 12.7 years). The rate of endorsement of stigmatizing terms was low overall. Canadian and Australian pharmacists differed (p < 0.05) for several variables (e.g. age, friend or relative with a mental illness, training in mental health crisis). Pharmacists without someone close to them living with a mental illness were more likely to strongly agree/agree with words describing those who die by suicide as pathetic, stupid, irresponsible, and cowardly. Those without a personal diagnosis of mental illness strongly agreed/agreed with the terms immoral, irresponsible, vengeful, and cowardly. More Australian pharmacists strongly agreed/agreed that people who die by suicide are irresponsible, cowardly, and disconnected. Independent variables associated with a higher stigma were male sex, Australian, and negative perceptions about suicide preventability. CONCLUSION: Community pharmacists frequently interact with people at risk of suicide and generally have low agreement of stigmatizing terms for people who die by suicide. Research should focus on whether approaches such as contact-based education can minimize existing stigma.