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Introduction Asthma exacerbations or ‘attacks’ can vary in severity from mild worsening of symptoms to life-threatening changes that require urgent hospital care. Understanding these exacerbations is crucial to improving treatment and support for patients. Electronic health records (EHR) using anonymised data from people with asthma in primary and secondary care can be used to understand exacerbations and outcomes. However, previous studies found significant heterogeneity in the algorithms used to define asthma exacerbations. Validating definitions of asthma exacerbations in EHR will lead to more robust and comparable evidence in future research.Methods and analysis Medline and Embase will be searched for the key concepts relating to asthma exacerbations, EHR and validation. All studies that validate exacerbations of asthma in EHR and administrative claims databases published before 30 May 2024 and written in English will be considered. Validated algorithms for asthma exacerbations or attacks must be compared against a reference or gold standard definition, and a measure of validity must be included. Articles will be screened for inclusion by two independent reviewers with any disagreements resolved by consensus or arbitration by a third reviewer. Study details will be extracted, and the risk of bias will be assessed using a QUADAS-2 tailored to this review.Ethics & dissemination No ethical approval is required as this is a review of previously published literature. Results will be disseminated in a peer-reviewed journal with the aim of being used in future research to help identify asthma exacerbation in EHR.PROSPERO registration number CRD42024545081

Introduction: EGFR-mutated NSCLC is minimally responsive to programmed cell death protein 1 or programmed death-ligand 1 blockade. We evaluated the safety, tolerability, and immunomodulatory effects of the EGFR tyrosine kinase inhibitor (TKI) afatinib in combination with the programmed cell death protein 1 antibody pembrolizumab in patients with EGFR-mutant NSCLC. Methods: Patients with advanced EGFR-mutant NSCLC with progression (PD) on previous EGFR TKI(s), aged above or equal to 18 years, Eastern Cooperative Oncology Group performance status less than or equal to 1, acceptable organ function, no significant autoimmune disease, measurable disease, and controlled brain metastases were eligible. Primary end point was determination of the maximum tolerated dose and recommended phase 2 dose. Serial specimens were collected to assess for alterations in cytokines and immune cell subsets by quantitative immunofluorescence in tissue and Luminex and flow cytometry in the blood. Results: A total of 11 patients were enrolled, six in dose finding and five in dose expansion. No dose-limiting toxicities were observed. The maximum tolerated dose was determined to be afatinib 40 mg orally daily and pembrolizumab 200 mg intravenously every 21 days. Four (36%) patients had immune-related adverse events (irAEs). Ten patients were assessable for response: two partial response, seven stable disease, and one PD. Peripheral natural killer and natural killer T-cells (p = 0.027, p = 0.01) increased and exhausted CD8+ T-cells decreased on treatment (p = 0.0035). Peripheral CD4/CD8 T-cells (area under the curve = 0.96, p = 0.042) and central memory T-cells (CD4/CD8) (area under the curve = 1.0, p = 0.0006) increased in patients who had disease control more than 6 months or partial response to afatinib/pembrolizumab as did CD3+ T-cells in a patient with progression-free survival more than 6 months after afatinib/pembrolizumab treatment. Conclusions: Afatinib and pembrolizumab were found to have modest activity associated with irAEs after PD on previous EGFR TKI setting. Proinflammatory changes in immune cell subsets in tissue and blood were detected and associated with antitumor activity and irAEs.

Background Insects often show adaptive phenotypic plasticity where environmental cues during early stages are used to produce a phenotype that matches the environment experienced by adults. Many tropical satyrine butterflies (Nymphalidae: Satyrinae) are seasonally polyphenic and produce distinct wet- and dry-season form adults, providing tight environment-phenotype matching in seasonal environments. In studied Mycalesina butterflies, dry-season forms can be induced in the laboratory by growing larvae at low temperatures or on poor food quality. Since both these factors also tend to reduce larval growth rate, larval growth rate may be an internal cue that translates the environmental cues into the expression of phenotypes. If this is the case, we predict that slower-growing larvae would be more likely to develop a dry-season phenotype. Methods We performed the first experimental study on seasonal polyphenism of a butterfly in the tribe Melanitini. We measured both larval growth rate and adult phenotype (eyespot size and wing shape) of common evening brown butterflies (Melanitis leda), reared at various temperatures and on various host-plant species. We constructed provisional reaction norms, and tested the hypothesis that growth rate mediates between external cues and adult phenotype. Results Reaction norms were similar to those found in Mycalesina butterflies. We found that both among and within treatments, larvae with lower growth rates (low temperature, particular host plants) were more likely to develop dry-season phenotypes (small eyespots, falcate wing tips). However, among temperature treatments, similar growth rates could lead to very different wing phenotypes, and within treatments the relationships were weak. Moreover, males and females responded differently, and eyespot size and wing shape were not strongly correlated with each other. Overall, larval growth rate seems to be weakly related to eyespot size and wing shape, indicating that seasonal plasticity in M. leda is primarily mediated by other mechanisms.

Abstract Background Multiple myeloma (MM) is the second most common haematological cancer worldwide. Along with related diseases including monoclonal gammopathy of undetermined significance (MGUS), plasma cell leukaemia (PCL) and plasmacytoma, MM incidence is rising, yet it remains incurable and represents a significant disease burden. Clinical registries can provide important information on management and outcomes, and are vital platforms for clinical trials and other research. The Asia–Pacific Myeloma and Related Diseases Registry (APAC MRDR) was developed to monitor and explore variation in epidemiology, treatment regimens and their impact on clinical outcomes across this region. Here we describe the registry’s design and development, initial data, progress and future plans. Methods The APAC MRDR was established in 2018 as a multicentre collaboration across the Asia–Pacific, collecting prospective data on patients newly diagnosed with MM, MGUS, PCL and plasmacytoma in Korea, Singapore, Malaysia and Taiwan, with China recently joining. Development of the registry required a multidisciplinary team of clinicians, researchers, legal and information technology support, and financial resources, as well as local clinical context from key opinion leaders in the APAC region. Written informed consent is obtained and data are routinely collected throughout treatment by hospital staff. Data are stored securely, meeting all local privacy and ethics requirements. Data were collected from October 2018 to March 2024. Results Over 1700 patients from 24 hospitals have been enrolled onto the APAC MRDR to date, with the majority (86%) being newly diagnosed with MM. Bortezomib with an immunomodulatory drug was most frequently used in first-line MM therapy, and lenalidomide-based therapy was most common in second-line. Establishment and implementation challenges include regulatory and a range of operational issues. Conclusion The APAC MRDR is providing ‘real-world’ data to participating sites, clinicians and policy-makers to explore factors influencing outcomes and survival, and to support high quality studies. It is already a valuable resource that will continue to grow and support research and clinical collaboration in MM and related diseases across the APAC region.

Summary: Background: To address inequitable diagnostic access and improve time-to-treatment for First Nations peoples, molecular point-of-care (POC) testing for chlamydia, gonorrhoea and trichomonas was integrated into 49 primary care clinics across Australia. We conducted an observational evaluation to determine clinical effectiveness and analytical quality of POC testing delivered through this national program. Methods: We evaluated (i) implementation by measuring trends in mean monthly POC testing; ii) clinical effectiveness by comparing proportions of positive patients treated by historical control/intervention period and by test type, and calculated infectious days averted; (iii) analytical quality by calculating result concordance by test type, and proportion of unsuccessful POC tests. Findings: Between 2016 and 2022, 46,153 POC tests were performed; an increasing mean monthly testing trend was observed in the first four years (p

Background: The University of Washington (UW) Center for Stewardship in Medicine (CSiM) supports a tele-antimicrobial stewardship (AMS) program (TASP) using the ECHO approach (Extension for Community Healthcare Outcomes) in small, rural, and Critical Access Hospitals (primarily in the western U.S.) with education, mentoring, organizational capacity building, and a community of peers. To evaluate the continuing education (CE) component of UW-TASP ECHO, CSiM surveyed individuals receiving CE credits as part of the program. This survey was designed to track individuals’ satisfaction with the program and to assess the impact of UW-TASP ECHO on AMS in participating facilities. Methods: The CE participants’ survey was completed annually by individuals participating in UW TASP ECHO using online survey software. The survey included closed-ended and open-ended questions. Responses to open-ended questions were entered into Atlas.ti qualitative analysis software and coded iteratively according to themes that emerged. When a new code emerged partway through the coding process, earlier surveys were re-coded for the new code. Final codes were grouped into themes and sub-themes and quotes from each theme identified were summarized and attached to the theme and reported. Results: Data from three administrations of this survey were available: 2018-2019 (n=66); 2020-2021 (n=27); and 2021-2022 (n=30). These surveys were completed by a total of 95 individuals from 53 hospitals. Seven of these individuals completed a survey in each year, 14 completed a survey in two years, and 74 completed only one survey. Themes identified were COVID-19 support (including procedures and policies, being kept up-to-date, research summaries, and peer support), the antibiotic pocket guide developed by UW, strength in community, staff education, role of CSiM in developing/strengthening the AMS program at the facility, change in use of antibiotics, UW imprimatur, learning/growing as a healthcare provider, and importance for small, rural hospitals (see examples in Table 1). Conclusions: This qualitative analysis provides evidence from surveys of individuals participating in CE that UW TASP ECHO has had a meaningful impact in such domains as building a strong community among small, rural and critical access hospitals, educating staff, changing antibiotic use and providing peer support, among others.

Abstract Background To maintain and improve the quality of the cancer nursing workforce, it is crucial to understand the factors that influence retention and job satisfaction. We aimed to investigate the characteristics of cancer nurses in Australia and identify predictors of job satisfaction. Methods We analysed data from an anonymous cross-sectional survey distributed through the Cancer Nurses Society Australia membership and social media platforms from October 2021 to February 2022. The survey was compared to national nursing registration data. Data were analysed with non-parametric tests, and a stepwise, linear regression model was developed to best predict job satisfaction. Results Responses were received from 930 cancer nurses. Most respondents (85%) described themselves as experienced nurses, and more than half had post-graduate qualifications. We identified individual, organizational, and systemic factors that contribute to job satisfaction and can impact in workforce shortages. The findings include strategies to address and prioritize workforce challenges. There were 89 different titles for advanced practice nursing roles. Managing high workload was a reported challenge by 88%. Intention to stay less than 10 years was reported by nearly 60%; this was significantly correlated with job satisfaction and age. Significantly higher scores for job satisfaction were associated with those who had career progression opportunities, career development opportunities, adequate peer support and a clearly defined scope of role. Conversely, job satisfaction scores decreased the more people agreed there was a lack of leadership and they had insufficient resources to provide quality care. Conclusion Cancer nurses are critical to the delivery of cancer care however, the workforce faces multiple challenges. This study provides an understanding of the Australian cancer nursing workforce characteristics, their roles and activities, and highlights important considerations for retaining nurses in the profession.

Background: Stigma related to mental illness (and its treatment) is prevalent worldwide. This stigma could be at the structural or organizational level, societal level (interpersonal stigma), and the individual level (internalized stigma). Vulnerable populations, for example, gender minorities, children, adolescents, and geriatric populations, are more prone to stigma. The magnitude of stigma and its negative influence is determined by socio-cultural factors and macro (mental health policies, programs) or micro-level factors (societal views, health sectors, or individuals’ attitudes towards mentally ill persons). Mental health stigma is associated with more serious psychological problems among the victims, reduced access to mental health care, poor adherence to treatment, and unfavorable outcomes. Although various nationwide and well-established anti-stigma interventions/campaigns exist in high-income countries (HICs) with favorable outcomes, a comprehensive synthesis of literature from the Low- and Middle-Income Countries (LMICs), more so from the Asian continent is lacking. The lack of such literature impedes growth in stigma-related research, including developing anti-stigma interventions. Aim: To synthesize the available mental health stigma literature from Asia and LMICs and compare them on the mental health stigma, anti-stigma interventions, and the effectiveness of such interventions from HICs. Materials and Methods: PubMed and Google Scholar databases were screened using the following search terms: stigma, prejudice, discrimination, stereotype, perceived stigma, associate stigma (for Stigma), mental health, mental illness, mental disorder psychiatric* (for mental health), and low-and-middle-income countries, LMICs, High-income countries, and Asia, South Asian Association for Regional Cooperation/SAARC (for countries of interest). Bibliographic and grey literature were also performed to obtain the relevant records. Results: The anti-stigma interventions in Asia nations and LMICs are generalized (vs. disorder specific), population-based (vs. specific groups, such as patients, caregivers, and health professionals), mostly educative (vs. contact-based or attitude and behavioral-based programs), and lacking in long-term effectiveness data. Government, international/national bodies, professional organizations, and mental health professionals can play a crucial in addressing mental health stigma. Conclusion: There is a need for a multi-modal intervention and multi-sectoral coordination to mitigate the mental health stigma. Greater research (nationwide surveys, cultural determinants of stigma, culture-specific anti-stigma interventions) in this area is required.

Abstract High grade serous ovarian carcinoma (HGSOC) is a highly heterogeneous disease that typically presents at an advanced, metastatic state. The multi-scale complexity of HGSOC is a major obstacle to predicting response to neoadjuvant chemotherapy (NACT) and understanding critical determinants of response. Here we present a framework to predict the response of HGSOC patients to NACT integrating baseline clinical, blood-based, and radiomic biomarkers extracted from all primary and metastatic lesions. We use an ensemble machine learning model trained to predict the change in total disease volume using data obtained at diagnosis (n = 72). The model is validated in an internal hold-out cohort (n = 20) and an independent external patient cohort (n = 42). In the external cohort the integrated radiomics model reduces the prediction error by 8% with respect to the clinical model, achieving an AUC of 0.78 for RECIST 1.1 classification compared to 0.47 for the clinical model. Our results emphasize the value of including radiomics data in integrative models of treatment response and provide methods for developing new biomarker-based clinical trials of NACT in HGSOC.

Nature connection through engagement with greenspaces plays an important role in promoting well-being. In England, certain groups, such as girls and young women from disadvantaged backgrounds, have limited access to high-quality greenspaces and face other barriers to engaging with nature. In Oxfordshire, the County Council has committed to improving access to greenspace and nature for all. In 2022, a group consisting of twenty girls and young women (aged 10–16) from East Oxford not-for- profit organisations, academic institutions and public bodies came together to start an initiative called ‘Greenspace & Us’. The girls and young women participated in six three- hour workshops in February to March 2022. Using the COM-B (Capability, Opportunity, Motivation, Behaviour) approach, we explored the enablers and barriers to girls and young women in Oxford engaging more with nature, which included: increasing equity of access; introducing meaningful co-production; taking safety concerns seriously; making nature normal; promoting the right to play; and increasing the ability to connect with greenspaces. The outputs of this process were synthesised into the ‘Greenspace & Us Manifesto’, which was crafted collectively. Furthermore, these insights were used to design inclusive park furniture, which was later installed in a local park in East Oxford. In this practice-based article, we outline the methods, outcomes as well as the strengths and weaknesses of the engagement, co-design and co-production approaches we used in Greenspace & Us. We hope the insights from our project will support more inclusive and equitable design of greenspaces for all.

Abstract The prognostic impact of t(11;14) in multiple myeloma (MM) needs to be better understood to inform future treatment decisions. The Australian Lymphoma Leukaemia Group embarked on a retrospective, observational cohort study using real‐world data to interrogate treatment patterns and outcomes in 74 MM patients with t(11;14) [t(11;14)‐MM] diagnosed over 10 years. This was compared to 159 and 111 MM patients with high‐risk IgH translocations (IgH HR‐MM) and hyperdiploidy (Hyperdiploid‐MM), respectively, from the Australian Myeloma and Related Diseases Registry. No appreciable differences in age, gender, ISS, LDH levels, 1q21 or del(17p) status, or treatment patterns were observed between groups. Median PFS‐1 was not different between groups but both t(11;14)‐MM and IgH HR‐MM had an inferior PFS‐2 vs. Hyperdiploid‐MM: median PFS–2 8.2 months, 10.0 months, and 19.8 months (p = 0.002), respectively. The 3‐year OS were 69%, 71%, and 82% (p = 0.026), respectively. In the t(11;14)‐MM group, gain or amplification of 1q21 at diagnosis predicted for poorer OS (HR 3.46, p = 0.002). Eleven patients had received venetoclax with 45% achieving better than a very good partial response. Results suggest that t(11;14) MM may confer an unfavorable risk profile and that the use of targeted therapies such as venetoclax earlier in the treatment algorithm should be explored.

Botulinum neurotoxin-A (BoNT-A) injections are effective for focal spasticity. However, the impact on muscle strength is not established. This study aimed to investigate the effect of BoNT-A injections on muscle strength in adult neurological conditions. Studies were included if they were Randomised Controlled Trials (RCTs), non-RCTs, or cohort studies (n ≥ 10) involving participants ≥18 years old receiving BoNT-A injection for spasticity in their upper and/or lower limbs. Eight databases (CINAHL, Cochrane, EMBASE, Google Scholar, Medline, PEDro, Pubmed, Web of Science) were searched in March 2024. The methodology followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and was registered in the Prospective Register of Systematic Reviews (PROSPERO: CRD42022315241). Quality was assessed using the modified Downs and Black checklist and the PEDro scale. Pre-/post-injection agonist, antagonist, and global strength outcomes at short-, medium-, and long-term time points were extracted for analysis. Following duplicate removal, 8536 studies were identified; 54 met the inclusion criteria (3176 participants) and were rated as fair-quality. Twenty studies were analysed as they reported muscle strength specific to the muscle injected. No change in agonist strength after BoNT-A injection was reported in 74% of the results. Most studies’ outcomes were within six weeks post-injection, with few long-term results (i.e., >three months). Overall, the impact of BoNT-A on muscle strength remains inconclusive.

BackgroundMany young people with mental health problems do not readily seek help or receive treatment and support. One way to address low help-seeking behavior is to improve access to information on mental health services and how to navigate the mental health system via a web-based tool. Seeking input from the end users (young people and parents or caregivers) on key features of the tool is imperative to ensure that it is relevant, engaging, and likely to meet their needs and expectations. ObjectiveThis study aims to investigate young person and parent or caregiver views on the design, content, functioning, and user experience of a web-based mental health navigation tool to support connection to mental health services for children and young people aged up to 25 years. MethodsA total of 4 online focus groups were conducted: 2 with young people aged 16 years and older (total n=15) and 2 with parents or caregivers (total n=13). Focus groups were structured around a series of guiding questions to explore participants’ views on content, features, user experience, and design of a mental health navigation website. Focus groups were audio recorded with detailed notes taken. In addition, 53 young people aged 16-25 years and 97 parents or caregivers completed an online survey, comprising closed- and open-ended questions; open-ended responses were included with the focus group data in the qualitative analysis. All qualitative data were analyzed using thematic analysis. ResultsA total of 2 topic areas and 7 themes were developed. The first topic area covered the types of information needs of young people and parents. Identified themes concerned the scope of the navigation website, as well as the provision of up-to-date and practical information on how to navigate the whole help-seeking process. The second topic area covered website features that would be beneficial and included the consideration of the website design; search engines; supported navigation; and forums, reviews, and user accounts. ConclusionsThis study provides important insights into the navigation needs of young people and parents or caregivers in seeking mental health services. Key findings identified through this research have directly informed the development of MindMap, a web-based youth navigation tool providing a searchable database of local services, including a clear description, their location, and potential wait times. The website can be navigated independently or with support.

Abstract Laboratory assays show that parasites often have lower heat tolerance than their hosts. But how physiological tolerances and behavioral responses of hosts and parasites combine to affect their ecological interactions in heterogeneous field environments is largely unknown. We addressed this challenge using the model insect system of the braconid wasp parasitoid, Cotesia congregata, and its caterpillar host, Manduca sexta. We used experimental manipulations of microclimate in the field to determine how elevated daytime temperatures altered the behavior, performance, and survival of host and parasite. Our experimental manipulation increased daily maximum temperatures on host plants, but had negligible effects on overall mean temperature. These increased maximum temperatures resulted in subtle, biologically relevant, changes in physiology and behavior of the host and parasitoid. We found that parasitism by the wasp did not significantly alter caterpillar thermoregulatory behavior, while experimentally increased daily maximum temperatures resulted in both parasitized and unparasitized caterpillars to be found more frequently in cooler microhabitats. Overall, we did not observe the complete parasitoid mortality seen at extreme temperatures in laboratory studies, but gained insight into the sublethal effects of increased daily maximum temperatures on host and parasitoid behavior and physiology. Climate change will alter both the biotic and abiotic environments that organisms face, and we show here that empirical experiments in the field are important for understanding organismal response to these new environments.

Abstract Circulating tumor DNA (ctDNA) in blood plasma is present at very low concentrations compared to cell-free DNA (cfDNA) of non-tumor origin. To enhance ctDNA detection, recent studies have been focused on understanding the non-random fragmentation pattern of cfDNA. These studies have investigated fragment sizes, genomic position of fragment end points, and fragment end motifs. Although these features have been described and shown to be aberrant in cancer patients, there is a lack of understanding of how the individual and integrated analysis of these features enrich ctDNA fraction and enhance ctDNA detection. Using whole genome sequencing and copy number analysis of plasma samples from 5 high grade serious ovarian cancer patients, we observed that (1) ctDNA is enriched not only in fragments shorter than mono-nucleosomes (~ 167 bp), but also in those shorter than di-nucleosomes (~ 240–330 bp) (28–159% enrichment). (2) fragments that start and end at the border or within the nucleosome core are enriched in ctDNA (5–46% enrichment). (3) certain DNA motifs conserved in regions 10 bp up- and down- stream of fragment ends (i.e. cleavage sites) could be used to detect tumor-derived fragments (10–44% enrichment). We further show that the integrated analysis of these three features resulted in a higher enrichment of ctDNA when compared to using fragment size alone (additional 7–25% enrichment after fragment size selection). We believe these genome wide features, which are independent of genetic mutational changes, could allow new ways to analyze and interpret cfDNA data, as significant aberrations of these features from a healthy state could improve its utility as a diagnostic biomarker.

Australia’s mental health system is failing young people. Calls for accountability, strategic long-term policy planning, and regional leadership have been identified as solutions to guide mental health reform. Developing system dynamics models using a participatory approach (participatory systems modelling (PSM)) is recognized as a useful method that can support decision-making for strategic reform. This paper reports evaluation findings of a youth mental health PSM process conducted in the Australian Capital Territory (ACT). Baseline and follow-up mixed-methods evaluation data were collected in 2022 across diverse stakeholder groups to investigate the feasibility, value, impact, and sustainability of PSM. Although youth mental health system reform was viewed as desirable and a necessity across all stakeholder groups, shared perceptions of disabling powerless was observed regarding their ability to influence current decision-making processes to improve the youth mental health system. This suggests greater accountability is required to support systemic reform in youth mental health. PSM offers promise in improving transparency and accountability of decision-making for youth mental health, as exemplified in the ACT. However, more support and time are required to facilitate transformational change. Future research should investigate empowerment strategies to complement the implementation of findings from dynamic models developed through PSM, as well as the effectiveness of regional youth mental health policy decision-making supported by systems modelling.

Abstract Diurnal fluctuations in temperature are ubiquitous in terrestrial environments, and insects and other ectotherms have evolved to tolerate or acclimate to such fluctuations. Few studies have examined whether ectotherms acclimate to diurnal temperature fluctuations, or how natural and domesticated populations differ in their responses to diurnal fluctuations. We examine how diurnally fluctuating temperatures during development affect growth, acclimation, and stress responses for two populations of Manduca sexta: a field population that typically experiences wide variation in mean and fluctuations in temperature, and a laboratory population that has been domesticated in nearly constant temperatures for more than 300 generations. Laboratory experiments showed that diurnal fluctuations throughout larval development reduced pupal mass for the laboratory but not the field population. The differing effects of diurnal fluctuations were greatest at higher mean temperature (30°C): Here diurnal fluctuations reduced pupal mass and increased pupal development time for the laboratory population, but had little effect for the field population. We also evaluated how mean and fluctuations in temperature during early larval development affected growth rate during the final larval instar as a function of test temperature. At an intermediate (25°C) mean temperature, both the laboratory and field population showed a positive acclimation response to diurnal fluctuations, in which subsequent growth rate was significantly higher at most test temperatures. In contrast at higher mean temperature (30°C), diurnal fluctuations significantly reduced subsequent growth rate at most test temperatures for the laboratory population, but not for the field population. These results suggest that during domestication in constant temperatures, the laboratory population has lost the capacity to tolerate or acclimate to high and fluctuating temperatures. Population differences in acclimation capacity in response to temperature fluctuations have not been previously demonstrated, but they may be important for understanding the evolution of reaction norms and performance curves.

The widespread psychological effects of contagion mitigation measures associated with the novel coronavirus disease 2019 (COVID-19) are well known. Phases of “lockdown” have increased levels of anxiety and depression globally. Most research uses methods such as self-reporting that highlight the greater impact of the pandemic on the mental health of females. Emergency medical data from ambulance services may be a better reflection of male mental health. We use ambulance data to identify unusual clusters of high rates of male mental health emergencies occurring in the East Midlands of the United Kingdom during the first national “lockdown” and to explore factors that may explain clusters. Analysis of more than 5,000 cases of male mental health emergencies revealed 19 unusual spatial clusters. Binary logistic regression analysis (χ 2 = 787.22, df = 20, p ≤ .001) identified 16 factors that explained clusters, including proximity to “healthy” features of the physical landscape, urban and rural dynamics, and socioeconomic condition. Our findings suggest that the factors underlying vulnerability of males to severe mental health conditions during “lockdown” vary within and between rural and urban spaces, and that the wider “hinterland” surrounding clusters influences the social and physical access of males to services that facilitate mental health support. Limitations on social engagement to mitigate effects of the pandemic are likely to continue. Our approach could inform delivery of emergency services and the development of community-level services to support vulnerable males during periods of social isolation.

The Population Health Research Network (PHRN) is an Australian national data linkage infrastructure that links a wide range of health and human services data in privacy-preserving ways. The data linkage infrastructure enables researchers to apply for access to routinely collected, linked, administrative data from the six states and two territories which make up the Commonwealth of Australia, as well as data collected by the Australian Government. The PHRN is a distributed network where data is collected and managed at the respective jurisdictional and/or cross-jurisdictional levels. As a result, access to linked data from multiple jurisdictions requires complex approval processes. This paper describes Australia's approach to enabling access to linked data from multiple jurisdictions. It covers the identification of, and agreement to, a minimum set of data items to be included in a unified national application form, the development and implementation of a national online application system and the harmonisation of business processes for cross-jurisdictional research projects. Utilisation of the online application system and the ongoing challenges of data linkage across jurisdictions are discussed. Changes to the data custodian and ethics committee approval criteria were out of scope for this project.

The novel coronavirus disease 2019 (COVID-19) pandemic and associated mitigation strategies such as “lockdown” are having widespread adverse psychological effects, including increased levels of anxiety and depression. Most research using self-reported data highlights the pandemic’s impact on the psychological well-being of females, whereas data for mental health emergency presentations may reflect the impact on male mental health more accurately. We analyzed records of male mental health emergencies occurring in the East Midlands of the United Kingdom during the first national “lockdown.” We computed two binary logistic regression models to (a) compare male mental health emergencies occurring during “lockdown,” 2020 (5,779) with those occurring in the same period in 2019 ( N = 4,744) and (b) compare male ( N = 5,779) and female ( N = 7,695) mental health emergencies occurring during “lockdown.” Comparisons considered the characteristics of mental health emergencies recorded by ambulance clinicians (Primary Impressions), and the socioeconomic characteristics of communities where emergencies use the Index of Multiple Deprivation. We found that during “lockdown,” male emergencies were more likely to involve acute anxiety (odds ratio [OR]: 1.42) and less likely to involve intentional drug overdose (OR: 0.86) or attempted suicide (OR: 0.71) compared with 2019. Compared with females, male emergencies were more likely to involve acute behavioral disturbance (OR: 1.99) and less likely to involve anxiety (OR: 0.67), attempted suicide (OR: 0.83), or intentional drug overdose (OR: 0.76). Compared with 2019, and compared with females, males experiencing mental health emergencies during “lockdown” were more likely to present in areas of high deprivation. Understanding the presentation of male mental health emergencies could inform improved patient care pathways.

Background The most immediate response of the research community to COVID-19 has been a focus on understanding the effects, treatment and prevention of infection. Of equal and ongoing importance is elucidating the impact of mitigation measures, such as lockdown, on the well-being of societies. Research about mental health and lockdown in the UK has predominately involved large surveys that are likely to encounter self-selection bias. Further, self-reporting does not constitute a clinical judgement. Aims To (a) compare the age, gender and ethnicity of patients experiencing mental health emergencies prior compared with during lockdown, (b) determine whether the nature of mental health emergencies has changed during compared with before lockdown, (c) explore the utility of emergency medical service data for identifying vulnerability to mental health emergencies in real time during a pandemic. Method A total of 32 401 clinical records of ambulance paramedics attending mental health emergencies in the East Midlands of the UK between 23 March and 31 July 2020 and the same period in 2019 were analysed using binary logistic regression. Results People of younger age, male gender and South Asian and Black ethnicity are particularly vulnerable to acute mental health conditions during lockdown. Patients with acute cases of anxiety have increased during lockdown whereas suicide and intentional drug overdose have decreased. Conclusions Self-reported data may underrepresent the true impact of lockdown on male mental health and ethnic minority groups. Emergency medical data can be used to identify vulnerable communities in the context of the extraordinary circumstances surrounding the current pandemic, as well as under more ordinary circumstances.

The aim of this study was to assess the feasibility of rapid sodium MRI (23Na-MRI) for the imaging of peritoneal cancer deposits in high grade serous ovarian cancer (HGSOC) and to evaluate the relationship of 23Na-MRI with tumour cellularity. 23Na-MRI was performed at 3 T on twelve HGSOC patients using a 3D-cones acquisition technique. Tumour biopsies specimens were collected after imaging and cellularity was measured from histology. Total 23Na-MRI scan time for each patient was approximately 11 min. At an isotropic resolution of 5.6 mm, signal-to-noise ratios (SNRs) of 82.2 ± 15.3 and 15.1 ± 7.1 (mean ± standard deviation) were achieved for imaging of tumour tissue sodium concentration (TSC) and intracellular weighted sodium concentration (IWS) respectively. Tumour TSC and IWS concentrations were: 56.8 ± 19.1 mM and 30.8 ± 9.2 mM respectively and skeletal muscle TSC and IWS concentrations were 33.2 ± 16.3 mM and 20.5 ± 9.9 mM respectively. There were significant sodium concentration differences between cancer and skeletal muscle, Wilcoxon signed-rank test, P

Practical theology is by nature a discipline of crisis, standing on the edge of reality and potential, what is and what can be. Crises can be gentle turning points, opportunities for radical transformation, or catastrophic moments in time. In the geological age of the Anthropocene, people face devastating planetary effects of human agency, which have created and escalated a climate crisis beyond the boundaries of imagination. Practical theology belongs at the epicenter of ecological crises, which have already produced harsh results, ecological despair, and a time-dated urgency for daring decisions and actions. Change is knocking at global doors—the necessity, foreboding, and hope for change. This article probes practical theology’s role in change, giving primary attention to changes in practical wisdom (phronesis) and life practices. Methodologically, the article draws from ecological scholars and activists, philosophers and theologians, indigenous communities, and the earth itself, presenting descriptions and analyses of their shared wisdom across time, culture, and areas of expertise. From these sources, the study identifies challenges, practices, and alternate worldviews that can potentially reshape practical wisdom and climate action. In conclusion, this paper proposes life practices for climate justice: practices of attending, searching, imagining, and communal living and acting.

Summary: Background: Remote Australian Aboriginal communities have among the highest diagnosed rates of sexually transmissible infections (STIs) in the world. We did a trial to assess whether continuous improvement strategies related to sexual health could reduce infection rates. Methods: In this stepped-wedge, cluster-randomised trial (STIs in remote communities: improved and enhanced primary health care [STRIVE]), we recruited primary health-care centres serving Aboriginal communities in remote areas of Australia. Communities were eligible to participate if they were classified as very remote, had a population predominantly of Aboriginal people, and only had one primary health-care centre serving the population. The health-care centres were grouped into clusters on the basis of geographical proximity to each other, population size, and Aboriginal cultural ties including language connections. Clusters were randomly assigned into three blocks (year 1, year 2, and year 3 clusters) using a computer-generated randomisation algorithm, with minimisation to balance geographical region, population size, and baseline STI testing level. Each year for 3 years, one block of clusters was transitioned into the intervention phase, while those not transitioned continued usual care (control clusters). The intervention phase comprised cycles of reviewing clinical data and modifying systems to support improved STI clinical practice. All investigators and participants were unmasked to the intervention. Primary endpoints were community prevalence and testing coverage in residents aged 16–34 years for Chlamydia trachomatis, Neisseria gonorrhoeae, and Trichomonas vaginalis. We used Poisson regression analyses on the final dataset and compared STI prevalences and testing coverage between control and intervention clusters. All analyses were by intention to treat and models were adjusted for time as an independent covariate in overall analyses. This study was registered with the Australia and New Zealand Clinical Trials Registry, ACTRN12610000358044. Findings: Between April, 2010, and April, 2011, we recruited 68 primary care centres and grouped them into 24 clusters, which were randomly assigned into year 1 clusters (estimated population aged 16–34 years, n=11 286), year 2 clusters (n=10 288), or year 3 clusters (n=13 304). One primary health-care centre withdrew from the study due to restricted capacity to participate. We detected no difference in the relative prevalence of STIs between intervention and control clusters (adjusted relative risk [RR] 0·97, 95% CI 0·84–1·12; p=0·66). However, testing coverage was substantially higher in intervention clusters (22%) than in control clusters (16%; RR 1·38; 95% CI 1·15–1·65; p=0·0006). Interpretation: Our intervention increased STI testing coverage but did not have an effect on prevalence. Additional interventions that will provide increased access to both testing and treatment are required to reduce persistently high prevalences of STIs in remote communities. Funding: Australian National Health and Medical Research Council.

Abstract Background Plasma cell dyscrasias (PCD) are a spectrum of disorders resulting from the clonal expansion of plasma cells, ranging from the pre-malignant condition monoclonal gammopathy of undetermined significance (MGUS) to multiple myeloma (MM). MM generates a significant burden of disease on the community and it is predicted that it will increase in both incidence and prevalence owing to an ageing population and longer survival secondary to new therapeutic options. Robust and comprehensive clinical data are currently lacking but are required to define current diagnostic, investigational and management patterns in Australia and New Zealand (ANZ) for comparison to both local and international guidelines for standards of care. A clinical registry can provide this information and subsequently support development of strategies to address any differences, including providing a platform for clinical trials. The Myeloma and Related Diseases Registry (MRDR) was developed to monitor and explore variations in practices, processes and outcomes in ANZ and provide benchmark outcomes nationally and internationally for PCD. This paper describes the MRDR aims, development and implementation and discusses challenges encountered in the process. Methods The MRDR was established in 2012 as an online database for a multi-centre collaboration across ANZ, collecting prospective data on patients with a diagnosis of MGUS, MM, solitary plasmacytoma or plasma cell leukaemia. Development of the MRDR required multi-disciplinary team participation, IT and biostatistical support as well as financial resources. Results More than 1250 patients have been enrolled at 23 sites to date. Here we describe how database development, data entry and securing ethics approval have been major challenges for participating sites and the coordinating centre, and our approaches to resolving them. Now established, the MRDR will provide clinically relevant and credible monitoring, therapy and ‘real world’ outcome data, to support the conduction of high quality studies. In addition, the Myeloma 1000 sub-study is establishing a repository of paired peripheral blood specimens from registry patients to study mechanisms underlying disease progression. Conclusion Establishment of the MRDR has been challenging, but it is a valuable investment that will provide a platform for coordinated national and international collaboration for clinical research in PCD in ANZ.