Australian Research Council Research Articles

Patterns of medicine use in the year prior to death by suicide: an Australian population-based case series study

Prescribed medicines are commonly used to treat mental health conditions but are also often implicated in suicide death by poisoning. This was a descriptive study quantifying changes in dispensing and initiation of antidepressants, benzodiazepines, and antipsychotics in the year prior to death by suicide. In this Australian population-based case series, we used national coronial data linked with dispensing claims for all people ≥10 years who died by suicide (2013-2019). Our primary outcome was change in aggregate weekly medicine dispensing the year before death, quantified using piecewise linear regression stratified by cause of death (medicine poisoning vs other causes). Our secondary outcome was change in medicine initiation rates. This study was performed between June 2021 and July2023. Our study included 14,207 people (24% female, median age 44 years). In the year prior to death, we observed higher rates of nervous system medicine use in people who died by medicine poisoning compared with those that did not: antidepressants (62.4% vs 42.9%), benzodiazepines (51.4% vs 29.0%), antipsychotics (25.6% vs 17.1%), opioids (43.8% vs 23.4%). For benzodiazepines, among people who died by medicine poisoning the slope (rate of increase) changed from 0.18 (95% CI-0.01, 0.37) to 4.12 (95% CI 0.98, 7.26) dispensings per 1000 people per week at 8 weeks prior to death. Among people who died of other causes, the slope changed from 0.18 (95% CI 0.14, 0.22) to 2.41 (95% CI 1.90, 2.91) also at 8 weeks prior to death. For antidepressants, among people who died of medicine poisoning we observed no change in the slope. Among people who died of other causes, the slope increased from 0.18 (95% CI 0.09, 0.28) to 1.68 (95% CI 1.20, 2.15) at 14 weeks prior to death. Dispensing of antidepressants and benzodiazepines increased more rapidly closer to date of death, regardless of medicine involvement in death. This suggests these changes may reflect worsening symptoms or increased help seeking and that the method of death by suicide may be due to greater means access. However, findings need to be interpreted with caution as our analyses were performed on aggregate data and may not reflect person-level changes. This study is funded by a grant from the Australian National Health and Medical Research Council (NHMRC) and the Translational Australian Clinical Toxicology Research (TACT) Group.

The impact of temperature on non-typhoidal Salmonella and Campylobacter infections: an updated systematic review and meta-analysis of epidemiological evidence

As temperatures rise, the transmission and incidence of enteric infections such as those caused by Salmonella and Campylobacter increase. This study aimed to review and synthesise the available evidence on the effects of exposure to ambient temperatures on non-typhoidal Salmonella and Campylobacter infections. A systematic search was conducted for peer-reviewed epidemiological studies published between January 1990 and March 2024, in PubMed, Scopus, Embase, and Web of Science databases. Original observational studies using ecological time-series, case-crossover or case-series study designs reporting the association between ambient temperature and non-typhoidal Salmonella and Campylobacter infections in the general population were included. A random-effects meta-analysis was performed to pool the relative risks (RRs) per 1°C temperature increase, and further meta regression, and subgroup analyses by climate zone, temperature metrics, temporal resolution, lag period, and continent were conducted. The Navigation Guide systematic review methodology framework was used to assess the quality and strength of evidence. The study protocol was registered with the International Prospective Register of Systematic Reviews (PROSPERO). Out of 3472 results, 44 studies were included in this systematic review encompassing over one million cases each of Salmonella and Campylobacter infections. Geographically, the 44 studies covered 27 countries across five continents and most of the studies were from high income countries. The meta-analysis incorporated 23 Salmonella studies (65 effect estimates) and 15 Campylobacter studies (24 effect estimates). For each 1°C rise in temperature, the risk of non-typhoidal Salmonella and Campylobacter infections increased by 5% (RR: 1.05, 95% CI: 1.04-1.06), and 5% (RR: 1.05, 95% CI: 1.04-1.07%), respectively, with varying risks across different climate zones. The overall evidence was evaluated as being of "high" quality, and the strength of the evidence was determined to be "sufficient" for both infections. These findings emphasise the relationship between temperature and the incidence of Salmonella and Campylobacter infections. It is crucial to exercise caution when generalising these findings, given the limited number of studies conducted in low and middle-income countries. Nevertheless, the results demonstrate the importance of implementing focused interventions and adaptive measures, such as the establishment of localised early warning systems and preventive strategies that account for climatic fluctuations. Furthermore, our research emphasises the ongoing need for surveillance and research efforts to monitor and understand the changing dynamics of temperature-related enteric infections in the context of climate change. Australian Research Council Discovery Projects grant (ARC DP200102571) Program.

Antimicrobial susceptibility profiles of invasive bacterial infections among children from low- and middle-income countries in the Western Pacific Region (WPRO) – a systematic review and meta-analysis

Antimicrobial resistance increasingly impacts paediatric mortality, particularly in resource-constrained settings. We aimed to evaluate the susceptibility profiles of bacteria causing infections in children from the Western Pacific region. We conducted a systematic review and meta-analysis of bacteria responsible for common infections in children. We included studies published from January 2011 to December 2023 (PROSPERO CRD42021248722). Pooled susceptibilities were evaluated against empiric antibiotics recommended to treat common clinical syndromes. Fifty-one papers met inclusion criteria, incorporating 18,330 bacterial isolates. Of available published data, only six countries from the region were represented. Escherichia coli revealed a pooled susceptibility to ampicillin of 17% (95% CI 12-23%, n=3292), gentamicin 63% (95% CI 59-67%, n=3956), and third-generation cephalosporins 59% (95% CI 49-69%, n=3585). Susceptibility of Klebsiella spp. to gentamicin was 71% (95% CI 61-80%, n=2323), third-generation cephalosporins 35% (95% CI 22-49%, n=2076), and carbapenems 89% (95% CI 78-97%, n=2080). Pooled susceptibility of Staphylococcus aureus to flucloxacillin was 72% (95% CI 58-83%, n=1666), and susceptibility of Streptococcus pneumoniae meningitis isolates to ampicillin was 26% (95% CI 11-44%, n=375), and 63% (95% CI 40-84%, n=246) to third-generation cephalosporins. The burden of antimicrobial resistance among bacteria responsible for common infections in children across the Western Pacific region is significant, and the currently recommended World Health Organization antibiotics to treat these infections may be inefficacious. Strategies to improve the availability of high-quality data to understand the burden of antimicrobial resistance in the region are necessary. The study was supported by an Australian GovernmentNational Health and Medical Research Council Investigator Grant. This research was funded in part by the Wellcome Trust [220211/Z/20/Z]. For the purpose of Open Access, the author has applied a CC BY public copyright licence to any Author Accepted Manuscript version arising from this submission.

Trimodal skin health programme for childhood impetigo control in remote Western Australia (SToP): a cluster randomised, stepped-wedge trial.

Skin infections affect physical health and, through stigma, social-emotional health. When untreated, they can cause life-threatening conditions. We aimed to assess the effect of a holistic, co-designed, region-wide skin control programme on the prevalence of impetigo. The SToP (See, Treat, and Prevent Skin Sores and Scabies) trial is a pragmatic, open-cohort, stepped-wedge cluster randomised trial involving participants aged 0-18 years in nine remote communities of the Kimberley, Western Australia. The trial involves programmatic interventions in three domains: See (skin checks and skin infection recognition training), Treat (skin infection treatment training, sulfamethoxazole-trimethoprim for impetigo, and ivermectin for scabies), and Prevent (co-designed health promotion and environmental health). Four clusters, defined as pragmatic aggregations of communities, were randomised in two steps to progressively receive the activities during ten visits. The primary outcome was the proportion of school-aged children (aged 5-9 years) with impetigo. We adopted an intention-to-treat analysis and compared the intervention with the control (usual care before the start of intervention) states to derive a time and cluster averaged effect using Bayesian modelling. This study is registered with Australian New Zealand Clinical Trials Registry, ACTRN12618000520235. Between Sept 19, 2018, and Nov 22, 2022, 915 children were consented and 777 (85%) had skin checks performed on at least one of ten possible visits between May 5, 2019, and Nov 22, 2022. Of the participants, 448 (58%) of 777 were aged 5-9 years at one or more of the visit timepoints and were eligible for primary outcome assessment. A decline in impetigo occurred across all clusters, with the greatest decline during the observational period of baseline skin checks before commencement of the interventional trial activities activities. The mean (95% credible interval) for the conditional posterior odds ratio for observing impetigo in the intervention compared with the control period was 1·13 (0·71-1·70). The probability that the intervention reduced the odds of observing impetigo was 0·33. A decreased prevalence of impetigo during the observational period before the commencement of trial activities was sustained across the trial, attributable to the trimodal skin health initiative. Although the prevalence of impetigo reduced, there is no direct evidence to attribute this to the individual effects of the trial activities. The wholistic approach inclusive of skin checks collectively contributed to the sustained reduction in impetigo. Western Australia Department of Health, Australian National Health and Medical Research Council, and Healthway.

Survival of men with metastatic hormone-sensitive prostate cancer and adrenal-permissive HSD3B1 inheritance.

BACKGROUNDMetastatic hormone-sensitive prostate cancer (mHSPC) is androgen dependent, and its treatment includes androgen deprivation therapy (ADT) with gonadal testosterone suppression. Since 2014, overall survival (OS) has been prolonged with addition of other systemic therapies, such as adrenal androgen synthesis blockers, potent androgen receptor blockers, or docetaxel, to ADT. HSD3B1 encodes the rate-limiting enzyme for nongonadal androgen synthesis, 3β-hydroxysteroid dehydrogenase-1, and has a common adrenal-permissive missense-encoding variant that confers increased synthesis of potent androgens from nongonadal precursor steroids and poorer prostate cancer outcomes.METHODSOur prespecified hypothesis was that poor outcome associated with inheritance of the adrenal-permissive HSD3B1 allele with ADT alone is reversed in patients with low-volume (LV) mHSPC with up-front ADT plus addition of androgen receptor (AR) antagonists to inhibit the effect of adrenal androgens. HSD3B1 genotype was obtained in 287 patients with LV disease treated with ADT + AR antagonist only in the phase III Enzalutamide in First Line Androgen Deprivation Therapy for Metastatic Prostate Cancer (ENZAMET) trial and was associated with clinical outcomes.RESULTSPatients who inherited the adrenal-permissive HSD3B1 allele had more favorable 5-year clinical progression-free survival and OS when treated with ADT plus enzalutamide or ADT plus nonsteroidal antiandrogen compared with their counterparts who did not have adrenal-permissive HSD3B1 inheritance. HSD3B1 was also associated with OS after accounting for known clinical variables. Patients with both genotypes benefited from early enzalutamide.CONCLUSIONThese data demonstrated an inherited physiologic driver of prostate cancer mortality is associated with clinical outcomes and is potentially pharmacologically reversible.FUNDINGNational Cancer Institute, NIH; Department of Defense; Prostate Cancer Foundation, Australian National Health and Medical Research Council.

Recommendations from the 2024 Australian evidence-based guideline for unexplained infertility: ADAPTE process from the ESHRE evidence-based guideline on unexplained infertility.

The 2024 Australian evidence-based guideline for unexplained infertility provides clinicians with evidence-based recommendations for the optimal diagnostic workup for infertile couples to establish the diagnosis of unexplained infertility and optimal therapeutic approach to treat couples diagnosed with unexplained infertility in the Australian health care setting. The guideline recommendations were adapted for the Australian context from the rigorous, comprehensive European Society of Human Reproduction and Embryology (ESHRE) 2023 Evidence-based guideline: unexplained infertility, using the ADAPTE process and have been approved by the Australian National Health and Medical Research Council. The guideline includes 40 evidence-based recommendations, 21 practice points and three research recommendations addressing: definition - defining infertility and frequency of intercourse, infertility and age, female and male factor infertility; diagnosis - ovulation, ovarian reserve, tubal factor, uterine factor, laparoscopy, cervical/vaginal factor, male factor, additional testing for systemic conditions; and treatment - expectant management, active treatment, mechanical-surgical procedures, alternative therapeutic approaches, quality of life. CHANGES IN ASSESSMENT AND MANAGEMENT RESULTING FROM THE GUIDELINE: This guideline refines the definition of unexplained infertility and addresses basic diagnostic procedures for infertility assessment not considered in previous guidelines on unexplained infertility. For therapeutic approaches, consideration of evidence quality, efficacy, safety and, in the Australian setting, feasibility, acceptability, cost, implementation and ultimately recommendation strength were integrated across multidisciplinary expertise and consumer perspectives in adapting recommendations to the Australian context by using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) framework, which had not been used in past guidelines on unexplained infertility to formulate recommendations. The Australian process also included an established data integrity check to ensure evidence could be trusted to guide practice. Practice points were added and expanded to consider the Australian setting. No evidence-based recommendations were underpinned by high quality evidence, with most having low or very low quality evidence. In this context, research recommendations were made including those for the Australian context. The full guideline and technical report are publicly available online and can be accessed at https://www.monash.edu/medicine/mchri/infertility and are supported by extensive translation resources, including the free patient ASKFertility mobile application (https://www.askfertility.org/).

Exhibiting slavery in Australia: Personal narratives and legacies

AbstractThe history of slavery has often been located on the same continuum as that of incarceration. This article explores the development of an exhibition representing the legacies of slavery in Australia, analysing Australian and international exhibitions alongside theories of museology, historiography and memory. It begins by considering the growth of slavery memory since the latter twentieth century, and Australia's own slavery heritage. The second half of the article focuses on curatorial directions and decisions taken in the exhibition, which our research team is currently developing in partnership with the Australian National Maritime Museum as part of an Australian Research Council project. Much of the project's research to date has been biographical, investigating the lives of individual slavers and colonists to explore colonial and racial frameworks still underpinning contemporary Australia. For the exhibition, we are investigating ways of expanding the scope to represent the lives and experiences of enslaved individuals. We are also exploring the challenges of retracing past lives, the potential limits of empathy, and the politics of ownership when telling stories about the past. This includes considering community participation, the biases and silences of the archives, and the use of art in representing the past.

Primaquine for uncomplicated Plasmodium vivax malaria in children younger than 15 years: a systematic review and individual patient data meta-analysis

Primaquine, the only widely available treatment to prevent relapsing Plasmodium vivax malaria, is produced as 15 mg tablets, and new paediatric formulations are being developed. To inform the optimal primaquine dosing regimen for children, we aimed to determine the efficacy and safety of different primaquine dose strategies in children younger than 15 years. We undertook a systematic review (Jan 1, 2000-July 26, 2024) for P vivax efficacy studies with at least one treatment group that was administered primaquine over multiple days, that enrolled children younger than 15 years, that followed up patients for at least 28 days, and that had data available for inclusion by June 30, 2022. Patients were excluded if they were aged 15 years or older, presented with severe malaria, received adjunctive antimalarials within 14 days of diagnosis, commenced primaquine more than 7 days after starting schizontocidal treatment, had a protocol violation in the original study, or were missing data on age, sex, or primaquine dose. Available individual patient data were collated and standardised. To evaluate efficacy, the risk of recurrent P vivax parasitaemia between days 7 and 180 was assessed by time-to-event analysis for different total mg/kg primaquine doses (low total dose of ∼3·5 mg/kg and high total dose of ∼7 mg/kg). To evaluate tolerability and safety, the following were assessed by daily mg/kg primaquine dose (low daily dose of ∼0·25 mg/kg, intermediate daily dose of ∼0·5 mg/kg, and high daily dose of ∼1 mg/kg): gastrointestinal symptoms (vomiting, anorexia, or diarrhoea) on days 5-7, haemoglobin decrease of at least 25% to less than 7g/dL (severe haemolysis), absolute change in haemoglobin from day 0 to days 2-3 or days 5-7, and any serious adverse events within 28 days. This study is registered with PROSPERO, CRD42021278085. In total, 3514 children from 27 studies and 15 countries were included. The cumulative incidence of recurrence by day 180 was 51·4% (95% CI 47·0-55·9) following treatment without primaquine, 16·0% (12·4-20·3) following a low total dose of primaquine, and 10·2% (8·4-12·3) following a high total dose of primaquine. The hazard of recurrent P vivax parasitaemia in children younger than 15 years was reduced following primaquine at low total doses (adjusted hazard ratio [HR] 0·17, 95% CI 0·11-0·25) and high total doses (0·09, 0·07-0·12), compared with no primaquine. In 525 children younger than 5 years, the relative rates of recurrence were also reduced, with an adjusted HR of 0·33 (95% CI 0·18-0·59) for a low total dose and 0·13 (0·08-0·21) for a high total dose of primaquine compared with no primaquine. The rate of recurrence following a high total dose was reduced compared with a low dose in children younger than 15 years (adjusted HR 0·54, 95% CI 0·35-0·85) and children younger than 5 years (0·41, 0·21-0·78). Compared with no primaquine, children treated with any dose of primaquine had a greater risk of gastrointestinal symptoms on days 5-7 after adjustment for confounders, with adjusted risks of 3·9% (95% CI 0-8·6) in children not treated with primaquine, 9·2% (0-18·7) with a low daily dose of primaquine, 6·8% (1·7-12·0) with an intermediate daily dose of primaquine, and 9·6% (4·8-14·3) with a high daily dose of primaquine. In children with 30% or higher glucose-6-phosphate dehydrogenase (G6PD) activity, there were few episodes of severe haemolysis following no primaquine (0·4%, 95% CI 0·1-1·5), a low daily dose (0·0%, 0·0-1·6), an intermediate daily dose (0·5%, 0·1-1·4), or a high daily dose (0·7%, 0·2-1·9). Of 15 possibly drug-related serious adverse events in children, two occurred following a low, four following an intermediate, and nine following a high daily dose of primaquine. A high total dose of primaquine was highly efficacious in reducing recurrent P vivax parasitaemia in children compared with a low dose, particularly in children younger than 5 years. In children treated with high and intermediate daily primaquine doses compared with low daily doses, there was no increase in gastrointestinal symptoms or haemolysis (in children with 30% or higher G6PD activity), but there were more serious adverse events. Medicines for Malaria Venture, Bill & Melinda Gates Foundation, and Australian National Health and Medical Research Council.

Developing the Society of Obstetric Medicine Australia and New Zealand (SOMANZ) Hypertension in Pregnancy Guideline 2023: Guideline development approaches, challenges and contextual considerations

AbstractThe Society of Obstetric Medicine Australia and New Zealand (SOMANZ) Hypertension in Pregnancy Guideline 2023 is the first evidence‐based guideline for hypertensive disorders of pregnancy that has been developed to the standards of the Australian National Health and Medical Research Council (NHMRC). This article describes the methodology, challenges and considerations in developing the guideline and includes details on group composition, literature search, evidence synthesis and development of recommendations. We also discuss several practical considerations and challenges related to contextual issues, topics of interest and resources available for guideline developers working with similar jurisdictions or topics.

Interventions to reduce harms related to drug use among people who experience incarceration: systematic review and meta-analysis

Mortality, suicide, self-harm, and substance use are elevated among people who are incarcerated. There is a wide range of heterogeneous interventions aimed at reducing these harms in this population. Previous reviews have focused on specific interventions or limited their findings to drug use and recidivism and have not explored interventions delivered after release from prison. Our aim is to examine the effect of interventions delivered to people who use drugs during incarceration or after release from incarceration, on a wide range of outcomes. In this systematic review and meta-analysis, we searched Embase, MEDLINE, and PsycINFO databases up until Sept 12, 2023 for studies published from Jan 1, 1980 onwards. All studies evaluating the effectiveness of any intervention on drug use, recidivism outcomes, sexual or injecting risk behaviours, or mortality among people who use psychoactive drugs and who were currently or recently incarcerated were included. Studies without a comparator or measuring only alcohol use were excluded. Data extracted from each study included demographic characteristics, interventions, and comparisons. Pooled odds ratios and risk ratios were calculated using random-effects meta-analyses. We identified 126 eligible studies (47 randomised controlled trials and 79 observational studies) encompassing 18 interventions; receiving opioid-agonist treatment (OAT) in prison reduced the risk of death in prison (one study; hazard ratio 0·25; 95% CI 0·13-0·48), whereas receiving OAT in the first 4 weeks following release reduced risk of death in the community (two studies; relative risk 0·24; 95% CI 0·15-0·37). Therapeutic community interventions reduced re-arrest at 6-12 months (six studies; odds ratio [OR] 0·72; 95% CI 0·55-0·95) and reincarceration at 24 months (two studies; OR 0·66; 95% CI 0·48-0·96). There was scarce evidence that OAT and syringe service provision are effective in reducing injecting risk behaviours and needle and syringe sharing. There are effective interventions to reduce mortality and recidivism for people who use drugs who have been incarcerated. Nonetheless, there are also substantial gaps in the research examining the effect of interventions on risk behaviours and mortality during incarceration and a need for randomised designs examining outcomes for people who use drugs after release. Australian National Health and Medical Research Council.

Student wellbeing in vertical schools: a multilayered student voice approach for inclusion and influence

AbstractVertical schools are a new type of school in Australia, with little research available to guide designers and school leaders how to address the physical and social challenges that density and interiority add to the students’ schooling experience. As students capably communicate their experiences and perspectives about school spaces for wellbeing, pioneering students in three new vertical schools demonstrated the power of student voice in the Thriving in Vertical Schools project, a 3-year mixed-methods Australian Research Council Linkage project. Young people showed adults how their school spaces enable them to be, feel, and do activities where they feel capable, and how the vertical school environment contributes to wellbeing. Students communicated their voice through multiple layers: the student voice processes (methods), stories with sensory atmospheres (experience), and participating in impactful discussions with adults (action/influence). Adult designers and education leaders were interviewed several weeks after listening to students, identifying how student perspectives had influenced their work. This paper demonstrates how the combination of participatory voice-inclusive methods enabled students to communicate immersive experiences that brought light to interactions for school wellbeing at a level of granularity that adults had not had access to before to influence future designs. This paper argues for the value of attending to student voice and sensitivity in providing choice and options when doing so, so that students are supported to express themselves and their rich experiences in ways of their choosing and ways comfortable to them.

Serum proteomic profiling of physical activity reveals CD300LG as a novel exerkine with a potential causal link to glucose homeostasis

Background:Physical activity has been associated with preventing the development of type 2 diabetes and atherosclerotic cardiovascular disease. However, our understanding of the precise molecular mechanisms underlying these effects remains incomplete and good biomarkers to objectively assess physical activity are lacking.Methods:We analyzed 3072 serum proteins in 26 men, normal weight or overweight, undergoing 12 weeks of a combined strength and endurance exercise intervention. We estimated insulin sensitivity with hyperinsulinemic euglycemic clamp, maximum oxygen uptake, muscle strength, and used MRI/MRS to evaluate body composition and organ fat depots. Muscle and subcutaneous adipose tissue biopsies were used for mRNA sequencing. Additional association analyses were performed in samples from up to 47,747 individuals in the UK Biobank, as well as using two-sample Mendelian randomization and mice models.Results:Following 12 weeks of exercise intervention, we observed significant changes in 283 serum proteins. Notably, 66 of these proteins were elevated in overweight men and positively associated with liver fat before the exercise regimen, but were normalized after exercise. Furthermore, for 19.7 and 12.1% of the exercise-responsive proteins, corresponding changes in mRNA expression levels in muscle and fat, respectively, were shown. The protein CD300LG displayed consistent alterations in blood, muscle, and fat. Serum CD300LG exhibited positive associations with insulin sensitivity, and to angiogenesis-related gene expression in both muscle and fat. Furthermore, serum CD300LG was positively associated with physical activity and negatively associated with glucose levels in the UK Biobank. In this sample, the association between serum CD300LG and physical activity was significantly stronger in men than in women. Mendelian randomization analysis suggested potential causal relationships between levels of serum CD300LG and fasting glucose, 2 hr glucose after an oral glucose tolerance test, and HbA1c. Additionally, Cd300lg responded to exercise in a mouse model, and we observed signs of impaired glucose tolerance in male, but not female, Cd300lg knockout mice.Conclusions:Our study identified several novel proteins in serum whose levels change in response to prolonged exercise and were significantly associated with body composition, liver fat, and glucose homeostasis. Serum CD300LG increased with physical activity and is a potential causal link to improved glucose levels. CD300LG may be a promising exercise biomarker and a therapeutic target in type 2 diabetes.Funding:South-Eastern Norway Regional Health Authority, Simon Fougners Fund, Diabetesforbundet, Johan Selmer Kvanes’ legat til forskning og bekjempelse av sukkersyke. The UK Biobank resource reference 53641. Australian National Health and Medical Research Council Investigator Grant (APP2017942). Australian Research Council Discovery Early Career Award (DE220101226). Research Council of Norway (Project grant: 325640 and Mobility grant: 287198). The Medical Student Research Program at the University of Oslo. Novo Nordisk Fonden Excellence Emerging Grant in Endocrinology and Metabolism 2023 (NNF23OC0082123).Clinical trial number:clinicaltrials.gov: NCT01803568.

Indigenous Early Career Researcher’s Perspectives of ‘safe spaces’’ in Higher Education

The Developing Indigenous Early Career Researchers Project is a three-year longitudinal study funded by the Australian Research Council that ran from January 2020 to December 2022. Its main focus was to investigate the experiences and perspectives of Indigenous Early Career Researchers working in universities across Australia. This article presents four main attributes identified by Indigenous Early Career Researchers as necessary to creating culturally safe spaces in Australian universities. These attributes include, safe to: (a) be Indigenous; (b) seek advice and make mistakes; (c) speak openly; and (d) trust. The successful implementation of these attributes requires institutional support and commitment in the form of relevant higher education policies and practices. Importantly, an overarching perspective of this article is that effective implementation of culturally safe spaces for Indigenous Early Career Researchers requires a significant shift in institutional discourse from the inclusion of Indigenous Peoples and Knowledges to recognising Indigenous Peoples as sovereign.

WILLINGNESS TO RANDOMIZE PATIENTS TO LUMBAR SPINE FUSION SURGERY OR CONSERVATIVE CARE IN THE FORENSIC-UK AND FORENSIC-AUSTRALIA TRIALS

Background and PurposeThe UK's NIHR and Australia's NHMRC have funded two randomised controlled trials (RCTs) to determine if lumbar fusion surgery (LFS) is more effective than best conservative care (BCC) for adults with persistent, severe low back pain (LBP) attributable to lumbar spine degeneration. We aimed to describe clinicians’ decision-making regarding suitability of patient cases for LFS or BCC and level of equipoise to randomise participants in the RCTs.MethodsTwo online cross-sectional surveys distributed via UK and Australian professional networks to clinicians involved in LBP care, collected data on clinical discipline, practice setting and preferred care of five patient cases (ranging in age, pain duration, BMI, imaging findings, neurological signs/symptoms). Clinicians were also asked about willingness to randomise each patient case.ResultsOf 174 responses (73 UK, 101 Australia), 70 were orthopaedic surgeons, 34 neurosurgeons, 65 allied health professionals (AHPs), 5 others. Most worked in public health services only (92% UK, 45% Australia), or a mix of public/private (36% Australia). Most respondents chose BCC as their first-choice management option for all five cases (81–93% UK, 83–91% Australia). For LFS, UK surgeons preferred TLIF (36.4%), whereas Australian surgeons preferred ALIF (54%). Willingness to randomise cases ranged from 37–60% (UK mean 50.7%), and 47–55% (Australian mean 51.9%); orthopaedic and neuro-surgeons were more willing than AHPs.ConclusionWhilst BCC was preferred for all five patient cases, just over half of survey respondents in both the UK and Australia were willing to randomise cases to either LFS or BCC, indicating clinical equipoise (collective uncertainty) needed for RCT recruitment.Conflicts of interestNoneSources of fundingNo specific funding obtained for the surveys. DB, SA, AG and NEF have funding from the National Institute for Health Research (NIHR) UK (FORENSIC-UK NIHR134859); NEF, DB and SA have funding from the Australian National Health and Medical Research Council (NHMRC FORENSIC-Australia GA268233). AG has funding from Orthopaedic Research UK (combined with British Association of Spine Surgeons and British Scoliosis Society) and Innovate UK. NEF is funded through an Australian National Health and Medical Research Council (NHMRC) Investigator Grant (ID: 2018182).

The association of adverse birth outcomes with flood exposure before and during pregnancy in Australia: a cohort study

Exposure to floods might increase the risks of adverse birth outcomes. However, the current evidence is scarce, inconsistent, and has knowledge gaps. This study aims to estimate the associations of flood exposure before and during pregnancy with adverse birth outcomes and to identify susceptible exposure windows and effect modifiers. In this cohort study, we obtained all the birth records occurring in Greater Sydney, Australia, from Jan 1, 2001, to Dec 31, 2020, from the New South Wales Midwives Data Collection and in the Brisbane metropolitan region, Australia, from Jan 1, 1995, to Dec 31, 2014, from the Queensland Health Perinatal Data Collection. For each birth, residential address and historical flood information from the Dartmouth Flood Observatory were used to estimate the numbers of days with floods during five exposure windows (Pre-1 was defined as 13-24 weeks before the last menstrual period [LMP], Pre-2 was 0-12 weeks before the LMP, trimester 1 [Tri-1] was 0-12 weeks after the LMP, trimester 2 [Tri-2] was 13-28 weeks after the LMP, and trimester 3 [Tri-3] was ≥29 weeks after the LMP). We estimated the hazard ratios (HRs) of adverse birth outcomes (preterm births, stillbirths, term low birthweight [TLBW], and small for gestational age [SGA]) associated with flood exposures in the five exposure windows using Cox proportional hazards regression models. 1 338 314 birth records were included in our analyses, which included 91 851 (6·9%) preterm births, 9831 (0·7%) stillbirths, 25 567 (1·9%) TLBW, and 108 658 (8·1%) SGA. Flood exposure in Pre-1 was associated with increased risks of TLBW (HR 1·06 [95% CI 1·01-1·12]) and SGA (1·04 [1·01-1·06]); flood exposure during Tri-1 was associated with increased risks of preterm births (1·03 [1·002-1·05]), stillbirth (1·11 [1·03-1·20]), and SGA (1·03 [1·01-1·06]). In contrast, flood exposures during Pre-2 and Tri-3 were associated with reduced risks. Exposures to floods in Pre-1 and Tri-1 are both associated with increased risks of adverse birth outcomes, and the risks increase with a higher exposure. Upon planning for conception and prenatal care, individuals and health practitioners should raise awareness of the increased risks of adverse birth outcomes after experiencing floods. The Australian Research Council and the Australian National Health and Medical Research Council.

Conditional loss of Brca1 in oocytes causes reduced litter size, ovarian reserve depletion and impaired oocyte in vitro maturation with advanced reproductive age in mice

An estimated 1 in 350 women carry germline BRCA1/2 mutations, which confer an increased risk of developing breast and ovarian cancer, and may also contribute to subfertility. All mature, sex steroid-producing ovarian follicles are drawn from the pool of non-renewable primordial follicles, termed the 'ovarian reserve'. The clinical implications of early ovarian reserve exhaustion extend beyond infertility, to include the long-term adverse health consequences of loss of endocrine function and premature menopause. We aimed to determine whether conditional loss of Brca1 in oocytes impacts ovarian follicle numbers, oocyte quality and fertility in mice with advancing maternal age. We also aimed to determine the utility of AMH as a marker of ovarian function, by assessing circulating AMH levels in mice and women with BRCA1/2 mutations, and correlating this with ovarian follicle counts. In this study, we addressed a longstanding question in the field regarding the functional consequences of BRCA1 inactivation in oocytes. To recapitulate loss of BRCA1 protein function in oocytes, we generated mice with conditional gene deletion of Brca1 in oocytes using Gdf9-Cre recombinase (WT: Brca1fl/flGdf9+/+; cKO: Brca1fl/flGdf9cre/+). While the length of the fertile lifespan was not altered between groups after a comprehensive breeding trial, conditional loss of Brca1 in oocytes led to reduced litter size in female mice. Brca1 cKO animals had a reduced ovarian reserve and oocyte maturation was impaired with advanced maternal age at postnatal day (PN)300, compared to WT animals. Serum anti-Müllerian hormone (AMH) concentrations (the gold-standard indirect marker of the ovarian reserve used in clinical practice) were not predictive of reduced primordial follicle number in Brca1 cKO mice versus WT. Furthermore, we found no correlation between follicle number or density and serum AMH concentrations in matched samples from a small cohort of premenopausal women with BRCA1/2 mutations. Together, our data demonstrate that BRCA1 is a key regulator of oocyte number and quality in females and suggest that caution should be used in relying on AMH as a reliable marker of the ovarian reserve in this context. This work was made possible through Victorian State Government Operational Infrastructure Support and Australian Government NHMRC IRIISS. This work was supported by funding from the Australian Research Council (ALW - DE21010037 and KJH - FT190100265), as well as the National Breast Cancer Foundation (IIRS-22-092) awarded to ALW and KJH. LRA, YML, LT, EOKS and MG were supported by Australian Government Research Training Program Scholarships. LRA, YML and LT were also supported by a Monash Graduate Excellence Scholarship. YC, SG and XC were supported by Monash Biomedicine Discovery Institute PhD Scholarships. LRA was also supported by a Monash University ECPF24-6809920940 Fellowship. JMS was supported by NHMRC funding (2011299). MH was supported by an NHMRC Investigator Grant (1193838).

Reading the Creative Industries With Deleuze: How Creative Are the Creative Industries?

This article develops a definition of creativity that is informed by the work of Gilles Deleuze, Dan Harris, Susan Luckman, and others. We explore its application in the context of the creative industries in Australia. Through our empirical interviews conducted as part of an Australian Research Council–funded project called Vital Arts, we delve into the multifaceted nature of creativity, which we argue is not always accounted for in the bureaucratic organization, categorization, and funding of the creative industries. We outline the measurements used by key governmental, nongovernmental, and policymaking bodies in Australia to categorize and fund the creative industries. These metrics reveal blind spots in how the creative industries are institutionally organized and treated when considering the Deleuzian ontology of creativity that actually motors creative work. We argue that many creative jobs and industries exist outside traditional bureaucratic definitions and categories, and through the concepts of affect, becoming, the major and the minor, as well as fabulation, from Deleuze and Guattari’s philosophy, we explore these dynamics further.

The nasopharyngeal microbiome in South African children with lower respiratory tract infection: a nested case-control study of the Drakenstein Child Health Study.

Lower respiratory tract infection (LRTI) is a leading cause of infant morbidity and mortality globally. LRTI may be caused by viral or bacterial infections, individually or in combination. We investigated associations between LRTI and infant nasopharyngeal (NP) viruses and bacteria in a South African birth cohort. In a case-control study of infants enrolled in the Drakenstein Child Health Study (DCHS), LRTI cases were identified prospectively and age-matched with controls from the cohort. NP swabs were tested using quantitative real-time polymerase chain reaction (qPCR) and 16S rRNA gene amplicon sequencing. We calculated adjusted Conditional Odds Ratios (aORs) for qPCR targets and used mixed effects models to identify differentially abundant taxa between LRTI cases and controls and explore viral-bacterial interactions. Respiratory Syncytial Virus (RSV) [aOR: 5.69, 95% CI: 3.03-10.69], human rhinovirus (HRV) [1.47, 1.03-2.09], parainfluenza virus [3.46, 1.64-7.26], adenovirus [1.99, 1.08-3.68], enterovirus [2.32, 1.20-4.46], Haemophilus influenzae [1.72, 1.25-2.37], Klebsiella pneumoniae [2.66, 1.59-4.46], or high-density (> 6.9 log10 copies/mL) Streptococcus pneumoniae [1.53, 1.01-2.32] were associated with LRTI. Using 16S sequencing, LRTI was associated with increased relative abundance of Haemophilus (q = 0.0003) and decreased relative abundance of Dolosigranulum (q = 0.001), Corynebacterium (q = 0.091) and Neisseria (q = 0.004). In samples positive for RSV, Staphylococcus and Alloprevotella were present at lower relative abundance in cases than controls. In samples positive for parainfluenza virus or HRV, Haemophilus was present at higher relative abundance in cases. The associations between bacterial taxa and LRTI are strikingly similar to those identified in high-income countries, suggesting a conserved phenotype. RSV was the major virus associated with LRTI. H. influenzae appears to be the major bacterial driver of LRTI, acting synergistically with viruses. The Gram-positive bacteria Dolosigranulum and Corynebacteria may protect against LRTI, while Staphylococcus was associated with reduced risk of RSV-related LRTI. National Institutes of Health of the USA, Bill and Melinda Gates Foundation, National Research Foundation South Africa, South African Medical Research Council, L'Oréal-UNESCO For Women in Science South Africa, Australian National Health and Medical Research Council.

First Australian estimates of incidence and prevalence of uterine fibroids: a data linkage cohort study 2000-2022.

What is the estimated prevalence and incidence of uterine fibroids diagnosed in Australian women of reproductive age? An estimated 7.3% of Australian women had a diagnosis of uterine fibroids by the age of 45-49 years, with age-specific incidence highest in women aged 40-44 years (5.0 cases per 1000 person-years). Uterine fibroids are associated with a high symptom burden and may affect overall health and quality of life. Studies in different countries show a wide variation in both the prevalence (4.5-68%) and incidence (2.2-37.5 per 1000 person-years) of uterine fibroids, which may be partly explained by the type of investigation, method of case ascertainment, or the age range of the study population, necessitating the reporting of country-specific estimates. This observational prospective cohort study using self-report survey and linked administrative data (2000-2022) included 8066 women, born between 1973 and 1978, in the Australian Longitudinal Study on Women's Health. A combination of self-report survey and linked administrative health data (hospital, emergency department, the Medicare Benefits Schedule, and the Pharmaceutical Benefits Scheme) were used to identify women with a report of a diagnosis of uterine fibroids between 2000 and 2022. Of the 8066 Australian women followed for 22 years, an estimated 7.3% of women (95% CI 6.9, 7.6) had a diagnosis of uterine fibroids by the age of 45-49 years. The incidence increased with age and was highest in women aged 40-44 years (5.0 cases per 1000 person-years, 95% CI 4.3, 5.7 cases per 1000 person-years). Women with uterine fibroids were more likely to experience heavy or painful periods. They were also more likely to report low iron levels, endometriosis, and poor self-rated health and to have two or more annual visits to their general practitioner. Our estimates are based on self-report of doctor diagnosis or treatment for fibroids and/or data linked to treatment and procedure administrative records. This predominantly captures women with symptomatic fibroids, but has the potential for misclassification of asymptomatic women and an underestimate of overall prevalence and incidence. In addition, questions on fibroids were only asked in surveys when women were 37-42 years of age to 43-48 years of age, so cases at younger ages may have been underestimated (particularly in women with less severe symptoms) as these were only ascertained through data linkage. These are the first population-based estimates of the prevalence and incidence of uterine fibroids in women of reproductive age in Australia. Establishing these first estimates will help inform health policy and health care provision in the Australian context. The ALSWH is funded by the Australian Government Department of Health and Aged Care. L.FW. was supported by an Australian National Health and Medical Research Council (NHMRC) Centres for Research Excellence grant (APP1153420) and G.D.M. was supported by an NHMRC Leadership Fellowship (APP2009577). The funding bodies played no role in the design, the collection, analysis or interpretation of data, the writing of the manuscript, or the decision to submit the manuscript for publication. There are no competing interests. N/A.

The prevalence of gambling and problematic gambling: a systematic review and meta-analysis

Gambling behaviours have become of increased public health interest, but data on prevalence remain scarce. In this study, we aimed to estimate for adults and adolescents the prevalence of any gambling activity, the prevalence of engaging in specific gambling activities, the prevalence of any risk gambling and problematic gambling, and the prevalence of any risk and problematic gambling by gambling activity. We performed a systematic review and meta-analysis. We systematically searched for peer-reviewed literature (on MEDLINE, Embase, and PsycInfo) and grey literature to identify papers published between Jan 1, 2010, and March 4, 2024. We searched for any gambling, including engagement with individual gambling activities, and problematic gambling data among adults and adolescents. We included papers that reported the prevalence or proportion of a gambling outcome of interest. We excluded papers of non-original data or based on a biased sample. Data were extracted into a bespoke Microsoft Access database, with the Joanna Briggs Institute Critical Appraisal Tool used to identify the risk of bias for each sample. Representative population survey estimates were firstly meta-analysed into country-level prevalence estimates, using metaprop, of any gambling, any risk gambling, problematic gambling, and by gambling activity. Secondly, population-weighted regional-level and global estimates were generated for any gambling, any risk gambling, problematic gambling, and specific gambling activity. This review is registered on PROSPERO (CRD42021251835). We screened 3692 reports, with 380 representative unique samples, in 68 countries and territories. Overall, the included samples consisted of slightly more men or male individuals, with a mean age of 29·72 years, and most samples identified were from high-income countries. Of these samples, 366 were included in the meta-analysis. Globally, 46·2% (95% CI 41·7-50·8) of adults and 17·9% (14·8-21·2) of adolescents had gambled in the past 12 months. Rates of gambling were higher among men (49·1%; 45·5-52·6) than women (37·4%; 32·0-42·5). Among adults, 8·7% (6·6-11·3) were classified as engaging in any risk gambling, and 1·41% (1·06-1·84) were engaging in problematic gambling. Among adults, rates of problematic gambling were greatest among online casino or slots gambling (15·8%; 10·7-21·6). There were few data reported on any risk and problematic gambling among adolescent samples. Existing evidence suggests that gambling is prevalent globally, that a substantial proportion of the population engage in problematic gambling, and that rates of problematic gambling are greatest among those gambling on online formats. Given the growth of the online gambling industry and the association between gambling and a range of public health harms, governments need to give greater attention to the strict regulation and monitoring of gambling globally. Australian National Health and Medical Research Council.