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Objective: This study investigated the association between gait speed, handgrip strength, and their combination, and the risk for developing clinically relevant depressive symptoms in community-dwelling older adults., Methods: A secondary analysis was conducted using data from the ASPirin in Reducing Events in the Elderly study. Participants were community-dwelling older adults in Australia and the United States of America followed for a median (interquartile range) of 3.97 (2.26) years. Baseline handgrip strength and gait speed were used as exposure variables, and their combination categories were also explored. Depression was measured using the modified Center for Epidemiological Studies Depression 10-item scale (CES-D 10). Cox regression was used to estimate Adjusted Hazard Ratios (AHR) with 95 % Confidence Intervals (CI) after adjusting for a range of potential confounders., Result: A total of 17,231 participants (55.3 % women) were included in the analysis. Slow gait and weak grip at baseline were associated with the risk of depression (AHR: 1.20; CI: 1.11-1.29 and 1.14; 1.06-1.23, respectively). The combination of the two physical performance measures was associated with a 31 % increase in the risk of depression (1.31; 1.16-1.47) and a significant dose-response association was observed for quintiles of gait and grip with depression., Limitations: Although the CES-D 10 is a validated scale, it is a self-reported tool rather than a clinical diagnosis of depression., Conclusion: Low physical function may be a risk factor for depression in older adults. This highlights the inextricable link between the physical and mental health of older adults, which can inform potential clinical and public health prevention strategies for depression in later life., Competing Interests: Declaration of competing interest TC has received honoraria for lectures from Roche. The authors declare no conflicts of interest., (Crown Copyright © 2024. Published by Elsevier B.V. All rights reserved.)

Autism is a rapidly growing phenomenon, with rates of diagnosed autism in the community rising every decade. Autism and traits of autism are also regularly part of presentation at youth mental health services, including early psychosis services. In early psychosis services young people's symptoms tend to be formulated through a psychosis lens, rather than a neurodevelopmental lens which can lead to unnecessary medicalised treatment, and treatment plans that do not consider the possible impact of neurodiversity. The following paper explores autism and traits of autism in relation to youth early psychosis, examining the complexity in accurate formulation, and the possible impacts for young people. Future directions for how services can address this issue and more effectively tailor treatment to young people are also discussed., Competing Interests: Declarations. Conflict of interest: No conflicts of interest were held by any member of the research team., (© 2025. The Author(s).)

Objectives: Workers in the stone benchtop industry in Australia are at high risk of silicosis due to exposure to respirable crystalline silica (RCS) from the dry processing of artificial stone. In Victoria, Australia, a multifaceted response including education, regulatory changes, inspection site visits, and occupational health screening programme began in 2019. We aimed to review the success of this approach to safety practices in the industry., Methods: Data were available from 2 sources: first, responses provided by workers during their occupational health screening (2019 to 2024), which included a systematic occupational history. Jobs examined included roles in the stone benchtop industry with RCS exposure and were analysed in relation to reported safety practices pre and postregulatory changes in August 2019, which prohibited unrestricted dry cutting. Second, data were obtained from the Regulator describing the numbers of visits to industry worksites and the numbers and types of compliance notices issued between 2018 and 2024., Results: In total, 1921 jobs from 1007 workers were eligible for analysis, of which 869 were prior to the 2019 regulatory change and 557 commenced after. The proportion of workers reporting "never" dry cutting rose from 17.3% to 67.2% (P < 0.001), use of recommended ventilation and respirator increased from 26.0% to 36.5% (P < 0.001), and 44.9% to 86.5% (P < 0.001), respectively. Of the 543 worksites visited (2757 site visits in total), 352 (64.8%) received at least one compliance notice and the types of notices varied over time. Administrative controls/housekeeping and health monitoring notices were the most common in 2019 to 2021 but tools/equipment notices increased substantially in 2022 onwards., Discussion: Prior to the changes, a large proportion of jobs involved unrestricted dry processing of artificial stone with inadequate protection. After the changes, practices improved although some jobs continued to involve dry processing without adequate control of dust., Conclusions: This multifaceted approach vastly improved safety practices in the stone benchtop industry over 5 years. These data are relevant to occupational health and safety professionals and regulators in countries where artificial stone is used and potentially for implementation of new measures in response to a new workplace hazard in future., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Occupational Hygiene Society.)

Background: Non-invasive ventilation (NIV) uses positive pressure to assist people with respiratory muscle weakness or severe respiratory compromise to breathe. Most people use this treatment during sleep when breathing is most susceptible to instability. The benefits of using NIV in motor neurone disease (MND) are well-established. However, uptake and usage are low (~ 19%) and there is no consensus on how to best implement NIV in MND in Australia. Consequently, clinical practice models are highly variable. Our team has recently provided evidence that specific and individualised NIV titration using a sleep study (polysomnography; PSG) leads to better outcomes in people with MND. However, for this clinical practice model to result in sustained benefits, evidence of effectiveness across multiple sites, as well as culture and practice change, must occur., Methods: A two-arm, assessor-blinded, individual participant randomised controlled trial in MND care centres across Australia will be undertaken. Two-hundred and forty-four participants will be randomised (1:1) to either the intervention group (PSG-assisted commencement of NIV settings; PSG) or a control group (sham PSG). Participants will be asked to use their NIV device for 7 weeks and will then return for follow-up assessments. Respiratory, sleep and patient-reported outcome measures will be collected at baseline and follow-up. The primary aim is to determine if the proportion of participants using NIV for > 4 h/day during the intervention period is higher in the PSG than the control group. A process evaluation, health economic evaluation and 12-month cohort follow-up will be undertaken and reported separately., Discussion: The results of this trial will demonstrate the effects of PSG-assisted titration of NIV on usage of NIV in people with MND. We hypothesise that the PSG intervention will improve synchrony between the user and the machine, which will lead to greater NIV usage compared to the control group., Trial Registration: ClinicalTrials.gov NCT05136222. Registered on November 25, 2021., Competing Interests: Declarations. Ethics approval and consent to participate: Ethical approval for all sites has been granted by Austin Health Human Research Ethics Committee (HREC/68088/Austin-2021). Written, informed consent to participate will be obtained from all participants. Any proposed amendments to the project including any changes to the protocol, Participant Information and Consent Form/s, agreed upon by the Trial Steering Committee, will be submitted to the reviewing HREC for approval prior to implementation. These changes will be communicated to the trial participants by members of the research team and re-consent for participation in the research will be collected if required. Consent for publication: Not applicable—no identifying images or other personal or clinical details of participants are presented here or will be presented in reports of the trial results. Competing interests: The authors declare that they have no competing interests., (© 2025. The Author(s).)

With the rising prevalence of type 2 diabetes mellitus (T2DM) and obesity, several previously under-recognised complications associated with T2DM are becoming more evident. The most common of these emerging complications are metabolic dysfunction-associated steatotic liver disease (MASLD), cancer, dementia, sarcopenia, and frailty, as well as other conditions involving the lung, heart, and intestinal tract. Likely causative factors are chronic inflammation and insulin resistance, whereas blood glucose levels appear to play a lesser role. We discuss these complications and the new approaches being developed to prevent and manage them, especially incretin-based therapies. We argue that these new interventions may work in a complementary way to other proven cardiorenal protective therapies to reduce the burden of T2DM complications., Competing Interests: Declaration of interests A.W.R. reports speaker honoraria from Boehringer-Ingelheim and Astra Zeneca paid to a University research account. S.T. reports grant support from the Medical Research Future Fund (MRFF) Cardiovascular Health Mission paid to Monash University, and travel and meeting support from Monash University Cardiovascular Research and Education in Therapeutics (CCRET), all independently of this work. S.Z. has received payment to Monash University from Eli Lilly Australia, Boehringer-Ingelheim, CSL Sequiris, AstraZeneca, Novo Nordisk, Sanofi, and Moderna for consultancy work and travel, and accommodation support from Eli Lilly and Novo Nordisk as well as funding from the National Health and Medical Research Council (NHMRC), the Australian Government Department of Health and Aged Care, the Juvenile Diabetes Research Foundation (JDRF) Centre of Excellence, and the MRFF, all independently of this work. P.S.H. declares no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

We extend existing techniques by using generative adversarial network (GAN) models to reduce the appearance of cast shadows in radiographs across various age groups. We retrospectively collected 11,500 adult and paediatric wrist radiographs, evenly divided between those with and without casts. The test subset consisted of 750 radiographs with cast and 750 without cast. We extended the results from a previous study that employed CycleGAN by enhancing the model using a perceptual loss function and a self-attention layer. The CycleGAN model which incorporates a self-attention layer and perceptual loss function delivered a similar quantitative performance as the original model. This model was applied to images from 20 cases where the original reports recommended CT scanning or repeat radiographs without the cast, which were then evaluated by radiologists for qualitative assessment. The results demonstrated that the generated images could improve radiologists' diagnostic confidence, in some cases leading to more decisive reports. Where available, the reports from follow-up imaging were compared with those produced by radiologists reading AI-generated images. Every report, except two, provided identical diagnoses as those associated with follow-up imaging. The ability of radiologists to perform robust reporting with downsampled AI-enhanced images is clinically meaningful and warrants further investigation. Additionally, radiologists were unable to distinguish AI-enhanced from unenhanced images. These findings suggest the cast suppression technique could be integrated as a tool to augment clinical workflows, with the potential benefits of reducing patient doses, improving operational efficiencies, reducing delays in diagnoses, and reducing the number of patient visits., Competing Interests: Declarations. Ethics Approval: This study was exempt from Human Research Ethics Committee review as a retrospective quality improvement project. It was consistent with the NHMRC Ethical Considerations in Quality Assurance and Evaluation Activities (2014) guideline. Consent to Participate: Not applicable. Consent for Publication: Not applicable. Competing Interests: The authors declare no competing interests., (© 2024. The Author(s) under exclusive licence to Society for Imaging Informatics in Medicine.)

Background and Aims: The optimal revascularization strategy in patients with ischaemic cardiomyopathy remains unclear with no contemporary randomized trial data to guide clinical practice. This study aims to assess long-term survival in patients with severe ischaemic cardiomyopathy revascularized by either coronary artery bypass grafting (CABG) or percutaneous coronary intervention (PCI)., Methods: Using the Australian and New Zealand Society of Cardiac and Thoracic Surgeons and Melbourne Interventional Group registries (from January 2005 to 2018), patients with severe ischaemic cardiomyopathy [left ventricular ejection fraction (LVEF) <35%] undergoing PCI or isolated CABG were included in the analysis. Those with ST-elevation myocardial infarction and cardiogenic shock were excluded. The primary outcome was long-term National Death Index-linked mortality up to 10 years following revascularization. Risk adjustment was performed to estimate the average treatment effect using propensity score analysis with inverse probability of treatment weighting (IPTW)., Results: A total of 2042 patients were included, of whom 1451 patients were treated by CABG and 591 by PCI. Inverse probability of treatment weighting-adjusted demographics, procedural indication, coronary artery disease extent, and LVEF were well balanced between the two patient groups. After risk adjustment, patients treated by CABG compared with those treated by PCI experienced reduced long-term mortality [adjusted hazard ratio 0.59, 95% confidence interval (CI) 0.45-0.79, P = .001] over a median follow-up period of 4.0 (inter-quartile range 2.2-6.8) years. There was no difference between the groups in terms of in-hospital mortality [adjusted odds ratio (aOR) 1.42, 95% CI 0.41-4.96, P = .58], but there was an increased risk of peri-procedural stroke (aOR 19.6, 95% CI 4.21-91.6, P < .001) and increased length of hospital stay (exponentiated coefficient 3.58, 95% CI 3.00-4.28, P < .001) in patients treated with CABG., Conclusions: In this multi-centre IPTW analysis, patients with severe ischaemic cardiomyopathy undergoing revascularization by CABG rather than PCI showed improved long-term survival. However, future randomized controlled trials are needed to confirm the effect of any such benefits., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Purpose: Self-awareness is a multifaceted phenomenon that comprises two main concepts: general awareness and online awareness. The latter is an emerging concept that requires further consensus on its definition. The aim of this paper is to define the key components of online awareness and identify approaches for measuring this concept for adults with neurological conditions., Materials and Methods: Concept analysis using Rodgers' evolutionary method was used to systematically review and summarise relevant literature. Papers were included if they provided a definition of online awareness or method for assessing online awareness for an adult neurological population., Results: Fifty-six papers were included in this review, with 21 online awareness assessment approaches identified. Online awareness was described to occur within the context of task performance, with the definition framework comprising four main aspects: 1/appraisal; 2/anticipation and prediction; 3/monitoring; and 4/self-evaluation. Self-regulation is a related concept that is considered to sit outside the conceptual boundaries of online awareness., Conclusions: The findings of this analysis highlight the complexity of online awareness and its importance in rehabilitation. Psychometrically robust measures of online awareness that are inclusive of the essential elements of this concept are needed to advance practice in this area.

Background: There is plenty of evidence supporting the clinical benefits of mHealth interventions for type 2 diabetes, but despite often being promoted as cost-effective or cost-saving, there is still limited research to support such claims. The objective of this review was to summarize and critically analyze the current body of economic evaluation (EE) studies for mHealth interventions for type 2 diabetes., Methods: Using a comprehensive search strategy, five databases were searched for full and partial EE studies for mHealth interventions for type 2 diabetes from January 2007 to March 2022. "mHealth" was defined as any intervention that used a mobile device with cellular technology to collect and/or provide data or information for the management of type 2 diabetes. The CHEERS 2022 checklist was used to appraise the reporting of the full EEs., Results: Twelve studies were included in the review; nine full and three partial evaluations. Text messages smartphone applications were the most common mHealth features. The majority of interventions also included a Bluetooth-connected medical device, eg, glucose or blood pressure monitors. All studies reported their intervention to be cost-effective or cost-saving, however, most studies' reporting were of moderate quality with a median CHEERS score of 59%., Conclusion: The current literature indicates that mHealth interventions for type 2 diabetes can be cost-saving or cost-effective, however, the quality of the reporting can be substantially improved. Heterogeneity makes it difficult to compare study outcomes, and the failure to report on key items leaves insufficient information for decision-makers to consider., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: The occurrence and sequelae of acute myocardial infarction (AMI) in major trauma patients is underexplored across both trauma and cardiology specialties. Coronary reperfusion greatly reduces the risk of significant morbidity and mortality in AMI. However, in patients presenting with significant injuries, concurrent AMI presents a competing management priority given the increase in risk of bleeding with standard anticoagulation and antiplatelet therapy, which may be contraindicated. This study aimed to evaluate the epidemiology and clinical outcomes associated with AMI in a contemporary major trauma cohort., Methods: This study used data from the Victorian State Trauma Registry (VSTR). All adult patients with major trauma from 1 January 2013 to 31 December 2022 were included. Patients that died prior to hospital arrival were excluded. AMI was identified by ICD-10-AM diagnosis codes recorded against the first hospital admission. Clinical outcomes included in-hospital mortality, length of stay, and discharge destination., Results: 28,928 patients were identified over the 10-year study period. AMI occurred in 401 patients (1.4 %). AMI patients were older, had more comorbidities and were more frequently on anticoagulation or antiplatelet therapy. Low impact fall was the most common trauma mechanism in AMI patients. Patients with AMI experienced longer hospital stays (12 [7-20] versus 7 [4-12] days, p < 0.001) and higher rates of in-hospital mortality (adjusted RR 1.45, 95 % CI 1.25-1.65)., Conclusion: AMI in the setting of major trauma occurs in an older, more comorbid, and vulnerable group of patients. AMI is associated with an increased risk of in-hospital mortality and prolonged hospital stay in the setting of major trauma, underscoring the importance of identifying and treating major trauma associated AMI in a timely and effective manner., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Crown Copyright © 2024. Published by Elsevier Ltd. All rights reserved.)

Purpose: To evaluate the implementation of a self-management program, My Therapy, designed to increase inpatient rehabilitation therapy dosage via independent practice., Materials and Methods: A process evaluation of My Therapy for adult patients admitted for rehabilitation for any condition supervised by physiotherapists and occupational therapists across eight rehabilitation wards compared usual care. Outcomes included reach , dosage , fidelity and adaptation., Results: The mean (SD) age of the process evaluation sample ( n  = 123) was 73 (11) years with a mean (SD) length of stay of 14.0 (6.6) days. The My Therapy program reached 68% of participants ( n  = 632/928), and resulted in an average increase in therapy dosage of 26 (95% CI 12 to 40) minutes/day of independent practice. All My Therapy audited programs ( n  = 28) included body function/structure impairment-based exercises, and half ( n  = 13/28) included activity/participation-based exercises. On average, participants completed programs 1.8 (SD 1.2) times/day, which were prescribed in accordance with the My Therapy criteria, demonstrating fidelity . There were no between-group differences in daily steps or standing time, however, My Therapy participants spent more time sitting ( p  ≤ 0.05). Implementation adaptations were minimal., Conclusion: A self-management rehabilitation program was implemented with fidelity for two in three rehabilitation patients, resulting in increased therapy dosage with minimal adaptations.

Objectives: The EuroQol 5D five level (EQ-5D-5L) instrument is a standardized measure of health-related quality of life and is routinely used in survivors of critical illness. However, information on its psychometric properties and minimal clinically important difference (MCID) in this patient group is lacking., Design: Secondary analysis of data from the previously published PREDICT (a registry in critically ill patients to determine predictors of disability-free survival) study, a prospective, multicenter cohort study., Setting: Six ICUs in the state of Victoria, Australia., Patients: Four hundred fifty adult patients admitted to the ICU and ventilated for over 24 hours., Interventions: None., Measurements and Main Results: The EQ-5D-5L was administered by telephone at 6 months following ICU admission. Internal consistency (inter-item correlations, Cronbach's α, and split-half reliability coefficients), construct validity (against age, body mass index, and other outcome measures), responsiveness (observing change over time and effect sizes), percentage of participants presenting no change, and MCID (triangulation of distribution-based and anchor-based estimates) were evaluated. The EQ-5D-5L showed high internal consistency, Cronbach α coefficients of 0.82 (between dimensions) and 0.79 (between the EuroQol-Visual Analogue Scale [EQ-VAS] and utility score), and average split-half coefficients of 0.79 each (between dimensions and between EQ-VAS and utility score). Construct validity was confirmed with a strong correlation between the EQ-5D-5L and the World Health Organization Disability Assessment Schedule 2.0 (EQ-VAS: r = 0.72; p < 0.001 and utility score: r = 0.81; p < 0.001). Effect sizes for change over time for EQ-VAS and utility score were low. The final MCID estimates were 10 (EQ-VAS) and 0.11 (utility score)., Conclusions: The EQ-5D-5L, using the Australian value set, demonstrated evidence of good internal consistency and validity, but poor responsiveness in a critically ill population., Competing Interests: Ms. De Silva disclosed that PREDICT study received funding from the National Health and Medical Research Council of Australia (GNT1132976). Dr. Higgins’ institution received funding from the National Health and Medical Research Council (NHMRC; GNT2008447); she received support for article research from the NHMRC. Professor Hodgson received funding from the NHMRC (GNT1173271). The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2024 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.)

Background and Purpose: Neoadjuvant stereotactic radiosurgery (NaSRS) is an emerging treatment option for brain metastases (BrM) planned for resection. The aim of this study was to report on the efficacy and safety of NaSRS in an individual patient data pooled analysis., Materials and Methods: Patients undergoing single- and multi-fraction NaSRS for BrM at nine institutions in five countries (Australia, Canada, South Korea, Switzerland and USA) were included. Eligibility criteria included BrM from any primary malignancy and no prior local therapy. The primary endpoint was a composite of local recurrence (LR), any grade radionecrosis (RN), and/or nodular leptomeningeal disease (nLMD). Secondary endpoints included these endpoints and Grade ≥ 2 RN. Endpoints were evaluated using cumulative incidence functions., Results: NaSRS was delivered to 179 patients with 189 BrM. Median follow-up was 28.4 months. Primary malignancies included non-small cell lung carcinoma (44 %) and melanoma (17 %). The median BrM diameter was 29 mm (IQR 21-36 mm). Single- and multi-fraction NaSRS was utilised in 100 (53 %) and 89 BrM (47 %) respectively. The median single-fraction dose was 18 Gy (IQR 16-20 Gy). Multi-fraction doses included 24 Gy in three fractions (55 %) and 27 Gy in three fractions (25 %). The 12-month incidence for the composite endpoint was 8.0 %. The 12-month incidence of LR was 4.6 %, any grade RN was 3.6 %, Grade ≥ 2 RN was 1.8 % and nLMD was 1.2 %., Conclusion: Neoadjuvant SRS results in favourable rates of LR, RN and nLMD. We provide a global experience of this treatment approach with long-term data and the largest cohort of patients undergoing multi-fraction SRS., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Given the introduction of new advanced therapies for inflammatory bowel diseases (IBDs), expanded risk mitigation strategies are essential., Aims: To create a comprehensive set of statements on assessment procedures and vaccinations before starting monoclonal antibodies, Janus kinase (JAK) inhibitors or sphingosine-1-phosphate (S1P) modulators for IBD., Methods: We examined literature, guidelines and drug product information regarding vaccination and assessment recommendations for initiating advanced IBD therapies. Using a modified Delphi approach, delegates voted anonymously on the acceptability of these statements prior to and following consensus discussion., Results: We developed eight statements on the domains of infectious diseases screening, vaccinations and assessments prior to commencing JAK inhibitors and S1P modulators. Six statements received agreement. Pre-advanced therapy screening for infectious diseases was established, and the vaccination protocol was revised. Malignancy, cardiovascular and thromboembolic risk assessments are necessary before initiating JAK inhibitors. Those starting S1P modulators need cardiac and ophthalmic assessments., Conclusions: These consensus statements combine vaccination and assessments on the currently available advanced therapies for IBD as a single comprehensive document that may reduce IBD complications associated with use of advanced therapies. Knowledge gaps identified during the consensus process will provide further research opportunities., (© 2024 The Author(s). Alimentary Pharmacology & Therapeutics published by John Wiley & Sons Ltd.)

Prevalence and incidence of HIV among people aged 50 years and older continue to rise worldwide, generating increasing awareness among care providers, scientists, and the HIV community about the importance of brain health in older adults with HIV. Many age-related factors that adversely affect brain health can occur earlier and more often among people with HIV, including epigenetic ageing, chronic medical conditions (eg, cardiovascular disease), and age-related syndromes (eg, frailty). Extensive dialogue between HIV community leaders, health-care providers, and scientists has led to the development of a multidimensional response strategy to protect and enhance brain health in people ageing with HIV that spans across public health, clinical spaces, and research spaces. This response strategy was informed by integrated ageing care frameworks and is centred on prevention, early detection, and management of brain health issues associated with HIV (eg, neurocognitive disorders), with specific considerations for low-resource or middle-resource countries. A collaborative, international, and data-informed update of the diagnostic criteria for HIV-associated neurocognitive disorders is a cornerstone of the proposed response strategy. The proposed response strategy includes a dynamic, international, online knowledge hub that will provide a crucial community resource for emerging evidence on the brain health of people ageing with HIV., Competing Interests: Declaration of interests BJB reports royalties from Oxford University Press and Cambridge University Press; honoraria for presentations sponsored by the Neurological Association of South Africa, Jansen, and Biogen; patents (monoclonal antibody for quinolinic acid as part of test kit for monitoring multiple sclerosis severity and progression [PCT/IB2013/055902; patent office Australia], 2010; method and prognostic kit for monitoring multiple sclerosis [WO/2015/008111], 2013; and automatic fall and seizure detector [application number 2016904045 IP Australia Batch Reference SPBI-0001069085 by My Medic Watch]); a position as Chairperson of the data monitoring and ethics committee for the Lighthouse 2 phase 3 study of the antiretroviral Triumeq in Amyotrophic Lateral Sclerosis (King's College London, UK, and Tysabri Advisory Board Australia); and a role as a past President of the International Society for Neurovirology (2019–23). JV reports honoraria for presentations and research grants in trials sponsored by Merck, Janssen Cilag, ViiV Healthcare, and Gilead Sciences. KG reports support from the Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections (ACGT) Network (funded by the US National Institutes of Health) as Protocol Director for ACTG trial A5402, Cipla, and Dr Reddy's Laboratories. All other authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Background and Objective: Severe asthma is a heterogeneous disease with subtype classification according to dominant airway infiltrates, including eosinophilic (Type 2 high), or non-eosinophilic asthma. Non-eosinophilic asthma is further divided into paucigranulocytic or neutrophilic asthma characterized by elevated neutrophils, and mixed Type 1 and Type 17 cytokines in the airways. Severe non-eosinophilic asthma has few effective treatments and many patients do not qualify for biologic therapies. The cystic fibrosis transmembrane conductance regulator (CFTR) is dysregulated in multiple respiratory diseases including cystic fibrosis and chronic obstructive pulmonary disease and has proven a valuable therapeutic target. We hypothesized that the CFTR may also play a role in non-eosinophilic asthma., Methods: Patient-derived human bronchial epithelial cells (hBECs) were isolated and differentiated at the air-liquid interface. Single cell RNA-sequencing (scRNAseq) was used to identify epithelial cell subtypes and transcriptional activity. Ion transport was investigated with Ussing chambers and immunofluorescent quantification of ionocyte abundance in human airway epithelial cells and murine models of asthma., Results: We identified that hBECs from patients with non-eosinophilic asthma had reduced CFTR function, and did not differentiate into CFTR-expressing ionocytes compared to those from eosinophilic asthma or healthy donors. Similarly, ionocytes were also diminished in the airways of a murine model of neutrophilic-dominant but not eosinophilic asthma. Treatment of hBECs from healthy donors with a neutrophilic asthma-like inflammatory cytokine mixture led to a reduction in ionocytes., Conclusion: Inflammation-induced loss of CFTR-expressing ionocytes in airway cells from non-eosinophilic asthma may represent a key feature of disease pathogenesis and a novel drug target., (© 2024 The Author(s). Respirology published by John Wiley & Sons Australia, Ltd on behalf of Asian Pacific Society of Respirology.)

Competing Interests: PS reports research grants paid to her institution from the Australian National Health and Medical Research Council, coauthorship of manuscripts with medical writing assistance from Novo Nordisk and Eli Lilly, and a position (unpaid) in the leadership group of the Obesity Collective. JA reports research support from Nestle Healthcare Nutrition, Eli Lilly, Epitomee, the UnitedHealth Group, Novo Nordisk, KVK Tech, Boehringer Ingelheim, Regenron, and Weight Watchers; and serves as a consultant for Amgen, Regeneron, Brightseed, Boehringer Ingelheim, Intuitive, Novo Nordisk, Eli Lilly, and WW.

Background: Upper limb dysfunction is a common debilitating feature of relapsing-remitting multiple sclerosis (RRMS). We aimed to examine the longitudinal trajectory of the iPad®-based Manual Dexterity Test (MDT) and predictors of change over time., Methods: We prospectively enrolled RRMS patients (limited to Expanded Disability Status Scale (EDSS) < 4). Longitudinal data was analysed using mixed-effect modelling and latent class mixed models. We then examined whether group membership in latent classes predicted confirmed slowing in MDT., Results: Seven hundred and twenty-one participants had complete data for analysis. At a population level, MDT remained stable over time. No practice effect was seen. Baseline disability and T2 lesion volume were the strongest predictors of longitudinal MDT performance. We identified two latent class trajectories of MDT. The slower latent class was typified by greater variability and a weak association with confirmed worsening of MDT and EDSS. When compared to trajectory analysis stratified by baseline MDT, latent class analysis (LCA) was able to identify those at greater risk of confirmed slowing, signifying the importance of latent processes in upper limb function in pwMS., Conclusion: In this cohort of mild to moderate RRMS, MDT scores remained stable over time with no evidence of a practice effect at a population level. Trajectory analysis based on LCA identified a cohort with greater variability and risk of disability progression and domain specific worsening. Our findings demonstrate the importance of latent processes in determining upper limb function in pwMS., (© 2024 The Author(s). European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

Without careful dissection of the ways in which biases can be encoded into artificial intelligence (AI) health technologies, there is a risk of perpetuating existing health inequalities at scale. One major source of bias is the data that underpins such technologies. The STANDING Together recommendations aim to encourage transparency regarding limitations of health datasets and proactive evaluation of their effect across population groups. Draft recommendation items were informed by a systematic review and stakeholder survey. The recommendations were developed using a Delphi approach, supplemented by a public consultation and international interview study. Overall, more than 350 representatives from 58 countries provided input into this initiative. 194 Delphi participants from 25 countries voted and provided comments on 32 candidate items across three electronic survey rounds and one in-person consensus meeting. The 29 STANDING Together consensus recommendations are presented here in two parts. Recommendations for Documentation of Health Datasets provide guidance for dataset curators to enable transparency around data composition and limitations. Recommendations for Use of Health Datasets aim to enable identification and mitigation of algorithmic biases that might exacerbate health inequalities. These recommendations are intended to prompt proactive inquiry rather than acting as a checklist. We hope to raise awareness that no dataset is free of limitations, so transparent communication of data limitations should be perceived as valuable, and absence of this information as a limitation. We hope that adoption of the STANDING Together recommendations by stakeholders across the AI health technology lifecycle will enable everyone in society to benefit from technologies which are safe and effective., Competing Interests: Declaration of interests JEA is a named researcher on grants funded by the Engineering and Physical Sciences Research Council (EPSRC), the National Institute for Health and Care Research (NIHR), and the Medical Research Council (MRC); is co-organiser of the Alan Turing Institute Clinical AI Interest Group; and was an NIHR Academic Clinical Fellow from 2017 to 2020. EL is employed as a research fellow at University Hospitals Birmingham NHS Foundation Trust and received support to attend the Symposium for Artificial Intelligence Learning Health Systems conference (May, 2023). JO is an employee of Roche Diagnostics but contributed while an employee of the UK MHRA; declares support from the AIRIS 2024 committee; and has shares in Roche Group. MG is a Canadian Institute for Advanced Research (CIFAR) AI Chair, CIFAR Azrieli Global Scholar, Herman L F von Helmholtz Career Development Professor, and Jameel Clinic Affiliate, and acknowledges support from these programmes. SRP is an employee of Google Research and has stock in Google. JS is an employee of Harrison.ai. NR is an employee of Google Research. HC-L is an employee of Google and has stock or stock options in Google. DS is Acting Deputy Editor of The Lancet Digital Health, Elsevier. BG was scientific advisor for Kheiron Medical Technologies (January, 2018, to September, 2021) and has had part-time employment with stock options as part of the standard compensation package (since October, 2021); has part-time employment at HeartFlow with stock options as part of the standard compensation package (since September, 2018); and is the Royal Academy of Engineering Research Chair in Safe Deployment of Medical Imaging AI. MCa is Director of the Birmingham Health Partners Centre for Regulatory Science and Innovation, Director of the Centre for Patient Reported Outcomes Research, and an NIHR Senior Investigator. MCa, NIHR Birmingham Biomedical Research Centre, Applied Research Collaboration West Midlands, UK SPINE, Research England, the European Regional Development Fund DEMAND Hub at the University of Birmingham, the University Hospitals Birmingham NHS Foundation Trust, and the NIHR Blood and Transplant Research Unit in Precision Transplant and Cellular Therapeutics; funding from Health Data Research UK, Innovate UK (part of UKRI), Macmillan Cancer Support, UCB Pharma, GSK, Anthony Nolan, Gilead Sciences, European Commission, European Federation of Pharmaceutical Industries and Associations, Janssen, Merck, and The Brain Tumor Charity; and personal fees from Aparito, ICON, CIS Oncology, Takeda Pharmaceuticals, Merck, Daiichi Sankyo, Glaukos, GSK, Halfloop, the Patient-Centered Outcomes Research Institute (PCORI), Pfizer, Genentech, and Vertex Pharmaceuticals, outside of the submitted work. MCa also declares royalties via revenue share from the commercial licence of Symptom Burden Questionnaire-Long COVID; payment or honoraria from the University of Maastricht, South-Eastern Norway Regional Health Authority, Cochrane Portugal, Singapore National Medical Research Council; and stock in GSK held by a family member. MCa has a leadership or fiduciary role in PROTEUS consortium (paid via a consultancy fee from Genetech and PCORI). TJP declares NIH awards (OT2OD032701 and R01EB030362), and grants or contracts from Google Cloud and Amazon Web Services. SK was an employee of Hardian Health. L-AF received consulting fees from Therapeutic Goods Administration, Australia, and WHO, and is a member of the AI in Healthcare Committee for Standards Australia and Director of Tethyan Consulting. CS received research funding from UKRI, NIHR, and the Wellcome Trust to support their research programme. BAM reports grants or contracts from MRC, the British Heart Foundation, the United States Agency for International Development, and HDRUK; consulting fees and support for attending meetings from the Bill & Melinda Gates Foundation; and was an employee of the Wellcome Trust at the time of the Delphi study. KH is an employee of Google Research. AK is an employee of Google and receives Google stock reimbursement. MM was an employee of Genomics England, Founder and Director of One HealthTech and Data Science for Health Equity (within One HealthTech), and received support from Nature Journals and Conde Nast. RP is an employee of MHRA. AKM is Deputy Editor of NEJM AI, NEJM Group. PM has a data custodian role as Director of the Clinical Practice Research Datalink and is an employee of MHRA. ZK was employed by Health Research Authority at the time of the consensus process. AAk received grants from the Economic and Social Care Research Council (ADR Wales ES/W012227/1) and HDRUK (HDR-9006). LB received support from the US National Institutes of Health (NIH) All of Us Research Programme to attend STANDING Together meetings. JWG is on the 2022 Robert Wood Johnson Foundation Harold Amos Medical Faculty Development Programme; declares support from the Radiological Society of North America Health Disparities grant (EIHD2204), Lacuna Fund (67), Gordon and Betty Moore Foundation, and NIH (NIBIB) Medical Imaging and Data Resource Center grant under contracts 75N92020C00008 and 75N92020C00021; has received honoraria from the National Bureau of Economic Research for authorship in their 2022 conference collection; has participated on the American Heart Association Deracing Algorithms advisory board; and is a board member of Hl7 and SIIM. LR is Senior Editor of the journal Nature Medicine, Nature Research, Springer Nature. MCh is an NIHR Academic Clinical Fellow. AAr is a panel member for various NIH Research committees, has received honoraria from HDRUK for attending panel meetings, and has an honorary affiliation with Moorfield's Eye Hospital. SP is employed by WHO. ES has had research funded by UK Research and Innovation (UKRI), NIHR, Wellcome Trust, Health Data Research UK (HDRUK), MRC, EPSRC, and Innovate UK, and declares support from the European Respiratory Society, British Thoracic Society, and Gilead. VT is Head of UK Approved Body as at the British Standards Institution. AD reports institutional research grants awarded by the NIHR, MRC, and EPSRC, and is an NIHR Senior Investigator, Director of the UK's incubator for Regulatory Science in AI and Digital Healthcare, deputy director of the Centre for Regulatory Science and Innovation, Birmingham Health Partners, system lead for AI diagnostics to NHS England, and a member of the UK Government's Regulatory Horizons Council. XL reports funding from the NIHR, the UK National Health Service AI Lab, The Health Foundation, Research England, the MHRA, the National Institute for Health and Care Excellence, and Hardian Health, and was previously a Health Studies Scientist at Apple; reports grants from the Medical Research Council, Wellcome Trust, NIHR, and Moorfields Eye Hospital Charity; received payment or honoraria for talks and book chapter reviews from the University of Turku and Elsevier; and received support from Harvard Medical School, SingHealth, and The Ada Lovelace Institute. All other authors declare no competing interests., (© 2024 World Health Organization. Published by Elsevier Ltd. This is an Open Access article published under the CC BY 3.0 IGO license which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. In any use of this article, there should be no suggestion that WHO endorses any specific organisation, products or services. The use of the WHO logo is not permitted. This notice should be preserved along with the article's original URL.)

Background: Wildfire smoke contains numerous hazardous air pollutants which pose serious health risks to humans. Despite this, there has been a limited focus on the assessment of the acute physiological and longer-term respiratory effects of wildfire exposure on firefighters and other emergency workers. Therefore, we undertook a systematic review of the evidence about the respiratory impacts of occupational wildfire smoke exposure among wildfire fighters (WFF)., Methods: Eligible studies from Medline, Embase and Scopus databases were included if they described the relationship between wildfire exposure and respiratory function, symptoms, measures and diseases amongst emergency personnel or firefighters who had responded to wildfires., Results: Twenty-six articles met the inclusion criteria. 24 out of 26 (22 out of 23 moderate/high quality) studies provided evidence of adverse respiratory effects, including reduced lung function, increased airway dysfunction and airway inflammation, upper and lower respiratory tract symptoms and increased asthma incidence related to wildfires or prescribed burns exposure among WFF and police responders. Fourteen out of 19 studies showed statistically significant declines in spirometry measures of lung function (mostly short-term studies). Two studies using complex lung function tests showed a significant effect on peripheral airway function., Discussion: This review found a convincing body of evidence that occupational exposure to wildfires or prescribed burns has both acute and possibly longer-term respiratory effects among WFFs and some other emergency personnel. Given that these events are increasing, more needs to be done to identify those most at risk and mitigate these risks., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier GmbH.. All rights reserved.)

Intimate partner violence is a serious, but underappreciated, issue that predominantly affects women and often results in concussion (i.e., mild traumatic brain injury). However, concussion in intimate partner violence is unique because it often involves a concomitant strangulation which may exacerbate or alter the physiology and clinical presentation of the brain injury. Therefore, here we conducted human and rodent studies to provide insight into knowledge gaps related to the detection, pathophysiology, and functional consequences of intimate partner violence-related brain injury. We conducted the first study to analyze blood biomarkers and symptoms of brain injury in intimate partner violence patients presenting to an emergency department within 72 h of concussion. Intimate partner violence concussion patients, some of whom had also experienced a concomitant strangulation, had elevated serum neurofilament light and worse brain injury symptoms compared to healthy control, orthopedic trauma, and non-intimate partner violence concussion groups. We also developed the first rat model of non-fatal strangulation and examined the consequences of strangulation and concussion in isolation and in combination on pathophysiology, blood biomarkers, and behavior at 2 h and 1wk post-injury. Rats exposed to combined strangulation and concussion had exacerbated motor and cognitive deficits, neuroinflammation, and serum glial fibrillary acidic protein levels compared with either injury in isolation. Taken together, these rodent findings demonstrate that a concomitant strangulation modifies and exacerbates concussion pathophysiology, biomarkers, and functional consequences. Overall, these findings provide novel insights into intimate partner violence-related brain injury and provides a foundation for future translational studies., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Introduction: Trauma is common and may lead to lasting adverse effects on health. Trauma-informed practice does not treat trauma but uses a strengths-based approach to encourage engagement in services., Objective: To understand how physiotherapy attends to trauma-informed principles., Methods: This qualitative ethnographic study was set in an Australian hospital. Three data collection methods were used, including observations of clinical practice, interactive reflexive group discussions with physiotherapists, and interviews with patients. Data analysis included an initial inductive phase followed by thematic mapping to trauma-informed principles. Critical reflexivity was used throughout to examine how the authors' perspectives and assumptions affected the analysis., Results: Twelve observations of consultations, ten interviews with people receiving physiotherapy, and five group discussions with physiotherapists were conducted. Themes produced within each of five principles of trauma-informed care included: Safety: not just a number, uncertainty beyond managing physical risks, upbeat approach as default needs balance, pragmatic environments inadequate; Trustworthiness: touch needs further consideration, assumed consent; Choice: limited options; Collaboration: let's do it together, variable consideration of the patient as expert, task focus, pushing the "right" treatment, missing insight into power imbalance; Empowerment: extending function and independence, building nonphysical skills but lack of clarity., Conclusion: Physiotherapy incorporates crucial aspects of trauma-informed care, but opportunities exist to enhance physiotherapists' skills and knowledge, particularly in relation to non-physical safety considerations.

Sex and sex hormones are thought to influence multiple sclerosis (MS) through effects on inflammation, myelination and neurodegeneration, and exogenous hormones have been explored for their therapeutic potential. However, our understanding of how sex hormones influence MS disease processes and outcomes remains incomplete. Furthermore, our current knowledge is derived primarily from studies that focus exclusively on cisgender populations with exclusion of gender-diverse people. Gender-affirming hormone therapy comprising exogenous sex hormones or sex hormone blocking agents are commonly used by transgender and gender-diverse individuals, and it could influence MS risk and outcomes at various stages of disease. A better understanding of the impact and potential therapeutic effects of both endogenous and exogenous sex hormones in MS is needed to improve care and outcomes for cisgender individuals and, moreover, for gender-diverse populations wherein an evidence base does not exist. In this Perspective, we discuss the effects of endogenous and exogenous sex hormones in MS, including their potential therapeutic benefits, and examine both established sex-based dimorphisms and the potential for gender-diverse dimorphisms. We advocate for future research that includes gender-diverse people to enhance our knowledge of the interplay of sex and sex hormones in MS, leading to the development of more effective and inclusive treatment strategies and improvement of care for all individuals with MS., Competing Interests: Competing interests: A.S.C. has received product from Besins Healthcare for investigator-initiated clinical studies using oestradiol and progesterone. No monetary support from Besins Healthcare has been received for any studies, and Besins Healthcare have had no input into study design, data analysis or writing of any manuscripts., (© 2024. Springer Nature Limited.)

The majority of patients hospitalised for trauma survive their injuries, with the quality of the survival potentially influenced by early acute hospital rehabilitation. The aim of this study was to review the outcomes of patients managed under an intensive Allied Health Model of Care (AHMOC) compared to a baseline cohort., Methods: The AHMOC was commenced in February 2020 on the Trauma ward at Alfred Health for 12 months. The baseline group included patients admitted to the trauma ward in 2019. All patients who were registered by either the Victorian Orthopaedic Trauma Outcomes Registry (VOTOR) or the Victorian State Trauma Registry (VSTR). The association between the groups (AHMOC and baseline) and outcomes were assessed using logistic (discharge destination, 12-month return to work) and linear (length of stay (LOS)) regression., Results: There were 1644 in the baseline group and 1732 in the AHMOC group, of which 70 % and 76 % respectively were discharged directly home from the acute hospital (p value < 0.001). The trauma ward LOS was 4.0 days for each group (p value 0.77). After accounting for confounders, the adjusted odds of discharge home and RTW at 12 months were 53 % (AOR 1.53 95 % CI 1.29, 1.82) and 65 % (AOR 1.65 95% CI 1.24, 2.21) higher for the AHMOC group compared to baseline, respectively. There was also a 6 % reduction in the LOS in the AHMOC group compared to baseline (Adjusted mean difference 6 %; 95 % CI (0.881, 0.999) p value = 0.050)., Conclusion: This study shows an association between an AHMOC for trauma patients with a focus on early and intensive therapy and improved odds of discharge directly home, as well as improved 12 month return to work outcomes., Competing Interests: Declaration of competing interest None., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background & Aims: Vedolizumab and ustekinumab pharmacokinetics in pregnancy and the infant after in utero exposure remain incompletely defined. We aim to define the antenatal stability of ustekinumab and vedolizumab levels and the time at which infant drug levels become undetectable., Methods: This multicenter prospective observational cohort study recruited pregnant or preconception women with inflammatory bowel disease receiving vedolizumab or ustekinumab. Trough drug levels, clinical data, and biochemical data were documented preconception, during each trimester of pregnancy, and postpartum. Maternal and cord blood drug levels were measured at delivery and in infants until undetectable. Infant outcomes were assessed until 2 years of age., Results: A total of 102 participants (vedolizumab, n = 58) were included. The majority of mothers were, and remained, in clinical and biochemical remission. Maternal vedolizumab levels decreased over the course of pregnancy in association with increasing weight, rather than increasing gestation. Maternal ustekinumab levels remained stable. The median time to drug becoming undetectable in the infant was shorter for vedolizumab (11 wk; range, 5-19 wk; n = 32) than ustekinumab (14 wk; range, 9-36 wk; n = 17) and correlated positively with infant delivery level. Thirty-two of 41 (88%) and 17 of 30 (67%) vedolizumab- and ustekinumab-exposed infants had undetectable drug levels by 15 weeks of age, respectively. Pregnancy and infant outcomes were favorable. Twenty infants with undetectable drug levels received the rotavirus vaccine, with no adverse reactions reported., Conclusions: Maternal vedolizumab levels decreased, whereas ustekinumab levels remained stable over the course of pregnancy. Most vedolizumab- and approximately half of ustekinumab-exposed infants had undetectable drug levels by 15 weeks of age. No concerning maternal or infant safety signals were identified., (Copyright © 2025 AGA Institute. All rights reserved.)

Background: Historically, hepatitis C virus (HCV) was difficult to treat among people with HIV. However, treatment with direct-acting antivirals (DAAs) results in 90%-95% of people being cured. There is a need to understand why a proportion of people are not cured. We aimed to examine characteristics that may indicate an increased probability of unsuccessful DAA HCV treatment., Methods: Data were from the International Collaboration on Hepatitis C Elimination in HIV Cohorts. People who commenced DAA HCV treatment between 2014 and 2019 were included. Unsuccessful treatment was defined as a positive HCV RNA test at a person's first RNA test at least 4 weeks (SVR4+) following the end of treatment. Multivariable mixed-effects logistic regression was used to examine characteristics associated with unsuccessful treatment., Results: Of 4468 people who commenced DAA treatment, 4098 (91.7%) had an SVR test 4+ weeks following the end of treatment, 207 (5%) of whom were unsuccessfully treated. Compared to a CD4+ cell count > 500 cells/mm 3 , cell counts < 200 (aOR 1.81, 95%CI 1.00-3.29) and between 200 and 349 (aOR 1.95, 95%CI 1.30-2.93) were associated with increased odds of unsuccessful treatment. Among 1921 people with data on injection drug use in the 12 months prior to treatment, there was some evidence that recent injection drug use was associated with increased odds of unsuccessful treatment; however, this was not statistically significant (aOR 1.67, 95%CI 0.99-2.82)., Conclusions: The overwhelming majority of people were successfully treated for HCV. Overall, 5% of those with an SVR4+ test were unsuccessfully treated; this was more likely among people with evidence of immunodeficiency and those who reported recently injecting drugs., (© 2024 The Author(s). Liver International published by John Wiley & Sons Ltd.)

Neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) are biomarkers of neuronal injury measurable in cerebrospinal fluid (CSF) and blood. Despite their potential as diagnostic tests for neurodegenerative disorders, it is unclear how they behave in mood and anxiety disorders. We conducted a systematic review and meta-analysis to investigate whether NfL and GFAP concentrations were altered in adults with mood and anxiety disorders compared to healthy controls. We searched PubMed, Web of Science, PsycINFO, MEDLINE and Embase through August 20, 2024, and assessed relevant studies and their risk of bias. The primary outcome was the standardised mean difference (SMD) and 95 % confidence interval (95 % CI) of NfL and GFAP concentrations. Twenty-nine studies comprising 2,962 individuals (927majordepression,804bipolardisorder,and1,231controls). When we compared individuals with major depression and healthy controls, there was no difference in NfL nor GFAP levels. In individuals with bipolar disorder, NfL was significantly elevated compared to controls (SMD = 0.53; 95 % CI: 0.20, 0.85; p = 0.005). Only one study reported on NfL levels anxiety disorders. Our study informs clinicians about how to interpret these emerging biomarkers in determining whether a person's symptoms are caused by a neurodegenerative or mood disorder. The mild elevation of NfL in bipolar disorder may suggest underlying neuroaxonal injury, warranting further research into its clinical and prognostic significance., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Aim: The study aimed to describe the incidence of pregnancy-associated colorectal cancer (PACRC) in New South Wales (NSW), Australia, and to examine the perinatal outcomes of women with PACRC and their babies., Methods: A population-based cohort study was conducted using linked data from NSW. The study group comprised all women diagnosed with colorectal cancer during pregnancy (gestational CRC) or postpartum (postpartum CRC). Women who gave birth without cancer during pregnancy or postpartum formed the comparison group (no-cancer group)., Results: A total of 123 women were diagnosed with PACRC (22 gestational, 101 postpartum), and 1 786 078 women were in the no-cancer group. The incidence of PACRC was 6.9/100 000 women giving birth. From 1994 to 2013, the incidence significantly increased even when adjusting for maternal age (adjusted increase of 5.8% per year). Women with gestational CRC had significantly higher odds of severe maternal complications (AOR 29.27, 95% CI: 11.18-76.63) and were more likely to give birth by labor induction or no-labor caesarean section (AOR 4.39, 95% CI: 1.50-12.84) than women in the no-cancer group. Although babies born to women with gestational CRC did not experience congenital anomalies, they had higher odds of planned preterm birth (AOR 9.91, 95% CI: 1.99-49.21) and severe neonatal adverse outcomes (AOR 8.65, CI: 3.65-20.5) than babies of women without cancer., Conclusions: The study found a significant increase in PACRC incidence in NSW over the study period, independent of maternal age. Increased interventions during gestational CRC births reflect management challenges with higher maternal and neonatal morbidities., (© 2024 Japan Society of Obstetrics and Gynecology.)

Background: It is common practice to administer oxygen to neurocritical patients in the Intensive Care Unit (ICU). Consequent hyperoxia has been associated with unfavourable outcomes including in patients with brain injury, after cardiac arrest, sepsis, and traumatic brain injury. The aim of this systematic review was to explore the association between hyperoxia exposure and unfavourable outcome in patients following a non-traumatic subarachnoid haemorrhage (SAH)., Methods: Systematic searches of Medline, Embase, Emcare, CINAHL and PubMed were performed in February 2024 using key words for SAH and hyperoxia. Non-human studies, articles in languages other than English, studies that did not measure blood oxygenation levels via pulse oximetry or arterial blood gas analyses, and studies exploring traumatic SAH were excluded. The Newcastle-Ottawa Risk of Bias tool (NOS) was used to assess the quality of included manuscripts. The primary outcome was a composite outcome combining mortality or poor functional neurological outcome. Secondary outcomes included mortality, poor functional neurological outcome, and development of delayed cerebral ischaemia (DCI)., Results: The literature search yielded 1,219 non-duplicate articles published after 1 January 2000, of which 21 articles were reviewed as full-texts and nine were included in this review. All included studies were rated good/high quality using the NOS. Hyperoxia exposure was associated with increased risk of adverse composite outcome of death or unfavourable functional neurological outcome (odds ratio (OR) 1.61, 95% confidence interval (CI) 1.19-2.16), poor functional neurological outcome alone (OR 1.79, 95% CI 1.33-2.42) and development of DCI (OR 2.63, 95% CI 1.79-3.85). The association of hyperoxia and hospital mortality alone was not statistically significant (OR 1.42, 95% CI 0.98-2.04)., Conclusion: Hyperoxia may contribute to unfavourable outcomes and the development of DCI after an non-traumatic SAH. Trials using restrictive oxygen therapy among patients with SAH are indicated., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Findings from the Women's Health Initiative studies led to menopausal hormone therapy (MHT) guidelines generally recommending the initiation of MHT be limited to women within 10 years of their menopause or before the age of 60 years. This recommendation has led to women who experience troublesome menopausal symptoms and who have not commenced MHT within these limits often being denied this type of therapy. Similarly, the majority of women who might benefit from the protective effects of MHT against bone loss and fracture are not offered this treatment option if they do not fit with these criteria. Based on review of the evidence that led to the conditional initiation of MHT, and subsequent studies, we propose that the recommendations regarding the initiation of MHT need to change to be more inclusive of women outside these chronological limits., Competing Interests: Declaration of interests SRD has prepared and delivered educational presentations for Besins Healthcare, Abbott, and Mayne Pharma; has been on advisory boards for Theramex, Astellas, Abbott Laboratories, Mayne Pharma, and Gedeon Richter; and has received institutional grant funding from Ovoca Bio and Lawley Pharmaceuticals. ST declares no competing interests., (Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Purpose of Review: Platelet transfusions, used as prophylaxis or treatment for bleeding, are potentially life-saving. In many countries, demand for platelet transfusion is rising. Platelets are a limited and costly resource, and it is vital that they are used appropriately. This study will explore the evidence behind platelet transfusions in different contexts, in particular recent and important research in this area., Recent Findings: Recent randomized clinical trials demonstrate the efficacy of platelet transfusions in some contexts but potential detrimental effects in others. Platelet transfusions also carry risk of transfusion reactions, bacterial contamination and platelet transfusion refractoriness. Observational and clinical studies, which highlight approaches to mitigate these risks, will be discussed. There is growing interest in cold-stored or cryopreserved platelet units, which may improve platelet function and availability. Clinical trials also highlight the efficacy of other supportive measures such as tranexamic acid or thrombopoietin receptor agonists in patients with bleeding., Summary: Although platelet transfusions are beneficial in many patients, there remain many settings in which the optimal use of platelet transfusions is unclear, and some situations in which they may have detrimental effects. Future clinical trials are needed to determine optimal use of platelet transfusions in different patient populations., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background and Objective: Time to testosterone recovery (TR) following androgen deprivation therapy (ADT) with gonadotropin-releasing hormone agonists varies widely. We evaluate TR kinetics and the oncological impact of an effective castration period in patients receiving definitive radiotherapy and ADT for prostate cancer., Methods: We obtained individual patient data from randomized controlled trials of radiotherapy with ADT and prospectively collected serial testosterone data from the MARCAP Consortium. We estimated the times to noncastrate TR (>1.7 nmol/l) and nonhypogonadal TR (>8.0 nmol/l) were estimated for each prescribed ADT duration, and developed corresponding nomograms. The association between effective castration period and metastasis-free survival (MFS) for any given ADT duration was evaluated via multivariable Cox regression. We conducted cubic spline analyses to assess nonlinear associations., Key Findings and Limitations: We included 1444 men from five trials in the analysis, of whom 115 received 4 mo, 880 received 6 mo, 353 received 18 mo, 36 received 28 mo, and 60 received 36 mo of ADT. Times to noncastrate TR and to nonhypogonadal TR varied considerably by ADT duration. Higher baseline testosterone and lower age were associated with a higher likelihood of TR (p < 0.001 for both). Effective castration period was not linearly associated with MFS for any ADT duration on Cox regression. Cubic spline analysis revealed that the optimal effective castration period for an MFS benefit was 10.6 mo for men who received 6 mo of ADT and 18 mo for men who received 18 mo of ADT., Conclusions and Clinical Implications: Time to TR varies according to the ADT duration, baseline testosterone, and age. The relationship between effective castration period and MFS may be nonlinear, with a longer effective castration period being helpful for men receiving 6 mo of ADT., (Copyright © 2024 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

The Victorian Government introduced a time-limited human papillomavirus (HPV) catch-up program for gay, bisexual, and other men who have sex with men (GBMSM) aged ≤ 26 years in 2017-2019. We conducted a retrospective observational study to examine the accuracy of the self-report of HPV vaccination status using computer-assisted self-interviewing versus their immunization history via electronic health records. We included GBMSM aged 23-30 years visiting the Melbourne Sexual Health Centre (MSHC) in 2020-2021 because they were age-eligible for the HPV catch-up program in Victoria, Australia. Individuals who were unsure about their vaccination status were categorized as 'unvaccinated'. Of the 1,786 eligible men, 1,665 men self-reported their HPV vaccination status: 48.8% ( n  = 812) vaccinated, 17.4% ( n  = 289) unvaccinated, and 33.9% ( n  = 564) unsure. Self-reported HPV vaccination had a sensitivity of 61.3% (95%CI: 58.3 to 64.2%; 661/1079), a specificity of 74.2% (95%CI: 70.5 to 77.7%; 435/586), a positive predictive value of 81.4% (95%CI: 78.6 to 84.0%; 661/812), a negative predictive value of 51.0% (95%CI: 47.6 to 54.4%; 435/853), and an accuracy of 52.6% (95%CI: 50.1 to 55.0%). Our results showed that only half of GBMSM know and report their HPV vaccination status correctly. Novel approaches such as digital vaccine passports may be useful for individuals to accurately report their vaccination status to guide accurate clinical decisions and management.

Background: The provision of ABO-incompatible fresh frozen plasma (FFP) in massive transfusion (MT) has become accepted to conserve AB FFP stock. There is an evidence gap in non-trauma settings. We compare characteristics of patients who received ABO-compatible or ABO-incompatible FFP during an MT episode due to any cause of critical bleeding, and assess the impact of incompatible FFP transfusion on inhospital mortality., Methods: Using the Australian and New Zealand Massive Transfusion Registry, data were extracted for patients aged ≥18 years who received an MT (defined as ≥5 red cell units in 4 h) between April 2011 and October 2018. Incompatible FFP was defined as transfusion of ≥1 unit of FFP with a bidirectional or minor ABO-mismatch in the first 24 h from MT initiation., Results: A total of 7340 patients from 28 hospitals were included. Seventy-seven (1%) patients received incompatible FFP (26 trauma, 51 non-trauma). Those who had incompatible FFP received a median of seven units of FFP, compared to those who only received compatible FFP receiving five units, p = .005. A total of 226 units of incompatible FFP were provided overall. Incompatible FFP provision was not independently associated with inhospital mortality in MT (HR of 1.40 [95% CI 0.84-2.26, p = .2]). Variables independently associated with inhospital mortality included increased FFP volume in the first 24 h, age, Charlson Comorbidity Index score, and lower pre-transfusion fibrinogen and peri-transfusion pH values., Conclusion: Transfusion of incompatible FFP in MT in our cohort was not independently associated with higher inhospital mortality, although the number of patients who received incompatible FFP was small., (© 2024 AABB.)

Introduction/aims: Previous studies have demonstrated high morbidity and mortality in patients with myasthenia gravis (MG) who acquired COVID-19. We aimed to identify the impact of the pandemic on MG disease control, treatment and quality of life., Methods: A prospective observational cohort study was conducted to identify the impact of the COVID-19 pandemic on Australian patients with MG. We conducted an online survey through Myasthenia Alliance Australia from May 2022 to July 2022., Results: Among the 229 patients who responded to the survey, most patients had three (80; 34.9%) or four (116; 50.7%) doses of the COVID-19 vaccines, 65 (28.4%) had contracted COVID-19, with 6 patients (9.4%) requiring hospitalisation. A large proportion of patients responded that the pandemic had no impact on their MG disease control (123; 53.7%) or treatment (111; 48.5%). Most patients felt the pandemic had either a mild (111; 48.5%) or moderate (50; 21.8%) impact on their mood., Conclusion: Our study provides a snapshot of the types of impacts experienced by myasthenic patients during the pandemic, in particular the psychosocial effects. As we continue to live with COVID-19, clinicians should consider its various impacts in the holistic management of their patients., Competing Interests: Declarations. Ethical publication statement: We confirm that we have read the Journal’s position on issues involved in ethical publication and affirm that this report is consistent with those guidelines. Disclosures of conflicts of interest: Pakeeran Siriratnam has received travel support from Novartis and Biogen. Katherine Buzzard has received speakers honoraria and/or educational support from Biogen, Sanofi Genzyme, Merck, Roche, Alexion and Teva and has served on medical advisory boards for Merck and Biogen. Stephen Reddel has received speaker’s honoraria and/or educational support from CSL and Grifols and serves on the National immunoglobulin government advisory committee, relevant to the subject matter of this paper. No disclosure from other authors. The study was conducted anonymously through members of Myasthenia Alliance Australia- no patient identifiers were collected. Date: 31/8/2024: All authors have agreed the contents of the submission., (© 2024. Crown.)

The increasing prevalence of LED technology heightened blue light (BL) exposure, raising concerns about its long-term effects on ocular health. This study investigated the transcriptomic response of conjunctiva to BL exposure, highlighting potential biomarkers for conjunctival injury. We exposed human conjunctival epithelial cells and C57BL/6 mice to BL to establish in vitro and in vivo models and identified the responsive genes in mice's conjunctiva to BL exposure by RNA sequencing transcriptome analysis. Western blotting, wound healing assays, transwell assay, and phalloidin staining assessed phenotypes of epithelial-mesenchymal transition (EMT). BL disrupted cell conjunction and regulated EMT-related proteins. RNA sequencing analysis revealed upregulation of ITGB4 and enrichment of cell migration and adhesion pathways. Reactive oxygen species-mediated damage caused by BL upregulated ITGB4 expression, promoting cell migration and EMT through the extracellular signal-regulated kinase /Snail pathway., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Many children with cerebral palsy (CP) are frail and require major hip and/or spine surgeries associated with substantial blood loss. Tranexamic acid (TXA) is commonly used to reduce blood loss, but there is uncertainty around the optimal dose and timing of administration. There have been reviews in sub-populations and specific dosing regimens, but a broad overview of the available literature is lacking. The aim of this review was to map available evidence on TXA in hip and spine surgery for children with CP. Given the heterogeneous literature, a prospectively registered scoping review was conducted. Eligibility criteria were broad. Three screeners were involved, with the senior author consulted when disagreements were not resolved through discussion.Titles and abstracts of 14,609 records were screened, with 52 records included. Two additional records were obtained from grey literature and citation searching. Cohort studies (50.0%) were the most common. Most records (76.9%) were on spine surgery. TXA dose varied widely. Loading doses range from 5 to 100 mg/kg and intraoperative infusions from 1 to 10 mg/kg/h. Dose was not reported in 35.2% of records. Primary outcome measures included blood loss and transfusion requirements. TXA was generally reported to be safe. None of the included records reported postoperative TXA administration.While TXA is generally considered safe, there was mixed evidence on efficacy. Much of the evidence was drawn from studies in which TXA was used in patients at higher risk of bleeding or with reduced physiological reserve. There was no evidence for TXA being used postoperatively, when a large proportion of transfusions occur., Competing Interests: Declarations. Competing interests: The authors declare that they have no competing interests., (© 2024. The Author(s).)

Ever since the first description of an inherited immunodeficiency in 1952 in a boy with gammaglobulin deficiency, new insights have progressed rapidly in disorders that are now referred to as inborn errors of immunity (IEI). In a field where fundamental molecular biology, genetics, immune signaling and clinical care are tightly intertwined, 2022-2024 saw a multitude of advances. Here we report a selection of research updates with a main focus on (1) diagnosis and screening, (2) new genetic defects, (3) susceptibility to severe COVID-19 infection and impact of vaccination, and (4) treatment. Importantly, new pathogenic insights more rapidly impact on treatment outcomes, either through an earlier and more precise diagnosis, or through implementation of novel, personalized treatment. As the field is growing rapidly, awareness, communication and collaboration are key to improving treatment outcomes., (Copyright © 2024. Published by Elsevier Inc.)

Objectives: In aquaporin-4 antibody-positive neuromyelitis optica spectrum disorder (AQP4-IgG NMOSD), disability accrual is mostly attributed to relapses. This study aimed to assess the prevalence of progression independent of relapse activity (PIRA) and relapse-associated worsening (RAW) in AQP4-IgG NMOSD., Methods: This was a retrospective cohort study of patients with AQP4-IgG NMOSD enrolled in the MSBase international data registry. Patients required a minimum of 3 recorded Expanded Disability Status Scale (EDSS) scores: baseline, event, and a 6-month confirmation score. Presence and absence of relapses between the baseline and event EDSS scores determined RAW and PIRA, respectively. Descriptive statistics were used to present the results., Results: A total of 181 patients followed for a median of 4.5 years (Q1 1.7, Q3 7.8) were included. Most patients were female (88.4%), and the median age at disease onset was 38.1 years. Overall, 4 patients (2.2%) developed 5 incidences of PIRA and 13 patients developed RAW (7.2%)., Discussion: This multicenter study highlights that PIRA is very rare in AQP4-IgG NMOSD. Limitations of this study include the sole focus of overall EDSS to measure disability, lack of requirement for a second EDSS score to confirm baseline EDSS, and the absence of magnetic resonance imaging information for all patients.

Aims: Clustering algorithms have been widely applied to tumor DNA methylation datasets to define methylation-based cancer subtypes. This study aimed to evaluate the agreement between subtypes obtained from common clustering strategies., Materials & Methods: We used tumor DNA methylation data from 409 women with breast cancer from the Melbourne Collaborative Cohort Study (MCCS) and 781 breast tumors from The Cancer Genome Atlas (TCGA). Agreement was assessed using the adjusted Rand index for various combinations of number of CpGs, number of clusters and clustering algorithms (hierarchical, K-means, partitioning around medoids, and recursively partitioned mixture models)., Results: Inconsistent agreement patterns were observed for between-algorithm and within-algorithm comparisons, with generally poor to moderate agreement (ARI <0.7). Results were qualitatively similar in the MCCS and TCGA, showing better agreement for moderate number of CpGs and fewer clusters (K = 2). Restricting the analysis to CpGs that were differentially-methylated between tumor and normal tissue did not result in higher agreement., Conclusion: Our study highlights that common clustering strategies involving an arbitrary choice of algorithm, number of clusters and number of methylation sites are likely to identify different DNA methylation-based breast tumor subtypes.