The dynamic physiological and hormonal changes through the menopause transition predispose women to an increased risk of chronic diseases including cardiovascular disease, metabolic disease, depression and dementia. The underlying mechanisms remain unclear, yet it is thought that chronic systemic inflammation and changes to lifestyle behaviours play important roles. The LIfestyle risk Factors for chronic disease across the stagEs of reproductive ageing (LIFE study) is a cross-sectional study aimed to characterise how hormonal and lifestyle (physical activity, diet and sleep) differences across pre, peri and postmenopause influence chronic systemic inflammation, visceral adiposity, cognitive function and sleep health.

Women aged between 40 and 65 years were recruited and classified into pre, peri or postmenopausal groups. Body composition measures and blood samples were collected. Sleep and physical activity were objectively measured using activPAL4 and ActiGraph GT9X link accelerometer over 7 days. Participants were also provided with a sleep diary. Physical function was assessed using the Short Physical Performance Battery. Cognitive function was evaluated using Addenbrooke’s Cognitive Examination-III and Cambridge Neuropsychological Test Automated Battery. Participants completed a series of questionnaires: Depression, Anxiety and Stress Scale-21, RuSATED, Berlin Questionnaire, Insomnia Severity Index, Activities-specific Balance Confidence Scale and the Australian Eating Survey.

Ethical approval was received from the relevant University Human Research Ethics Committee (ethics approval number #S221718) prior to the commencement of the research project. Data collection is ongoing and expected to be completed by April 2026. Results are expected to be available from July 2026. Findings will be disseminated in national and international conferences and in peer-reviewed journals and expected to inform how differences in lifestyle behaviours across menopause influence chronic systemic inflammation, visceral adiposity and cognitive function. Understanding and characterising the links between lifestyle behaviours and menopausal symptoms will inform targeted strategies to improve long-term well-being, heart, brain and metabolic health.

In kidney transplantation, immunosuppressive therapy is essential to control alloimmune reactions, prevent graft rejection and improve patient survival rates. However, commonly used drugs like tacrolimus (TAC) and mycophenolate mofetil (MMF) have a narrow therapeutic window and exhibit significant inter- and intra-individual variability in pharmacokinetics (PK) and dose-response relationships. Recent pilot studies suggest that the gut microbiome may influence this variability.

ElucidatiNg Immunosuppressant pharmacokinetic variabilities by investigating Gut Microbiome modulations After kidney transplantation (ENIGMA) is a prospective, low-interventional, naturalistic longitudinal trial designed to identify biomarkers of TAC and MMF PK variability by examining gut microbiome changes and modulations after kidney transplantation and their link with TAC and MMF PK. Biological samples from 50 patients will be collected at nine specific timepoints pre- and post-transplantation using a rich PK and biological sampling strategy. This approach will enable the derivation of PK parameters for the investigated drugs and the creation of a biobank for future hypothesis testing.

The ENIGMA trial has received ethical approval from the European Medicines Agency (EMA). The reference number of our project is R&D/1325226 and is registered on the Clinical Trial Information System (CTIS) platform with European Union Clinical Trial number 2023–5 08 335-31-00. Results of the trial will be published in scientific journals and presented at different (inter)national conferences.

2023–5 08 335-31-00 EMA.

As fatigue is among the most frequent manifestations of post-COVID syndrome (PCS), this study aimed to assess the prevalence and severity of cognitive and physical fatigue after occupational SARS-CoV-2 infection and to identify sociodemographic, clinical and occupational predictors of fatigue severity.

Cross-sectional analysis of a multicentre prospective registry.

Six German Social Accident Insurance hospitals distributed across Germany, providing standardised post-COVID assessments for individuals with persistent symptoms following occupational SARS-CoV-2 infection.

Workers with confirmed SARS-CoV-2 infection recognised as an occupational disease or work-related accident who presented with persistent symptoms and were enrolled in a multicentre post-COVID registry.

Cognitive and physical fatigue severity assessed using validated self-administered questionnaires (Fatigue Scale for Motor and Cognitive Functions, Modified Fatigue Impact Scale and Würzburg Fatigue Inventory for Multiple Sclerosis). Clinical relevance was determined based on established cut-offs reported in the literature. Fatigue severity was operationalised using median splits of the respective subscales to identify factors associated with higher fatigue levels.

Among 1511 registry cases, 628 participants had complete fatigue data. Median age was 54 years, 77% were female and most worked in nursing (43%) or educational/care professions (19%). Clinically relevant fatigue was highly prevalent: cognitive fatigue affected 78%–93% and physical fatigue 87%–98%. Both fatigue dimensions were positively correlated with older age, work incapacity and persistent symptom burden. In multivariate analyses, a higher number of acute symptoms was associated with lower odds of cognitive fatigue (adjusted OR 0.39, 95% CI 0.19 to 0.81), while physical fatigue remained associated with profession (adjusted OR 2.04, 95% CI 1.17 to 3.59). Sex, pre-existing conditions, hospitalisation and variant wave were not significant predictors in either model.

Fatigue is a prevalent and disabling PCS-symptom among occupationally exposed workers. Distinct determinants of cognitive and physical fatigue emphasise the need for early recognition, targeted management and rehabilitation strategies to support recovery and work reintegration.

To review the literature reporting patient preferences for ambulatory heart rhythm monitoring (AHRM) and what factors affect experience and engagement.

The prevalence of arrhythmia continues to rise and contributes significantly to outpatient care burden. There is limited understanding of patient experience and compliance with monitoring. As innovative technologies are developed and healthcare strategies move towards surveillance and prevention, understanding this is key.

A scoping review was conducted using guidance from the Joanna Briggs Institute and reported using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews. The review included studies of adults under investigation or surveillance for arrhythmia with a range of devices (Holter monitor, patch device, event recorder, mobile cardiac telemetry, external and implantable loop recorders, wearables and other implantable cardiac devices) in ambulatory care settings worldwide. The final search was conducted on 3 January 2026 across Medline (PubMed), Embase (Ovid), Web of Science (Clarivate Analytics), Cumulative Index to Nursing and Allied Health Literature (EBSCOhost), PsycINFO (Ovid) and Google Scholar. Quantitative, qualitative, mixed methods, multiple methods and any type of review articles were included.

54 studies were eligible for inclusion from the initial search that identified 1320 articles. Two overarching themes emerged from the quantitative and qualitative data: patient factors and device factors affecting experience and engagement. Patient factors included clinical and demographic factors, education and expectations, experience and preferences and impact on daily life and healthcare. Device factors could be common to several devices, for example, skin irritation or device specific, for example, the nature of activation.

Patient and device factors influence preferences for and experience and engagement with AHRM. While existing literature is incomplete and heterogeneous, it identifies key considerations that should be integrated into the development and testing of novel approaches for arrhythmia surveillance in healthcare contexts.

https://doi.org/10.17605/OSF.IO/6K3W8 (Open Science Framework).

Healthcare contributes considerably to greenhouse gas emissions, particularly from operating theatres. The global demand for total hip replacements (THR) is rising, highlighting the need to understand its impact on the environment. The study aims to assess the environmental impact of THRs using life cycle assessment (LCA) and to identify key contributors.

A process-based LCA focusing on the surgical procedure was conducted in accordance with global standards (ISO 14040:2006 and ISO 14044:2006). Eleven sensitivity scenarios were performed to assess the robustness of the results.

A Danish University Hospital.

The empirical data involved the quantity and type of surgical equipment, material composition, energy usage and clinical infrastructure. There were no study participants.

No study interventions were performed.

18 environmental impact scores, such as global warming, human toxicity and water consumption, were assessed.

The carbon footprint of a THR was 62.0 kg CO₂e, with major contributors being single-use disposable utensils (54 %), implants (22 %), and sterilisation of non-disposable utensils (18 %). Operating theatre energy usage, non-disposable utensils and clinical infrastructure contributed less, at 3 %, 2 % and 1 % each. Although the results of the other 17 environmental impact scores varied, they were predominantly influenced by the same factors as the carbon footprint. The sensitivity analysis showed that the overall carbon footprint varied by no more than 6 % unless the energy system shifted to less renewable energy, potentially increasing the footprint by 47 %.

THRs impose a substantial environmental burden, and sustainable solutions should focus on the primary drivers of this impact: disposable utensils, implants and the sterilisation process. In contrast, clinical infrastructure and non-disposable utensils appear to have a relatively minimal environmental impact.

Equity, diversity and inclusion (EDI), patient engagement and shared decision-making are important considerations throughout clinical trials, including the research ethics review stage. Meaningfully integrating these considerations can enhance the relevance and generalisability of trial results and reduce participation barriers among equity-deserving populations. Presently, it is unclear to what extent such guidance is provided at the ethics application stage for clinical trials. This study aimed to report the degree of guidance on EDI, patient engagement and shared decision-making in clinical trial research ethics documents.

This was an embedded mixed methods study conducted in collaboration with Clinical Trials Ontario.

This study analysed research ethics board (REB) forms and templates from 17 institutions across seven provinces in Canada.

15 REB application forms, 9 protocol templates and 17 informed consent document (ICD) templates were assessed for guidance related to EDI, patient engagement and shared decision-making. The Place of residence, Race, ethnicity, culture and language, Occupation, Gender and sex, Religion, Education, Socio-economic status, Social capital (PROGRESS)-Plus framework, International Association for Public Participation Spectrum of Public Participation, Patient-Oriented Research Level of Engagement Tool, Indigenous Research Level of Engagement Tool and shared decision-making standards guided our coding. We engaged with patients and persons with lived experience to inform interpretation, reporting and dissemination.

EDI guidance from 15 ethics application forms and 9 protocol templates predominantly covered the ‘Race, ethnicity, culture, language’ (n=14; 93.3%), ‘Age’ (n=13; 86.7%) and ‘Gender and sex’ (n=12; 80%) categories of PROGRESS-Plus but lacked nuance on diverse gender identities (n=1; 6.7%). Patient engagement guidance mostly covered the ‘inform’ level (n=7; 46.7%) and applying ‘knowledge in practice’ with non-Indigenous (n=7; 46.7%) or Indigenous communities (n=13; 86.7%). All 17 (100%) ICD templates included guidance on information about options, disclosures, key elements, ethical issues and study design. No guidance was available on time-dependent relationships, empowering patients and communities in co-leading trials or providing structured guidance in making trial participation decisions (all n=0; 0%).

We provided a comprehensive view of EDI, patient engagement and shared decision-making guidance in trial ethics applications in Canada. REB guidance may be strengthened in several areas to support the inclusion of equity-deserving populations in trials, meaningful engagement with patients and Indigenous communities and evidence-informed, values-aligned decisions about trial participation.

Persons with childhood-onset intellectual or complex disabilities have an elevated probability of encountering delayed or erroneous diagnoses during hospital treatment. It is imperative to consider the possibility that mistreatment may worsen their health. Persons with intellectual disabilities face numerous challenges in accessing and using healthcare. These challenges include structural and communication barriers, as well as a dearth of competencies among health professionals in interacting with persons with intellectual disabilities. Nevertheless, there is a paucity of studies that analyse the challenges faced by persons with intellectual disabilities in hospital and even fewer that involve persons with intellectual disabilities in the research process. Therefore, the objective of the study described in this protocol is to identify the salient research questions for improving hospital care of adults with childhood-onset intellectual disabilities by collecting and prioritising the different perspectives of patients, caregivers and clinicians.

The study design is based on the Priority Setting Partnership procedure of the James Lind Alliance, encompassing four steps to identify and prioritise issues with patients, caregivers and clinicians. Initially, problems and issues pertinent to those affected are collated using an open online questionnaire and subsequently clustered into topics. In the second step, the topics are transformed into potential research questions and reviewed by available scientific literature. Subsequently, research questions that cannot yet be answered by current literature are prioritised by participants in a second online questionnaire. Finally, the 25 questions rated most relevant are to be discussed in a one-day workshop with participants reflective of all target groups. The salient 10 research questions are to be determined using nominal group technique.

The study has received a positive ethics vote from the Ethics Committee at the Ludwig Maximilian University of Munich in accordance with the Declaration of Helsinki on 21 March 2025 (reference 25-0106). This study’s findings will be shared in academic conferences and published in scientific peer-reviewed journals.

DRKS00037347.

With an ageing population, understanding leading causes of hospitalisation in older adults is critical for care strategies. These leading causes may vary across residential settings and by seasonal patterns. This study examines the temporal trends of leading causes of hospitalisation among older adults in community-dwelling and nursing home settings, specifically comparing patterns during winter and summer seasons.

A retrospective analysis of electronic medical records from Hong Kong public hospitals (2012–2018) was conducted for three million adults aged ≥65. Age-standardised and sex-standardised monthly hospitalisation rates and average annual percentage change (AAPC, representing the average yearly percentage change in rates) were examined for leading causes during summer and winter across settings.

Among community-dwelling individuals, the top five causes in 2018 were symptoms, signs and abnormalities not classified elsewhere (NEC), neoplasms, genitourinary, circulatory and respiratory diseases in winter, with digestive diseases replacing respiratory diseases in summer. Symptoms, signs and abnormalities NEC (AAPC: 2.7% (95% CI 1.8% to 3.6%) in winter; 3.4% (2.8% to 4.0%) in summer), neoplasms (2.4% (1.4% to 3.4%) in winter; 2.5% (1.6% to 3.4%) in summer), genitourinary (2.5% (2.1% to 2.9%) in winter; 2.4% (1.8% to 3.0%) in summer) and digestive diseases (2.5% (1.6% to 3.3%) in winter; 2.6% (1.7% to 3.5%) in summer) increased, while circulatory diseases decreased in winter. In nursing home residents, the top five causes in 2018 were respiratory diseases, symptoms, signs and abnormalities NEC, genitourinary, circulatory and digestive diseases in winter and summer. Symptoms, signs and abnormalities NEC increased (2.9% (0.9% to 5.0%) in winter; 2.9% (0.8% to 5.1%) in summer), while circulatory diseases declined across seasons. Genitourinary diseases remained stable across seasons, whereas digestive diseases declined in winter.

In Hong Kong’s ageing population, seasonal and temporal shifts in hospitalisation causes were observed. Symptoms, signs and abnormalities NEC emerged as the top two causes across settings, highlighting challenges for primary care and hospital management and need for enhanced prevention and care strategies.

Circadian regulation modulates metabolic and hormonal processes throughout the day, yet it remains unclear whether these diurnal fluctuations are reflected in exhaled volatile organic compound (VOC) profiles and whether such temporal patterns differ between individuals with and without diabetes. Previous breath analysis studies in diabetes have shown heterogeneous results, which may reflect differences in analytical approaches and the lack of standardised sampling times.

This prospective, single-centre observational study examines daytime VOC dynamics from 08:00 to 16:00 among adults without diabetes, and individuals with type 1 diabetes or type 2 diabetes. 60 participants will complete one in-person visit with repeated breath measurements using a BreathSpec^® gas chromatography–ion mobility spectrometry system (GC-IMS) device, capillary glucose testing, body composition assessment, questionnaires, and oral and stool microbiota sampling. A standardised breakfast is provided; subsequent meals follow structured timing but are not standardised. The primary outcome is temporal variation in VOC intensities. Secondary outcomes include between-group differences and associations with glucose levels, body composition and microbiota composition. Analyses will use established GC–IMS tools and exploratory multivariate approaches.

Ethics approval was granted by the Ethics Committee of the Canton of Bern (BASEC 2023-01143). Results will be shared via peer-reviewed publications, conferences and lay summaries.

NCT05984979.

Patients with systemic autoimmune rheumatic disease (SARD) are at high risk of developing interstitial lung disease (ILD). We sought to gain insight into the pharmacological and non-pharmacological treatments being used by patients with SARD-associated ILD (SARD-ILD) following ILD progression.

This was a retrospective, observational cohort study.

Optum Clinformatics Data Mart administrative medical and pharmacy claims database in the USA.

Patients with SARD-ILD who had an incident ILD diagnosis and progression between January 2018 and March 2023.

Treatment patterns and healthcare services utiliation were descriptively summarised for baseline and follow-up periods.

We identified 6431 patients with SARD-ILD and evidence of ILD progression (mean age, 71.2 years; 75.3% female; 68.9% white). The mean (SD) time between the initial SARD-ILD diagnosis and the onset of ILD progression (index date) was 104 (201) days. On average, patients were followed for 936 (467) days.

Oral corticosteroids were the most common treatment post-progression (69.5%), followed by non-biologic disease-modifying antirheumatic drugs (non-biologic DMARDs) (41.6%), biologic DMARDs (15.5%) and immunomodulators (15.4%). Antifibrotics were received by 3.5% of patients. Supplemental oxygen was the most frequent non-pharmacological treatment (48.9%). For the baseline period, 53.0% and 42.1% of patients used inpatient and emergency department services, respectively. During the follow-up, 69.7% and 62.8%, respectively, used these services.

The high use of corticosteroids and limited use of DMARDs and antifibrotics post-progression in this descriptive study implies a significant gap between current practice and optimal management of patients with SARD-ILD.

Growing evidence exists about the pivotal role of immune mechanisms in the physiopathology of atrial fibrillation (AF). Drugs that modulate the immune system (immunomodulators) may contribute to the development of AF. We aimed to identify immunomodulators that are associated with AF to better define their safety profile, and elucidating their mechanisms of action could yield novel insights into AF’s immune physiopathology.

A descriptive and disproportionality analysis of claims data.

World pharmacovigilance database VigiBase until 1 March 2025.

First, we ascertained the association of immunomodulators with AF over-reporting with a disproportionality analysis evaluating the multivariable-adjusted reporting odds ratio (aROR) for AF reporting performed for 141 immunomodulators in VigiBase. Then, a literature review was done to explore the underlying mechanisms of AF through immunomodulator mechanisms.

A total of 6 148 556 reports encompassing at least one of the 141 immunomodulators were identified in Vigibase. Our primary analysis revealed 20 immunomodulators associated with AF over-reporting. The three immunomodulators with the greatest signal were: recombinant interleukin-11 with an aROR=20.91 (99.96% CI 12.08 to 36.17), efgartigimod alfa with an aROR=6.75 (99.96% CI 3.96 to 11.52) and recombinant interleukin-2 with an aROR=6.15 (99.96% CI 3.62 to 10.45). A derivative literature review posited a hypothetical immune ‘vicious circle’ promoting AF, involving T helper cells, macrophages and natural killer cells which could lead to electrophysiologic and histologic atrial remodelling.

Twenty Food and Drug Administration (FDA)-labelled immunomodulators are associated with AF overreporting in Vigibase with a substantial signal on recombinant IL-11. These data contribute substantively to the prevailing understanding of the safety profile of these immunomodulators. Moreover, these findings support a multidirectional interaction between the immune system and AF development and might lead to considering future therapeutic targets.

NCT06095791.

To develop and user-test a patient decision aid for people diagnosed with degenerative cervical myelopathy and who are considering surgery.

Mixed-methods study describing the development of a patient decision aid.

A draft decision aid was developed by a multidisciplinary steering group (including study authors with degenerative cervical myelopathy, health professionals and researchers) informed by the best available evidence, authorship consensus and existing patient decision aids.

Patient-participants and health professional-participants who manage people with degenerative cervical myelopathy were recruited through social media and the steering group’s research and practice network. Quantitative questionnaires were used to gather baseline data, descriptive feedback, refine the decision aid and assess its acceptability. Qualitative semi-structured interviews were conducted online to gather feedback on the decision aid and were analysed using reflexive thematic analysis.

We conducted 32 interviews: 19 patient-participants and 13 health professional-participants who manage people with degenerative cervical myelopathy (neurosurgeons, neurologists, physiotherapists, orthopaedic surgeons, general practitioners, rehabilitation and pain specialists and consultant occupational physicians and chiropractors). Participants were from 10 countries (Australia, Canada, Cyprus, Germany, Ireland, New Zealand, Sweden, Switzerland, United Kingdom and USA). Most participants rated the decision aid’s acceptability as good-to-excellent and agreed with most aspects of the decision aid (eg, defining degenerative cervical myelopathy, management recommendations, potential benefits and harms, questions to consider asking a health professional).

Our patient decision aid was rated as an acceptable tool by both health professional-participants who treat degenerative cervical myelopathy and patient-participants with lived experience of degenerative cervical myelopathy. This decision aid can be used by clinicians and people with degenerative cervical myelopathy to help with shared decision making following a diagnosis of degenerative cervical myelopathy. A study testing the potential benefits of this decision aid in a clinical setting is recommended.

Suicide is a major public health concern among youth in Canada and worldwide. The most rapid increases in suicidal ideation, self-harm, and suicide attempts have been observed among adolescent girls, particularly since the COVID-19 pandemic. Recent studies report disproportionately high rates of emergency department visits and hospitalisations for suicide-related concerns among adolescent girls. Despite these concerning trends, limited evidence exists on the life trajectories, needs, and service pathways of adolescent girls who attempt suicide. This protocol describes a qualitative suicide audit focused on adolescent girls aged 12–17 who were hospitalised following a suicide attempt in two regions of the province of Québec, Canada. The aim is to understand developmental trajectories, document services received and identify individual, relational and systemic factors influencing these trajectories to generate recommendations that inform suicide prevention.

Using a narrative qualitative design and a community-based research approach, data will be collected from semi-structured interviews with adolescents and parents, parent questionnaires and hospital health records. These data will be integrated to develop anonymised case vignettes. A multidisciplinary panel, including clinicians, health system stakeholders, community partners and individuals with lived experience, will review each case to identify gaps and strengths in care and generate case-level and cross-case recommendations for clinical practice, health policy and professional training.

Ethics approval was obtained from the research ethics committee (REC) of the Centre intégré de santé et de services sociaux de Chaudière-Appalaches, which serves as the reviewing REC, with administrative reviews underway at two other health authorities. Findings will be disseminated through peer-reviewed publications, conference presentations and collaborative knowledge-mobilisation activities with clinical and community partners, including practice-oriented tools and accessible materials for adolescents and parents.