Approximately one-third of people with epilepsy (PWE) experience resistance to treatment, including pharmacological therapies, epilepsy surgery, vagus nerve stimulation (VNS) and dietary interventions such as the ketogenic diet (KD). Emerging evidence suggests that the gut microbiota may influence seizure susceptibility and treatment response through the microbiota-gut-brain axis, potentially contributing to treatment resistance. The MiCrobiota-gut-brain Axis in Resistant Epilepsy project investigates how gut microbial features and associated host epigenetic signatures affect clinical outcomes in PWE undergoing diverse treatment strategies.

This is a multicentre, prospective, longitudinal study involving four clinical centres in Italy and one self-financing partner. Participants aged 3–50 years will be enrolled and stratified into four intervention cohorts: newly diagnosed drug-naïve epilepsy scheduled to start anti-seizure medications, focal drug-resistant epilepsy (DRE) undergoing epilepsy surgery, DRE receiving VNS, and DRE initiating KD. Clinical assessments (including body mass index calculation, self-reported monthly seizure count, dietary evaluation, quality of life scale and gastrointestinal symptoms scale), electroencephalography, MRI and biological sample collection (stool and blood) will be obtained at baseline and longitudinally at two or three timepoints over a 12-month observation period. Gut microbiota changes over time will be assessed via metagenomics (using 16S ribosomal RNA sequencing) and metaproteomics; the associated host DNA methylation profiles will be obtained from blood using Illumina EPIC arrays. Primary endpoints include identification of microbial or host methylation changes predictive of therapeutic response (ie, reduction from baseline in monthly seizure count) to the intervention. Data will be analysed using multivariate models and mixed-effect regression. Further, omics data and corresponding metadata will be integrated using multi-omics approaches to identify molecular signatures biomarkers predictive of treatment response and prognosis in PWE.

The study received ethical approval from the Research Ethic Board (Comitato Etico Territoriale Lombardia 3, ID 4896 – parere numero 4896_17.07.2024_N_bis). All participants or their legal guardians will provide written informed consent. Results will be disseminated through peer-reviewed publications, conference presentations or lay summaries targeting patient organisations.

ClinicalTrials.gov Identifier NCT07010445, registered on 2 May 2025.

Patient safety is crucial in healthcare, especially in home-based settings where unregulated environments and limited supervision pose unique challenges. With the expansion of home healthcare due to an ageing population and healthcare workforce shortages, there is a pressing need for tools to assess patient safety culture in this context. Current instruments, developed for hospitals, do not adequately address the specific dynamics of home healthcare, such as patient autonomy and caregiver involvement. This protocol outlines the development and validation of the Patient Safety Culture in Home Health Care Centers Instrument (PSCHCI), using a sequential exploratory mixed-methods approach.

This sequential exploratory mixed-methods protocol consists of three phases. Phase 1 fieldwork (semi-structured interviews with 15 participants, 3 participant observations and field notes) has been completed. Qualitative data are currently being analysed using conventional content analysis. The scoping review component of Phase 1 is planned but has not yet been conducted. Phase 2 (instrument development) is planned to include item generation from qualitative results followed by expert panel review. Phase 3 (psychometric evaluation), scheduled for late 2026, will employ a cross-sectional study to assess face, content and construct validity; reliability; interpretability; and feasibility. This phase features pilot testing (n=30–50), face and content validity assessment (n=10 each), test-retest reliability (n=15) and exploratory and confirmatory factor analyses (n=300–400).

Ethical approval was obtained from the Ethics Committee of Iran University of Medical Sciences. All participants will provide written informed consent. Confidentiality, voluntary participation and withdrawal rights are guaranteed. Findings will be published in peer-reviewed journals, presented at conferences and shared with participating home healthcare centres, policymakers and stakeholders.

To estimate the prevalence and frequency of workplace incivility and bullying across multiple healthcare roles; compare experiences among occupational groups; examine associations with psychological symptoms (stress, anxiety and depression); assess interrelations among mistreatment dimensions (experienced workplace incivility (EWI), witnessed workplace incivility (WWI), instigated workplace incivility (IWI and experienced workplace bullying (EWB)); and evaluate associations with demographic and contextual variables.

Cross-sectional study.

Three teaching hospitals in Arak, Iran, between March and December 2023.

A stratified random sample of 550 healthcare workers was invited; 392 responded (response rate 71.3%) and 359 with complete data were included, comprising nurses, interns, residents, general practitioners and administrative staff.

Workplace incivility (Workplace Incivility Scale), workplace bullying (Negative Acts Questionnaire-Revised) and psychological symptoms (Depression, Anxiety and Stress Scale-21 Items).

The sample (N=359) was 64% female with a mean age of 32 years. Significant differences were observed across occupational groups for WWI, IWI and EWB (all p

Workplace incivility and bullying are widespread across healthcare roles, with broadly comparable exposure across clinical staff. Direct experiences of mistreatment showed the most consistent associations with psychological distress, and mistreatment dimensions appeared to operate within interconnected patterns. Addressing these issues requires system-level interventions targeting structural and cultural drivers to promote psychologically safe clinical environments.

To identify psychosocial and structural barriers to prompt malaria care-seeking in Malawi by applying the Three Delays Model (delay 1: deciding to seek care; delay 2: reaching a facility; delay 3: receiving quality care).

cross-sectional study.

Nationally representative data collected from Malawi communities between 25 May 2021 and 1 July 2021.

913 female caregivers who reported a child with fever in the past 2 weeks.

Prompt care-seeking for fever (same or next day) from a qualified health provider.

Prompt care-seeking was primarily associated with delay 1 (adjusted OR (aOR) 0.58, 95% CI 0.43 to 0.78) and psychosocial (aOR 0.59; 95% CI 0.44 to 0.79) factors. Significant factors included incorrect knowledge of malaria symptoms, cause and diagnosis (aOR 0.71: 95% CI 0.53 to 0.97), negative attitudes towards care-seeking (aOR 0.58; 95% CI 0.41 to 0.82), incorrect knowledge of when and where to seek care (aOR 0.19: 95% CI 0.07 to 0.50) and far distance from a health facility (aOR 0.67, 95% CI 0.49 to 0.93).

Despite the availability of free malaria services, significant bottlenecks remain in the initial decision-making phase. To reduce malaria mortality, national programmes should prioritise social and behaviour change interventions that move beyond general awareness to target specific care-seeking attitudes and intra-household decision-making dynamics.

Post-COVID-19 condition (PCC) has emerged as a major public health concern. We aimed to estimate the 1-year incidence of PCC in adults with confirmed SARS-CoV-2 infection in Lombardy, Italy, comparing community-managed and hospitalised patients and to assess the prognostic value of the National Institutes of Health (NIH) Researching COVID to Enhance Recovery (RECOVER) score to support estimation of long-term PCC prevalence.

Retrospective-prospective observational cohort study enrolling patients infected between 1 March 2020 and 31 December 2022. The study visit was conducted between 16 January and 23 December 2024.

Multicentre study involving seven public hospitals and general practitioners across Lombardy.

Randomly sampled adults aged 18–70 years with confirmed SARS-CoV-2 infection. Hospitalised patients (HP) were admitted for COVID-19; general practitioner patients (GPP) were managed in the community. The total sample comprised: 1162 (546 HP, 616 GPP).

This is an observational study with no active intervention.

Primary outcome: 1-year incidence of PCC retrospectively assessed at the study visit.

Secondary outcomes: symptom profiles, long-term PCC prevalence at the study visit and predictive value of the NIH RECOVER score.

Median age was 57.1 years in HP and 42.9 years in GPP; 66.1% of HP and 47.7% of GPP were male. PCC developed in 280 patients (223 HP, 57 GPP). The 1-year cumulative incidence was 39.9% in HP (95% CI 35.9% to 44.1%) and 9.1% in GPP (95% CI 7.1% to 11.7%). The NIH RECOVER score was associated with PCC at 1 year (OR 1.18, 95% CI 1.14 to 1.21). Model-based long-term PCC prevalence was 31.8% in HP and 6.3% in GPP.

PCC remained frequent and heterogeneous, particularly among previously HP. In this cohort, the NIH RECOVER score showed prognostic value for estimating longer-term PCC burden. These findings underscore the need for structured long-term follow-up across both hospital and primary care settings.

Treatment for women with endometriosis is only partially or temporarily effective. Moreover, medical hormonal treatment is associated with debilitating side effects and interferes with fertility, while surgery has a relatively high risk of complications. Meanwhile, women with endometriosis show increasing interest in implementing lifestyle interventions to alleviate symptoms and improve health-related quality of life (HRQoL). Integrating these lifestyle interventions can provide a holistic approach to the treatment of this debilitating disease. However, scientific evidence supporting the effectiveness of these interventions is limited. This study is designed to investigate the effectiveness of two lifestyle interventions and the combination of both: an anti-inflammatory diet intervention (AIDI) could improve immune cell function and reduce inflammation, resulting in improved HRQoL and alleviating pain. In addition, the integration of cognitive behavioural therapy (CBT) aims to provide insight into pain mechanisms and coping with pain, and to assist in sustaining dietary adjustments.

The Pain in Endometriosis And the Relation to Lifestyle (PEARL) study is a five-arm randomised controlled trial with a pre-post factorial design with two factors: an AIDI and CBT. The study population will consist of 250 premenopausal women, of whom 200 are diagnosed with endometriosis and experience pain symptoms and 50 are healthy controls (HC). Women with endometriosis will be recruited from one academic tertiary and five secondary hospitals in the Netherlands. They will be randomised (1:1:1:1) among four intervention groups: standard care (SC) (SC group), SC and an AIDI (SC + AIDI group), SC and CBT (SC + CBT group), and SC, AIDI and CBT (SC + AIDI + CBT group). Women with endometriosis will visit the hospital twice during the intervention period, at the start (T0) and end (T2) of the 13-week intervention period. HC will not undergo any of the interventions and will have one hospital visit (T0). Participants will complete questionnaires regarding pain symptoms, HRQoL, physical activity level, sleep, diet quality, pain cognitions, and stress at T0 and T2. Furthermore, they are instructed to collect menstrual effluent, a vaginal swab and a faecal sample. During the study visits, peripheral blood will be drawn and scalp hair samples will be taken. The primary outcome is average pain, measured using a numerical rating scale. Secondary outcomes focus on HRQoL, inflammation, immune system characteristics, vaginal- and gut microbiome, and hair cortisol levels. These are considered to reflect potentially underlying mechanisms of the effect of both interventions on the primary outcome. Biological samples and questionnaires of women with endometriosis and HC will be compared to establish the differences in secondary outcomes.

This study protocol has been approved (approval number: NL86247.091.24) by the METC Oost-Nederland from Radboud University Medical Centre on July 11, 2024. Prior to participation, participants are required to provide informed consent. The results will be widely disseminated through scientific peer-reviewed journals, and presentation to a broad audience in scientific meetings, congresses, patient meetings, as well as in policy-relevant forums.

NCT06332560.

Congenital malformations (CMs) are the leading cause of infant mortality. Still, the aetiology remains unknown in 70% of cases. The most accepted hypothesis is that hereditary and environmental elements concur in altering embryo-fetal development. Recently, the role of the environment has been emphasised.

Women are exposed to several xenobiotics during pregnancy. This review aims to study the available literature on the exposure of pregnant women to pesticides through drinking water to see if there is any evidence of correlation to the onset of any kind of congenital anomalies.

We will conduct a systematic literature review in The Cochrane Library, Embase and PubMed for studies published between 1 January 2005 and 31 January 2026. Articles will be included if they examine pregnant women as the study population, exposure to pesticide active ingredients and metabolites present in drinking water, and any type of CM in their children as the main outcome. The screening of title, abstract and full text as well as the data extraction will be conducted independently through two investigators. A third investigator will resolve any eventual conflicts. Each included study will be evaluated according to the NIH’s quality assessment tools. Grading of Recommendations Assessment, Development and Evaluation approach will be used for summarising and assessing certainty in the bodies of evidence produced by the review. This study is registered with PROSPERO, CRD420251063011.

The completed work will be published in a scientific journal for dissemination. Due to the nature of the study, an ethical approval is not necessary since no patient data or other information will be directly collected.

Frostbite is a common reason for emergency department (ED) presentations in Canada. Iloprost, a prostacyclin analogue, has been investigated to reduce the risk of amputation with its use expanding. Two Canadian cities implemented iloprost over different times leading to a practice variation that allowed for treatment comparison. Our objective is to evaluate the effectiveness of iloprost compared with non-iloprost treatment. Secondary objectives include assessing the impact of iloprost dosage and homelessness.

A retrospective cohort study was conducted on adult severe frostbite cases presenting to EDs in Calgary and Edmonton between November 2021 and April 2024. Data were abstracted from clinical databases and analysed for demographic and injury characteristics, treatment and amputation outcomes.

Of 1812 total ED encounters for frostbite, 257 patients with grades 2–4 extremity frostbite were included for analysis. Logistic regression found that overall patients receiving iloprost were associated with reduced likelihood of any amputation (OR=0.49, 95% CI 0.25 to 0.96) and fewer digit amputations (p

Iloprost infusion was associated with a reduction in amputation rates in grade 3 and 4 frostbite with the greatest association seen in grade 3 cases. Greater iloprost dosage was associated with improved digit salvage. Homelessness was associated with delayed ED presentation.

Metabolic dysfunction-associated steatohepatitis (MASH), formerly known as non-alcoholic steatohepatitis (NASH), is the hepatic manifestation of the metabolic syndrome. When it co-occurs with type 2 diabetes (T2DM), it presents a significant therapeutic challenge due to a higher risk of fibrosis progression and adverse outcomes. While new treatments for MASH are emerging, their efficacy in the T2DM subpopulation remains an unmet need. Chiglitazar is a novel peroxisome proliferator-activated receptor pan-agonist that regulates key pathways in lipid metabolism, glucose homeostasis and inflammation. This trial aims to evaluate the efficacy and safety of chiglitazar as a combination therapy for patients with MASH and T2DM.

This is a prospective, multicentre, randomised, double-blind, placebo-controlled study. This trial will enrol 300 adult patients aged 18–75 years with biopsy-confirmed MASH and fibrosis stage F1 or higher. Participants will be randomised (1:1) to receive either chiglitazar 48 mg daily or a matching placebo. All participants will also receive background therapy consisting of vitamin E (100 mg three times a day) and polyene phosphatidyl choline (456 mg three times a day). The treatment duration is 78 weeks. The primary efficacy endpoint is resolution of steatohepatitis with no worsening of liver fibrosis. Key secondary endpoints include improvement in liver fibrosis by at least one stage and changes in metabolic and liver safety biomarkers.

Ethical approval has been obtained from the Shanghai Punan Hospital of Pudong New District Ethics Committee (Punan Branch of Renji Hospital Ethics Committee, Shanghai Jiaotong University School of Medicine). KY2025-066. The findings will be disseminated through publication in peer-reviewed journals and presentations at scientific conferences.

NCT07303803.

Chronic musculoskeletal pain often extends beyond pathology alone. Augmented central pain processing is linked to pain severity, persistence and treatment outcomes. A practical clinical tool is needed to identify individuals likely to have persistent or worsening pain, likely due to augmented central pain mechanisms. Quantitative Sensory Testing (QST) offers mechanistic insight, while the Central Aspects of Pain (CAP) Questionnaire captures symptom profiles that potentially reflect central mechanisms. Combining a brief clinical QST protocol with CAP may support early risk stratification and guide personalised pain management.

This prospective observational study will recruit 250 individuals with inflammatory arthritis, osteoarthritis, chronic low back pain or fibromyalgia from existing cohorts, primary or secondary care. Participants will complete validated patient-reported outcomes at baseline, 6 and 12 weeks, with no additional intervention. The risk stratification tool completed at baseline will include clinical QST (Pressure Pain Threshold, Temporal Summation of Pain, Conditioned Pain Modulation), tender point count and the CAP questionnaire. Baseline laboratory versions of the clinical QST, plus Heat Pain Threshold, Offset Analgesia and the Central Sensitisation Inventory short form-9 questionnaire, will provide pain profiling to evaluate the predictive validity and psychometric properties of the tool. Data collection will include demographics, medical history, cognitive and neurological assessments and sleep quality via actigraphy (Actigraph wGT3X-BT). Interviews with patients and healthcare professionals will inform refinement, feasibility and acceptability of the tool.

Ethical approval was obtained from the Yorkshire & The Humber—South Yorkshire Research Ethics Committee (reference number: 24/YH/1062). Findings will be disseminated through peer-reviewed publications, conference presentations and patient-facing summaries and podcasts. The study aims to develop a clinically feasible tool to identify individuals at risk of persistent or worsening pain due to augmented central pain processing, enabling targeted treatment strategies.

NCT06518278.

To explore administrators’ and clinicians’ views on the factors that influence their use and adoption of a machine learning clinical decision support system (ML-CDSS) to predict patients’ risk of hepatic and renal deterioration during chemotherapy.

This was a qualitative study that used purposive sampling. 18 participants with administration and clinical backgrounds working in cancer care in England were recruited. Qualitative data were collected by conducting semi-structured interviews and a focus group. Data were analysed thematically using the framework method to identify key themes.

Participants acknowledged that monitoring blood chemistry is a core component of chemotherapy as it helps clinicians assess patient fitness and treatment response. The ML-CDSS was perceived as a potentially valuable tool for identifying patients at increased risk of hepatic and renal deterioration, supporting clinical decision-making and enhancing care efficiency. However, several concerns were raised regarding its potential implementation in practice. Participants questioned clinicians’ willingness and capacity to integrate the tool into their existing workflows. Participants also believed it was important to demonstrate the ML-CDSS’s sensitivity, specificity and validity in accurately predicting patients’ risk to build clinicians’ trust in the tool, demonstrating evidence of its efficacy and effectiveness in practice.

Administrators and clinicians recognised the potential benefits of the ML-CDSS to enhance the delivery of chemotherapy by identifying patients at risk for hepatic and renal deterioration. Successful adoption in practice depends on building trust with the tool by being transparent in its development, its effectiveness and impact. Future work should demonstrate the ML-CDSS being used in practice to generate real-world evidence.

Older patients admitted under surgical care have longer length of stay (LOS) and are at risk of functional decline, hospital-acquired complications and geriatric syndromes. Embedded specialist geriatrician models within surgical care teams can reduce length of stay and perioperative complications. Evidence gaps remain regarding the implementation of these models of care and their impact on patient outcomes. This study aims to measure hospital, patient and implementation outcomes of an embedded perioperative geriatric service in a large Australian tertiary referral hospital.

This hybrid type 1 effectiveness-implementation trial involves four services (emergency general, elective general, urology and vascular surgery), with a predicted reach of >2000 patients over 24 months. The intervention consists of a proactive geriatrician-led service providing a comprehensive geriatric assessment and ongoing review during the acute admission. Service evaluation will be via (1) traditional hospital outcomes (primary outcome LOS); (2) implementation outcomes; and (3) patient reported outcomes across three 6 month phases: (1) prior to service implementation; (2) during service implementation and (3) continued service but without active implementation. Data analysis will include descriptive statistics of patient demographics, clinical characteristics and implementation outcomes; cost-effectiveness; univariate and multivariate analysis of outcomes against demographic and clinical characteristics and thematic analysis of qualitative data.

This trial has been approved by the Hunter New England Research Ethics Committee (2024_ETH023259). The findings will be disseminated via peer-reviewed publications and conference presentations. The research team will facilitate adoption more broadly within the health service.

Australian New Zealand Clinical Trials Registry (ACTRN12625000404426)

Some cancers are diagnosed late, making them harder to treat. People with an undiagnosed cancer may use over-the-counter medications to manage non-specific cancer-related symptoms that often mimic other more common, easily treatable conditions. Results from the original Cancer Loyalty Card Study (CLOCS) suggest there may be an increase in purchases of pain and indigestion medication 8–9 months before an ovarian cancer diagnosis. We aim to validate the CLOCS findings by exploring whether a significant change in medication purchases could be an indication for early signs of the following cancer types: oesophageal, stomach (gastric), colorectal (bowel), pancreatic, liver, bladder, endometrial, uterine sarcoma, ovarian and vulval, using data collected through store loyalty cards.

Using a retrospective case-control design, we aim to recruit 1450 participants with one of the cancers of interest (cases) and 1450 participants without cancer (controls) in the UK who (or whose household members) hold a loyalty card with at least one participating high street retailer. We will use pre-existing loyalty card data to compare past purchase patterns of cases with those of controls. To assess cancer risk in participants and their purchasing patterns, we will collect information on demographic characteristics, health risk factors, lifestyle habits and behaviours, family history of cancer and any symptoms experienced prior to diagnosis (cases) and in the last year prior to study recruitment (controls). In addition, cases will be asked about their cancer diagnosis.

CLOCS-2 was reviewed and approved by the East Midlands-Leicester South Research Ethics Committee (23/EM/0224). Study outcomes will be disseminated through peer-reviewed publications, conferences, presentations to the research communities as well as patients and the public, the study website and other social media outlets.

NCT06447064, CPMS58679; pre-results.

Chronic respiratory diseases (CRDs), such as asthma and chronic obstructive pulmonary disease (COPD), are heterogeneous conditions with a high multimorbidity burden. However, existing risk assessment instruments prioritise physiological measures while overlooking systemic comorbidities. We aim to develop and validate an electronic health record (EHR)-embedded artificial intelligence (AI) model—AiRES (AI in patients with RESpiratory disease)—to predict the 30-day, 90-day and 180-day risks of all-cause and index-disease hospitalisations. This model represents a first step towards a clinical decision support tool for personalised multimorbidity management in patients with CRD.

Patients aged ≥18 years with a validated case definition of asthma and COPD will be identified from Singapore health administrative data (2012–2020). Candidate predictors will include age, sex, ethnicity, housing type, and comorbidities, measured across multiple care settings as visit frequency, grouped at quarterly intervals in Year 1 and annually for Years 2 and 3 over a 3-year lookback window. We will predict 30-day, 90-day, and 180-day risks of (1) all-cause and (2) asthma/COPD-specific hospital admissions using up to five randomly selected index dates per individual. Three machine learning algorithms—logistic regression (LR) with Lasso regularisation, eXtreme Gradient Boosting, and Categorical Boosting—will be trained using 10-fold cross-validation (CV) with an ensemble feature selection strategy. The optimal model, selected based on performance and feature importance, will be benchmarked against two reference models: a full LR and a Zero-Inflated Negative Binomial regression with hospitalisation history as the sole predictor. Discrimination and calibration will be assessed using internal-external cluster-based and temporal CV. Clinical utility will be evaluated using decision curve analysis.

This study obtained ethics approval from the National University of Singapore (NUS-IRB-2024-849). Results will be published in international peer-reviewed journals.

To examine whether satisfaction with information provision and involvement in decision-making among people with breast cancer (BC) treated in English hospitals was associated with age and other patient characteristics.

Retrospective population-based cohort study, conducted as part of the National Audit of Primary Breast Cancer and the National Audit of Metastatic Breast Cancer.

National Cancer Patient Experience Survey (CPES) responses linked to National Cancer Registration data for BC patients (stage 0–4) diagnosed between 2017 and 2021.

40 018 patients diagnosed with BC who responded to CPES between 2017 and 2021.

Responses to questions about overall experience of care, satisfaction with information provision, involvement in decision-making and clinical nurse specialist (CNS) contact were examined. The relationships between responses, personal, disease and clinical characteristics were analysed using multivariable Poisson regression.

90% of patients rated their overall care as ≥8 out of 10 (0=very poor; 10=very good), decreasing to 82% for those aged 40 years (p

Most patients reported high satisfaction with their BC care. Satisfaction was consistently lower among younger people and those with advanced disease; this finding might partly reflect more complex pathways but requires further exploration, ideally in partnership with patients to codesign solutions. Actionable remedial strategies are proposed.