Primary sclerosing cholangitis (PSC) is the classical hepatobiliary manifestation of inflammatory bowel disease (IBD). No therapy currently halts disease progression. The strong gut–liver axis implicated in PSC pathogenesis supports the investigation of microbiome-targeted treatments. Oral vancomycin (OV), an antibiotic with potential immunomodulatory properties, has shown encouraging results in improving clinical symptoms and liver biochemistry in PSC. However, prospective data on its safety and efficacy remain limited.

Oral Vancomycin for primary sclerosing Cholangitis in ITaly (VanC-IT) is a phase II, dose-finding, randomised, placebo-controlled, trial designed to evaluate the efficacy and safety of OV in patients with PSC, with or without underlying IBD. Adults and adolescents aged 15–75 years will be enrolled following a 10-week screening and run-in period and randomised in a 1:1:1 ratio to receive either placebo, OV 750 mg/day or OV 1500 mg/day for 24 weeks. Randomisation will be stratified by baseline liver stiffness (

The protocol has been approved by the Ethics Committee CE Brianza on 10 February 2023, number 4017. Trial registration number NCT05876182. Participants will be required to provide written informed consent. The results of this trial will be disseminated through national and international presentations and peer-reviewed publications.

NCT05876182.

Cardiovascular disease (CVD) risk remains high but unevenly distributed in patients with type 2 diabetes mellitus (T2DM). Current risk stratification strategies are far from optimal, leading to both undertreatment and overtreatment of patients. The STENO INTEN-CT trial aims to evaluate a strategy of improved CVD risk management by using cardiac CT (coronary artery calcification (CAC)) for stratification and tailoring of multifactorial cardiovascular treatment based on CAC score. We hypothesise that (1) intensified medical treatment will lower CVD event rates in high-risk patients (CAC≥100), and (2) less intensive multifactorial treatment is safe in very low-risk patients (CAC=0).

The Steno INTEN-CT trial is an investigator-initiated, pragmatic, open-label, event-driven randomised controlled trial including patients with T2DM without known CVD. All participants (expected n=7300) will be invited for a non-contrast coronary CT scan. After the scan, participants will be randomised to either standard treatment (blinded for CAC results) or CAC-based treatment. Participants in CAC-based treatment and their general practitioner (GP) will receive information on CAC and a recommendation of multifactorial treatment. High-risk participants in the interventional arm will be invited for one or more initial study visits to intensify treatment with a combination of sodium glucose co-transporter 2 inhibitors, glucagon-like peptide 1 receptor agonists, high-dose lipid-lowering, antihypertensive and antithrombotic treatment. Very low-risk patients in the interventional arm will be recommended less intensive treatment targets. After initial study-related activities, all participants will continue to be taken care of by their GP guided by specific treatment recommendations. The primary outcome in the primary hierarchical analysis (the rate of the combined CVD endpoint of cardiovascular death, non-fatal myocardial infarction, non-fatal stroke and hospitalisation for heart failure) will be monitored through national health registries. The trial is event-driven, but a median follow-up of 5 years is expected. Key secondary outcomes include patient-reported outcomes, quality-adjusted life years and healthcare costs.

The protocol V.1.9 is approved by the Research Ethics Committee and the Danish Medicines Agency and the Danish Data Protection Agency. The results of the study—positive, negative or neutral—will be published in peer-reviewed journals and through www.clinicaltrials.org.

NCT05700877.

Breast cancer is the most common cancer in women worldwide. While research in recent decades has focused on minimising treatment, the disease still impacts women’s lives in many ways. Because increased sleep disturbances affect approximately...

Cardiovascular autonomic neuropathy (CAN) is a serious, untreatable complication of diabetes that contributes to excess cardiovascular mortality and morbidity. CAN is associated with increased fibrosis and inflammation, possibly driven by increased sympathetic activity and overactive mineralocorticoid receptors (MRs). These may represent a potential therapeutic target. MR antagonists (MRAs) improve autonomic function in non-diabetic diseases, and finerenone, a non-steroidal MRA, has demonstrated promising results in managing diabetic kidney disease and cardiovascular complications, suggesting its potential as a novel therapy for early-stage CAN. This trial aims to evaluate whether daily administration of finerenone can modify the disease progression of early-stage CAN.

This trial is a two-centre, double-blind, parallel-group, 1:1 randomised, placebo-controlled study evaluating the effect of 78 weeks of intervention with finerenone or placebo on early-stage CAN in 100 individuals with type 2 diabetes in Denmark. The primary endpoint is the between-group difference in the expiration:inspiration ratio of the cardiovascular autonomic reflex tests (CARTs). Secondary endpoints are the between-group differences in the remaining CARTs, heart rate variability measures and fibrosis markers. Treatment effects on other forms of neuropathy and related pathological mechanisms will be explored.

The study complies with the Declaration of Helsinki and the International Counsil for Harmonisation good clinical practice guidelines, with ethics approval obtained from the Danish Medical Research Ethics Committee. All participants will provide written informed consent. Due to the risk of hyperkalaemia associated with finerenone, safety will be closely monitored throughout the study. Findings will be disseminated through peer-reviewed publications, conference presentations and clinical trial registries. A lay summary will be provided to participants on study completion.

ClinicalTrials.gov: NCT06906081; registration date: 25 March 2025. Clinical Trials Information System: EUCT no. 2024-516597-30-00; registration date: 3 September 2024.

Only symptomatic treatments are available for patients with Parkinson’s disease (PD), the second most common chronic neurodegenerative disease worldwide, and it is therefore imperative to identify disease-modifying interventions that can alter the course of the disease. Epidemiological studies in PD patients suggest that a Mediterranean diet is associated with better motor and non-motor symptoms, slower progression and reduced mortality. Few interventional studies, however, investigated the relationship between diet and PD severity and progression. This study aims to determine whether a Mediterranean nutritional intervention can benefit motor and non-motor symptoms experienced by PD patients. As a secondary aim, the effects of a modified Mediterranean diet on the immune system, metabolomics and microbiome will also be assessed.

This is an interventional, non-pharmacological, superiority, randomised, controlled, single-centre, masked study with two parallel groups to evaluate the efficacy and safety of a modified Mediterranean diet on motor and non-motor patient-reported symptoms. PD patients meeting inclusion criteria will be enrolled (44 participants, aged between 40 years and 85 years), block-randomised and split into two parallel arms to either maintain their usual diet (control) or follow a modified Mediterranean diet for 6 months (intervention).

Patient-reported symptomatology is the primary outcome, measured through the Movement Disorders Society Unified PD Rating Scale (MDS-UPDRS) I+II score. Secondary outcomes include the immunophenotype of circulating cells of the adaptive immune system, the nasal and faecal microbiome composition, faecal and urinary metabolites and the measurement of inflammatory and metabolic markers. Disease severity (MDS-UPDRS III), non-motor symptomatology (Non-Motor Symptoms Scale), participant’s well-being (36-Item Short Form Health Survey), gastrointestinal symptomatology (Gastrointestinal Symptom Rating Scale and the Patient Assessment of Constipation Quality of Life) and intensity of dopaminergic replacement therapy (levodopa equivalents) will also be assessed. Evaluations will be conducted before the start and at the end of the intervention.

The Ethical Committee ‘Comitato Etico Territoriale Lombardia 5’ first approved this study on 17 September 2024 Prot. Nr. 420/24. Findings will be disseminated via peer-reviewed research papers and conference presentations.

NCT06705517.

There are global concerns about the rise in opioid prescribing. Patients undergoing potentially curative surgery for colorectal cancer (CRC) are at high risk of adverse outcomes from opioid-related complications, including delayed discharge and adjuvant chemotherapy, long-term opioid use and reduced cancer-free survival. We aimed to develop a set of actionable quality indicators for opioid stewardship for patients undergoing CRC surgery, and an implementation toolkit to support professional behaviour change to improve appropriateness of perioperative opioid prescribing.

A five-round modified RAND consensus process was conducted in 2021–2024.

14 secondary care trusts across the UK Yorkshire and Humber region.

Consultant anaesthetists and national perioperative opioid stewardship experts (expert panel) and patient and public panel.

Potential indicators were identified from a literature review, guideline search and expert panel. All potential indicators were rated on relevance and actionability (online survey, expert panel) and importance to patient care (online meeting, patient panel). A hybrid consensus meeting involving a patient representative and the expert panel discussed and rerated the indicators. An online expert survey identified potential barriers to implementation. An actionable toolkit was developed using implementation strategies and supporting resources developed where appropriate.

73 potential indicators were identified. All indicators remained in the process through the online survey and patient panel. After the final meeting, four indicators remained: (1) hospital trust presence of an opioid stewardship protocol; (2) inpatient functional post-operative pain assessments; (3) patient education and discharge leaflet; and (4) senior clinician review of ‘strong’ opioids on discharge (British National Formulary definition). The number of barriers identified ranged from 8 to 22 per indicator. 49 different implementation strategies were identified for the toolkit (range 32–45 per indicator).

We identified four actionable quality indicators and developed an implementation toolkit that represents consensus in defining quality of care in opioid stewardship for CRC surgery.

Carers of people with non-memory-led dementias such as posterior cortical atrophy (PCA), primary progressive aphasia (PPA) and behavioural variant frontotemporal dementia (bvFTD) face unique challenges. Yet, little evidence-based support and guidance are available for this population. To address this gap in services, we have developed a novel, web-based educational programme: the Better Living with Non-memory-led Dementia programme (BELIDE). BELIDE was co-designed with people with lived experience of non-memory-led dementia and a previous pilot study confirmed its feasibility as an online intervention. This protocol outlines the randomised controlled trial (RCT) to evaluate the clinical and cost-effectiveness of BELIDE.

This is a parallel-group, single-blind, RCT of 238 unpaid caregivers of people diagnosed with PCA, PPA or bvFTD recruited internationally among members of the UK-based organisation Rare Dementia Support. The intervention (BELIDE programme) consists of six structured online educational modules tailored to each phenotype, a virtual onboarding session, real-life practice tasks and up to two follow-up facilitation sessions. The group receiving the intervention will be given access to the programme, while the control group will receive treatment as usual and be placed on a wait-list to receive access to the programme once they complete their participation in the trial. The allocation ratio will be 1:1 stratified by dementia diagnosis and gender. The primary outcome is reduction in caregiver depressive symptoms. Secondary outcomes include stress, anxiety, self-efficacy, quality of life and caregiver-patient relationship quality. Data will be collected online via Qualtrics surveys at baseline, 8 weeks and 6 months post-randomisation. A mixed-method process evaluation with a subgroup of intervention participants will explore barriers and facilitators for engagement. A health economics evaluation will also be conducted to assess cost-effectiveness. If effective, this programme could improve access to caregiver support for non-memory-led dementias by providing scalable, tailored education.

Ethical approval has been granted by University College London Research Ethics Committee (8545/007). The results will be disseminated via peer-reviewed publications, conferences, stakeholder events and open-access resources.

This trial has been registered prospectively on the Clinical Trials registry, first posted on 5 February 2024 under registration number NCT06241287.

To measure the perceived autonomy level in managing lower respiratory tract infections (LRTIs) among paediatric residents and to compare perceived autonomy with the assessments by tutors who directly supervise and evaluate residents

A survey on managing LRTIs was distributed among all Italian paediatric residents and tutors via Google Forms between January 1 and 31, 2024.

Participants, residents and tutors were classified according to their training year and clinical setting: primary care paediatrics (PCP), emergency department (ED) and hospital ward (HW).

Perceived autonomy of paediatric residents in managing LRTI in different settings; overall perceived autonomy and interest in employment.

A total of 391 questionnaires were returned, with 273 completed by residents and 118 by tutors. Among residents, 3% in their first year felt fully capable of managing LRTIs without supervision in both ED and HW settings. This percentage remained below 25% until the third year and increased to 72% in ED and 83% in HW by the fifth year. In PCP settings, autonomy ranged from 15% in the first year to 96% in the final year. No differences were found between residents’ self-evaluations and tutors’ assessments. Confidence in skills showed no regional differences across Italy.

Most residents did not feel ready to manage winter respiratory infections in children without supervision, especially in the ED compared with the HW; however, self-confidence was higher in the PCP setting. Tutors shared similar perceptions. The location did not affect the response pattern. These findings caution against employing residents to work autonomously, particularly in emergency settings.

Many observational studies showed that sedentary behaviours1 and low serum levels of vitamin D2 are independent risk factors for mortality in cancer survivors. Nevertheless, data from trials on vitamin D supplementation3 and interventions promoting physical activity4 did not obtain the effect on mortality in cancer survivors that...