Depression and sub-diagnostic depressive syndromes are prevalent and associated with suffering and reduced life expectancy. Access to care is limited even in countries with developed healthcare systems. In this context, it is important to strengthen the self-management expertise of people suffering from depressive symptoms. Smartphones offer the possibilities for improved self-management based on long-term monitoring of symptoms.

The present multicentre randomised controlled trial (the Protecting mental health in times of change (MENTINA) trial) aims to evaluate whether (1) daily smartphone-based monitoring and automatic rule-based feedback+smartphone-based outcome evaluations versus (2) smartphone-based outcome evaluations alone will improve depressive symptoms and other clinically relevant outcomes in participants with current depressive symptoms and/or one or more prior depressive episodes during a 12-month trial period.

The MENTINA trial is a multicentre randomised controlled parallel-group trial conducted in Denmark, Germany and Spain. Participants with current depressive symptoms and/or one or more previous depressive episodes are invited to participate. The included participants will be randomised to (1) daily smartphone-based monitoring and automatic rule-based feedback+outcome evaluations via smartphone (intervention group) or (2) outcome evaluations via smartphone alone (control group). All participants can continue with ongoing treatment in case they receive it. The trial started in May 2025 and has currently included 115 participants. The outcomes are differences between the intervention group and the control group in (1) Patient Health Questionnaire 9-items (PHQ-9) measured every 14th day during the 12-month trial period (primary), (2) WHO Quality of Life-BREF, Generalised Anxiety Disorder-7, monthly change in PHQ-9, proportion of participants with ≥50% reduction in PHQ-9, remission rate defined as PHQ-9≤9 and ≥5-point improvement, PHQ-9 scores after 6 months, area under the curve for PHQ-9 over the 12 months trial period, subgroup analyses in PHQ-9 in participants with or without lifetime depression, Perceived Stress Scale, user-reported healthcare contacts, usability of the app and negative effects, number of depressive episodes+duration and depressive-free days based on PHQ-9. A total of 660 participants will be included in the MENTINA trial.

The MENTINA trial is funded by the European Union under Grant Agreement No. 101 080 651. Ethical approval and approval from Medical Agencies have been obtained from Denmark (CIV-25-02-051094), Germany (CIV-25-02-05109) and Spain (CIV-25-02-051094). The results will be published in peer-reviewed academic journals, presented at scientific meetings and disseminated to patients’ organisations and media outlets.

NCT06919133.

Version 6, January 2026.

Minimally invasive endoscopic procedures constitute the cornerstone of first-line treatment for bulbar urethral strictures, although their long-term effectiveness is limited by high recurrence rates. The Optilume drug-coated balloon (DCB) is a novel intervention combining mechanical dilation with localised delivery of paclitaxel to reduce recurrence by inhibiting scar tissue formation. While its efficacy has been demonstrated in patients with recurrent strictures, its potential as a first-line option in treatment-naïve patients remains unexplored. The FIRST-CARE trial aims to assess the efficacy and safety of Optilume DCB compared with standard endoscopic treatment in treatment-naïve patients with bulbar urethral strictures.

Design: Two-arm, randomised, single-blind (participant), investigator-initiated, parallel-group, multicentre clinical trial. Patients: The study will enrol 140 adult male patients with treatment-naïve, single bulbar urethral strictures ≤3 cm in length. Interventions: All patients will undergo the assigned procedure under general anaesthesia with 1.5 g intravenous cefuroxime. Optilume group patients will receive ≥5 min balloon dilation with localised paclitaxel delivery. The control group will receive standard endoscopic treatment (eg, direct visual internal urethrotomy, laser or dilatation). In both groups, a 12–14 French Foley catheter will be left in place for 3–5 days. Primary outcome: Freedom from repeat intervention within 12 months of follow-up. Primary analysis: Time-to-event will be defined from the date of intervention to the date a repeat intervention is decided (indicated and planned) due to confirmed recurrence, with censoring at 12 months. Groups will be compared using Kaplan-Meier survival analysis and the log-rank test. Cox regression and modified Poisson regression will be used to estimate HRs and relative risks.

The trial is approved by the Danish National Committee on Health Research Ethics (2401370) and will be conducted in accordance with the Declaration of Helsinki and principles of Good Clinical Practice. In line with national guidelines, all eligible patients are counselled regarding available treatment options prior to enrolment. Results will be disseminated via peer-reviewed publications and scientific presentations.

NCT06827210.

To explore patients’ experiences and perspectives on using a direct-to-consumer smartwatch with single-lead electrocardiography (1L-ECG) for ambulatory rhythm diagnostics in primary care.

Qualitative study using semi-structured interviews and thematic analysis.

Primary care patients referred for ambulatory rhythm monitoring in a diagnostic centre.

Eighteen adults with paroxysmal palpitations, of whom nine were female patients (50%), aged 32–85 (median 66) years.

Participants simultaneously wore a smartwatch with 1L-ECG capability (Withings ScanWatch) and a conventional Holter monitor for 7 days.

Patient experiences and perceived barriers and facilitators to smartwatch use for rhythm monitoring, reported after the monitoring period.

Patients found the smartwatch more user-friendly and feasible than the Holter monitor. Difficulties included uncertainty about when to initiate recordings, challenges capturing brief episodes and anxiety triggered by automated algorithm outputs. Participants emphasised the importance of accessible healthcare support for interpretation and reassurance.

This study shows that smartwatch-based 1L-ECG monitoring is feasible and acceptable for ambulatory rhythm diagnostics in primary care. Prior to routine implementation, it is crucial to address the identified challenges: particularly anxiety related to algorithm results, uncertainty about when to record and accessible clinician support.

Structured Early detection of Asymptomatic Liver fibrosis and cirrhosis (SEAL) is a population-based screening programme using non-invasive tests for the early detection of liver fibrosis. This study evaluates the cost implications if the SEAL programme were to be implemented in routine care in Germany.

This study models cost differences with and without the SEAL screening programme. We regress costs of care on patient characteristics (age, comorbidities, sex, liver diseases, liver cancer and liver fibrosis and cirrhosis (LCI) stage) using statutory health insurance (SHI) data from routine care patients with LCI (n=4177). Based on these results, we predict per-patient costs for the patients newly diagnosed with LCI by SEAL (n=45). Costs with and without screening are estimated using patient age and LCI stage distributions from either SEAL or routine care.

SEAL was conducted in two German states. Initial screening was performed by patients’ primary care physicians.

Individuals insured by SHI without a prior diagnosis of LCI, eligible for Check-up 35, a general health check-up programme primarily targeting adults aged 35 and older, conducted by primary care physicians.

Screening via aspartate aminotransferase to platelet ratio index in primary care, for further evaluation serological diagnostics and ultrasound examinations in secondary care and specific assessment for definite diagnosis including transient elastography and liver biopsy for selected cases in tertiary care.

Primary outcome measures: expected 5-year cost changes for SEAL patients diagnosed with fibrosis or cirrhosis compared to costs without a screening programme. Secondary outcome measures: case mix of leading chronic liver disease and LCI stages among patients diagnosed with advanced fibrosis or cirrhosis in SEAL versus routine care without screening.

Screening leads to fewer decompensated cases at initial diagnosis (4.6% in SEAL vs 22.8% in routine care) and thus savings in the costs of care within the first years of diagnosis: total expected costs per case were 2175 lower (bias-corrected bootstrap CIs (BCI): 527 to 3734), and LCI-associated costs were reduced by 1218 (BCI: 296 to 2164). Comparing the savings to the additional costs of diagnosis (range: 1575–1726 per detected LCI case) reveals that average changes in costs with screening range from moderate savings to moderate extra costs.

SEAL liver screening identifies patients in less advanced stages of LCI. If only costs were considered that are directly attributable to LCI, savings within 5 years are unlikely to fully outweigh the costs of screening. However, since this approach might miss additional LCI-related costs, SEAL appears to be cost-neutral compared with routine care when considering total healthcare costs.

The SEAL registration number is DRKS00013460. This study relates to its results.

Combined vascular endothelial growth factor/programmed death-ligand 1 blockade through atezolizumab/bevacizumab (A/B) is the current standard of care in advanced hepatocellular carcinoma (HCC). A/B substantially improved objective response rates compared with tyrosine kinase inhibitor sorafenib; however, a majority of patients will still not respond to A/B. Strong scientific rationale and emerging clinical data suggest that faecal microbiota transfer (FMT) may improve antitumour immune response on PD-(L)1 blockade. Early trials in melanoma with FMT and reinduction of immune checkpoint blockade (ICI) therapy in patients with anti-PD-1-refractory metastatic melanoma were reported in 2021 and demonstrated reinstatement of response to ICI therapy in many patients. Due to anatomical vicinity and the physiological relevance of the gut-liver axis, we hypothesise HCC to be a particularly attractive cancer entity to further assess a potential benefit of FMT in combination with ICI towards increased antitumour immunity. Additionally, HCC often occurs in patients with liver cirrhosis, where liver function is prognostically relevant. There is evidence that FMT may increase hepatic function and therefore could positively affect outcome in this patient population.

This prospective, multicentre, randomised, placebo-controlled, double-blind phase II clinical trial has been designed to assess immunogenicity and safety of FMT via INTESTIFIX 001 combined with A/B in advanced HCC in comparison to A/B with placebo. Primary endpoints are measured as tumour CD8+ T cell infiltration after 2 cycles of treatment with vancomycin, A/B+INTESTIFIX 001 in comparison to vancomycin-placebo, A/B+INTESTIFIX 001-placebo and safety of the therapeutic combination in advanced HCC. INTESTIFIX 001 is an encapsulated FMT preparation by healthy donors with a high alpha-diversity in their gut microbiome for oral administration, manufactured by the Cologne Microbiota Bank (CMB). Sample size was calculated to achieve a specific expected accuracy for the primary immunological endpoint. 48 subjects will be randomised to reach a goal of 42 usable measurements in the modified intention-to-treat set. Subjects will be randomised in a 2:1 ratio to A/B or placebo (28 A/B, 14 placebo).

The study was approved by ethics committee review and the German Federal Ministry of Drugs and Medical Devices. The trial is registered under EU CT no. 2023-506887-15-00. The outcome of the study will be disseminated via peer-reviewed publications and at international conferences.

NCT05690048.

European cardiovascular guidelines recommend systematic atrial fibrillation (AF) screening in community-dwelling high-risk patients. However, little is known about the impact of abnormal screening findings, including AF and non-AF incidental findings on the target population. This gap highlights the need to assess both the benefits and potential harms from patients’ perspectives to fully understand the impact of AF screening. Therefore, the aim of this study is to explore patients’ experiences with AF screening among those who received abnormal findings from ambulatory ECG monitoring.

We conducted a qualitative study using semistructured interviews, analysed thematically. Participants in the PATCH-AF trial, based in Amsterdam primary care, were purposively sampled based on their screening results (AF or non-AF incidental findings), sex and socioeconomic status.

We achieved data saturation after conducting 16 interviews (6 with interviewees diagnosed with AF and 10 with non-AF incidental findings). Participants had a median age of 76 (73–79) years, and 56% were male. Their experiences, whether positive or negative, fluctuated throughout the screening process and depended on their initial motivations for participation in AF screening (seeking extra health checks, finding explanations for pre-existing symptoms or contributing to medical research), expectations and perceived benefits from clarification, diagnostic workup or treatment. Influencing factors included the type of finding (AF or non-AF incidental finding), healthcare provider communication and individual characteristics such as age, socioeconomic status and medical history.

This qualitative study highlights both positive and negative AF screening experiences from the patients’ perspective. It underscores how patients’ motivations and expectations for participation, the type of ambulatory ECG finding and communication and follow-up by healthcare providers shape their overall experiences. Healthcare providers should be aware of these factors to optimise screening consultations. Clear guidelines on communicating abnormal ambulatory ECG findings, especially incidental findings, are warranted.

The Netherlands Trial Register (NTR) number NL9656.

The efficacy and safety of SMS text message-delivered interventions for providing pain self-management education and improving clinical pain outcomes have been demonstrated in several randomised controlled trials. However, little is known about the feasibility and effectiveness of these interventions within Australian hospital settings. The current protocol describes a trial designed to evaluate the effectiveness and implementation of an SMS text message-delivered intervention designed to support patients’ engagement with pain self-management strategies and improve clinical pain outcomes after total knee replacement surgery.

A hybrid, type 1 effectiveness-implementation trial will be conducted at a private hospital in Australia. Participants (n=130) will be randomised to either the intervention group (receiving a pain self-management educational video prior to surgery, plus daily SMS text message reminders for 3 weeks after surgery) or an active control group (receiving the pre-surgery video alone, without text message reminders) in addition to usual care. Effectiveness outcomes will be pain intensity (primary), opioid dose, knee function and pain-related distress and will be recorded at baseline, 3 days, 3 weeks, 6 weeks, 3 months and 6 months after surgery using self-reported surveys. Pain self-efficacy and health-related quality of life will be measured at 6 weeks, 3 months and 6 months post-surgery. Implementation outcomes (Reach, Experience, Adoption, Implementation, Maintenance) will be evaluated using mixed (qualitative and quantitative) methods. This trial represents a first step towards the translation of digitally delivered postoperative support for engaging with pain self-management in the Australian healthcare system.

The study protocol was reviewed and approved by the Austin Health Human Ethics Research Committee (Australia, HREC/110142/Austin-2024). Study results will be published in a peer-reviewed journal and presented at scientific and professional meetings.

ACTRN12624001060538