Up to 30% of individuals with depression develop persistent depressive disorder (PDD), an often disabling and difficult to treat condition. The Cognitive Behavioural Analysis System of Psychotherapy (CBASP) is the only psychotherapy developed specifically for treating individuals with PDD. While several randomised controlled trials (RCTs) have demonstrated its efficacy in outpatient settings, evidence for its use in inpatient settings remains limited. Pilot studies of CBASP inpatient programmes in Germany have shown promising feasibility and effectiveness; however, no RCTs to date have systematically evaluated their outcomes. This study represents the first RCT to compare the short- and long-term efficacy and safety of CBASP with Behavioural Activation (BA), a first-line psychotherapy for depression, within an intensive multimodal inpatient setting.

In this prospective, multicentre, rater-blinded RCT with an active control group, we aim to recruit 396 adults (aged 18–70 years) with treatment-resistant PDD at eight German university hospitals. Participants will be randomly assigned to receive either (1) CBASP or (2) BA within an intensive treatment programme consisting of 10 weeks acute treatment in an inpatient and/or day clinic setting, followed by 6 weeks of outpatient continuation treatment. Primary and secondary outcome assessments will be conducted at multiple time points: baseline (T0), treatment onset (T1), after 5 and 10 weeks of acute treatment (T2, T3), at the end of continuation treatment (T4, week 16) and every 2 months up to week 64 (T5, naturalistic follow-up).

The primary outcome measure will be the change in depression severity, as assessed by the Hamilton Depression Rating Scale (24-item version), after 16 weeks of treatment (from T0 to T4). Secondary outcomes will include response, remission, deterioration and relapse rates, self-reported depression and anxiety symptoms and additional psychological variables. A cost-benefit analysis will evaluate the health-economic benefits of both interventions. Additionally, this RCT will explore personalised treatment selection and mechanisms of change, including potential moderators and mediators of treatment effects. The findings from this trial are expected to provide clinicians with evidence-based guidance on choosing CBASP versus BA for inpatients with treatment-resistant PDD.

This study has received ethical approval from the ethics committees of all participating university hospitals. All participants will provide written informed consent before enrolment. Study findings will be published in peer-reviewed journals and presented at national and international conferences. We have involved people with lived experience from the earliest pilots onward, using their feedback to refine our study design. Ongoing consultation at conferences and public events has further ensured that our research remains grounded in patient perspectives.

NCT04996433.

Despite the availability of curative treatments, hepatitis C diagnosis and treatment coverage is suboptimal globally with few countries on track to achieve the WHO’s 2030 elimination targets. In 2022, an estimated 50 million people were living with hepatitis C, with 1 million new infections annually. Most people living with hepatitis C reside in low- and middle-income countries, and people who inject drugs are disproportionately affected by hepatitis C.

Continuing simplification of diagnostic pathways and treatment care models is required to improve linkage to care and reduce costs associated with hepatitis C treatment and cure.

This study is a multi-country non-randomised, quasi-experimental, prospective comparative two-arm trial. It aims to assess the feasibility of implementation, retention in hepatitis C care and achievement of cure and cost-effectiveness outcomes, comparing two simplified hepatitis C testing and treatment pathways.

Arm 1 is a standard simplified test and treat model of care following global guidance, and arm 2 is an innovative rapid, same-day treatment initiation model of care using a presumptive treatment approach based on shortened read-time of the point-of-care OraQuick hepatitis C antibody test result. Secondary outcomes include assessing the accuracy of the OraQuick hepatitis C antibody test in predicting viraemia and the acceptability of each pathway.

This study will be implemented in Armenia, Georgia and Tanzania. Treatment-naïve people who inject drugs aged over 18 years in each country will be eligible for enrolment.

Recruitment commenced in October 2024 in Armenia, June 2025 in Georgia and August 2025 in Tanzania and is anticipated to close by December 2026.

This trial has been reviewed by WHO Ethics Review Committee (ERC), Alfred Hospital Ethics Committee (Australia) and local country ERCs. Alongside journal publications and conferences, the results from this study will be disseminated through summary reports and workshops with key stakeholders and with communities of people affected by HCV through relevant organisations/networks, including the global Community Advisory Board (CAB). The study results will inform national scale-up of simplified care models and inform potential pathways for further simplification of care models, including the potential for one-step diagnostic pathways and same-day treatment in particular scenarios for the three study countries, and other low- and middle-income countries globally.

NCT06159504.

Ensuring equity in medical specialist distribution is essential for achieving universal health coverage (UHC). This study explored the changes in the availability and distribution of medical specialists in Thailand from 2015 to 2024 and assessed the equity impacts on workforce.

A retrospective longitudinal analysis of national administrative workforce data.

Public and private hospitals across Thailand, covering 1471 facilities in 77 provinces.

The primary outcomes were specialist-to-population ratios and geographical equity measured using the Gini coefficient (G), where values closer to 0 indicate greater equity. Explanatory variables included specialty type, geographical region and the timing of major workforce policies, including mandatory service and specialty-specific legislative interventions.

Between 2015 and 2024, the GPs and specialists in Thailand expanded significantly, with improvements in both density and distribution. The Gini coefficient for GPs showed the largest equity improvement (G=0.42 in 2015 and G=0.22 in 2024), reflecting the impact of mandatory service programme and rural recruitment programmes. Among specialists, emergency and family medicine have shown rapid growth and significant reductions in distribution inequity, reflecting the success of legislative policies. Sustainability of workforce policies was challenged by the ‘leaking stock’ phenomenon due to attraction of career opportunities and economic drives.

Workforce targeted interventions have led to improvements in the availability and equitable distribution of GPs and medical specialists over the past decade. Further policy, such as retention incentives and assisted technology, is needed to achieve equitable distribution across all specialties, particularly in low-density fields. Thailand’s experience offers the lessons for other low- and middle-income countries as the evidence-based and equity-focused workforce policies for UHC advancement.

To adapt the SOCAV programme—originally developed for residential dementia care—for home care use, and to evaluate its feasibility and potential to foster behavioural change in nurses and informal caregivers supporting self-direction in people with dementia.

Development and feasibility study guided by the Medical Research Council framework for complex interventions. Feasibility was evaluated using Bowen’s framework (demand, acceptability, practicality, implementation, limited efficacy). Data collection involved semistructured interviews, focus groups and reflective coaching diaries, as well as validated outcome measures (self-direction, quality of life and depressive symptoms) assessed at multiple time points. Qualitative data were analysed using qualitative content analysis (Bowen’s feasibility framework) and constant comparative analysis; quantitative data were analysed descriptively.

Two home care teams in different Dutch municipalities.

Development phase: 16 participants (4 people with dementia, 6 informal caregivers, 6 nurses). Feasibility phase: 59 participants (12 people with dementia, 14 informal caregivers, 33 nurses).

SOCAV-Home Care integrates person-centred communication training with reflective coaching for nurses and joint meetings involving people with dementia and informal caregivers. It aims to embed self-direction into daily care routines.

The programme was feasible and well-received, though demanding. Nurses reported increased reflection, more person-centred communication and greater professional confidence. Informal caregivers showed attitudinal shifts from control to autonomy-supportive care. Programme complexity, scheduling difficulties and emotional burden contributed to dropout. Quantitative trends showed reduced behavioural symptoms in people with dementia, though no statistical analysis was performed due to sample size.

SOCAV-Home Care shows potential to foster behavioural change in nurses and informal caregivers, promoting self-direction and relational care in dementia home care. Findings, grounded in rich reflective data, offer a valuable foundation for further evaluation. Simplifying delivery and enhancing flexibility are key to broader implementation. Future research should evaluate the sustainability strategies proposed and examine long-term outcomes in diverse home care contexts.

NCT07347639; Post-results.

Allergic rhinoconjunctivitis (ARC) is a highly prevalent immune-mediated condition associated with substantial symptom burden, impaired quality of life and increased healthcare use. Emerging evidence highlights the role of the gut microbiome in immune regulation and allergic disease. Fermented foods may contain live microbes (when unpasteurised or uncooked) and bioactive postbiotic metabolites that can modulate immune responses. Despite growing interest in dietary strategies targeting the microbiome, no randomised controlled trial has compared fermented versus unfermented red cabbage for ARC.

This single-centre, randomised, controlled trial with a sensory-matched, unfermented cabbage comparator investigates the effects of daily consumption of fermented red cabbage for 8 weeks compared with an unfermented red cabbage control in young adults (18–35 years) with ARC. A total of 158 participants will be randomly assigned (1:1). The primary outcome is change in Total Nose and Eye Symptom Score from baseline to week 8. Secondary outcomes include daily symptoms and medication use captured via mobile ecological momentary assessments, quality of life, psychological well-being, gastrointestinal symptoms, systemic inflammatory markers, total IgE, immune cell profile and metagenomic characterisation of stool samples. A nested qualitative component explores participants’ experiences and acceptability of the intervention. Analyses will include mixed-effects models, time-series analyses incorporating daily pollen counts and comprehensive microbiome statistics. Safety outcomes and adverse events will also be assessed.

This study was approved by the Ethics Committee of Charité—Universitätsmedizin Berlin (EA4/043/25) and is conducted in accordance with the Declaration of Helsinki and Good Clinical Practice. Results will be disseminated through peer-reviewed publications, conference presentations and a lay summary provided to participants. Anonymised datasets and analysis scripts will be made available in public repositories, and metagenomic sequencing data will be deposited in an international sequence archive to ensure transparency and reproducibility.

DRKS00036475.

Stress and burnout are pervasive among physicians. Academic physicians who are female and physicians who are under-represented in medicine (URM) face inequities in the workplace and beyond. Understanding their experiences is crucial for workforce sustainability and diversity, especially given the disproportionate effects on these individuals and overall workforce capacity.

To qualitatively explore the perspectives of academic female and URM physicians and identify key themes affecting their careers and well-being.

Semi-structured interviews were conducted with 30 physicians at an urban academic health system. Interviews were audio-recorded, transcribed and thematically analysed using a general inductive approach. Interview guides were informed by prior literature and constructs.

None.

Female and URM physicians from a large, academic medical centre were recruited via email. Participants self-reported demographic information, including sex, race, ethnicity and tenure.

The primary outcomes encompassed the main themes identified through the analysis of interviews with female and URM physicians regarding their perspectives on well-being, mental health and academic medicine.

30 female or URM physicians were interviewed (27 (90%) female; 14 (47%) black, Asian or multi-racial). Thematic analysis revealed four key themes: physician identity (URM, female, family), well-being in the workplace (emotional health, staffing burden, non-clinical responsibilities), barriers to accessing well-being resources (workplace environment, culture, overgeneralisation) and facilitators to well-being (physician camaraderie, leadership support). Physicians discussed how their identities influenced their experiences of well-being. They highlighted emotional health challenges, staffing burdens and administrative tasks contributing to stress. Barriers to accessing resources included workplace culture and broad-based interventions, while supportive leadership and camaraderie were identified as facilitators of access.

Female and URM physicians face systemic challenges impacting their well-being and careers. These findings underscore the need to address systemic changes and specifically design programmes focused on promoting the well-being and inclusivity of female and URM physicians. Tailored interventions to these individuals, supportive leadership structures and collaborative working cultures are crucial for addressing these issues and sustaining a diverse physician workforce.

Optimising post-operative pain management is crucial for recovery in orthopaedic surgery. Methadone has attracted interest due to its long half-life, N-methyl-D-aspartate -receptor antagonism and potential to reduce post-operative opioid consumption. Existing reviews combine multiple surgical populations, limiting applicability to orthopaedic settings. This protocol outlines a systematic review assessing the analgesic efficacy and safety of peri-operative methadone in adult and adolescent orthopaedic patients.

This review will include randomised controlled trials evaluating intravenous peri-operative methadone vs placebo or standard analgesic regimens in orthopaedic surgery. Primary outcomes are post-operative rescue opioid consumption and pain intensity within 72 hours. Secondary outcomes include adverse events, mobility scores and the length of hospital stay. If available data permit, a methadone dose–response pattern may be investigated. Searches will be conducted in MEDLINE (Ovid), Embase (Ovid), CINAHL, CENTRAL, Web of Science and ClinicalTrials.gov without date restrictions. Two reviewers will independently screen studies, extract data and assess risk of bias using the Cochrane risk-of-bias tool for randomised trials. When appropriate, random-effects meta-analysis methods will be performed. Certainty of evidence will be assessed using Grading of recommendations assesment, development and Evaluation (GRADE).

As this study uses previously published data, ethical approval is not required. Findings will be disseminated through a peer-reviewed publication and conference presentations.

CRD42025616291.

Laparoscopic hiatal hernia (HH) repair is associated with a high recurrence rate. Repair reinforced with mesh lowers short-term recurrence but can cause dysphagia and visceral erosion. Results of the PRIME trial, in which non-absorbable mesh reinforcement of the posterior crural repair was investigated, showed equal recurrence compared with primary suture repair after 6 months. This study investigates the use of circular absorbable mesh reinforcement in primary HH repair.

Prospective double-blinded randomised controlled superiority trial comparing two laparoscopic procedures for HH repair (110 vs 110). Adult patients with proven HH Skinner types II–IV (defined by preoperative CT scan) are included. Patients are randomised to undergo a laparoscopic primary crural repair with sutures alone or suture repair augmented with biosynthetic absorbable, circular mesh at the hiatus. Radiologic integrity of the hiatal repair 1 year after surgery is the main endpoint. Secondary objectives are clinical recurrence of the hernia, development of postoperative reflux disease, postoperative side effects and satisfaction with surgical outcome. Outcome assessors are blinded to allocation. Data are collected at baseline, and follow-up includes interviews and digital questionnaires at 3, 12, 24, 36, 48 and 60 months, as well as CT scan at 12 and 60 months. All patients randomised will be analysed according to the intention-to-treat principle.

Ethics approval has been obtained by the local ethics committee at Isala, Zwolle, the Netherlands (Medical Ethics Review Committee (METc) Isala, study number: 190516). METc Isala is no longer active; all duties have been taken over by METc of the University Medical Center Groningen. The trial’s results will be submitted to a peer-reviewed international journal as well as (inter)national conferences.

Registered in the Dutch national trial registry: OMON (NL-OMON48062).

The functional resonance analysis method (FRAM) is increasingly used to analyse healthcare processes. FRAM uses four steps to analyse a process and its potential variability. We systematically reviewed studies using FRAM in healthcare on how the four steps in FRAM are reported, defined and supported by data.

Systematic review following the preferred reporting items for systematic reviews and meta-analyses 2020 guidelines.

Web of Science, PubMed, Embase, Scopus, PsycINFO, Dimensions and Lens were searched up to December 2025.

All peer-reviewed studies using FRAM in a healthcare context that presented a FRAM visualisation were included. The papers had to be written in English.

Two independent reviewers screened titles and abstracts, and subsequently the full text of selected papers. Data was extracted reporting on the steps of FRAM, how functions were supported by data, and the functions and couplings of the visualisations.

Sixty-eight papers were included, of which 20 (29%) reported at least one aspect of all four steps in FRAM. While most studies (85%) described how functions were supported by data, the methods used varied widely. Terminology was interpreted differently concerning variability, the output of variability and the effect of combined variability.

Most FRAM studies in healthcare do not report all steps of FRAM, and interpretations of key terms differ. FRAM studies should more clearly describe which steps of the method are conducted, and how data is collected and analysed. Refinement of FRAM guidelines, particularly on data use and terminology, would enhance consistency and comparability across studies.

CRD42024592858.

The primary objective of this clinical trial is to determine the clinical and cost-effectiveness of psychoeducation and emotional stabilisation (PES), together with eye movement desensitisation and reprocessing (EMDR) plus treatment-as-usual (TAU) in reducing symptoms of post-traumatic stress disorder (PTSD) among adults with intellectual disabilities compared with TAU. Secondary objectives include: (1) determining whether PES/EMDR plus TAU is superior to TAU in improving mental health problems and quality of life (QoL) among adults with intellectual disabilities who had a diagnosis of PTSD and (2) completing a process evaluation to examine intervention implementation and acceptability.

This is a two-arm parallel single-blind randomised controlled trial comparing PES-EMDR+TAU to TAU including an internal pilot phase. Outcome data will be captured prior to randomisation, and at 4 (after PES), 8 (after EMDR) and 14 months postrandomisation by masked assessors. 144 adults with intellectual disabilities with a diagnosis of PTSD will be allocated (1:1) randomly using minimisation from National Health Service (NHS) community and inpatients services for adults with intellectual disabilities in England. Participants are eligible to take part in this trial if: (1) they are aged 18 or older, but younger than 66, (2) have a Full Scale IQ

The primary outcome will be assessed using an intention-to-treat analysis. Baseline characteristics will be compared between arms to determine whether any potentially influential imbalance occurred. The primary outcome will be analysed by analysis of covariance, adjusting for baseline values of the outcome and any variables used in the randomisation process. Secondary outcomes will be analysed using linear or logistic regression models as appropriate reflecting the distribution of the outcome variable. The treatment effect will be estimated as an adjusted difference between sample means, presented with 95% CIs and p values. A complier average causal effect analysis will be considered should the data availability be sufficient to estimate the impact of non-compliance. A series of subgroup analyses on the primary outcomes will be considered considering differences in the Impact of Event Scale–Intellectual Disabilities scores at 14 months for (1) differing levels of general intellectual functioning and (2) PTSD versus complex PTSD.

This clinical trial was designed to allow for conclusions about whether PES/EMDR+TAU is efficacious in reducing symptoms of PTSD, relative to TAU, for adults with intellectual disabilities. A favourable ethical opinion has been received from an NHS ethics committee in the UK. The findings from this trial will be published within peer-reviewed journals and shared at national and international conferences. We will also aim to record and distribute podcasts detailing our findings together with our partners.

ISRCTN35167485.

This study investigates how lean management (LM) practices align with and contribute to strategic objectives in healthcare using the congruence model as a conceptual framework.

This study employed a qualitative research design, integrating both inductive and deductive approaches. Data were collected from multiple hospital departments using primary and secondary sources. Primary data included semi-structured interviews, guided by a standardised interview protocol. Secondary data consisted of reports on courses of action, annual reports, policy documents and findings from exploratory meetings. The analysis involved iterative cycles of open coding, axial coding and selective coding to systematically identify and refine themes, supporting thematic analysis.

Six departments: Kidney and vascular surgery, Care core movement, Clinical department, Systemic diseases, Oncology, Care core Hepato-Pancreato-Biliary disease (HPB), which were part of one business unit within a tertiary care institution, a University Medical Centre in the Netherlands.

22 respondents aged 18 years or older were purposefully selected based on their organisational roles and LM experience. Respondents had to be involved in LM practices, which meant they had to understand LM and have passed at least one LM training programme, or they should be enrolled in a training course during the research.

Interviewees identified several barriers to LM implementation, including insufficient management support for a culture of continuous improvement, limited time for LM projects, inadequate recognition from management and poor communication of strategic objectives. Despite positive individual experiences with LM projects, their contribution to strategic objectives was deemed limited due to these barriers. Specific challenges included an experienced lack of leadership commitment, inadequate follow-up on projects, insufficient resource allocation, limited access to training and leaders failing to acknowledge employee value. Facilitators of success were fostering a culture of continuous improvement, committed managers and providing training.

LM practices have the potential to contribute to strategic objectives in healthcare organisations by reducing waste, improving patient care quality and optimising processes. However, their impact is constrained by organisational barriers and misalignments. Challenges such as insufficient resources, poor project follow-up, lack of management support and the absence of a continuous improvement culture minimise LM’s effectiveness.

Postictal agitation (PIA) is a common adverse effect following electroconvulsive therapy (ECT). Current pharmacological treatments for PIA have undesirable side effects, and interventions to prevent PIA are unsatisfactory. The aim of this study is to assess the effect of peri-interventional music on PIA for patients undergoing ECT. Additionally, the study will assess the impact of music on pretreatment anxiety and post-treatment cognitive impairment.

This multicentre, open-label, parallel randomised controlled trial (RCT) aims to include 92 patients from two centres in Rotterdam, the Netherlands. Participants will be randomised into two groups: a music intervention group and a control group. The music group listens to recorded music 30 min before and 12 min after each of the first six ECT sessions of the full ECT course, while the control group will receive standard care. The primary outcome is the presence of PIA, measured using the Richmond Agitation-Sedation Scale (RASS). Secondary outcomes include the severity and duration of PIA, pretreatment anxiety, recovery duration, peri-treatment medication requirements, cognitive impairment and depression severity. Data will be analysed according to an intention-to-treat principle.

This study protocol has been approved by the Medical Ethical Review Committee of the Erasmus Medical Centre on 28 January 2025 (MEC-2024–0467) and subsequently received local approval at Antes Parnassia group. The trial will be carried out following the Declaration of Helsinki principles. Study results will be reported in a peer-reviewed journal according to the Consolidated Standards of Reporting Trials guidelines.

NCT06817330.

To analyse demographic trends and decision-making patterns regarding prenatal diagnosis (PND) in couples at risk for hereditary haemoglobinopathies at the Thalassemia and Rare Haematological Disease Centre in Turin over a 40-year period.

Retrospective observational study analysing demographic and clinical data from 1983 to 2023.

Tertiary care genetic service Centre in Orbassano (TO), Northern Italy.

Couples seeking genetic counselling and PND for hereditary haemoglobinopathies. Selection criteria included couples at risk of having children affected by β-thalassaemia major or Sickle Cell Disease (SCD).

Primary outcomes included acceptance rates of PND and pregnancy termination (TOP). Variables analysed included couples’ age at first consultation, age at first PND, birthplace, employment status, specific haemoglobinopathy risk and number of pregnancies.

The analysis identified three main factors influencing PND and TOP decisions: nationality, type of haemoglobinopathy risk and number of previous pregnancies. Age showed no significant correlation with decision-making patterns. The impact of education level and employment status could not be definitively determined due to unavailable or unfit data.

The 40-year analysis of prenatal diagnosis for haemoglobinopathies in Turin shows evolving trends influenced by immigration patterns, improved medical treatments and cultural factors, leading to increased acceptance of affected pregnancies in recent years, particularly after 2015, due to better disease management and comprehensive healthcare support. This comprehensive analysis of our centre’s experience provides valuable insights that can serve as a model for similar institutions worldwide in supporting couples through carrier screening and PND processes.