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.

To determine the personal, National Health Service and wider societal resource use in relation to caring responsibilities for carers of people living with non-memory led dementias (NMLDs); and to design a resource use measure (RUM) that can be delivered in the Better Living with Non-memory-led Dementia (BELIDE) randomised controlled trial, part of the Rare Dementia (RD) - TALK research programme.

The first stage was to identify and review any existing RUMs that could be used or adapted to the trial population and setting. If no measures were identified, the second stage was initial informal discussions with healthcare professionals (HCPs) and the programme patient and public involvement representatives to inform the perspective, settings of care and main resource items to develop a new RUM. In the third stage, a first draft of the RUM was tested for content and face validity in a modified Delphi study comprising HCPs and carers. The measure was revised and, in the final stage, piloted in the first 3 months of the BELIDE trial to assess acceptability and feasibility of collecting the economic outcomes and the completeness of data collection. The key drivers of resource use and costs were assessed, and appropriate face validity checks were applied to ensure accurate description of the treatment pathways.

Carers and family of people living with NMLD recruited from Rare Dementia Support members in the UK, and a broad range of HCPs with experience of working with people who have NMLD to capture the different dimensions of experience, grade and skill mix.

In total, 20 people participated in the modified Delphi study, 11 HCPs and 9 carers. Rare Dementia Support groups and 1:1 calls were highly rated, as were general practitioner appointments. The greatest consensus was in the productivity and carer tasks; all caring tasks were highly rated. Healthcare practitioners rated healthcare items as higher importance than carers themselves.

Unpaid carers and HCPs are the experts in the resource impact of caring for someone with NMLD and have been underserved in research to date. This research, as part of preparatory stages of the BELIDE trial, has enabled the timely development of a comprehensive and valid RUM for unpaid carers of people with NMLD.

CRD42022356943.

NCT06241287.

To examine the associations between socioeconomic position (SEP) and the incidence of serious hand infections—pyogenic flexor tenosynovitis (PFT) and septic arthritis (SA)—as well as risks of opioid overuse following diagnosis using nation-level data.

In a registry-based nationwide retrospective cohort study, (1) associations between SEP and incidence of PFT/SA; (2) SEP and infection-type effects on opioid overuse in the general population and (3) SEP and clinical predictors of opioid overuse among individuals diagnosed with PFT/SA were examined.

Using linked Swedish national registers (2010–2015), (1) a multinomial regression to assess SEP and infection risk (n=5 697 865); (2) logistic regression on opioid overuse (≥2 dispensations within 3 months) related to SEP and infection status and (3) a restricted analysis among diagnosed individuals (n=3701) to isolate clinical determinants of opioid overuse was conducted.

Among the study population, 0.04% had PFT and 0.02% had SA. In the general population, 0.31% received two or more opioid prescriptions, compared with 4.5% of those with PFT and 6.8% of those with SA. Male sex, older age, being native, low occupational qualification, comorbidity and—specifically for SA—low income were associated with higher infection risk. Both infections independently predicted opioid overuse (adjusted OR for PFT: 13.23 (95% CI 10.92 to 16.02); adjusted OR for SA: 15.16 (11.99 to 19.17)). Additional predictors of overuse included low SEP, female sex, older age, native birth, living alone and comorbidity. Infected individuals with SA were more likely to overuse opioids than those with PFT, but SEP had limited predictive power within this subgroup.

Despite universal healthcare, socioeconomic disparities exist in hand infection incidence and opioid prescribing. PFT and SA increase the risk of opioid overuse, but SE inequalities, except comorbidity, are less relevant among individuals. Targeted, equitable pain management strategies that reduce unnecessary opioid exposure while ensuring adequate care are needed.

Progress at the intersection of artificial intelligence and paediatric neuroimaging necessitates large, heterogeneous datasets to generate robust and generalisable models. Retrospective analysis of clinical brain MRI scans offers a promising avenue to augment prospective research datasets, leveraging the extensive repositories of scans routinely acquired by hospital systems in the course of clinical care. Here, we present a systematic protocol for identifying ‘scans with limited imaging pathology’ through machine-assisted manual review of radiology reports.

The protocol employs a standardised grading scheme developed with expert neuroradiologists and implemented by non-clinician graders. Categorising scans based on the presence or absence of significant pathology and image quality concerns facilitates the repurposing of clinical brain MRI data for brain research. Such an approach has the potential to harness vast clinical imaging archives—exemplified by over 250 000 brain MRIs at the Children’s Hospital of Philadelphia—to address demographic biases in research participation, to increase sample size and to improve replicability in neurodevelopmental imaging research. Ultimately, this protocol aims to enable scalable, reliable identification of clinical control brain MRIs, supporting large-scale, generalisable neuroimaging studies of typical brain development and neurogenetic conditions.

Studies using datasets generated from this protocol will be disseminated in peer-reviewed journals and at academic conferences.

Adolescence is a critical period marked by rapid brain development and the onset of many mental health disorders. Brain MRI studies during adolescence, especially when paired with behavioural phenotypes and information about genetic risk factors, hold promise to advance early identification of mental health risk and spur the creation of targeted treatments to improve patient function, prognosis and quality of life. However, prospective neuroimaging is costly and time-intensive, and individuals who participate may not be reflective of the general population. These challenges are compounded when examining adolescents, as many families lack the time, energy or resources to participate in studies that use research-grade imaging. Repurposing clinical MRIs obviates many of the challenges of neuroimaging research. Here, we describe the brain-behaviour-genetics study protocol. This protocol describes procedures used to recruit participants with recent high-quality clinical brain MRIs and prospectively acquire genetic and sociobehavioural data, resulting in a highly cost-efficient design that harnesses a vast and underused neuroscientific resource.

The brain-behaviour-genetics protocol aims to recruit 1000 adolescents who have clinical brain MRIs contained in Children’s Hospital of Philadelphia’s electronic health record. One or both parents of the adolescent proband will be recruited when possible. Parents and adolescents will complete a series of self-report scales spanning the domains of mental health, trauma, risk and resilience. Saliva samples will be collected from the adolescent and at least one biological parent, using an at-home saliva collection kit. Subsequent analysis will examine associations between brain development, genetics and behavioural measures in adolescence.

Approval for the study had been obtained from the Children’s Hospital of Philadelphia’s institutional review board (IRB #23–0 20 851). Results will be published in peer-reviewed journals.

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.