Delays in cancer diagnosis for patients with non-specific symptoms (NSSs) lead to poorer outcomes. Rapid Diagnostic Clinics (RDCs) expedite care, but most NSS patients do not have cancer, highlighting the need for better risk stratification. This study aimed to develop biomarker-based clinical prediction scores to differentiate high-risk and low-risk NSS patients, enabling more targeted diagnostics.

Retrospective and prospective cohort study.

Secondary care RDC in London.

Adult patients attending an RDC between December 2016 and September 2023 were included. External validation used data from another RDC.

The primary outcome was a cancer diagnosis. Biomarker-based risk scores were developed using Latent Class Analysis (LCA) and Least Absolute Shrinkage and Selection Operator (LASSO). Model performance was assessed using logistic regression, receiver operating characteristic curves (AUROC) and decision curve analysis.

Among 5821 RDC patients, LCA identified high white cell count, low haemoglobin, low albumin, high serum lambda light chain, high neutrophil-to-lymphocyte ratio, high serum kappa light chain (SKLC), high erythrocyte sedimentation rate (ESR), high C-reactive protein (CRP) and high neutrophils as cancer risk markers. LASSO selected high platelets, ESR, CRP, SKLC, alkaline phosphatase and lactate dehydrogenase. Each one-point increase in score predicted higher odds of cancer (LCA: AOR 1.19, 95% CI 1.16 to 1.23; LASSO: AOR 1.29, 95% CI 1.25 to 1.34). Scores ≥2 predicted significantly higher cancer odds (LCA: AOR 3.79, 95% CI 2.91 to 4.95; LASSO: AOR 3.44, 95% CI 2.66 to 4.44). Discrimination was good (AUROC: LCA 0.74; LASSO 0.73). External validation in 573 patients confirmed predicted increases in cancer risk per one-point LASSO score rise (AOR 1.28, 95% CI 1.15 to 1.42), with a borderline increase for LCA (AOR 1.16, 95% CI 1.06 to 1.27).

Biomarker-based scores effectively identified NSS patients at higher cancer risk. LCA captured a broader biomarker range, offering higher sensitivity, while LASSO achieved higher specificity with fewer markers. These scores may also help detect severe benign conditions, improving RDC triage. Further validation is needed before broader clinical implementation.

To explore the patient and informal-carer reported factors that influence prescribing decisions in the management of borderline personality disorder (BPD).

The study employed a qualitative methodology of semi-structured interviews with patients and informal carers to examine perspectives on prescribing decisions and the factors shaping them.

Interviews were conducted across both primary and secondary care settings in England.

A total of 10 participants were recruited for the study, comprising eight females and two males, all aged 18 years or older. Participants either had a formal diagnosis of BPD or were informal carers of individuals diagnosed with BPD. All participants had experience with the prescribing of medication for the management of BPD.

Thematic analysis, employing both inductive and deductive strategies and informed by agency theory, yielded three interrelated themes: prescribing for symptom relief, the impact of risk on prescribing and difficulties in accessing services. Participants described medication as a necessary means of managing distress, especially when access to psychological therapies was constrained. Despite awareness of potential adverse effects, many expressed a strong desire to make their own decision around medication.

Improving clarity around the likelihood of both symptomatic relief and potential adverse effects through co-designed informational resources may support more informed decision-making in the treatment of BPD. Furthermore, to change prescribing patterns, systemic gaps in the provision of long-term psychological therapies must be addressed.

There is limited evidence regarding the outcomes and impacts of Patient and public involvement (PPI) in research, mainly based on narrative studies. Existing frameworks for supporting and evaluating PPI often require adaptation to specific contexts, and comprehensive instruments are needed. From an international perspective, strengthening the scientific foundation that underpins PPI is crucial to generate stronger evidence to understand which approaches work best, in which contexts, and with what effects.

To promote PPI implementation in German health research, this project aims to (1) Establish an evaluation framework, (2) Develop a modular evaluation tool in the form of a questionnaire and (3) Pilot and psychometrically validate the tool.

A three-phase mixed methods approach will be employed, integrating qualitative and quantitative data. First, we will explore with researchers, research partners and other stakeholders in health services research what contributes to meaningful and successful PPI through a web-based survey and focus groups. Findings are discussed in a codesign workshop in which participants agree on an evaluation framework based on a LOGIC model. Second, items from international instruments that evaluate PPI are deductively assigned to the evaluation framework. Further items are developed based on the focus groups from phase 1. Cognitive pretests and qualitative review will be conducted with researchers and patients in order to refine the item pool and develop the evaluation tool. Third, the evaluation tool with modules for researchers and patients will be piloted in a web-based survey. Data analysis will include thematic analysis for qualitative data and descriptive and psychometric analyses for quantitative data. A participatory research team will provide ongoing support throughout all project phases.

Ethical approval has been obtained from the Local Ethics Committee of the Centre for Psychosocial Medicine, University Medical Centre Hamburg-Eppendorf (LPEK-0889). The study will follow the principles of the Helsinki Declaration and good scientific practice. Results will be disseminated at national and international conferences, public symposiums and in peer-reviewed journals, contributing to the internationally developing field of PPI in research and addressing relevant research gaps.

Few studies have quantified the vulnerability of people experiencing homelessness and its association with emergency department (ED) reattendances. The study objectives were to identify the health and social-related vulnerability, comorbidities and reattendance to an ED within 28 days, of people experiencing homelessness and people living in stable housing.

Prospective cohort study, 28 September 2023 to 12 October 2023.

Metropolitan ED in an inner-city public hospital.

Eligible participants were those who attended the ED between 8am and 5pm during the 2 week study period (2023), those aged 18 years and over and able to provide informed consent, and those deemed well enough to participate.

The homeless health access to care tool (HHACT) assesses a person’s unmet needs and quantifies their level of health and social-related vulnerability (low, moderate, high). The HHACT was applied to each participant. Routinely collected administrative data was used to identify participant demographics and ED usage on the day of study enrolment and any ED reattendance within 28 days.

Outcome measures were the identification of participants’ level of health and social-related vulnerability and its relationship to ED reattendance.

Of the 300 ED participants, 38 (12.6%) were experiencing homelessness. There was a greater than twofold increase in odds of 28-day ED reattendance for participants experiencing homelessness (OR=2.93, CI 1.29 to 6.36; p=0.008) or had moderate to high vulnerability scores (participants living in stable housing and participants homeless) (OR=2.67, CI 1.29 to 5.36; p=0.007). Compared with participants in stable housing, prevalence of comorbidities among participants experiencing homelessness was greater regarding mental health challenges (65.8% vs 21.8%); three or more physical health conditions (36.8% vs 13%) and greater alcohol and other drug use (36.8% vs 17.2%).

The high ED reattendance suggests that people experiencing homelessness are not being adequately screened for unmet needs on their first presentation. Comprehensive screening using the HHACT may enhance the identification of the risk of reattendance and provide opportunities to intervene through targeted responses, such as integrated care pathways. While EDs are not designed to address the multifaceted needs of people experiencing homelessness, there is an urgent need to consider how to optimise this population’s access to appropriate care.

This study aimed to evaluate the feasibility of delivering a vocational rehabilitation intervention (Return to Work After Trauma—ROWTATE), remotely to individuals recovering from traumatic injuries. The primary objectives were to assess therapists’ training and competence, adapt the intervention and training for remote delivery and assess the feasibility and fidelity of remote delivery to inform a definitive randomised controlled trial.

A mixed-methods feasibility study incorporating (1) telerehabilitation qualitative literature review, (2) qualitative interviews preintervention and postintervention with therapists and patients, (3) a team objective structured clinical examination to assess competency, (4) usefulness of training, attitudes towards (15-item Evidence-Based Practice Attitude Scale) and confidence in (4-item Evidence Based Practice Confidence Scale) evidence-based practice, intervention delivery confidence (8-bespoke questions) and intervention behaviour determinants (51-items Theoretical Domains Framework) and (5) single-arm intervention delivery feasibility study.

The study was conducted in two UK Major Trauma Centres. The intervention and training were adapted for remote delivery due to the COVID-19 pandemic.

Therapists: Seven occupational therapists (OTs) and clinical psychologists (CPs) were trained, and six participated in competency assessment. Seven OTs and CPs participated in preintervention interviews and surveys; six completed post-intervention interviews and four completed post-training surveys. Patients: 10 patients were enrolled in the single-arm feasibility study and 4 of these participated in postintervention qualitative interviews. Inclusion criteria included therapists involved in vocational rehabilitation delivery and patients admitted to major trauma centres. Exclusion criteria included participation in other vocational rehabilitation trials or those who had returned to work or education for at least 80% of preinjury hours. Intervention: The ROWTATE vocational rehabilitation intervention was delivered remotely by trained OTs and CPs. Training included competency assessments, mentoring and adaptation for telerehabilitation. The intervention was delivered over multiple sessions, with content tailored to individual patient needs.

Therapists found the training useful, reported positive attitudes (Evidence-Based Practice Attitude Scale mean=2.9 (SD 0.9)) and high levels of confidence in delivering evidence-based practice (range 75%–100%) and the ROWTATE intervention (range 80%–100%). Intervention barriers identified pretraining became facilitators post-training. Half the therapists needed additional support post-training through mentoring or additional training. The intervention and training were successfully adapted for remote delivery. High levels of fidelity (intervention components delivered: OTs=84.5%, CPs=92.9%) and session attendance rates were found (median: OT=97%, CP=100%). Virtually all sessions were delivered remotely (OT=98%, CP=100%). The intervention was acceptable to patients and therapists; both considered face-to-face delivery where necessary was important.

The ROWTATE intervention was delivered remotely with high fidelity and attendance and was acceptable to patients and therapists. Definitive trial key changes include modifying therapist training, competency assessment, face-to-face intervention delivery where necessary and addressing lower fidelity intervention components.

ISRCTN74668529.

Black and Asian women experience significantly higher rates of mortality and morbidity perinatally compared with white women and are more likely to lose their babies. These groups are also under-represented in clinical research, resulting in evidence that may not be generalisable. Tools have been developed to facilitate the inclusion of ethnic minority groups, but it is unknown to what extent representation and inclusion are considered in maternity trials.

To provide an overview of how ethnically diverse recruitment is considered and reported in maternity trials in the UK.

A scoping review was conducted, undertaking a systematic search to identify published trial protocols and their subsequent results papers, conducted within the UK, recruiting women during pregnancy or within 6 weeks postnatally between 2004 and 2024.

Data was extracted from protocols on whether representation of participants was considered in the study design and if specific recruitment and retention strategies were planned for ethnic minority groups.

Data extracted from results papers identified whether representation of participants was discussed and if recruitment strategies were discussed; these were compared against the protocol.

A total of 96 published protocols met the inclusion criteria; 8 mentioned specific recruitment strategies and 5 mentioned specific retention strategies. Only two included both recruitment and retention strategies. The most common strategies included providing different types of language support and adapting interventions to be culturally appropriate. Strategies were not evaluated.

67 results papers were available. Ethnicity was reported in 57 papers, with heterogeneity of categories between papers. Only 32 papers discussed representativeness of participants.

Few maternity trials report considerations on how they ensure they are recruiting and retaining ethnically representative participants. Minimal discussion is undertaken around the extent to which trial participants reflect the population to which findings will be applied.

Further work is needed to support implementation and evaluation of inclusive research guidance. Failing to ensure those from ethnic minority groups are included in research can exacerbate inequalities.

Nicotine replacement therapy (NRT) helps pregnant women quit smoking. Usual National Health Service (NHS) cessation care in pregnancy starts only after women stop smoking and comprises behavioural support and NRT. NRT is stopped if women restart smoking. We hypothesised that NRT would have a bigger effect on cessation in pregnancy if used: (1) to reduce smoking before quitting (‘preloading’), (2) during brief smoking lapses after quitting and (3) to help those who cannot stop smoking, to reduce instead.

A two-arm parallel group, open-label, multicentre, assessor-blind randomised controlled trial. Participants are recruited at hospital antenatal clinics and other NHS settings throughout England and Wales or via social media advertising. Those enrolled are in antenatal care,

Ethics approval was granted by the West Midlands—Coventry & Warwickshire Research Ethics Committee (REC reference: 21/WM/0172; Protocol number 21001; IRAS Project ID: 291236). Written informed consent will be obtained from all participants. Findings will be disseminated to the public, funders, relevant practice and policy representatives and other researchers.

ISRCTN84798566.

The utility of brain MRI in dementia diagnosis offers critical insights into structural brain changes, such as hippocampal and thalamic atrophy, which are hallmark features of Alzheimer’s disease and Alzheimer’s disease-related dementias . However, its use, especially in low- and middle-income countries (LMICs), is affected by limited accessibility. This protocol outlines a systematic review and meta-analysis to assess the diagnostic utility, feasibility and challenges of integrating brain MRI for dementia diagnosis in LMICs.

The review follows Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols with a priori eligibility criteria and is registered in PROSPERO. Searches (from inception to September 2025) will be run in MEDLINE/PubMed, EMBASE, Web of Science and PsycINFO, with supplementary bibliography screening. Adults ≥50 years in LMIC settings undergoing brain MRI for dementia evaluation will be eligible. Data will be synthesised narratively and, where appropriate, via random-effects meta-analysis with planned subgroup analyses by MRI approach (qualitative vs quantitative), magnet strength, sequence availability and reference standard. Screening and data extraction are planned for 1 November to 30 December 2025.

Ethical approval was obtained from the Makerere University School of Medicine Research and Ethics Committee (Mak-SOMREC; Ref Mak-SOMREC-2022-337). For verification, contact the SOMREC Administrator at rresearch9@gmail.com. Departmental contact: Dr Geoffrey Erem, Head, Department of Radiology, Makerere University College of Health Sciences (dreremgeoffrey@gmail.com). Only published data will be used, with no new patient contact. Findings will be disseminated via peer-reviewed publication, conference presentations and policy briefs (and, where feasible, mainstream media) to inform clinical practice and training in LMICs.

CRD42024510241.

Adults living with multiple long-term conditions (MLTC)—defined as the presence of two or more physical or mental health conditions—often face fragmented and complex care. Digital tools offer scalable self-management solutions but may exacerbate inequities due to the digital divide and other factors. The aim of this scoping review is to map and summarise the existing literature on digital self-management tools used in MLTC, with a particular focus on how equity of access is considered in their development, implementation and evaluation.

Scoping review methodology will be based on the Joanna Briggs Institute guidance for scoping reviews and Arskey and O’Malley’s framework and will be reported in alignment with Preferred Reporting Items for Systematic Review and Meta-Analyses extension for Scoping Reviews. Comprehensive search terms based on ‘multimorbidity’, ‘digital tools’ and ‘self-management’ have been developed. Peer-reviewed publications will be identified using MEDLINE, Embase, Emcare, Scopus, CINAHL and PubMed. Two reviewers will independently screen titles and abstracts, with subsequent full text review also being performed in duplicate to ensure they meet the eligibility criteria. Discrepancies will be resolved by discussion with a third reviewer. Included studies will focus on digital tools for the self-management of MLTC in adults (≥18 years old) in any setting. Equity dimensions will include, but are not limited to, digital literacy, treatment burden, socioeconomic status, polypharmacy and access disparities.

Ethical approval is not required for this scoping review. The results of the scoping review will be published in an open access, peer-reviewed journal for wider dissemination. Additionally, findings will contribute to topic guides and mapping of a research networking event with key stakeholders (including patient and public involvement and engagement members, clinicians, researchers and industry) in MLTC, around the same subject area.

Physical activity improves physical and psychosocial outcomes in healthy children and in children with a range of chronic health conditions. Unfortunately, children with chronic health conditions have lower levels of physical activity compared to their healthy peers due to multiple restrictions in physical activities and therefore tend to have lower levels of physical activity compared with their peers. This paper describes the protocol for Move to Improve, a pragmatic trial of an individualised physical activity intervention for children with chronic health conditions.

Using the RE-AIM framework, this study aims to test the feasibility of Move to Improve, an 8-week hospital-based individualised physical activity intervention. We will recruit 100 children aged 5–17 years who are diagnosed with type 1 diabetes, cancer, postburn injuries and cerebral palsy to a single-arm, pragmatic feasibility trial. The primary outcomes (objective moderate to vigorous physical activity, quality of life and goal attainment) and secondary outcomes (including aerobic capacity, body composition, motor function, grip strength and psychosocial outcomes) will be assessed at baseline, post intervention and at 6-month and 12-month follow-ups. We will conduct semistructured interviews with participants and their primary caregiver at a 2-month follow-up to capture aspects of feasibility. Quantitative data will be reported descriptively, and qualitative data will be analysed using thematic analysis. Data gathered from this study will inform service decision-making and future trials.

The study has received ethics approval from the Government of Western Australia Child and Adolescent Health Service Human Research Ethics Committee (RGS6677). Findings of this research will be communicated to the public through peer-reviewed publications, conference presentations, reports, infographics and information sheets. Modifications to the protocol will be outlined in the trial registry and journal publications. Authorship will be in accordance with the International Committee of Medical Journal Editors.

Australian and New Zealand Clinical Trials Registry Number: ACTRN12624000836538.

Effective haemorrhage control is crucial in cases of limb trauma involving arterial injury, such as shark attacks, to prevent potentially fatal outcomes. International first aid consensus recommends the use of arterial tourniquets (proprietary or makeshift) as a primary treatment for life-threatening external bleeding. Manual pressure applied directly over a major artery proximal to the injury, such as inguinal fist compression (IFC), is more accessible in a first-aid situation, but is currently not recommended due to limited evidence. The purpose of this study is to determine whether the application of IFC is superior to commercial windlass tourniquets (CWTs) in reducing blood flow in the femoral artery when performed by untrained bystanders.

Stopping Haemorrhage by Application of Randomised Compression or Tourniquet (SHARC-2) is a superiority, assessor-blinded, cross-over, randomised controlled trial conducted with healthy untrained adult volunteers in non-clinical settings. Participants will be rotated as providers and recipients of both IFC and CWT, with providers randomised to the order that they perform the techniques. Providers will be exposed to an educational infographic before applying that technique to a recipient behind a drop sheet. A sonographer, blinded to the technique, will measure the peak systolic velocity of blood flow in the superficial femoral artery using Doppler ultrasound at baseline and then during application of each technique for 5 min. The mean percentage reduction in peak systolic velocity will be compared between IFC and CWT groups.

Ethics approval for this study was granted by the Bond University Human Research Ethics Committee (BUHREC JF01036) on 23 January 2023. All participants will be provided with written informed consent prior to enrolment and the trial will involve healthy adult volunteers. To minimise risk, preintervention screening, sonographic assessment and postintervention follow-up will be implemented with adverse events monitored and reported in accordance with HREC guidelines. Results will be disseminated through peer-reviewed journals, academic conferences, local resuscitation forums and public health education initiatives. A lay summary will also be shared with relevant community groups and via social media platforms to enhance public accessibility.

ACTRN12624001054505.

School feeding programmes (SFPs) are widely implemented to address child poverty, food insecurity and malnutrition, yet evidence on their influence on children’s health outcomes is limited. With ongoing debate around universal versus targeted provision, this scoping review aims to map global literature on SFPs, identify which health and well-being outcomes are reported, and explore how these outcomes vary by programme type (targeted vs universal).

Scoping review conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The protocol was pre-registered on the Open Science Framework.

Four electronic databases—Medline, PubMed, Web of Science and Google Scholar—were searched in December 2023 and July 2025. Reference lists of included papers were also screened.

Included studies examined the impact of SFPs on physical, emotional, psychological and social health outcomes in children aged 5–16. Only English-language studies published between 2009 and 2025 were included.

Data were extracted using a structured template and reviewed by multiple authors. Due to the heterogeneity in study designs and reported outcomes, a narrative synthesis approach was used to group findings thematically, following established guidance for narrative synthesis in systematic reviews.

A total of 44 papers were included in the final review, spanning 13 countries and published between 2009 and 2025. SFPs were associated with healthier weight status, improved dietary intake, better social engagement and reductions in stigma. Targeted programmes addressed food insecurity but were more often linked to stigma and poorer mental health outcomes.

Universal SFP were effective at improving children’s health outcomes such as healthy weight, improved behaviour and social support. Overall, both targeted and universal SFP positively impact children’s health outcomes and address health disparities.

First post-contrAst SubtracTed (FAST) MRI, an abbreviated breast MRI scan, has high sensitivity for sub-centimetre aggressive breast cancer and short acquisition and interpretation times. These attributes promise effective supplemental screening. Until now, FAST MRI research has focused on women above population-risk of breast cancer (high mammographic density or personal history). DYAMOND aims to define the population within the population-risk NHS Breast Screening Programme (NHSBSP) likely to benefit from FAST MRI. The study population is the 40% of screening clients aged 50–52 who have average mammographic density (BI-RADS (Breast Imaging Reporting and Data System) B) on their first screening mammogram. DYAMOND will answer whether sufficient numbers of breast cancers, missed by mammography, can be detected by FAST MRI to justify the inclusion of this group in a future randomised controlled trial.

Prospective, multicentre, diagnostic yield, single-arm study with an embedded qualitative sub-study: all recruited participants undergo a FAST MRI. An internal pilot will assess the willingness of sites and screening clients to participate in the study. Screening clients aged 50–52, with a clear first NHSBSP mammogram and BI-RADS B mammographic density (by automated measurement) will be invited to participate (recruitment target: 1000). The primary outcome is the number of additional cancers detected by FAST MRI (missed by screening mammography). A Fleming’s two-stage design will be used as this allows for early stopping after stage 1, to save participants, funding costs and time continuing to the end of the study if the question can be answered earlier.

The NHSBSP Research and Innovation Development Advisory Committee and the Yorkshire and Humber–Sheffield Research Ethics Committee (23/YH/0268, study ID (IRAS): 330059) approved this research protocol. Participation involves a two-stage informed consent process, enabling screening for eligibility through automated mammographic density measurement. Patients with breast cancer helped shape the study design and co-produced participant-facing documents. They will disseminate the results to the public in a clear and meaningful way. Results will be published with open access in international peer-reviewed scientific journals.

ISRCTN74193022

Chronic tic disorders (CTDs)—such as Tourette Syndrome (TS)—are neurodevelopmental disorders affecting at least 1% of the population, causing repetitive involuntary movements and vocalisations known as tics. This study aimed to explore the lived experiences of accessing healthcare for people with CTD or TS and their families in the United Kingdom (UK), as part of a larger programme of work to inform change to healthcare services for this population.

Informed and designed with extensive patient and public involvement, the design utilised qualitative research using focus groups. Reflexive thematic analysis was used to analyse the data.

Participants were recruited via online support groups, social media and research registers.

Seven focus groups were held separately with young people with tics (n=2), adults with tics (n=10) and parents/guardians of children with tics (n=11), led by a lived experience expert (coauthor PS) and facilitated by researchers. Discussion focused on three areas: the impact of living with tics, experience accessing healthcare for tics and management of tics.

Five themes were developed highlighting challenges across the healthcare pathway, including gaining a diagnosis, and receiving treatment, resulting in the use of self-support methods to reduce tic expression or the impact of tics. Themes also illustrated perceptions that healthcare provider's knowledge impacted initial interactions with the healthcare system, and how healthcare systems were not felt to be prioritising CTDs.

The findings highlight a lack of prioritisation for tic disorders compounded by a healthcare structure which does not support a complex condition that requires a multidisciplinary approach. This research calls for improvements to UK healthcare services for CTD.

Difficulty with walking can lead to reduced quality of life for people with Parkinson’s disease (pwPD); improving walking is considered a treatment priority. Drug therapies can control PD symptoms; however, pwPD often still experience mobility problems.

Functional electrical stimulation (FES) induces movement in weak muscles via external electrical stimulation. FES is used in stroke and multiple sclerosis patients to correct dropped foot by stimulating the common peroneal nerve and is associated with improved quality of life and mobility. The randomised feasibility study preceding this definitive study showed that daily FES can produce a clinically meaningful improvement in walking speed in pwPD; this was sustained 4 weeks after FES was withdrawn. STEPS II is the first definitive randomised controlled trial, with blinded outcome assessment, aiming to determine the efficacy of FES in pwPD.

STEPS II is a two-group, parallel, assessor-blinded, superiority randomised controlled trial with an internal pilot, designed to compare FES plus usual care versus usual care alone. 234 participants will be randomised across eight UK sites. Telephone pre-screening and face-to-face screening will determine eligibility. The intervention group will attend four unblinded FES visits to receive the device and assess walking with and without FES. All participants have blinded assessments at baseline and weeks 2, 6, 18 and 22. The primary objective is to compare whole body bradykinesia at 18 weeks post-baseline via changes in 10m walking speed. Secondary objectives will assess the wider effects of FES on Parkinsonian gait and quality of life. An embedded qualitative component will explore wider experiences of FES.

This study received ethical approval from the Yorkshire and The Humber-Sheffield Research Ethics Committee (reference 23/YH/0193). A Data Monitoring Committee and Trial Steering Committee will provide independent oversight. Dissemination will be via publications, conferences and social media. FES intervention and training materials will be made open access.

ISRCTN13120555.

Many cancer treatments can result in reduced fertility, impacting survivors’ opportunities for biological parenthood. Fertility preservation (FP) methods for boys and young men, such as cryopreservation of testicular tissue or sperm, offer hope but are currently underused among young male patients with cancer. Despite guidelines recommending early discussion of fertility implications, many newly diagnosed males do not receive FP counselling or referral to fertility services. Male cancer survivors face a higher likelihood of infertility than their peers, yet focused FP decision-making support is lacking. This study aims to address this gap by developing and evaluating the first dedicated patient decision aid (PtDA) for boys and young male patients with cancer aged 11–25 years old, to help them make informed FP decisions before receiving cancer treatment.

The current study follows a multistage process: developing the PtDA, alpha testing for acceptability with former patients, parents and healthcare professionals, and beta testing in clinical settings to ensure effective integration into routine care. Using a combination of interviews and questionnaire data, this research will assess the PtDA’s acceptability and impact on decision-making.

This study has been prospectively registered on the Research Registry (10273). Ethics approval has been obtained from Leeds Beckett University and the National Health Service/Health Research Authority before undertaking data collection. The final resource will be disseminated widely and made freely available online via our dedicated Cancer, Fertility and Me website, for use in clinical and research practice.

Many people with psychosis find the world very frightening. It can be difficult for them to do everyday things—for example, walking down a busy street, travelling on a bus or going to the shops. Sometimes, the fears are so great that individuals rarely leave their homes. gameChange virtual reality therapy is designed to reduce this agoraphobic avoidance. In gameChange, users practise going into computerised immersive versions of ordinary situations. A virtual therapist guides users through the programme. A mental health worker also supports people. People normally do six sessions of gameChange, but now they can do more as headsets can be left with many people. We originally tested gameChange with 346 patients with psychosis. People saw a significant reduction in their fears. People with the most severe problems made the biggest improvements. This led to gameChange receiving National Institute for Health and Care Excellence (NICE) Early Value Assessment (EVA) approval for its use with patients with psychosis who have severe agoraphobic avoidance. NICE EVA approval is conditional on further evidence generation. We aim to carry out a real-world trial of gameChange used in the NHS. The overall aim is to gather evidence on the four essential areas (clinical benefits on agoraphobia, level of engagement and adherence, healthcare resource use, adverse effects) and the two further supporting areas (health-related quality of life, generalisability) identified in the NICE evidence generation plan for gameChange.

200 patients with psychosis and severe agoraphobic avoidance will be randomised (1:1) to receive gameChange in addition to treatment as usual (TAU) or to a waitlist control group receiving TAU. Assessments will be conducted blind to group allocation at baseline, 8 weeks (end of treatment) and 26 weeks (follow-up). The trial will be embedded in services in at least seven National Health Service (NHS) trusts across England. The primary outcome is agoraphobic avoidance at 26 weeks assessed with the Oxford Agoraphobic Avoidance Scale. The secondary clinical outcomes are agoraphobic distress, paranoia and social contacts. There will be tests of moderation of the main clinical outcome. Treatment acceptability, adverse effects and cost-effectiveness will also be assessed. The target estimand is the treatment policy estimand and all primary and secondary analyses will be carried out incorporating data from all participants including those who do not complete treatment.

The trial has received ethical approval from the NHS Health Research Authority and Health and Care Research Wales (25/WA/0081). A key output will be the evidence needed for a NICE guidance update on gameChange and a clear recommendation concerning future routine use in the NHS.

ISRCTN79060696.

Progressive supranuclear palsy (PSP) is a devastating neurodegenerative disease characterised by cognitive, behavioural and motor problems. Motor symptoms are highly disabling, while cognitive and behavioural changes have a major impact on carer burden, quality of life and prognosis. Apathy and impulsivity are very common, often coexistent in PSP, and negatively predict survival. In preclinical models and other diseases, apathy and impulsivity are associated with noradrenergic deficits, which can be severe in PSP.

Noradrenaline for Progressive Supranuclear Palsy Syndromes trial is a randomised, double-blind, placebo-controlled, crossover design, Phase IIb clinical trial to evaluate the efficacy and safety of oral atomoxetine for the treatment of cognitive and behavioural changes in PSP. Participants receive atomoxetine 40 mg (10 mg/mL oral solution) once daily or a matched placebo solution, in random order, each for 8 weeks. An ‘informant’, who knows the patient with PSP well, is co-recruited to complete some of the trial outcome measures. Participants remain in the trial for 22 weeks after randomisation. The primary objectives are to assess (1) safety and tolerability and (2) efficacy versus placebo on challenging behaviours as reported in a subscale of the Cambridge Behavioural Inventory. Secondary and exploratory measures relate to cognition, the PSP Rating Scale, mood and potential baseline predictors of individual response to atomoxetine computed from imaging, genetic and cognitive measures at baseline.

The trial was approved by the South Central-Oxford B Research Ethics Committee (REC) and the Medicines and Healthcare products Regulatory Agency (REC reference: 20/SC/0416). Dissemination will include publication in peer-reviewed journals, presentations at academic and public conferences and engagement with patients, the public, policymakers and practitioners.

ISRCTN99462035; DOI: https://doi.org/10.1186/ISRCTN99462035; EudraCT (European Union Drug Regulating Authorities Clinical Trials Database)/CTIS (Clinical Trial Information System) number: 2019-004472-19; IRAS (Integrated Research Application System) number: 272063; Secondary identifying numbers: CPMS (Central Portfolio Management System) 44441.

Childhood cancer treatment can cause subfertility in adulthood. Ovarian or testicular tissue preservation is a rapidly evolving field with significant potential benefits. However, the establishment of patient-centred reproductive survivorship pathways remains a challenge in clinical settings due to a lack of robust evidence to inform its development. Patient and public involvement and engagement (PPIE) consultation may help ensure that future studies align with patient needs and that tailored survivorship care pathways are developed for young people with preserved fertility tissue.

This PPIE consultation aimed to identify priority areas for future research that would support the development of a tailored survivorship care pathway for childhood cancer survivors who have preserved tissue for future fertility.

Recruitment occurred through national networks, including collaborations with advocacy groups such as Candlelighters and clinical networks. Data were collected via telephone or online unstructured interviews, with some supplementary email exchanges. Thematic analysis was used to identify emergent themes. The Guidance for Reporting Involvement of Patients and the Public (GRIPP)-2 guidelines were used to help guide PPIE.

An online focus group and/or a one-to-one interview with e-mail interactions.

In total, 12 unique participants took part in a focus group and/or interview. Participants included parents of children who had stored tissue, young adult cancer survivors with stored tissue and five clinicians from the leading National Health Service (NHS) centres in the UK.

Six key themes emerged that highlighted unmet needs and priority areas for research: (1) Lack of communication and information; (2) unmet needs in follow-up care; (3) emotional impact and psychological support; (4) importance of patient and parental involvement; (5) desire for information and education; and (6) long-term concerns and support. Parents, young adults and healthcare clinicians found talking about fertility issues difficult. They noted that consistency of care, education resources and access to emotional support were important areas where improvements could be made. We used thematic analysis to help identify patterns in the data, and we used the Guidance for Reporting Involvement of Patients and the Public (GRIPP)-2 reporting guidelines for PPIE work.

PPIE provided valuable insights into the experiences of childhood cancer survivors with preserved fertility tissue, their parents and clinicians, highlighting priority areas to guide future research and ensure it addresses the concerns of care recipients. Our findings suggest that childhood cancer survivors who preserve tissue for future fertility need personalised follow-up care with information and psychological support. A larger sample of participants, studied using a qualitative research design, is needed to capture the full range of experiences, needs and preferences and to ensure that care is inclusive and relevant to the wider population.

While group, task-oriented, community-based exercise programs (CBEPs) delivered in-person can increase exercise and social participation in people with mobility limitations, challenges with transportation, cost and human resources, threaten sustainability. A virtual delivery model may help overcome challenges with accessing and delivering in-person CBEPs. The study objective is to estimate the short-term effect of an 8-week, virtual, group, task-oriented CBEP called TIME™ (Together in Movement and Exercise) at Home compared with a waitlist control on improving everyday function in community-dwelling adults with mobility limitations.

A randomised controlled trial incorporating a type 1 effectiveness-implementation hybrid design is being conducted in four Canadian metropolitan centres. We aim to stratify 200 adults with self-reported mobility limitations by site, participation alone or with a partner, and functional mobility level, and randomise them using REDCap software to either TIME™ at Home or a waitlist control group. During TIME™ at Home classes (2 classes/week, 1.5 hours/class), two trained facilitators stream a 1-hour exercise video and facilitate social interaction prevideo and postvideo using Zoom. A registered healthcare professional at each site completes three e-visits to monitor and support implementation. Masked evaluators with physical therapy training evaluate participants and their caregivers at 0, 2 and 5 months using Zoom. The primary outcome is the change in everyday function from 0 to 2 months, measured using the physical scale of the Subjective Index of Physical and Social Outcome. The study is powered to detect an effect size of 0.4, given α=0.05, power=80% and a 15% attrition rate. Secondary outcomes are mobility, well-being, reliance on walking aids, caregiver assistance, caregiver mood, caregiver confidence in care-recipient balance and cost-effectiveness. A multimethod process evaluation is proposed to increase understanding of implementation fidelity, mechanisms of effect and contextual factors influencing the complex intervention. Qualitative data collection immediately postintervention involves interviewing approximately 16 participants and 4 caregivers from the experimental group, and 8 participants and 4 caregivers from the waitlist control group, and all healthcare professionals, and conducting focus groups with all facilitators to explore experiences during the intervention period. A directed content analysis will be undertaken to help explain the quantitative results.

TIME™ at Home has received ethics approval at all sites. Participants provide verbal informed consent. A data safety monitoring board is monitoring adverse events. We will disseminate findings through lay summaries, conference presentations, reports and journal articles.

NCT06245135.