Patients with cirrhosis have reduced gut bacterial diversity and a gut microbiota dominated by pathobionts. These changes, coupled with increased gut permeability and bacterial translocation, increase susceptibility to infection and death. There is also considerable concern that high antimicrobial exposure in the cirrhotic population drives the development of antimicrobial resistance (AMR). We previously performed a randomised feasibility trial of endoscopically administered jejunal faecal microbiota transplant (FMT) slurry derived from stringently screened donors, and showed it to be safe and well-tolerated in patients with cirrhosis (PROFIT Trial: NCT02862249). FMT was associated with reduced enteropathogenic bacteria in the gut, augmented ammonia excretion, ameliorated systemic inflammation, and enhanced innate immune responses to pathogen challenge. The trial was not powered to detect differences in clinical outcomes. The PROMISE study will evaluate the efficacy of lyophilised encapsulated FMT to reduce infection, decompensating events and mortality in patients with cirrhosis secondary to alcohol-related liver disease (ALD), metabolic dysfunction-associated steatotic liver disease (MASLD) cirrhosis and metabolic dysfunction and alcohol-related liver disease (MetALD). The PROMISE study is a phase 3 multicentre, randomised, double-blinded, placebo-controlled trial that will evaluate encapsulated lyophilised FMT in 300 participants with ALD, MetALD or MASLD cirrhosis (Model for End-Stage Liver Disease Sodium (MELD-Na) score 8–16). Participants will be randomly allocated (1:1) to receive FMT or matched placebo capsules every 91 days for 21 months, with 24-month follow-up. The primary endpoint is time-to-infection or decompensating event resulting in presentation to the emergency department or hospitalisation. Secondary endpoints include all hepatic decompensation, all-cause infection, antibiotic usage, incidence of AMR, hospitalisation rates, liver disease severity scores, quality of life scores, Hospital Anxiety and Depression Scale score (HADS), alcohol use, and mortality. Mechanistic endpoints include quantification of plasma bacterial DNA, plasma and faecal cytokines/biomarkers, plasma and faecal metabolome, faecal proteome, faecal microbiome composition and diversity (including resistome) and monocyte and mucosal-associated invariant T (MAIT) cell frequency, phenotype and function. Recruitment commenced in June 2023. Results will be disseminated via peer-reviewed journals, international conferences and patient support groups. The PROMISE study will assess the efficacy and evaluate the mechanisms of action of FMT in patients with ALD, MASLD and MetALD cirrhosis. FMT may provide an alternative non-antibiotic treatment for these patients through ecological reconstitution of microbial balance. ISRCTN, ISRCTN17863382. Registered on 25th March 2022, https://www.isrctn.com/ISRCTNISRCTN17863382. ClinicalTrials.gov NCT06461208. Registered on 4th June 2024, https://clinicaltrials.gov/study/NCT06461208#study-overview.

The heritability of hypertensive disorders of pregnancy (HDP) and HDP's association with cardiovascular disease in adult offspring were explored through a systematic review and meta-analysis. MEDLINE and EMBASE were searched independently by 2 reviewers (inception to February 18, 2025). Maternal chronic hypertension, antenatal complications, and pediatric cardiovascular disease were excluded. The Critical Appraisal Skills Program checklist was used for critical appraisal. Random-effects meta-analysis was conducted using a generic inverse variance method. Narrative synthesis and pooled results were expressed as odds ratios with 95% CIs. Of 225 studies screened, 11 studies (n=59 185; 48.3% women) assessed cardiovascular disease, and 9 studies (n=58 512) assessed HDP. Offspring age ranged from 19 to 55 years. There were 11 good- and 9 fair-quality studies. Fifteen studies were included in the meta-analysis (n=266 244). Adult offspring exposed to HDP had systolic and diastolic blood pressure that was 3.40 mm Hg (95% CI, 2.44-4.37; I2=40%) and 2.19 mm Hg higher (95% CI, 1.40-2.98; I2=51%). Higher odds of hypertension were observed (odds ratio, 1.50 [95% CI, 1.18-1.91]; I2=66%). Female offspring exhibited 72% increased odds of HDP (OR, 1.72 [95% CI, 1.41-2.09]; I2=81%) and 90% increased odds of preeclampsia (odds ratio, 1.90 [95% CI, 1.47-2.46]; I2=36%) following exposure to the same disorders. Increased odds of premature acute coronary syndrome and higher stroke risk were observed following HDP and severe preeclampsia exposure, respectively. In adult offspring, heritability of HDP was high. HDP were associated with hypertension, acute coronary syndrome, and stroke. Lifestyle modifications, cardiovascular disease monitoring, and prevention are paramount.

Objectives Little is known about how young people use social media during periods of self-harm. This study aimed to explore how they express themselves online through images posted on social media before and after self-harm and how this expression may change across these periods, employing visual content and thematic analyses.Design A prospective cohort study, with qualitative analysis conducted using a recurrent cross-sectional approach and codebook methodology, accounting for chronological changes across time points before, during and after episodes of self-harm.Setting Participants were recruited from a mental health NHS Trust in the UK.Participants Image data during episodes of self-harm was available for 20 participants. The majority of whom were aged 18 years or older (n=15), female (n=14) and met criteria for moderate or severe anxiety and depression (n=18). The sample reflected diverse ethnic backgrounds, with six participants identifying as Asian or Mixed/Multiple ethnic backgrounds.Results None of the images investigated had direct visual presentations of self-harm. A few images referenced self-harm through the medium of text, and this was largely to normalise and promote help-seeking. Several themes were identified, including participation in activities that support well-being, love and relationships, connecting through humour, expressions of distress, and promoting mental health awareness and support. Subtle temporal changes were also observed.Conclusions Findings suggest that young people may temporarily withdraw from social media on the day of a self-harm event and rarely post graphic self-harm images around that time. This may reflect concerns about being stigmatised, but also improved platform moderation. Instead, platforms may serve as spaces for expressing self-care behaviours and connecting with others about both positive and challenging emotions, and across a range of topics including mental health.Trial registration number ClinicalTrials.gov: NCT04601220.

Background Exposure and response prevention (ERP) is the gold-standard psychological treatment for obsessive compulsive disorder (OCD). However, its delivery typically requires frequent therapist availability and repeated patient travel to treatment settings, which limits accessibility. In addition, the idiosyncratic nature of obsessive-compulsive symptoms presents challenges for conducting effective exposures within the time and material constraints of traditional clinical environments. Virtual reality (VR)-based interventions may help address these limitations. This study aims to assess the feasibility of a novel approach that uses generative artificial intelligence (GenAI) to create personalised, immersive 3D exposure environments tailored to individual patient fears. Methods This is a randomised controlled feasibility study with three parallel arms and an assessor-blinded design. Forty-five adults with a primary diagnosis of OCD and moderate to extremely severe symptoms will be randomly allocated in a 1:1:1 ratio to OCD-related exposure administered via VR environments, neutral VR environments, or OCD-related stimuli presented on a widescreen display. Participants will complete a baseline assessment and an GenAI-based stimulus titration session, followed by two therapist-led ERP sessions that frame five consecutive days of asynchronous exposure (exposure blocks/scenarios that are not therapist-led ERP). The intervention uses text-to-image synthesis, image conversion into 3D Gaussian Splatting environments, and delivery via VR headsets or widescreen display. Primary feasibility outcomes include recruitment and retention rates, data completeness, and adherence to the asynchronous exposure protocol. Secondary outcomes include progression through personalised exposure hierarchies, physiological reactivity (electrodermal activity and heart rate), cybersickness, and subjective distress measures. Discussion This study will determine whether AI-driven VR exposure is feasible, safe, and acceptable for adults with OCD. The proposed approach standardises the process of content generation while personalising the actual stimuli, towards leveraging technology to ensure the personalised needs of these patients are more effectively met. Results can inform the refinement of the intervention and the study procedures, including sample size estimation for a future randomised controlled trial. If successful, this methodology could have the potential to improve scalability, reduce costs, and enhance the ecological validity of exposure therapy while maintaining clinical efficacy. Trial registration ISRCTN13869986. Registered 29 December 2025. Prospectively registered.

Psilocybin-assisted therapy may be a promising new treatment for treatment-resistant depression. We examined the feasibility of administering a single 25-mg dose of psilocybin or placebo with psychological support in a randomized controlled trial design with 6 weeks of follow-up. A two-arm, double-blind, randomized, placebo-controlled feasibility trial was conducted at one National Health Service (NHS) site in England. Eligible participants met Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria for major depressive disorder and had an inadequate response to ≥2 antidepressant treatments or ≥1 antidepressant plus ≥1 psychotherapy. Participants received 25-mg psilocybin or placebo with preparation, dosing support and integration. Primary outcomes were recruitment, retention and estimation of the Montgomery-Åsberg Depression Rating Scale (MADRS) variance. A multilevel regression analysis with an intention-to-treat population was used. Sixty participants were randomized (1:1), balanced by age, sex and prior psilocybin exposure, and 59 of 60 participants completed the MADRS at all follow-up visits. The adjusted between-group difference at week 3 on the MADRS was -10.41 (95% confidence interval: -14.86 to -5.95; Cohen's d = -1.70), favoring psilocybin, which was sustained at week 6. In total, 123 and 164 nonserious adverse events occurred in the placebo and psilocybin arms, respectively. Findings support a future confirmatory trial. EudraCT no.: 2018-003573-97 .

Background: Statistical Analysis Plans (SAPs) are essential for trial transparency and credibility but are resource-intensive to produce. While Large Language Models (LLMs) have shown promise in drafting protocols, their ability to generate high-quality, protocol-compliant SAPs remains untested against current content guidance. This study developed and validated an LLM-based pipeline for drafting SAPs from clinical trial protocols. Methods: We developed a structured, section-by-section prompting pipeline aligned with standard SAP guidance. We applied this pipeline to nine clinical trial protocols using three leading LLMs: OpenAI GPT-5, Anthropic Claude Sonnet 4, and Google Gemini 2.5 Pro. The resulting 27 SAPs were evaluated against a 46-item quality checklist derived from the published SAP guidelines. Items were double-scored by independent trial statisticians on a 0 to 3 scale for accuracy. We compared performance across LLMs and between item types (descriptive vs. statistical reasoning) using mixed-effects logistic regression. Results: Across 9 trials, the models produced SAP drafts with high overall accuracy (77% to 78%), with no difference in performance between the three LLMs (p=0.79) but varied by content type (p < 0.001). All models performed well on descriptive items (e.g., administrative details, trial design), with lower accuracy for items requiring statistical reasoning (e.g., modelling strategies, sensitivity analyses). Accuracy for statistical items ranged from 67% to 72%, whereas descriptive items achieved 81% to 83% accuracy. Qualitatively, models were prone to specific failure modes in complex sections, such as omitting necessary details for secondary outcome models or hallucinating sensitivity analyses. Discussion: Current LLMs can effectively draft portions of SAPs, offering the potential for substantial time savings in trial documentation. However, a human-in-the-loop approach remains mandatory; while models demonstrate strong capability in producing descriptive content, their independent application to complex statistical methodology design still requires further methodological development and training. Future work should explore advanced prompt engineering, such as retrieval-augmented generation or agentic workflows, to improve reasoning capabilities. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement No specific funding was obtained for the delivery of this study. Richard Emsley and Gordon Forbes are part-funded by the National Institute for Health and Care Research (NIHR) Maudsley Biomedical Research Centre (BRC), NIHR203318 ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes SAP-AI is live and free to use for anyone at https://sapai-streamlit-production.up.railway.app/ Source code for SAP-AI can be found at https://github.com/rct-sap-ai/sap-kcl Source Code for all analysis reported can be found at https://github.com/rct-sap-ai/validation-study-analysis/

Abstract Background Walking frame users are at increased risk of falls due to gait and balance impairments and restrictions caused by the frame itself. While exercise is an effective fall prevention intervention in the general population, there are no programmes specific to walking frame users. Adaptations may be required for walking frame users to achieve an appropriate intensity and dose of fall prevention exercise without increasing the propensity to fall while exercising. The Frame Fit intervention is a home exercise programme adapted for the needs of frame users. The aim of this study was to evaluate safety, acceptability and effectiveness of the Frame Fit intervention. Methods Community dwelling older people (aged ≥ 65) who use a walking frame were recruited to the randomised controlled trial and allocated to the 6-month Frame Fit intervention, a programme of home exercises prescribed and progressed by a physiotherapist, or to usual care. Falls (primary outcome) were recorded using diaries for 12 months from randomisation. Physical performance (grip strength, balance, gait speed and sit-to-stand), timed up and go, physical activity, fear of falling and health-related quality of life was measured at baseline and after six months. Secondary healthcare use and mortality was collected from electronic records for 12 months from randomisation. Results Of 117 participants randomised, (59 to intervention, 58 to usual care), 86 were followed up at six months and 83 provided 12 month falls data. There were two intervention-related adverse events. There were more falls reported by the intervention group than control group at six months (adj, IRR: 2.10, 95%CI 1.06–3.98) but no difference in falls at 12 months (adj.IRR:1.76, 95%CI 0.93–3.33). Adherence was satisfactory but there was low uptake to the trial. There were no differences found in the secondary outcome measures. Conclusions Frame Fit intervention offered a satisfactory safety profile, was acceptable to those who participated and feasible. Due to low recruitment rates, the study was underpowered to detect a difference in falls or other outcomes. Further research is needed to optimally tailor fall prevention interventions to walking frame users. Trial registration The protocol was prospectively registered as a clinical trial with the ISRCTN (clinical trial number: 57645734) on 11/09/2014.

Background:Physical restraints are widely used in intensive care units (ICUs) despite uncertain clinical benefit and risks. We aimed to characterise patterns of restraint use, demographic and clinical predictors, and temporal trends before and after introduction of federal restraint-related reporting requirements. Methods:We conducted a retrospective cross-sectional study of 51,838 adults admitted to ICUs at Beth Israel Deaconess Medical Center, Boston, MA, USA, between 2008 and 2022, using data from the Medical Information Mart for Intensive Care IV (MIMIC-IV) electronic health record repository. Primary outcome was the proportion of ICU days with documented physical restraint use. Associations between restraint use and demographic and clinical factors were estimated using a binomial generalised linear model with a logit link. Propensity score matching compared Black and White patients under varying adjustment specifications. Findings:Among 51,838 patients (mean age 63.8 years; 57% male), 21,091 (40.7%) experienced restraint. Use increased from 36.9% in 2008-10 to 44.0% in 2020-22 (p < 0.0001). Asian (aOR 0.84, 95% CI 0.79-0.89) and Hispanic/Latino patients (aOR 0.87, 95% CI 0.83-0.92) had lower odds of restraint than White patients. Propensity score matching between Black and White patients revealed ethnic patterns were highly sensitive to model specification: excluding demographic characteristics revealed significant disparities, which were attenuated when psychiatric diagnoses were also excluded. Matched White patients were not representative of all White ICU patients but rather a subset resembling Black patients on observed characteristics. Interpretation:Restraint practices appear to vary with patient acuity, institutional factors, and communication barriers. The sensitivity of ethnic disparities to psychiatric diagnosis adjustment suggests these diagnoses may function as mediators rather than confounders, potentially reflecting systematic differences in clinical assessment along the causal pathway between ethnicity and restraint decisions. The non-representativeness of matched cohorts underscores that disparities depend on which patient subgroups are compared. Prospective multisite studies with standardized assessment protocols are needed to validate findings, disentangle true clinical variation from systematic bias and provide a more comprehensive understanding of restraint practices across US ICU settings. Funding:No study-specific funding was received.

BACKGROUND/AIMS:Take-home naloxone (THN) programmes have been introduced in many European countries to provide non-medically trained people who are likely to witness an opioid overdose, including people who use opioids, with a naloxone kit and training. This study used data obtained from people supplied with THN and systematically followed up for 6 months to determine the proportion witnessing an overdose, administering naloxone and successfully reversing opioid overdose in real-world settings. The study aimed to compare reports of witnessed opioid overdose between participants in treatment and not in treatment at the time of recruitment. DESIGN:A multi-country, observational prospective cohort study. Participants supplied with THN were asked to report any witnessed overdose events and participate in a systematic follow-up over a 6-month period. SETTING:Participants were recruited from THN programmes at 22 drug treatment and harm reduction services in England, Wales, Scotland and Sweden. PARTICIPANTS:A total of 1025 people who used opioids and who were supplied with THN were recruited between June 2021 and November 2023, of whom 594 (58%) were successfully followed at 6 months. The participants were predominantly men (75%) and white (80%), with a mean age of 45.5 years (standard deviation 10). MEASUREMENT:Main outcomes: whether or not THN was administered at a witnessed overdose and overdose outcome where THN administered. Accurate recognition of opioid overdose, availability of naloxone and appropriate responses (including administering naloxone) to an opioid overdose were captured. Outcomes were compared between participants in treatment and not in treatment. FINDINGS:Of the 594 followed over 6 months, 160 (27%) witnessed at least one overdose. The likelihood of witnessing an overdose was higher among participants not in treatment than participants in treatment [56% vs. 23%; odds ratio = 4.4; 95% confidence interval (CI) = 2.69-7.21; P = 0.001]. THN was administered at most witnessed overdose events (83%; 95% CI = 74-85). Seven deaths were reported (4.4%; 95% CI = 0.02-8.8) by participants to be due to an overdose. For five deaths, naloxone was administered but was believed by participants to have been administered after death. Ninety-five percent (152) of participants were able to recognise one or more critical signs of overdose and respond appropriately. When naloxone was available, it was administered in almost all (90%; 142) emergency situations. CONCLUSIONS:In the United Kingdom and Sweden, people who use opioids appear to be likely to witness and recognise an opioid overdose, be the only person carrying naloxone at the overdose and be both willing and able to safely and effectively administer naloxone in a timely response. Clinical trial registration details (if applicable): ClinicalTrials.gov Identifier: NCT05072249. Date of Registration: 8.10.2021.

Introduction Smartphone ownership among UK adolescents is near universal, and teachers report phones increasingly being involved in classroom disruption, with misuse during school hours among the more common serious behavioural issues in secondary schools. Evidence on whether restrictive policies improve behaviour, attainment, or wellbeing remains limited. The primary objective is to assess the impact of a lockable smartphone pouch on educational attainment and behaviour. Secondary objectives are to assess impacts on general functioning, psychological wellbeing, and school-level indicators such as exclusions, and to examine whether effects differ for pupils who may be most at risk. Methods and analysis We will conduct a mixed methods cohort study in secondary schools across Northern Ireland and England during the 2025 to 2026 academic year. The quantitative component uses a serial cross-sectional design, with students completing an online questionnaire at 0, 4, and 8 weeks covering homework completion, classroom disruption, participation in PE and extracurricular activities, peer interaction, and smartphone use. Measures include the Strengths and Difficulties Questionnaire, the Revised Child Anxiety and Depression Scale, the short form of the Smartphone Addiction Scale, and the Bergen Social Media Addiction Scale. Schools will also supply half-termly aggregate data on exclusions, detentions, CAMHS referrals, counsellor visits, and parent visits from September 2023 to May 2026. Assuming 90% power, a two-sided type 1 error of 0.05, an intracluster correlation of 0.02, and 25% loss to follow up, we aim to recruit a minimum of 3,200 students from six or more schools to detect a small effect (Cohen's d = 0.2) on SDQ hyperactivity score. Continuous outcomes will be analysed with linear regression and binary outcomes with logistic regression. Aggregate school data will be analysed using an interrupted time series design. Prespecified subgroup analyses cover SEN or neurodivergent status, area-level deprivation, and existing school phone policy. Qualitative data from focus groups with students and staff and semi-structured interviews with school leads will be analysed thematically using Braun and Clarke's six-phase approach. Ethics and dissemination The study has been approved by the King's College London Research Ethics Committee. A Data Protection Impact Assessment has been agreed with the Northern Ireland Department of Education. Findings will be disseminated through a final report to the Department of Education, peer-reviewed publications, conference presentations, and accessible summaries for participating schools, pupils, parents, and policy makers. Keywords: Smartphone; Schools, Secondary; Adolescent Behavior; Mental Health; Academic Performance

Employment is a crucial part of recovery for individuals with severe mental illness. Individual placement and support (IPS) is the gold standard for vocational rehabilitation, yet IPS reaches only a fraction of who could benefit. Large language models (LLMs) have been proposed as potential tools for vocational guidance, but their utility for vulnerable populations is unknown. We conducted an analysis of LLM-generated job recommendations for individuals with schizophrenia spectrum disorders, and for a matched control cohort without psychiatric diagnoses. We used discharge summaries from 450 patients with a primary diagnosis of schizophrenia spectrum disorder and 50 control cases in the MIMIC-IV database, fitting three independent job recommendations per case with Gemini 2.0 Flash and Claude Sonnet 4. Recommendations were summarised as a frequency and LLM-automated content analysis was used to analyse reasoning patterns, workplace accommodations, and alignment with supported employment principles. Both, Gemini and Claude, showed little diversity and strong bias toward entry-level roles. In the schizophrenia cohort, Gemini mostly recommended data entry and other clerical jobs while Claude produced a similarly narrow pattern with the majority suggesting library-related. The controls revealed comparable clustering, with Gemini defaulting to clerical work and medical secretary roles, and Claude to customer service. There was limited diversity in the role settings, which almost uniformly suggested flexible schedules and minimal social interaction. Nor was there diversity in how roles were tailored to patient strengths, qualifications, or prior experience; instead, demographic stereotypes such as age-based framing, gendered role allocation, and assumptions about language skills often shaped the recommendations. Based on our data and procedures, preliminary evidence does not support immediate deployment of LLMs for job recommendations for the tested population; further evaluation is needed after integrating human oversight and bias-mitigation steps.

BACKGROUND:Placental malperfusion, categorised into maternal vascular malperfusion (MVM) and foetal vascular malperfusion (FVM), is a main placental pathology known to affect placental functioning and offspring outcomes. The aim of this review is to evaluate the association between exposure to placental malperfusion and offspring neurodevelopment from birth to 18 years of age. METHODS:Following the registered protocol on Prospero, Medline, Cochrane, CINHAL, Embase and PsycINFO databases were searched systematically from inception to 01/11/2023. Included were publications examining exposure to placental malperfusion detected on histopathological examination and clinically measured neurodevelopmental outcomes. Publications on multi-pregnancies or animals, exposure to malformations, surgical or medical interventions, review and opinion articles, or those not translated to English, were excluded. Grey literature search and forward and backward citation chaining were performed. The Joanna Briggs Institute's checklists were used for quality assessment. Three studies were pooled using percentages of adjusted associations. RESULTS:Nine observational studies fulfilled the eligibility criteria. The included neurodevelopmental outcomes were assessed from 5 days to 8 years when age of assessment is reported. Four publications showed an association between exposure to MVM and poor neurodevelopment at 10-40 months and 8 years, however, no association was observed when examining preterm infants up to 24 months. Conversely, in the six studies examining exposure to FVM, FVM association with neurodevelopmental disorders was reported in two studies looking at preterm infants assessed at 24 months and 8 years and better neurodevelopmental scores in other two studies at 10-40 months. CONCLUSIONS:The pattern of association between MVM and FVM with neurodevelopmental outcomes varied among the included studies. Clinical and methodological heterogeneities and poor reporting of relevant populations' characteristics hindered full understanding of the results. Methodologically rigorous research is required to help utilise histopathological findings of placental malperfusion in predicting offspring's neurodevelopmental outcomes.

There is an urgent need for psychological interventions that can target depression in late adolescence and prevent it from having lifelong implications. Schools have been identified as a promising setting to enhance access to interventions and offer support earlier. We have co-developed a novel intervention, IMAGINE, that targets key cognitive mechanisms implicated in depression across the lifespan. Depression has been associated with distressing negative mental images, a deficit in positive future images and overgeneral autobiographical memories. Interventions targeting these factors have shown clinical promise in adults. Here, we combine techniques targeting these cognitive processes into a novel, brief psychological intervention for adolescent depression. This Phase IIb randomised controlled trial will evaluate IMAGINE compared to an active psychological intervention. One hundred sixty adolescents (aged 16–18) with high levels of depressive symptoms will be recruited from schools. Participants will be randomly allocated to IMAGINE or the active psychological control intervention, non-directive support (NDS). Assessment will take place at baseline, 8-, 16- and 24-week post randomisation. The primary objective is to establish whether IMAGINE reduces symptoms of depression, relative to NDS, at 8 weeks following randomisation. Secondary objectives include whether changes in depression are maintained at 16- and 24-week follow-up, the efficacy of IMAGINE on secondary clinical outcomes and key cognitive mechanisms and, finally, to assess outcomes around acceptability, safety and adherence. If IMAGINE is shown to be safe and clinically effective, an effectiveness-implementation hybrid RCT will be indicated. If rolled out as an intervention, IMAGINE would significantly extend the range of effective therapies available for adolescent depression. ISRCTN, ISRCTN14015295. Registered 11 September 2023, https://doi.org/10.1186/ISRCTN14015295 .

Drug development is lengthy and costly, making drug repurposing an attractive alternative. Identifying repurposing candidates from vast biomedical literature is challenging. Natural language processing (NLP) offers potential for literature-based discovery. We present and evaluate a novel, accessible NLP-based method using the Word2Vec algorithm to identify, test, and validate candidate medications for repurposing, demonstrated by seeking treatments for psychotic disorders. A Word2Vec model trained on 2.3 million PubMed abstracts (2000–2023) identified potential repurposing candidates based on cosine similarity to a known antipsychotic drug. We tested one candidate, a cephalosporin antibiotic, across independent datasets: MIMIC-IV, CRIS, and BRATECA. Cephalosporin antibiotics in MIMIC-IV demonstrated a reduced hazard ratio (aHR) for psychosis hospitalisation overall (0.94, 95

Whilst 30-60% of women with hypertensive disorders of pregnancy (HDP) suffer from ocular manifestations, longer term ophthalmic sequelae are unclear. We performed a systematic review and meta-analysis assessing the relationship between HDP and future ophthalmic morbidity, specifically retinal disorders (primary outcome) and/or other ophthalmic disorders (secondary outcomes). Four databases were searched until February 2025. Studies were screened according to inclusion/exclusion criteria, and quality assessed using the Newcastle-Ottawa scale. Random-effects was performed using generic inverse variance method, producing pooled odds ratios (ORs) with 95% confidence intervals (Cis). Eight studies were included (2 174 991 women; 5.40% HDP), typically of good (n = 4) to fair (n = 2) quality. Meta-analysis for retinal detachment and diabetic retinopathy were performed using two studies (n = 1 211 724; 6% HDP). Preeclamptic women had near double odds of retinal detachment (1.87; 95% CI 1.57-2.22; I2 = 0%) and over six times the odds of diabetic retinopathy (6.57; 95% CI 3.41-12.65; I2 = 51%). Studies reported generally poorer ophthalmic outcomes in women with HDP.

There has been extensive debate about the role of social media and smartphone use in youth mental health and self-harm. Research to date lacks sufficient detail to determine the mechanisms underpinning any associations. The Social Media, Smartphone use and Self-harm in Young People (3S-YP) study is a prospective cohort study that was co-produced with young people to investigate temporal patterns of social media and smartphone use prior to an episode of self-harm in a clinical youth sample. Young people were actively involved in all key stages of the research process to ensure the research would be relevant and acceptable to the intended population. This included defining the research question and designing the methods. This qualitative sub-study nested within the main 3S-YP study aimed to evaluate young people's experiences of engaging in this innovative digital mental health study. This will help inform understanding regarding the added value of co-production and future research in this field. Semi-structured interviews were conducted with a purposive sample of participants from the 3S-YP study. Interview data was analysed using codebook thematic analysis. Sixteen young people (mean 19.8 years old, SD 2.9; n = 10 female, 63%) participated in the interviews. Participants were generally comfortable answering questions about sensitive topics using remote digital tools, appreciating the greater privacy, convenience and opportunity for self-reflection they provide, whilst noting periods of poor mental health may affect study engagement. The remote research methods (including the participation information and tools for recruitment and data collection) were considered user-friendly and were complemented by the active role of the research team who facilitated young people's engagement with the study. Despite the relevance and support for research on the impact of digital technology use on youth mental health, concerns about data sharing and a complex process for accessing data from social media platforms complicated study engagement. The role of parental involvement was also described. User-friendly remote research methods, coupled with proactive, responsive researchers and parental support are beneficial for conducting research with clinical youth populations. Whilst young people endorse research in this field, concerns about data sharing and barriers to data access need addressing if researchers are to effectively employ innovative solutions to investigating the impact of smartphones and social media use on youth mental health and self-harm. The findings from this study demonstrate the value of actively involving those with lived experience throughout the research process and provide useful insight for researchers intending to conduct similar research. This study is registered on ClinicalTrials.gov (ID no. NCT04601220).

Importance:Intraventricular hemorrhage (IVH) is a significant complication of preterm birth, affecting approximately 20% of preterm infants. Despite its prevalence, the effect of IVH beyond the impact of prematurity alone has been scarcely studied beyond early childhood, posing an important knowledge gap. Objective:To investigate the association of IVH with national school performance throughout childhood to adolescence. Design, Setting, and Participants:This population-based cohort study included all very preterm infants (<32 weeks' gestation) and full-term infants (≥37 weeks' gestation) born in New South Wales, Australia, between January 1, 2007, and December 31, 2013. Cohorts were very preterm children with low-grade (grades 1-2) or high-grade (grades 3-4) IVH, very preterm controls without IVH, and full-term controls. Analyses were conducted from January 30 to September 18, 2024. Exposure:IVH grade 1 to 4. Main Outcomes and Measures:The primary outcome was overall performance on standardized national school assessments at age 8 to 9, 10 to 11, and 12 to 13 years, including adjusted mean differences (AMDs) in z scores between children with IVH and very preterm controls. Secondary outcomes were domain-specific performance in reading, writing, spelling, grammar, and numeracy and whether children met the national minimum standards overall and for each domain. Academic trajectories were also compared by group. Results:This study included 408 189 children: 557 with low-grade IVH, 85 with high-grade IVH, 2557 very preterm controls without IVH, and 404 990 full-term controls. Children with low-grade IVH performed similarly to preterm controls at age 8 to 9 years (AMD in overall academic z score, -0.06; 95% CI, -0.14 to 0.03), 10 to 11 years (AMD, -0.09; 95% CI, -0.21 to 0.03), and 12 to 13 years (AMD, -0.04; 95% CI, -0.24 to 0.16). Children with grade 2 IVH (n = 145), however, performed significantly worse than very preterm controls at age 8 to 9 years (AMD, -0.20; 95% CI, -0.36 to -0.04). Children with high-grade IVH performed significantly worse than very preterm controls at age 8 to 9 years (AMD, -0.50; 95% CI, -0.71 to -0.30), 10 to 11 years (AMD, -0.59; 95% CI, -0.85 to -0.34), and 12 to 13 years (AMD, -0.61; 95% CI, -1.05 to -0.17). Numeracy was a consistently weak domain for children with high-grade IVH throughout school age (eg, at age 8 to 9 years, AMD in the numeracy z score compared with very preterm controls was -0.49 [95% CI, -0.70 to -0.28]). Differences in academic trajectories between groups remained fixed with increasing age; however, all groups showed improvement over time (eg, adjusted β for very preterm children, 32.3 [95% CI, 31.2-33.5]; children with low-grade IVH, 31.5 [95% CI, 29.0-34.0]; high-grade IVH, 30.2 [95% CI, 24.1-36.4]). Conclusions and Relevance:In this cohort study, the association of low-grade IVH with worse school performance appeared limited to children with grade 2 IVH. Children with high-grade IVH consistently showed poorer academic performance into adolescence than their peers born very preterm without IVH. Nevertheless, very preterm children, regardless of IVH grade, demonstrated academic progress over time, underscoring the need for ongoing educational support to help them to realize their full potential.

Objectives To investigate if frailty status alters following solid organ transplantation (lung, liver, kidney and heart) without rehabilitation intervention.Research design and methods Studies published between 1 January 2000 and 30 May 2023 were searched across five databases. Studies measuring frailty, using a validated or established frailty measure, pre- and post-transplant were included. Narrative synthesis was used to describe the included studies according to the time post-transplant and according to solid organ group. Where data allowed a meta-analysis was conducted to compare frailty prevalence pre- and 6-12 months post-transplant across studies.Results Twelve studies were included in this review (6 kidney transplant, 2 liver transplant, 3 lung transplant and 1 heart transplant), with a total of 3065 transplant recipients with 62% being male. The mean age across studies was 51.35 years old. When narratively synthesised after an initial worsening of frailty immediately post-transplant, there appears to be a significant improvement in frailty by 3 months post-transplant that is sustained by 6 to 12 months following solid organ transplantation. Five studies were included in the meta-analysis which demonstrated an odds ratio = 0.27 (95% CI, 0.12, 0.59, P = .001, ${I}<^>2$ = 82%) for frailty prevalence post-solid organ transplantation (SOT) compared to frailty prevalence pre-SOT. When the single paper deemed to be of poor quality was removed the remaining four studies demonstrated a reduced odds ratio of being frail at 6-12 months post-transplant (OR 0.45 (95% CI, 0.32, 0.65, P = .001, ${I}<^>2$ = 13%).Conclusions Transplant may be associated with a reversal in frailty, although heterogeneity was demonstrated across studies.