Microbiology

The increasing deployment of artificial intelligence (AI) assistive systems across healthcare, education, and organisational domains necessitates a deeper understanding of dispositional factors shaping trust and acceptance. This study investigated the Big Five personality traits as predictors of trust in and acceptance of AI assistive systems among a large adult sample (N = 380) in Makurdi Benue State. Anchored in the Technology Acceptance Model (TAM) developed by Davis (1989), the study examined both direct and indirect pathways linking personality traits to AI acceptance through trust. Participants completed standardised measures of the Big Five Inventory, Trust in AI Scale, and AI Acceptance Scale. Data were analysed using structural equation modelling (SEM) with maximum likelihood estimation. The hypothesised model demonstrated good fit indices (CFI = .84, TLI = .82, RMSEA = .05). Openness to experience ({beta} = .34, p < .001) and agreeableness ({beta} = .27, p < .01) significantly predicted trust in AI systems, which in turn strongly predicted AI acceptance ({beta} = .62, p < .001). Neuroticism negatively predicted trust ({beta} = -.29, p < .001), while conscientiousness showed a modest positive direct effect on acceptance ({beta} = .18, p < .05). Extraversion was not a significant direct predictor but exerted an indirect effect through trust. Mediation analysis confirmed that trust significantly mediated the relationship between personality traits and AI acceptance. The findings underscore the centrality of dispositional traits in shaping technological trust formation and highlight the psychological architecture underlying human AI interaction. These results contribute to social psychological theory and provide empirical guidance for designing personality sensitive AI systems to enhance user adoption and sustained engagement.

Introduction: Group interpersonal psychotherapy may improve outcomes beyond depressive symptoms, but evidence on functioning, social support, and household welfare remains limited. We examined these outcomes using mixed methods in a pilot cluster-randomized controlled trial of a six-week intervention in rural Uganda. Methods: Twenty-four villages were randomized to group interpersonal psychotherapy or enhanced care as usual. Eligible participants were female, aged at least 13 years, with Patient Health Questionnaire-9 scores of 10 or more. Outcomes were assessed at baseline, two weeks, and three months after treatment. Regression models used village-clustered standard errors. Exploratory sensitivity analyses compared controls with 33 intervention participants assessed independently of facilitators and after an honesty and confidentiality prompt. Fourteen interviews and three focus group discussions with 30 intervention participants were analysed thematically and integrated by outcome domain. Results: Of 292 randomized participants, 263 completed the three-month assessment. Intervention participants had lower anxiety scores than controls at three months (mean difference -7.18; p<0.001), higher subjective wellbeing (mean difference 3.70; p<0.001), lower disability scores (mean difference -1.01; p<0.001), greater perceived social support (difference 23.4 percentage points; p<0.001), and more meals reported for children in the previous 24 hours (mean difference 0.62; p<0.001). Household food insecurity was lower in the full-sample analysis (difference -23.3 percentage points; p=0.008), but not in the exploratory sensitivity analysis (difference 1.5 percentage points; p=0.883). Qualitative accounts described recovery as restored capacity to work, manage relationships, care for children, and respond to hardship despite material constraints. Conclusions: These preliminary findings suggest that group interpersonal psychotherapy may improve outcomes beyond depressive symptoms, although household welfare findings were less consistent. Larger trials with independent outcome assessment and longer follow-up are needed. Trial registration: The trial was retrospectively registered with the Pan African Clinical Trials Registry (PACTR202606549854263) on 29 June 2026.

Introduction Auto-Induced Cognitive Trance (AICT) is a non-ordinary state of consciousness (NOSC) that can be accessed by will alone once a standardised self-induction procedure has been learnt. The first research publication on AICT dates back only ten years, meaning that research on this phenomenon is still in its infancy. Previous reports concerning the phenomenology and neurophysiology of AICT revealed similarities with more extensively described NOSCs, as well as unusual features, raising questions about the potential benefits of AICT practice for well-being. Objective This study aimed to gather quantitative descriptive data on features associated with well-being in a large comparative sample of AICT practitioners and non-practitioners. Method This research followed a web-based survey study design which enquired AICT-trained and yet-to-be trained participants to self-report through validated standardised questionnaires on vitality, self-esteem, mental well-being, trait anxiety, life satisfaction, happiness, positive and negative affect, nature-relatedness and connectedness. Data on NOSCs practices, life history events that could have led to spontaneous NOSCs, and demographic data were collected for further inclusion as control variables in statistical models. Results The online questionnaire yielded 607 valid responses, (171 yet-to-be trained participants and 436 AICT-trained participants). AICT practice was found to be associated with increased self-esteem (RSE), overall connectedness (WCS) as well as all subdimensions of connectedness (WCS Self, WCS Others, WCS World). AICT practice Duration exhibited significant effects on global connectedness and all subdimensions of connectedness, self-esteem, trait anxiety (STAIT-5), and positive affect (PANAS+). Conclusions AICT seems to benefit to practitioners well-being shortly after training through increases in self-esteem and in the sense of connectedness. Prolonged AICT practice is associated with added decreased trait anxiety and increased positive affect. Further research is needed to confirm these findings with a sample including AICT-uninterested participants, and to clarify the underlying mechanisms of AICT.

Background: Children and young people (CYP) with intellectual disability (ID) frequently have co-occurring neurodevelopmental (ND) and mental health (MH) difficulties. While copy number variants (CNVs) are identified as an important aetiology of ID, it is unclear whether and how CNV risk scores predict ND and MH characteristics within the CNV-associated ID population. Methods: We analysed data from the UK-based IMAGINE-ID cohort of CYP (aged 4-19 years) with ID and clinically-reported CNVs (N = 1,640). CNVs were annotated with Gencode 19 in ENSEMBL to calculate CNV risk scores, including summed probability of loss-of-function intolerance (pLI) and dosage sensitivity. Multivariate regression models examined the prediction of CNV variables and inheritance on ND and MH characteristics, assessed via the Development and Well-Being Assessment (DAWBA). Post-hoc analyses explored CNV variable stratification (lower vs. higher range pLI). Results: Higher summed pLI scores (indexing CNV genes' intolerance to loss of function) unexpectedly predicted fewer MH difficulties and a lower likelihood of ND diagnoses, even after accounting for demographic factors and CNV inheritance. Post-hoc analyses identified a threshold effect. Within the lower pLI range, higher pLI scores were associated with greater MH difficulties, consistent with findings from population-based samples. In contrast, within the higher pLI range, higher pLI scores were associated with fewer MH difficulties (among individuals more likely to have severe ID). Conclusion: These findings challenge the assumption that CNV genomic "risk scores" universally predict ND and MH difficulties. Instead, within CNV-associated ID, complex relationships exist between CNV risk scores, inheritance and phenotypes. These insights emphasise the necessity of integrating genomic results with familial and developmental context to understand individual vulnerabilities and support needs.

Background. UK clinical guidance recommends that structured risk prediction tools and risk stratification should not be used in self-harm, to predict suicide or determine who is offered treatment. Underpinning this position is the premise that routinely collected health data contain no useful predictive signal, which has received little direct scrutiny. Objective. To test whether routinely collected electronic health record data can distinguish groups at higher and lower risk of severe outcomes following paracetamol overdose. Methods. We analysed 4,095 adults presenting to NHS Lothian emergency departments with paracetamol overdose (2017-2023). Elastic-net logistic regression was fitted to 37 routinely collected electronic health record features to predict a composite of death or mental health inpatient admission at 0-7, 8-30 and 31-365 days following attendance, evaluated on a held-out 20% test set with bootstrapping. Findings. Events occurred in 5.5% of patients at 0-7 days, 2.0% at 8-30 days and 7.9% at 31-365 days, dominated by mental health admission. Bootstrap AUROC 95% confidence intervals lay above 0.5 in every window (0.65-0.82, 0.63-0.90, 0.71-0.85): models ranked patients better than chance. Calibration slopes (1.04, 1.14, 1.07) were close to one. Ranking drew primarily on mental health-related features. Conclusions. Routinely collected health data carried predictive signal for severe outcomes after paracetamol overdose, although discrimination fell short of what is needed for individual-level clinical use. Clinical implications. These models are not proposed for clinical deployment; however, treating risk prediction as a settled question will redirect research efforts, potentially excluding this patient population from machine learning advances driving improvements in care in other medical specialties.

Lithium has been the gold standard for the treatment and prevention of relapse in bipolar disorder for over 60 years. Guidance from the National Institute for Health and Clinical Excellence states explicitly to 'offer lithium as a first-line, long-term pharmacological treatment for bipolar disorder'. Yet, in the last two decades its use has been in decline with clinicians favouring anticonvulsants or antipsychotics when treating this condition. In this study, we have used three openly available datasets containing prescribing data from primary and secondary care to explore trends in the use of lithium in England, showing both regional and temporal variance between 2015-2024. We have shown that lithium use declined in primary care by 20.9% in the last ten years (2015-2024) and 10.9% overall in the last five years (2019 to 2025). We have also shown how there is some regional variation in the source of lithium for patients, although the vast majority is prescribed in primary care. Further research into clinical behaviour is needed to understand what is driving the decrease in lithium usage, and what barriers and enablers may influence its use across the country.

Executive function (EF) deficits are central features of schizophrenia and strongly influence long-term functional outcomes. Conventional cognitive assessments often lack ecological validity and cultural relevance. This study introduces the Luk Chup Augmented Reality (LCAR) tool a video guided, clay modeling task delivered through wearable AR that integrates culturally familiar activity with realtime neurophysiological monitoring. Thirty individuals diagnosed with schizophrenia (mean age = 38.9, SD. = 7.15 years) completed a series of modeling and memory tasks using LCAR while undergoing quantitative EEG (QEEG). Task duration and theta/beta power were analyzed across procedural and color shape memory phases. Memory phases took significantly longer to complete and were associated with decreased lateral prefrontal theta and increased frontal midline theta activity (Fz, Cz), indicating higher EF demand. A repeated-measures ANOVA revealed significant condition, site, and interaction effects on theta power. The LCAR tool shows promise as a culturally grounded, dual-mode assessment of EF in schizophrenia. It offers a novel integration of performance-based and neurophysiological metrics that may inform future interventions in psychiatric rehabilitation.

Background: Urinary tract infection (UTI) is the most common secondary condition among people with spinal cord injury/disease (SCI/D). Intravesical Lacticaseibacillus rhamnosus GG (LGG) is an antibiotic-sparing approach to managing urinary symptoms. Objective: Determine the optimal number of doses of intravesical LGG for urinary symptom reduction. Design: Prospective, randomized, two-arm dosing trial. Setting: National recruitment with a local subsample providing urine samples in Washington, DC, USA. Participants: Adults with SCI/D and neurogenic lower urinary tract dysfunction (NLUTD) who use intermittent catheterization (IC); 177 enrolled and randomized (intention-to-treat), with 76 compliant instillers (39 low-dose, 37 high-dose) in the per-protocol analytic sample. Interventions: Two (2 doses/24 hours) or four (4 doses/36 hours) intravesical LGG regimens, self-initiated in response to cloudier or malodorous urine per the Self-Management Protocol using Probiotics (SMP-Pro). Main Outcome Measures: Primary: proportion achieving [&ge;]20% reduction on the Urinary Symptom Questionnaire for Neurogenic Bladder-Intermittent Catheter version (USQNB-IC). Secondary: urinary biomarkers (leukocyte esterase, nitrite, white blood cells, urinary neutrophil gelatinase-associated lipocalin [uNGAL]) and standard urine culture (SUC) in a local subsample. Results: By Day 2, 57.9% (63.8% low-dose; 51.2% high-dose) achieved [&ge;]20% total symptom reduction; high-dose success rose to 70.0% by Day 4. Thirty percent of high-dose participants did not respond at either time point and could not be distinguished from responders by demographics or urine biomarkers. Urinary biomarkers and SUC were unchanged pre- to post-instillation. No serious adverse events were adjudicated as attributable to intravesical LGG by an independent Data Safety Monitoring Board (DSMB). Conclusions: A two-dose course of intravesical LGG yields clinically meaningful symptom improvement in the majority of people with SCI/D and NLUTD who use IC; four doses benefits a meaningful subgroup of two-day non-responders, while a small cohort remains nonresponsive. These results provide preliminary dosing guidance and support progression to a definitive trial.

Abstract Background: Remote clinical reviews have become an integral component of contemporary nursing practice across community and acute care settings. Nurses increasingly make autonomous clinical decisions using telephone, video, and online/digital systems, often with limited sensory information and under conditions of uncertainty. However, empirical understanding of how nurses make clinical decisions via remote reviews remains limited. Aim: To explore and understand how registered nurses (RNs) make clinical decisions about patient care via remote reviews. Methods: A convergent mixed-methods design was employed. Quantitative data (analytic quantitative sample N=53) were collected using validated questionnaires that measured decision-making processes, physician-nurse collaboration, decision-making stress, and perceived decision-making ability. Qualitative data (N=23) were generated through semi-structured interviews. Data collection took place between October 2024 and April 2025. Quantitative data were analysed using descriptive statistics, correlation, and multiple regression. Qualitative data were analysed using framework analysis. Integration was achieved through pillar-building and theory-driven synthesis and illustrated by joint display tables. Results: Most nurses demonstrated a flexible decision-making style, integrating analytical and intuitive reasoning. Both analytical and intuitive processes were positively associated with perceived decision-making ability. Physician-nurse collaboration emerged as a strong predictor of decision-making confidence, while decision-related stress was not a significant predictor. Qualitative findings identified three themes: characteristics of remote review; making adaptive decisions shaped by both internal and external constraints and enablers; and external influencing factors. The integrated findings informed a theory-informed ICE framework to illustrate how nurses make clinical decisions via remote reviews. Conclusion: Remote clinical decision-making is a dynamic cognitive-environmental process rather than a purely individual cognitive act. The ICE framework conceptualises this interaction, extending existing decision-making theories to digitally mediated care. Impact: Understanding remote decision-making supports training design, clinical governance, and the development of Artificial Intelligence-enhanced decision-support tools grounded in ecological bounded rationality. Patient or Public Contribution: Patient and public representatives contributed to stakeholder discussions that informed the development of the interview topic guide and the theoretical model. Patients or members of the public were not involved in recruitment, data collection, analysis, interpretation of findings, or preparation of the manuscript. Keywords: clinical decision-making, remote reviews, telehealth, nursing, mixed methods, ecological bounded rationality

Background and objectives Spontaneous bacterial peritonitis (SBP) is a life-threatening complication of cirrhosis with ascites, carrying one- and two-year mortality rates exceeding 70% and 80%, respectively. Fluoroquinolone prophylaxis is the cornerstone of SBP prevention. Real-world longitudinal data on prescribing practices and clinical outcomes from Indian tertiary care centers are sparse. We aimed to evaluate fluoroquinolone prescribing patterns, guideline adherence, and six-month clinical outcomes in SBP patients at a tertiary academic center in North India. Methods This was a pre-specified sub-analysis of a 15-month analytical longitudinal study at AIIMS Rishikesh. Adults (age >/=18 years) admitted with SBP and initiated on fluoroquinolone prophylaxis were enrolled consecutively and followed for six months. Prescribing practices were compared against EASL and AASLD recommendations. The primary outcome was the rate of guideline-directed prescribing. Secondary outcomes included clinical cure at discharge, six-month cure, relapse, regimen modification, adverse drug reactions, and treatment compliance. Categorical variables were compared by Fisher's exact test or chi-squared test (SPSS). Results Forty-eight SBP patients were included (mean age 44.75 +/- 11.94 years; 85.4% male). Guideline-directed fluoroquinolone prophylaxis was prescribed to all patients (100%). Norfloxacin 400 mg once daily was predominant (85.4%), followed by levofloxacin (10.4%) and moxifloxacin (4.2%). Cure at discharge was 85.4%. At six months, 64.6% maintained sustained cure and 22.9% relapsed. Regimen modification occurred in 22.9%, most commonly antimicrobial substitution. Nausea was the only adverse drug reaction (4.8%). Treatment compliance was 73.8%. No patient underwent therapeutic drug monitoring. Conclusions Fluoroquinolone prescribing for SBP prophylaxis at AIIMS Rishikesh was fully concordant with standard guidelines. Despite complete adherence, a relapse rate of 22.9% and frequent regimen modification underscore the limitations of long-term fluoroquinolone prophylaxis, likely reflecting emerging quinolone resistance. Strengthening antimicrobial stewardship is essential to sustain prophylaxis effectiveness in Indian tertiary care settings.

Background: Antimicrobial resistance (AMR) disproportionately affects low- and middle-income countries (LMICs) such as Pakistan, where obstetric and gynaecological (OBGYN) patients carry high antibiotic exposure. Specialty-specific drug utilization data with concurrent stewardship audit remain scarce. This study evaluated antibiotic prescribing patterns, consumption metrics, and antimicrobial stewardship program (AMS) compliance in OBGYN inpatients at a public sector tertiary care hospital. Methods: A prospective cross-sectional study was conducted in OBGYN wards of Dow University Hospital, Karachi, from 1 September to 31 October 2025. Women receiving [&ge;]1 systemic antibiotic were included. Daily AMS rounds were conducted by an Infectious Diseases physician and pharmacist. Antibiotic consumption was measured as Defined Daily Doses (DDD) and Days of Therapy (DOT) per 1,000 patient-days (total = 821). Antibiotics were classified by WHO AWaRe (2023) framework. Results: Of 812 total admissions, 278 patients (34.2%) received [&ge;]1 antibiotic and were enrolled (205 obstetric, 73 gynaecological), generating 636 prescriptions (mean 2.29/patient). Surgical prophylaxis was the predominant documented indication (213, 33.5%); 65.1% carried no documented indication. By AWaRe classification, 53.6% were Access-group and 46.1% Watch-group. Ceftriaxone (38.4%) and metronidazole (36.8%) together represented 75.2% of prescriptions. Combined DDD/1,000 patient-days was 1,758.6 and DOT/1,000 patient-days was 1,852.7. AMS compliance was 0%. Conclusions: This study documents high antibiotic prescribing burden, near-universal documentation failure, and zero AMS compliance in OBGYN inpatients at a Pakistani public sector hospital. The predominance of Watch-group antibiotics and undocumented surgical prophylaxis highlights structural stewardship gaps. Findings support urgent need for institutional OBGYN antibiotic guidelines and structured pharmacist-led AMS programs.

Sensory processing differences are a core feature of autism, affecting 60-95% of individuals, yet the associated neural mechanisms remain unclear. An excitation-inhibition (E/I) imbalance in brain circuits has been proposed, but in vivo evidence linking genetic variation in E/I pathways, regional neurochemistry, neural circuit function, and sensory behaviour has been lacking. Here we performed a multimodal investigation in 206 individuals (130 autistic), integrating gene-set polygenic scores for excitatory glutamatergic and inhibitory gamma-aminobutyric acid (GABA)-ergic pathways, magnetic resonance spectroscopy (MRS) measures of regional GABA and Glx (glutamate + glutamine) levels, vibrotactile psychophysical measures of tactile perception, and questionnaire measures of behavioural sensory reactivity. We found that glutamatergic polygenic scores predicted thalamic glutamate levels in neurotypical but not autistic individuals, suggesting altered genotype-neurochemistry coupling in autism. Thalamic Glx:GABA levels associated with tactile perception in both groups, but with opposing directions of effect, indicating that autistic and neurotypical individuals achieve similar perceptual outcomes with potentially differing thalamocortical circuit mechanisms. Within autistic individuals, tactile perceptual differences further related to behavioural sensory reactivity. Together, these findings suggest that autistic sensory processing potentially relies on distinct circuit mechanisms linking genetic variation, neurochemistry and perception. This work thus has important implications for how sensory differences are conceptualised, studied, and interpreted, and ultimately for how interventions and support are developed.

Psilocybin shows therapeutic promise for several psychiatric disorders, but the acute perceptual and cognitive alterations produced by conventional doses (10-25 mg) require in-clinic supervision, which limits scalability. Whether the therapeutically relevant pharmacology of psilocybin can be separated from its hallucinogenic activity remains unresolved. To address this gap, we conducted a Phase 1, randomized, double-blind, placebo-controlled, single ascending dose study to characterize the safety, pharmacokinetics and pharmacodynamics of low doses of psilocybin. Fifty-six healthy adults received a single oral dose of psilocybin (0.5, 1.0, 1.5, 2.5, 3.5 or 4.0 mg) or matching placebo across seven sequential cohorts, with each dose escalation reviewed by a Drug Safety Review Committee. All participants completed the study with no serious adverse events or discontinuations. Treatment-emergent adverse events were comparable to placebo and most prominently arose as somnolence. Plasma psilocin appeared rapidly with a median time to maximum concentration < 1 h with dose-proportional exposure and a short terminal half-life. Subjective drug effects were dose-related and became distinguishable from placebo at doses at or below 2.5 mg. Peak subjective ratings increased with dose, while any signs of hallucinations or altered-states scores remained low and not different than placebo. Psychophysiological engagement was confirmed by a clear dose-dependent pupillary dilation while cognitive performance (attention, vigilance, working memory, impulse control) showed no dose-dependent decrement and state anxiety did not increase at any dose. These findings indicate that the perceptible pharmacology of psilocybin can be dissociated from significant perceptual alterations and cognitive impairment at low doses. They further support controlled investigations in outpatient Phase 2 studies evaluating the safety and feasibility of repeated, self-administered low-dose psilocybin. ClinicalTrials.gov #NCT07710027

Background: Oral care is a critical nursing intervention for mechanically ventilated patients in intensive care units because it reduces oral microbial colonization and contributes to the prevention of ventilator-associated pneumonia, a major cause of morbidity, prolonged hospitalization, and increased healthcare costs among critically ill patients. Despite the availability of evidence-based guidelines, gaps in nurses knowledge and inconsistent implementation of oral care practices remain challenges, particularly in low- and middle-income settings. Objective: This study aimed to assess the level of knowledge among intensive care unit nurses regarding oral care for mechanically ventilated patients at Tenwek Hospital, Kenya, determine factors influencing knowledge, and examine the relationship between nurses knowledge and selected demographic and professional characteristics. Methods: An analytical cross-sectional study design was employed. The study was conducted among intensive care unit nurses at Tenwek Hospital. A sample of 38 nurses was selected from a target population of 60 intensive care unit nurses using simple random sampling. Data were collected using a structured self-administered questionnaire assessing socio-demographic characteristics, knowledge of evidence-based oral care practices, awareness of guidelines, and factors influencing knowledge. Data were analyzed using descriptive statistics, chi-square tests, Pearson correlation, and logistic regression, with statistical significance set at probability value less than 0.05. Results: Thirty-five nurses participated, yielding a response rate of 92.1 percent. The findings demonstrated generally high knowledge levels regarding oral care practices for mechanically ventilated patients. Most nurses correctly identified recommended oral care frequency (88.6 percent), oral assessment before care (91.4 percent), suctioning before and after oral care (94.3 percent), and the role of oral care in preventing ventilator-associated pneumonia (97.1 percent). However, knowledge gaps were identified in areas such as toothbrushing practices and documentation of oral care procedures. Training, continuing professional education, availability of guidelines, workload, resources, supervision, and teamwork were identified as important factors influencing knowledge. The findings revealed that professional qualification (probability value equal to 0.02), intensive care unit experience (probability value equal to 0.030) and formal oral care training (probability value equal to 0.021) were significantly associated with nurses knowledge of oral care practices. Conclusion: Intensive care unit nurses at Tenwek Hospital demonstrated adequate knowledge of evidence-based oral care practices for mechanically ventilated patients. However, targeted educational interventions are required to address identified gaps and strengthen standardized oral care delivery. Continuous professional development, consistent use of guidelines, supportive supervision, and adequate resource provision are recommended to enhance patient safety and reduce preventable intensive care unit complications such as ventilator-associated pneumonia. Keywords: Intensive care unit nurses; Oral care; Mechanically ventilated patients; Ventilator-associated pneumonia; Nursing knowledge; Evidence-based practice

Introduction Adolescent idiopathic scoliosis (AIS) requires frequent x-rays for management, exposing young patients to cumulative radiation risks. While radiation-sparing imaging modalities exist, access across the National Health Service (NHS) remains uneven and information given to patients is variable. This qualitative study investigated the systemic, geographic, and interpersonal dynamics of AIS imaging in England. Design This qualitative study employed in-depth semi-structured interviews with healthcare professionals (HCPs) from NHS paediatric spinal centres, patients aged 13 to 25 years old with AIS and parents/carers of young people with AIS. Setting England. Participants A total of 22 HCPs from 13/24 NHS paediatric spinal centres in England, 19 10-25 years with AIS and 11 parents/carers. Results Conventional x-ray remains the main imaging modality. Significant geographic inequality exists. The most commonly available radiation-sparing imaging modality available is the EOS system, which uses slot-scanning technology, is available at 7 centres in England, primarily in London imaging networks. Acquisition of EOS systems is currently driven by local charitable funding rather than a centralised strategy, with high capital and installation costs cited as primary barriers. Inconsistent knowledge of imaging within primary care and a lack of specialist expertise in local secondary care services led to diagnostic redundancy, gatekeeping, and low value inconsistent imaging. These systemic delays frequently closed the window for conservative treatments like bracing. A professional balancing act exists between the duty to inform and the desire to minimise patient anxiety. HCPs often use selective communication regarding radiation risks. Conversely, families demonstrate high relational trust with HCPs and low baseline knowledge of cumulative exposure, often viewing frequent imaging as a reassuring marker of clinical progress. In centres with EOS systems, clinicians felt empowered to lead proactive, transparent risk discussions. In standard X-ray settings, dialogue remains reactive and infrequent, leading to a reliance on implied rather than truly informed consent. Conclusions AIS imaging in England is variable. Geographic location dictates access to low-dose radiation technology and the quality of informed consent. Systemic inefficiencies and fragmented referral pathways contribute to diagnostic redundancy and delayed specialist care. National standardisation of clinical pathways, information provision and a centralised strategy for low-dose technology procurement are essential to eliminate structural inequalities and ensure equitable, transparent care for all patients.

Background: Early detection of pancreatic ductal adenocarcinoma (PDAC) is critical. While faecal elastase-1 (FE-1) is a standard clinical marker for pancreatic function, its diagnostic accuracy for malignancy is limited. We sought to identify plasma metabolites that enhance FE-1 performance in symptomatic "at-risk" patients. Methods: Using the DEPEND cohort (CRUK C45617/A29908), plasma metabolomics was performed on patients with resectable PDAC (n=23) and healthy volunteers (n=24). Predictive modelling included feature selection and cross-validation, with further validation in an independent external cohort. Results: Citrulline was identified as significantly depleted in PDAC patients across discovery and validation cohorts. In isolation, Citrulline achieved an AUC of 0.86 (internal) and 0.88 (external validation). Standalone FE-1 demonstrated an AUC of 0.67. However, combining Citrulline and FE-1 significantly improved diagnostic performance, achieving a combined AUC of 0.96. Stratification revealed distinct metabolomic signatures associated with poorly differentiated tumours, suggesting a link to histological grade. Conclusions: Integrating Citrulline with FE-1 testing substantially improves PDAC detection in symptomatic patients. This non-invasive panel offers high diagnostic potential, though prospective validation is required to establish clinical cut-offs for routine practice.

Purpose: Suicide mortality is underestimated due to misclassification under undetermined and accidental deaths. This study examined national trends in suicide and related external causes of death in Portugal from 2002 to 2023, by sex and age group, assessing potential shifts suggesting masked suicide and quantifying the relationship between undetermined, suicide, and accident death rates through ratio indices. Methods: Using official mortality data from Portugal's Statistics Institute (INE) for 2002-2023, we calculated age-standardised (SDR) and age-specific death rates (ASDR) for suicide (X60-X84), undetermined intent deaths (Y10-Y34), and unintentional deaths (V01-X59), disaggregated by sex and four age groups (15-24, 25-44, 45-64, 65+). We estimated undetermined-to-suicide (UnD:Suic) and undetermined-to-accidents (UnD:Accs) rate ratios for SDRs and ASDRs. Trends were analysed using joinpoint regression (APC/AAPC) and structural breakpoint analysis (Chow test, BIC). Results: Suicide SDRs declined across the period for males (AAPC: -2.25%) and females (AAPC: -1.32%), with the sharpest reductions among males aged 25-44 (AAPC: -2.56%) and females aged 65+ (AAPC: -2.44%). Deaths of undetermined intent rose steeply from 2002 to 2005-2006 and declined thereafter. Unintentional deaths declined in most age groups, except females aged 65+ (AAPC: +1.41%). Both ratio series peaked around 2005-2009, declined progressively through the 2010s, and reached their lowest values in 2021-2022. Age-specific analyses revealed a significant and sustained increase in both ratios among females aged 45-64. Structural breakpoints clustered around 2004, 2013-2015, and 2019-2020. Conclusion: Suicide mortality declined in Portugal from 2002 to 2023, but divergent trends in undetermined and accidental deaths across sex and age subgroups highlight ongoing misclassification. Age- and sex-specific ratio analyses identify the population subgroups where misclassification is most concentrated, providing a foundation for future imputation-based estimates of probable suicide burden.

Electronic health records (EHR) are increasingly recognised as critical digital infrastructure for integrated, patient-centred care in the context of rising multimorbidity. In low-resource settings, national EHRs may also support locally driven learning to improve adaptive care across chronic conditions. However, there is limited empirical evidence on whether and how these systems enable learning within routine care in ways that inform broader system adaptation. We conducted a qualitative multi-method assessment of Impilo, Zimbabwe's national EHR, to examine its capacity to support learning for integrated multimorbidity care at primary care level, using HIV-hypertension as a tracer condition pair. Guided by Friedman's socio-technical infrastructure model as the analytical framework and Learning Health Systems (LHS) theory as the interpretive framework, data were drawn from documentary review, ethnographic observation, patient journey mapping, and interviews with frontline health workers and key stakeholders. Frontline learning for person-centred multimorbidity care was actively generated through interpretation of patient trajectories, experiential adjustment, and coordination across HIV and hypertension services using both the EHR and paper-based artefacts such as registers and patient booklets. However, this learning remained largely encounter-bound and weakly stabilised. Impilo did not routinely provide usable longitudinal patient views, practice-facing analytic tools, or institutionalised mechanisms for collective reflection required to support integrated multimorbidity care. Consequently, learning was largely confined to incremental adjustment within existing workflows, with limited capacity to inform broader changes to care pathways, routines, or system design. These findings suggest that the principal barrier to developing LHS is not the absence of data or frontline learning capacity, but the lack of socio-technical arrangements that enable learning to stabilise and inform system adaptation. Digitalisation alone is insufficient to support adaptive multimorbidity care. Co-production with frontline health workers may provide a pathway for aligning digital system design with routine care realities.

Introduction: As healthcare systems increasingly shift toward prevention and community-based care, the demand for physicians in extramural specialties continues to grow. Yet, a mismatch persists between workforce needs and medical students career aspirations. Little is known about how medical students and trainees develop an interest in extramural specialties such as youth health care (YHC). This study explores trainees trajectories toward becoming a youth health care physician (YHCP). Methods: We conducted a qualitative study using semi-structured online interviews with fourteen YHCPs in training. We combined an inductive and deductive approach, applying the person-environment (PE) fit framework to explore participants evolving experiences of fit and misfit. Results: Participants described growing misfit with clinical culture of medical school (i.e. the hidden curriculum), particularly during hospital-based clerkships, combined with limited exposure to YHC. For some, this misfit extended to doubts about becoming a doctor. Over time, participants developed a sense of fit and belonging within YHC, either directly or after exploring other specialties including extramural specialties. Discussion: These findings reframe specialty choice as a longitudinal search for belonging and alignment, in which trainees iteratively explore, evaluate, and refine their sense of fit across contexts. Clerkships serve as key sites for testing fit, yet also expose learners to the clinical culture, including the hidden curriculum. Broadening exposure and supporting reflective fit processes may encourage more medical students to choose extramural specialties, ultimately fostering a more balanced and sustainable alignment of the medical workforce.

Background: Bidirectional next-day associations between sleep disturbances and affective symptoms have been shown in previous research, yet the consecutive day effects between these factors remains poorly understood. Methods: We analysed longitudinal ecological momentary assessment (EMA) data obtained from a subsample of young persons in the Brazilian High-Risk Cohort (BHRC) study collected in 2020-2021. Participants reported sleep quality each morning and rated affective symptoms relating to mood, anxiety, and energy four times daily for 28 days. We selected 88 individuals (17.83{+/-}1.74 years, 56 [63.6%] female gender) with at least one instance where individuals were observed three-days in a row. Within-person bidirectional next-day effects between sleep quality and affective symptoms were estimated using mixed-effects regression analysis adjusting. We then applied g-estimation approaches to estimate the effect that lagged sleep quality and consecutive improvements in sleep quality had on affective symptoms. Results: Sleep quality and affective symptoms had bidirectional next-day effects, with sleep quality tending to have greater influence on affective symptoms than the reverse. Improved lagged sleep quality had positive effects on affective symptoms incrementally above the prior night's sleep quality. Also, improvement of sleep quality across consecutive days had incremental and approximately equal effects on affective symptoms. Conclusions: Sleep quality and affective symptoms exhibit a feedback loop, whereby poor sleep quality influences affective symptoms over consecutive days. Breaking these feedback loops, by improving sleep quality across several consecutive nights should improve affective symptoms. This supports interventions that target sustained improvement in sleep and possibly circadian regulation to improve affective symptoms.