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Impaired dynein function preserves spinal interneuron survival and positioning in an ALS-like mouse model

by Eleni Christoforidou, Jordan S. Rowe, Fabio A. Simoes, Raphaelle Cassel, Luc Dupuis, Peter Nigel Leigh, Majid Hafezparast

Impaired cytoplasmic dynein function has been implicated in amyotrophic lateral sclerosis (ALS) pathogenesis, yet the contributions of spinal interneurons to disease phenotypes remain unclear. We tested the hypothesis that hypomorphic dynein function in cholinergic neurons disrupts the development, survival, or positioning of inhibitory interneuron populations in the lumbar spinal cord. Using ChAT-Cre recombination, we generated four mouse genotypes with graded reductions in dynein activity in ChAT+ cells: Dync1h1+/+ (wildtype), Dync1h1−/+ (hemizygous wildtype), Dync1h1+/Loa (heterozygous Loa mutation), and Dync1h1−/Loa (hemizygous Loa). At 52 weeks of age, lumbar spinal cords (L3–L6) were harvested, cryosectioned, and immunostained for ChAT, GAD-67, Parvalbumin, and Calbindin. Cell counts were performed on confocal images from eight sections per mouse (N = 3 male mice/genotype), and radial distances from the central canal were normalised to gray matter width. Angular distributions were analysed via circular statistics. There were no significant genotype-dependent differences in the numbers of ChAT+, GAD-67+, Parvalbumin+, or Calbindin+ cells, nor in ChAT+ subpopulations (motor neurons versus interneurons) or double‐positive interneuron subsets (e.g., ChAT+–GAD-67+, Parvalbumin+–GAD-67+, Parvalbumin+–Calbindin+). Radial positioning relative to the central canal was similarly preserved across all markers and genotypes. Circular‐median tests revealed statistically significant shifts in mean angle for ChAT+, GAD-67+, and certain double‐positive cells, but these amounted to only 5–10° displacements, translating to lateral shifts of ~10–20 µm, well within single laminar bands, and are unlikely to impact circuit connectivity. Despite substantial motor deficits and hallmark TDP-43 pathology previously seen in these models, impaired dynein function does not precipitate interneuron loss or gross migratory defects in the lumbar spinal cord. Instead, our findings suggest that the primary contributions of dynein to ALS-like phenotypes likely arise from functional disruptions in axonal transport, synaptic maintenance, and neuronal physiology rather than from structural alterations or loss of interneuron populations.

Global maternal and infant health monitoring systems: a scoping review protocol

Por: Al-Habbal · K. · Hassan · Z. · Kaddoura · R. · Yousef · S. · Fetty · J.
Introduction

Enhancing maternal and infant health is a cornerstone of global health advancement. This can be achieved by building sustainable health monitoring systems that can accurately and reliably generate high-quality data and produce evidence-based recommendations for policymakers. By identifying gaps and strengths in current systems, this review aims to highlight current practices in monitoring maternal and infant health outcomes, including low birth weight.

Methods and analysis

The review will adopt the Arksey and O’Malley framework and the Joanna Briggs Institute’s Scoping Review Methods Manual. Three databases, including PubMed, Embase and CINAHL (Cumulative Index to Nursing and Allied Health Literature), as well as relevant grey literature sources, will be searched for articles describing active global population-based maternal and infant health monitoring systems published in English from the year of database inception till 30 September 2025. Two reviewers will independently screen titles and abstracts, followed by independent full-text screenings against predefined eligibility criteria, with data extracted using a data extraction form. After data extraction, a narrative synthesis will be performed. The findings will adhere to Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews guidelines.

Ethics and dissemination

This review is based on publicly available data; no ethical approval is required. The findings of this scoping review will be published in journals and presented at relevant conferences.

SOCAV: a nurse-led support programme for self-direction in people with dementia receiving home care, involving informal caregivers - a feasibility study with process evaluation in the Netherlands

Por: Das · P. · Douma · G. · Donkers · H. · Roets-Merken · L. · Graff · M.
Objectives

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

Design

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

Setting

Two home care teams in different Dutch municipalities.

Participants

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

Intervention

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

Results

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

Conclusions

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

Trial registration number

NCT07347639; Post-results.

Evaluation of Work‐Related Stress, Moral Reward and Job Satisfaction Among Healthcare Professionals in the Postpandemic Era

ABSTRACT

Aim

This study investigates work-related stress, moral reward and job satisfaction among healthcare professionals in the postpandemic era, focusing on the psychological and professional challenges they face. The study examines the role of excessive demands, inadequate support and reward imbalances, and explores the impact on healthcare workers' well-being and patient care quality.

Design

Utilising a quantitative research design, the study involved Greek healthcare professionals across various specialities.

Methods

Data were gathered via standardised questionnaires: the Perceived Stress Scale (PSS-14), Effort–Reward Imbalance (ERI) Questionnaire and Employee Satisfaction Index (ESI). The instruments assessed stress levels, effort–reward balance and job satisfaction, with analysis conducted using SPSS to identify key stressors and their correlation with job satisfaction.

Results

The findings indicated high levels of perceived stress among participants without significant gender differences. Nurses particularly reported higher efforts and reward imbalances. Overall job satisfaction was moderate, with specific dissatisfaction with rewards, benefits and career advancement opportunities. Statistical analyses revealed significant correlations between increased stress, ERI and emotional overcommitment.

Conclusions

The study highlights the critical need for interventions that address ERIs and improve psychosocial support and working conditions, especially for nursing staff. It emphasises the importance of equitable compensation, professional advancement opportunities and a supportive work environment to enhance job satisfaction and reduce stress among healthcare professionals in a postpandemic context.

Impact

This study underscores the need for systemic interventions to alleviate work-related stress, ensuring better work-life balance and improved job satisfaction among healthcare professionals.

Patient or Public Contribution

No public or patient involvement.

Prevalence and associated risk factors of tinnitus among Palestinian adolescents aged 15–18: A cross-sectional study

by Saad Al-Lahhaam, Raghad Dweikat, Tala Nazzal, Aman Maraqa, Joud Khalil, Tala Albadawi, Raghad Doufish, Wa'd Amer, Mustafa Ghanim, Mohammad Abuawad, Amer Ghrouz, Samar Alkhaldi, Laith El-lahham, Majdi Dwikat, Maha Rabayaa, Malik Alqub

Background

Tinnitus is a prevalent condition worldwide, particularly among adolescents, that has a substantial impact on quality of life, yet it remains an understudied issue.

Objectives

This study aims to determine the prevalence of tinnitus and its associated risk factors among Palestinian adolescents aged 15–18.

Methods

A cross-sectional study was conducted from January to March 2025. A convenience sample of participants was recruited. The study utilized the European School for the Interdisciplinary Tinnitus Research Screening Questionnaire.

Results

A total of 1,131 participants were enrolled in the study, with 64.5% being females. The prevalence of tinnitus among the study sample was 532, representing 47% of the population. Females had a higher prevalence of tinnitus, with 370 affected (50.7%) compared to males (40.4%). Significant associations were found between tinnitus and several factors: age, positive family history of tinnitus (threefold increased risk), sensitivity to external sounds (2.7 times higher likelihood), slight hearing difficulty in noisy environments (1.7 times higher risk), pain symptoms (double the risk), and difficulty falling asleep (1.8 times higher risk). Notably, the majority of affected participants (71.5%) had never sought professional care for their tinnitus.

Conclusion

Although Tinnitus is common among Palestinian adolescents aged 15–18 years, the majority of affected participants did not seek professional care for tinnitus. These findings highlight the importance of conducting further research to shed insight into this prevalent and neglected health priority.

Organ failure type in fatal and near-fatal anaphylaxis: a systematic review

Por: McKenzie · B. · Marshall · S. D. · Sanci · L. · Poonian · J. · Nair · R. · J Selman · C. · Douglass · J. A.
Objectives

Anaphylaxis is a sudden onset multiorgan allergic reaction that infrequently but regularly causes fatalities which may be preventable with appropriate organ support. There is limited data about the type of organ failure leading to death or near-fatal episodes resulting in permanent neurological disability. To assist clinicians facing anaphylaxis in diverse clinical settings, we aimed to quantify the frequency of organ failure type contributing to death or neurological disability from anaphylaxis according to allergen trigger.

Design

Systematic review of published peer-reviewed literature.

Data sources

Three databases were searched to January 2025: MEDLINE from 1946, Embase from 1947 and Web of Science from 1900.

Eligibility criteria

Studies were eligible if they contained data about the type of clinical deterioration during anaphylaxis resulting in death or permanent neurological disability. No language restriction was implemented. Exclusion criteria were: hydatid anaphylaxis; five or more stings from an insect; death from acute atheromatous myocardial infarction and where anaphylaxis was only a differential diagnosis.

Data extraction and synthesis

We extracted information using pre-specified criteria to determine the primary organ failure involved: either upper airway obstruction, lower respiratory obstruction (bronchospasm) or cardiovascular failure. Baseline demographics including age and asthma status were collected along with the allergen trigger, time course and treatment. We reported frequencies according to allergen trigger for case reports and a narrative analysis of case series weighted by risk of bias assessment.

Results

277 case studies and 14 case series were identified reporting 896 deaths and 28 disabilities. There were no other study types. Separate case series and case report analyses produced similar findings despite varying quality of published clinical data. Respiratory failure was the most common primary organ failure in case reports (73.4%), whereas primary cardiovascular failure was reported in 26.6% of case reports. Primary organ failure type differed in frequency by allergen trigger and was primarily caused by: respiratory failure when food was the allergen trigger (95%); respiratory failure in 65% of cases of drug allergen triggers; cardiovascular failure in 65% venom allergen triggers.

Conclusion

In this review, respiratory failure (primarily bronchospasm) is the most common primary physiological event leading to decompensation in fatal anaphylaxis, particularly for food and drug allergen deaths. Emphasising the significance of respiratory involvement, particularly from bronchospasm, in both patient and clinician facing anaphylaxis treatment guidelines may help further reduce the risk of fatalities. Prospective anaphylaxis management registries or whole population data are needed to better capture primary organ failure present in fatal anaphylaxis to validate this finding.

PROSPERO registration number

CRD42023434206.

Enhancing communication with bereaved relatives about emergency and critical care trials (ENHANCE): a mixed-methods study

Por: Doughty · H. · Deja · E. · Young · B. · Welters · I. · Shepherd · V. · Milosevic · S. · OHara · K. · Carman · J. · Sankar · V. · Thomas-Jones · E. · Euden · J. · Woolfall · K.
Objectives

Clinical research in emergency and critical care is vital, but recruitment and consent are complex. Research may be conducted without prior consent when patients are critically ill, and interventions are time critical. Some patients may die before research participation can be discussed with relatives, leaving the bereaved unaware of their involvement. This study explored potential communication strategies for informing bereaved relatives when a patient has died following enrolment into an emergency or critical care study without prior consent.

Design and setting

A mixed-methods study using a telephone survey and semi-structured interviews conducted simultaneously. The survey was conducted within a National Health Service Trust in North West England with relatives of deceased study participants. Semi-structured interviews were conducted with bereaved relatives and research and clinical staff across the UK, and medical examiner (ME)/ME officers based in England and Wales. Quantitative data were analysed descriptively, and qualitative data were analysed using reflexive thematic analysis. Data were synthesised using a constant comparison approach.

Participants

11 bereaved relatives completed the survey. 53 individuals (21 research and clinical staff, 18 relatives and 14 MEs/officers) participated in semi-structured interviews.

Results

Although many trials do not include a process for notifying bereaved relatives about research participation, most relatives valued the opportunity to learn about their family member’s participation, emphasising the importance of transparency and trust. However, some raised concerns over the potential burden of automatic disclosure by the ME service. Offering bereaved relatives the option to receive sensitively worded information about research involvement at an appropriate time, soon after death, was recommended.

Conclusion

Bereaved relatives should have the choice to be informed about research participation without prior consent. Our findings support the need for transparent and sensitive communication and will contribute to future guidance for the design and conduct of adult emergency and critical care studies.

ALARUM: Active One Health surveillance in LMICs to monitor and predict Antimicrobial Resistance Using Metagenomics - a cross-sectional study protocol

Por: van der Sande · M. A. B. · Valia · D. · Tigoi · C. · Stoesser · N. · Stamm · L. · Marten · A. · Riems · B. · Musyimi · R. · Sibidou · Y. · Schurch · A. C. · Tiendrebeogo · E. W. · Mwaringa · S. · Kohns Vasconcelos · M. · Ingelbeen · B. · Tinto · H. · Bielicki · J. A. · Cooper · B. S. · B
Background

In rural sub-Saharan Africa (sSA), the burden of antimicrobial resistance (AMR) remains high. As AMR continues to rise, there is a strong need for practical, implementable surveillance to monitor and mitigate risks, as well as inform timely, evidence-based clinical decision-making. Emerging evidence points to possible community-level drivers, such as transmission between human, animal and environmental reservoirs as contributing factors, yet microbiological surveillance or opportunities for wastewater-based surveillance are often limited and insufficient in these settings. Therefore, alternative sustainable and affordable approaches are needed. We intend to build on the demonstrated potential of metagenomic profiling of pooled faecal material, which accurately predicted population-level AMR prevalence in invasive Enterobacterales infections.

Methods and analysis

We aim to validate this metagenomic pooled approach on additional populations, and to evaluate whether AMR patterns could be similarly predicted from surveillance of community One Health reservoirs. We will assemble existing data from hospital-based microbiology diagnostic laboratories in rural Burkina Faso and Kenya, and determine to what extent community-level metagenomic data, and/or faecal material of patients on hospital admission, can predict AMR in clinical isolates. We will perform community-level surveys in eight clusters per country, randomly selecting 15 households per cluster. We will systematically sample suspected environmental AMR exposure sites in and around households (soil, drinking water, latrines, chicken faeces) and collect data on community-level antibiotic use, hygiene practices, contact with domestic animals and sanitary facilities. Samples and data will be collected twice: during the dry and during the rainy season.

In addition to evaluating the accuracy of predicting resistance in clinical isolates, we will quantify community-level exposure risks. We will conduct metagenomic profiling on pooled DNA extracts from human stool samples (hospital and community-level) and from household environments. Bayesian statistical models will quantify relationships between AMR gene abundance in the environment and in human stool, and invasive bacteria identified among clinical patients, accounting for geography and seasonality. A cost-utility analysis will determine under what circumstances the use of pooled metagenomic data to inform empirical antibiotic policies would represent an efficient use of resources.

Ethics and dissemination

The proposed surveillance protocol is developed in partnership with local communities and local and international researchers and has received ethical approval in Kenya and Burkina Faso. It will assess whether intermittent, pooled-sample metagenomics provides a viable, low-cost and practical approach for population-level AMR surveillance in settings that—like many in rural sSA—lack systematic microbiological diagnostics and where sewage systems for wastewater-based surveillance are absent. By providing an alternative to routine microbiological-based surveillance where this proves challenging to implement, this approach may help improve treatment outcomes, contribute to equity and public health. Findings will be disseminated through peer-reviewed publications and academic conferences and will contribute to the recently proposed WHO AMR surveillance strategy, which combines survey-based approaches with routine AMR surveillance.

Community pharmacists’ history taking practice in responding to acute uncomplicated cystitis: A simulated patient study from Sudan

by Riham M. Hamadouk, Esra D. Albashair, Einass M. Alshareif, Ali Awadallah Saeed, Bashir A. Yousef

Background

Today, community pharmacists’ responsibilities have expanded beyond the traditional role to include the management of minor ailments. Acute uncomplicated cystitis is one of the most prevalent medical conditions seen in primary healthcare and can be managed by community pharmacists (CPs).

Objectives

To evaluate community pharmacists’ history-taking practice when responding to patients with acute uncomplicated cystitis.

Methods

A cross-sectional simulated patient study was conducted from November 2022 to January 2023 in Khartoum locality targeting only pharmacists. Six trained female students played the simulation in which they pretended to have the clinical symptoms of acute uncomplicated cystitis and requested treatment for their condition. The Interactions during the simulation were documented immediately in a data collection form after each visit. Descriptive statistics were used to report the study outcomes.

Results

A total of 238 community pharmacies were visited. The majority of the pharmacists were female. The mean of the number of questions that were asked by the pharmacists was 1 (SD = 1.6) questions. Among the studied pharmacists, 45.4% asked at least one question during patient assessment. The most asked question was if the patient has a fever, representing 61 (25.6%) CPs, followed by if there is vaginal discharge, representing 38 (16%) CPs. In response to scenario 47 (19.7%) CPs decided to refer the patient to a physician, and 45 (18.9%) of the CPs advised the patient to increase water intake.

Conclusions

The study has revealed a poor history-taking practice towards acute uncomplicated cystitis during patient assessment. Further studies exploring pharmacists’ involvement in patient assessment are required. Strategies to improve community pharmacists’ practice, like continuing pharmacy education and providing a national guideline regarding patient assessment should be considered seriously.

Feasibility and results of joint ambulatory monitoring of exposure to particulate matter pollution and lung function in children in Abidjan, Cote dIvoire: a cross-sectional observational study

Por: Pajot · A. · Yapo · M. · Liousse · C. · Doumbia · M. · Gnamien · S. · Ahoua · S. · Dje · S. · Dick · F. · Fayon · M. · Yoboue · V. · Marcy · O.
Background

Children are largely exposed to air pollution in low- and middle-income countries, yet data on exposure and respiratory effects of air pollution remain limited. This study aimed to assess the feasibility and outcomes of joint ambulatory monitoring of exposure to fine particulate matter (particles with a diameter of less than 2.5 µm (PM2.5)) and spirometry in children living in Abidjan, Côte d’Ivoire.

Methods

We did a cross-sectional observational study among children aged 7–17 years. After a baseline spirometry, children were asked to wear portable PM2.5 sensors and to perform 2x3 daily flow–volume curves using a portable spirometer for 7 days. We described the proportion of acceptable measurements, per cent predicted forced expiratory volume (ppFEV1), and hourly geometric mean PM2.5 concentrations, and analysed the cumulative delayed effects of PM2.5 on ppFEV1 using distributed lag non-linear models.

Results

Of 29 children enrolled, 18 (62.1%) were female, median age 12 years, all performed spirometry with 1101 (90.4%) of 1218 expected flow-volume curves obtained. Of these, 625 (51.3%) acceptable curves were received and 313 valid, non-duplicate curves were analysed. The median ppFEV1 was 79.6% (71.5–87.4), with lower values in the morning than in the evening (p2.5 measurements, 93 689 (64.1%) were obtained; 6328 aberrant data were excluded. The median hourly PM2.5 concentrations were 164.2 (107.0–272.2) µg/m3. PM2.5 levels varied throughout the day, with pollution peaks observed in the morning. A significant decrease in ppFEV1 was observed between 0 and 2 hours post-exposure, after an IQR increase of 120.9 µg/m3 in PM2.5 exposure (β=–2.21; CI –3.74 to –0.69).

Conclusion

Ambulatory spirometry and PM2.5 measurements are feasible with portable devices in African children. High PM2.5 exposure and individual variability in lung function highlight the need for further research on the respiratory effects of air pollution in children.

Biobanking knowledge and donation willingness among musculoskeletal patients in England: a multisite cross-sectional study

Por: Boakye Serebour · T. · Kerasidou · A. · Gray · N. · Griffin · X. L. · Peach · C. · Singh · H. P. · Wheway · K. · Ambrosio · M. d. G. · Baldwin · M. · Snelling · S. J. B.
Objective

To date, few studies have investigated the factors associated with musculoskeletal patients’ willingness to donate biological samples and their knowledge regarding the use of such samples. We investigated the associations between these distinct knowledge factors, patients’ willingness to donate and socio-demographic factors.

Design

Cross-sectional survey.

Setting

Musculoskeletal outpatient clinics across four sites in England, representing varied demographic populations.

Participants

A total of 469 adult patients attending musculoskeletal appointments were recruited through convenience sampling.

Primary and secondary outcome measures

Ordinal regression models were employed to identify socio-demographic and clinical predictors of patients’ willingness to donate biological samples. Other outcome measures specifically in two areas of patient knowledge include: (1) knowledge of sample use and (2) knowledge of surgical waste tissue value and management.

Results

Only 37% of participants were aware of the term ‘biobank’. Despite this, participants showed a high level of knowledge regarding both biological sample use and surgical waste tissue management, although their understanding varied considerably by ethnicity and education. Participants with no formal education exhibited a lower level of knowledge in both areas related to sample use and surgical waste tissue management for biomedical research ((OR 0.30, 95% CI 0.14 to 0.61; p=0.001); (OR=0.29, 95% CI 0.16 to 0.52, p

Conclusions

Despite low awareness, musculoskeletal patients showed a high willingness to participate in biobanking. However, significant disparities by ethnicity and education persist. Targeted, inclusive engagement strategies are needed to address under-representation and foster informed, equitable participation of musculoskeletal patients in biomedical research.

Relationships between alcohol use and dementia: protocol for an observational study in the UK Clinical Practice Research Datalink

Por: Fatih · N. · Bhaskaran · K. · Kwok · A. C. H. · Ebmeier · K. P. · Nichols · T. · Gelernter · J. · Christodoulou · M. D. · Topiwala · A.
Introduction

Alcohol consumption is an increasingly recognised modifiable risk factor for dementia, yet whether it has differential impacts on dementia subtypes and its role in disease progression remains unclear. This study aims to: (1) quantify the association between alcohol intake and incidence of dementia subtypes and (2) examine whether individuals who drink heavily and develop dementia referred to hereafter as ‘alcohol-related’—have poorer post-diagnosis outcomes compared with other dementia cases. Clarifying these relationships will determine whether alcohol selectively increases risk for specific dementia phenotypes or broadly heightens neurodegenerative vulnerability, with implications for prevention, clinical counselling and therapeutic targeting.

Methods and analysis

This population-based cohort study of alcohol and dementia will use linked UK electronic health records from Clinical Practice Research Datalink, Hospital Episode Statistics and Office for National Statistics (ONS). Participants will be eligible if they have available linked data from January 1998, when ONS death registrations became available, until the end of follow-up. Alcohol exposure will be defined through self-reported recorded weekly alcohol units and diagnostic codes for harmful or dependent alcohol use. Primary outcomes including incident all-cause and subtype-specific dementia (eg, Alzheimer’s, vascular, Lewy body, Parkinson’s, frontotemporal) as well as secondary outcomes (ie, mortality, care-home entry and neuropsychiatric symptoms). Key covariates encompassing socio-demographic factors, smoking and relevant comorbidities will be adjusted for. Multivariable Cox proportional hazards and Fine-Gray competing risk models will estimate associations with dementia incidence. Post-diagnosis prognosis will be compared for dementia in individuals with a history of heavy alcohol use (‘alcohol-related’) and dementia in individuals with minimal alcohol exposure (‘non-alcohol-related’) cases using survival and logistic regression models. Multiple testing correction will be applied across dementia subtype comparisons. Alcohol exposure will be modelled continuously and non-linearly using restricted cubic splines and categorically using binary indicators of harmful/dependent use. Missing covariate data will be assessed and addressed using appropriate methods, including multiple imputation and complete-case analysis. Data extraction and analysis are scheduled from October 2025 to October 2026.

Ethics and dissemination

Use of de-identified routine data will proceed under existing Research Ethics Committee and data governance approvals. Findings will be disseminated via open-access peer-reviewed journals, academic conferences and summaries targeted at patient, public and policy audiences. The results of this study will be reported according to the STROBE (Strengthening the Reporting of Observational Studies in Epidemiology) and The REporting of studies Conducted using Observational Routinely-collected health Data (RECORD) guidelines.

Chronic intestinal immune activation reveals separable impacts of inflammation and barrier loss on hallmarks of ageing

by Jeanette Alcaraz, Charlotte Keyse, Charles Hall, David W. Walker, David P. Doupé, Rebecca I. Clark

Inflammaging is considered a driver of age-associated pathology across tissues. Similarly, intestinal permeability is a feature of ageing and underlies a range of inflammatory and age-related diseases. Increased intestinal permeability has been described as both a cause and a consequence of inflammation. Both intestinal permeability and inflammation are closely associated with microbial dysbiosis, epithelial dysplasia and mortality but dissecting the complex interplay between these phenotypes remains challenging. Here we genetically induce intestinal immune activation in Drosophila and stratify animals by their intestinal barrier status using the Smurf assay. We demonstrate that intestinal barrier failure has a distinct impact on the microbiota. Further, immune activation, both within the intestine and systemically, drives intestinal barrier failure and mortality even in the absence of the microbiota. Importantly, immune-induced intestinal barrier failure takes time to develop and is closely associated with the onset of mortality. Our work adds to building evidence that the impact of intestinal permeability on the microbiota and on animal health needs to be considered independently of its relationship with inflammation.

Effect of race and sex on lupus diagnosis in primary care: A randomized factorial survey study

by Alyssa Howren, Quan L. Tran, Sadaf Sediqi, Saadiya Hawa, Douglas K. Owens, Eleni Linos, Titilola O. Falasinnu, Yashaar Chaichian, Julia F. Simard

Background

Systemic lupus erythematosus (SLE) is a heterogeneous autoimmune rheumatic disease whose epidemiology and clinical prognosis vary by race and sex. Observed disparities in SLE may be partly attributable to cognitive processes in clinical decision-making, which can influence diagnostic accuracy and clinical management. We aimed to examine variation in primary care physicians’ (PCP) diagnosis and management of SLE when all content of a clinical case is identical, apart from race and sex.

Methods

We distributed an online randomized factorial survey from 04/11/2024–06/10/2024 to PCPs across the US. Participants were presented with one of four possible SLE vignettes – Black female, White female, Black male, White male – for which all other clinical content was identical. Block randomization was used to randomly modify the race (Black/White) and sex (female/male) of the SLE “case”. Primary outcomes were correct text-based responses for SLE diagnosis at initial case presentation and after reviewing additional lab results. Secondary outcomes were participants’ review time and planned next steps (treatment, referral, tests) as a proxy for cognitive bias and certainty, respectively. We calculated descriptive statistics for all outcomes stratified by assigned randomized factor and used chi-square tests to evaluate between-group differences.

Results

1031 PCPs (42.7% women, mean age 52.1 ± 12.1 years) completed the case. At initial presentation, 63.9% of participants correctly identified SLE as a differential diagnosis. An initial diagnosis of SLE significantly differed by the race and sex of the case (p  Conclusion

A patient’s race and sex may influence diagnostic accuracy and clinical decision-making for SLE in primary care. The observed variation in diagnostic accuracy, which aligns with the descriptive epidemiology of SLE, highlights the need for targeted interventions to ensure equitable diagnostic processes.

Health service contacts for mental health and substance use on release from prison: a retrospective population-based data linkage study

Por: Connell · C. · Kjellgren · R. · Savinc · J. · Dougall · N. · Kurdi · A. · Watson · J. · Haddow · C. · Brown · A. · Parkes · T. · Hunt · K.
Background

Mental health and substance use problems among people released from prison contribute substantially to premature mortality and emergency services demand. Understanding of mental health and substance use-related health service contacts prior to these severe and costly outcomes is limited. We assessed mental health and substance use-related contact with multiple services, comparing rates of contact among people released from prison to a matched general population sample who had not recently been in prison.

Objectives

To compare rates of health service contacts for mental health and substance use between people released from prison and a matched general population sample.

Design

We conducted a retrospective cohort study using linked administrative data with nationwide coverage. The cohort contained all people released from any Scottish prison in 2015 (exposed group), and a random general population sample matched (ratio 1:5) on sex, age, postcode and deprivation indices, who had no imprisonment in the 5 years prior (unexposed group). We linked individual-level administrative healthcare (prescriptions, outpatient, inpatient, emergency/unscheduled care: 2010–2020), prison (admissions, releases: 2010–2020) and deaths records (2015–2020). We estimated adjusted incidence rate ratios (aIRRs) with 95% CIs using fixed-effects Poisson regression with cluster-robust standard errors, controlling for time-in-community, pre-index mental health and substance use-related health service contacts, and comorbidities. We stratified models by mental health (MH), substance use (SU) and dual diagnosis (attributable to both MH and SU).

Setting

Scotland.

Results

We linked records for 8313 people released from prison, and 41 213 matched individuals. Mental health and substance use-related contact rates were significantly higher for people released from prison across all services, and particularly for emergency and unscheduled care. aIRRs for ambulance contacts were MH=7.75 (95% CI 5.76 to 10.42), SU=7.58 (95% CI 5.71 to 10.08), dual diagnosis=8.28 (95% CI 6.50 to 10.55); and accident and emergency department contacts were MH=4.88 (95% CI 3.78 to 6.29) and SU=7.98 (95% CI 5.71 to 11.17). aIRRs for community prescriptions were MH=1.80 (95% CI 1.67 to 1.94), SU=5.95 (95% CI 4.83 to 7.32), dual diagnosis=5.33 (95% CI 3.70 to 7.68); drug and alcohol services were 7.13 (95% CI 6.00 to 8.48); and outpatient attendances were 2.61 (95% CI 2.17 to 3.16). aIRRs for 24-hour unscheduled telephone support were MH=7.63 (95% CI 4.93 to 11.83) and SU=8.29 (95% CI 3.99 to 17.22); and out-of-hours general practice were MH=5.14 (95% CI 3.66 to 7.22), SU=5.89 (95% CI 3.11 to 11.14) and dual diagnosis=8.85 (95% CI 2.94 to 26.63). aIRRs for general/acute hospital admissions and day cases were MH=2.97 (95% CI 1.43 to 6.16), SU=7.85 (95% CI 4.42 to 13.91), dual diagnosis=13.11 (95% CI 7.95 to 21.61); and for psychiatric admissions were MH=3.62 (95% CI 2.39 to 5.49), SU=10.74 (95% CI 6.12 to 18.84) and dual diagnosis=7.74 (95% CI 4.30 to 13.94).

Conclusions

Improved post-release mental health and substance use care is vital for individual and public health. Despite elevated rates of contact with community mental health and substance use services, people released from prison have disproportionately high rates of contact with emergency and unscheduled care services. This suggests that early support is either inadequate or not accessed by those in greatest need.

Policymakers and service providers should consider investment in tailored transitional and post-release intervention at individual and population level, to improve health and thus prevent later high-cost service use and avoidable mortality. Our results also suggest high-quality care must be available and accessible beyond the immediate post-release period to permit sustained engagement or engagement at a later date.

Geriatric Models of Surgical Care: A Scoping Review

ABSTRACT

Aim

To synthesise literature on hospital-based geriatric models of care for older adults undergoing surgery, examining structures, team composition, governance and nursing contributions.

Design

Scoping review.

Methods

Following JBI methodology, two reviewers independently screened articles against eligibility criteria (Population: adults ≥ 65 years, Concept: multidisciplinary geriatric surgical care model; Context: acute hospital settings), with conflicts resolved by a third reviewer. Data were extracted and charted for descriptive synthesis.

Data Sources

Six databases (CINAHL, MEDLINE, Embase, Scopus, AgeLine, Cochrane Library) searched for studies published between January 2015 and February 2025.

Results

Of 2753 records identified, 81 studies were included. Models were commonly co-managed between surgical and geriatric teams, implemented at varying surgical pathway points. Orthopaedics represented 57% of studies. Geriatricians were involved in 90% of models; 38% included advanced practice nurses or specialist gerontological nurses. Comprehensive Geriatric Assessment was used in nearly half the studies, typically preoperatively. Considerable heterogeneity existed in model design, professional roles and care settings.

Conclusion

Integrated geriatric perioperative care is expanding globally but remains limited outside orthopaedics. Research should shift from improvement projects to rigorous implementation for sustainable transformation, including nurse-led models. Critical examination is needed of whether current outcomes address comprehensive needs of older surgical patients or primarily optimise hospital flow.

Implications for the Profession and/or Patient Care

Findings highlight opportunities to expand geriatric models beyond orthopaedics and enhance nursing roles, particularly advanced practice nurses, in delivering comprehensive perioperative care for older adults.

Impact

Addressed the gap in understanding how geriatric models of surgical care are operationalised. Identified underutilisation of nursing expertise and limited expansion beyond orthopaedics. Will impact service design, policy development and clinical implementation for older surgical patients.

Reporting Method

Adhered to PRISMA Extension for Scoping Reviews (PRISMA-ScR) guidelines.

Patient or Public Contribution

No patient or public involvement.

Protocol Registration

Open Science Framework Registries Network.

Assessing the Effectiveness of Interventions Implemented by Nurses to Reduce Medication Administration Errors in Hospitalised Acute Adult Patient Settings: Systematic Review and Meta‐Analysis

ABSTRACT

Background

Medication administration errors are high-risk patient safety issues that could potentially cause harm to patients, thereby delaying recovery and increasing length of hospital stay with additional healthcare costs. Nurses are pivotal to the medication administration process and are considered to be in the position to recognize and prevent these errors. However, the effectiveness of interventions implemented by nurses to reduce medication administration errors in acute hospital settings is less reported.

Aim

To identify and quantify the effectiveness of interventions by nurses in reducing medication administration errors in adults' inpatient acute hospital.

Methods

A systematic review and meta-analysis was conducted up to 03/24. Six databases were searched. Study methodology quality assessment was conducted using the Joanna Briggs Institute (JBI) critical appraisal tools, and data extraction was conducted. Meta-analysis was performed to combine effect sizes from the studies, and synthesis without meta-analysis was adopted for studies that were not included in the meta-analysis to aggregate and re-examine results from studies.

Results

Searches identified 878 articles with 26 studies meeting the inclusion criteria. Five types of interventions were identified: (1) educational program, (2) workflow smart technologies, (3) protocolised improvement strategy, (4) low resource ward-based interventions, and (5) electronic medication management. The overall results from 14 studies included in meta-analysis showed interventions implemented by nurses are effective in reducing medication administration errors (Z = 2.15 (p = 0.03); odds ratio = 95% CI 0.70 [0.51, 0.97], I 2 = 94%). Sub-group analysis showed workflow smart technologies to be the most effective intervention compared to usual care. Findings demonstrate that nurse-led interventions can significantly reduce medication administration errors compared to usual care. The effectiveness of individual interventions varied, suggesting a bundle approach may be more beneficial. This provides valuable insights for clinical practice, emphasizing the importance of tailored, evidence-based approaches to improving medication safety.

Reporting Method

PRISMA guided the review and JBI critical appraisal tools were used for quality appraisal of included studies.

The efficacy of trauma-informed yoga in treating post-traumatic stress disorder symptoms in trauma-exposed adults: a protocol for a systematic review and meta-analysis

Por: Wang · Y. · Xing · Y. · Meng · X. · Cao · W. · Dou · J. · Sun · C. · Fu · Q.
Introduction 

Research indicates that most individuals will experience at least one traumatic event in their lifetime. Some individuals may develop post-traumatic stress disorder, while others may exhibit subclinical levels of post-traumatic stress disorder symptoms alongside comorbid conditions such as depression and anxiety. As a body-based adjunctive intervention, trauma-informed yoga is increasingly used to mitigate post-traumatic stress disorder symptoms in individuals who have experienced trauma, including those with or without a formal post-traumatic stress disorder diagnosis. However, the efficacy of this approach remains a topic of contention in published studies.

Method and analysis

To identify relevant trials, a literature search will be conducted across seven electronic databases. We will include randomised controlled trials and pre-post studies that assess trauma-informed yoga in trauma-exposed adults. Data obtained from these sources will be synthesised and analysed meta-analytically using RevMan 5.4. The primary outcome measure will be the total score of post-traumatic stress disorder symptoms, while secondary outcome measures will encompass anxiety and depression scores. The methodological quality and risk of bias of the included trials will be evaluated using the 12-item National Institutes of Health quality assessment tool and the revised Cochrane Risk of Bias tool (version 2). Furthermore, the overall strength of the evidence will be rated according to the Grading of Recommendations, Appraisals, Developments and Evaluations framework.

Ethics and dissemination

No formal research ethics approval is required. The results will be submitted for publication in a peer-reviewed journal.

PROSPERO registration number

CRD420251113495.

Statistical analysis plan for the Strategy to Avoid Excessive Oxygen using Autonomous Oxygen Titration Intervention (SAVE-O2 AI) trial: protocol

Por: Douin · D. J. · Rice · J. D. · Xiao · M. · Beaty · L. · Guo · C. · Withers · C. · Sullivan · A. · Anderson · E. L. · Cheng · A. C. · Banasiewicz · M. K. · Semler · M. W. · Lloyd · B. D. · Maiga · A. · Gibbs · K. W. · Stettler · G. R. · Khan · A. · Sally · M. B. · Wright · F. L. · Aggarwal
Introduction

Administering supplemental oxygen to prevent hypoxaemia is a fundamental treatment for patients hospitalised with acute injury or illness. However, the amount of oxygen administered frequently exceeds that needed to maintain normoxaemia, causing patients to experience hyperoxaemia and wasting supplemental oxygen. Closed-loop, autonomous oxygen titration systems are designed to optimise oxygen delivery by administering the lowest possible oxygen flow that maintains peripheral oxygen saturation (SpO2) within a predefined range. For adults hospitalised with an acute injury or illness, it remains uncertain whether the use of a closed-loop, autonomous oxygen titration system safely increases the proportion of time spent in normoxaemia (SpO2 90%–96%) compared with usual care.

Methods and analysis

The Strategy to Avoid Excessive Oxygen using Autonomous Oxygen Titration Intervention trial is a multicentre, unblinded, parallel-group, randomised trial being conducted at four level 1 trauma centres in the USA. The trial compares an autonomous oxygen titration system versus usual care among 300 adults hospitalised for major trauma, burn, acute care surgery or acute respiratory illness. The primary outcome is the proportion of patient-time spent within the targeted normoxaemia range (SpO2 90%–96%) as measured by continuous non-invasive pulse oximetry, during the first 72 hours after randomisation. Secondary outcomes include the amount of supplemental oxygen administered and the proportion of time spent in hypoxaemia (SpO22 >96%). Specifying the protocol and statistical analysis plan before the conclusion of enrolment increases the rigour, reproducibility and interpretability of the trial. Enrolment began on 6 May 2024.

Ethics and dissemination

The trial protocol was approved by the single institutional review board at the University of Colorado School of Medicine and the Office of Human Research Oversight at the Department of Defense. We will present the results at scientific conferences and submit them for publication in a peer-reviewed journal.

Trial registration number

NCT06374225.

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